Amy Karon

The gender gap in gastroenterology persists – currently, women constitute 39% of fellows, but only 22% of senior AGA members and less than 18% of all practicing gastroenterologists – and it has gained even greater significance within the “current historical moment” of the COVID pandemic and growing cognizance of systemic sexism and racism, according to experts.

During the pandemic, women have been more likely to stay home to care for ill family members and children affected by school closures, which increases their already disproportionate share of unpaid work, wrote Jessica Bernica, MD, of Baylor College of Medicine in Houston with her associates in Techniques and Innovations in Gastrointestinal Endoscopy. They noted that, according to one study, this “holds true for female physicians, who despite their more privileged positions, also experience higher demands at home, impacting their ability to contribute to teaching, service, and research.”

At the same time, the pandemic has brought into focus which jobs are “truly essential” – and that they are “overwhelmingly [held] by women and people of color, who are often underpaid and undervalued,” the experts wrote. The growing focus on systemic racism has also increased awareness of the chronic gender discrimination faced by female minorities, as well as by women in general, they added. In the field of gastroenterology, inherent gender bias – both systemic and self-directed – can bar women from advancing beginning as early as medical school.

To help address these issues, the experts outlined key opportunities for change as women navigate professional “forks in the road” throughout their careers.
 

Throughout their careers

During medical school and residency, women can specifically request gastroenterology rotations (“ideally with both inpatient and outpatient exposure”), attend society conferences, participate in research themselves, and join a research track or serve as chief medical resident. When applying for gastroenterology fellowships, they can prioritize programs with female faculty, which were recently found to be more likely to hire female fellows.

During fellowship, women can avail themselves of female mentors, who can help them strategize about ways to address gender bias, connect with GI groups and societies, and learn endoscopy techniques, including “unique approaches ... [that] overcome the challenges of standard scope sizes and accessibility.” At the institutional level, opportunities to affect positive changes for women trainees include “formal education on the benefits of hands-on learning and encouraging explicit and open communication between parties regarding invitation to, comfort with, and type of physical contact prior to a case.”

After fellowship, early-career gastroenterologists should scrutinize contracts for details on pay and research support, and they should ideally join a practice that either already has many women physicians on staff, or that ensures salary transparency and has “parental leave policies that are compatible with [applicants’] personal and professional goals.” But the experts advocated caution about part-time positions, which may purport to offer more flexibility but turn into full-time work for part-time pay and can preclude participation in practice management.

The experts recommended midcareer female gastroenterologists call out their own achievements rather than waiting for recognition, “actively seek promotion and tenure,” negotiate their salaries (as men tend to do routinely), and think twice before accepting professional roles that are uncompensated or do not clearly promote career advancement.

Senior gastroenterologists have unique opportunities to spearhead changes in institutional policies and practices, according to the experts. Specific examples include “explicitly stating [in job listings] that salary is negotiable, creating transparent written compensation plans, and conducting audits of job offers” to help mitigate any inequities in pay or hiring practices. In addition, senior women gastroenterologists can mentor individual women in the field, implement formal trainings on implicit bias, ensure that their practice or department tracks the gender of gastroenterologists who join, leave, or are promoted.

The experts did not report receiving funding for the work. They reported having no conflicts of interest.

The gender gap in gastroenterology persists – currently, women constitute 39% of fellows, but only 22% of senior AGA members and less than 18% of all practicing gastroenterologists – and it has gained even greater significance within the “current historical moment” of the COVID pandemic and growing cognizance of systemic sexism and racism, according to experts.

During the pandemic, women have been more likely to stay home to care for ill family members and children affected by school closures, which increases their already disproportionate share of unpaid work, wrote Jessica Bernica, MD, of Baylor College of Medicine in Houston with her associates in Techniques and Innovations in Gastrointestinal Endoscopy. They noted that, according to one study, this “holds true for female physicians, who despite their more privileged positions, also experience higher demands at home, impacting their ability to contribute to teaching, service, and research.”

At the same time, the pandemic has brought into focus which jobs are “truly essential” – and that they are “overwhelmingly [held] by women and people of color, who are often underpaid and undervalued,” the experts wrote. The growing focus on systemic racism has also increased awareness of the chronic gender discrimination faced by female minorities, as well as by women in general, they added. In the field of gastroenterology, inherent gender bias – both systemic and self-directed – can bar women from advancing beginning as early as medical school.

To help address these issues, the experts outlined key opportunities for change as women navigate professional “forks in the road” throughout their careers.
 

Throughout their careers

During medical school and residency, women can specifically request gastroenterology rotations (“ideally with both inpatient and outpatient exposure”), attend society conferences, participate in research themselves, and join a research track or serve as chief medical resident. When applying for gastroenterology fellowships, they can prioritize programs with female faculty, which were recently found to be more likely to hire female fellows.

During fellowship, women can avail themselves of female mentors, who can help them strategize about ways to address gender bias, connect with GI groups and societies, and learn endoscopy techniques, including “unique approaches ... [that] overcome the challenges of standard scope sizes and accessibility.” At the institutional level, opportunities to affect positive changes for women trainees include “formal education on the benefits of hands-on learning and encouraging explicit and open communication between parties regarding invitation to, comfort with, and type of physical contact prior to a case.”

After fellowship, early-career gastroenterologists should scrutinize contracts for details on pay and research support, and they should ideally join a practice that either already has many women physicians on staff, or that ensures salary transparency and has “parental leave policies that are compatible with [applicants’] personal and professional goals.” But the experts advocated caution about part-time positions, which may purport to offer more flexibility but turn into full-time work for part-time pay and can preclude participation in practice management.

The experts recommended midcareer female gastroenterologists call out their own achievements rather than waiting for recognition, “actively seek promotion and tenure,” negotiate their salaries (as men tend to do routinely), and think twice before accepting professional roles that are uncompensated or do not clearly promote career advancement.

Senior gastroenterologists have unique opportunities to spearhead changes in institutional policies and practices, according to the experts. Specific examples include “explicitly stating [in job listings] that salary is negotiable, creating transparent written compensation plans, and conducting audits of job offers” to help mitigate any inequities in pay or hiring practices. In addition, senior women gastroenterologists can mentor individual women in the field, implement formal trainings on implicit bias, ensure that their practice or department tracks the gender of gastroenterologists who join, leave, or are promoted.

The experts did not report receiving funding for the work. They reported having no conflicts of interest.

The gender gap in gastroenterology persists – currently, women constitute 39% of fellows, but only 22% of senior AGA members and less than 18% of all practicing gastroenterologists – and it has gained even greater significance within the “current historical moment” of the COVID pandemic and growing cognizance of systemic sexism and racism, according to experts.

During the pandemic, women have been more likely to stay home to care for ill family members and children affected by school closures, which increases their already disproportionate share of unpaid work, wrote Jessica Bernica, MD, of Baylor College of Medicine in Houston with her associates in Techniques and Innovations in Gastrointestinal Endoscopy. They noted that, according to one study, this “holds true for female physicians, who despite their more privileged positions, also experience higher demands at home, impacting their ability to contribute to teaching, service, and research.”

At the same time, the pandemic has brought into focus which jobs are “truly essential” – and that they are “overwhelmingly [held] by women and people of color, who are often underpaid and undervalued,” the experts wrote. The growing focus on systemic racism has also increased awareness of the chronic gender discrimination faced by female minorities, as well as by women in general, they added. In the field of gastroenterology, inherent gender bias – both systemic and self-directed – can bar women from advancing beginning as early as medical school.

To help address these issues, the experts outlined key opportunities for change as women navigate professional “forks in the road” throughout their careers.
 

Throughout their careers

During medical school and residency, women can specifically request gastroenterology rotations (“ideally with both inpatient and outpatient exposure”), attend society conferences, participate in research themselves, and join a research track or serve as chief medical resident. When applying for gastroenterology fellowships, they can prioritize programs with female faculty, which were recently found to be more likely to hire female fellows.

During fellowship, women can avail themselves of female mentors, who can help them strategize about ways to address gender bias, connect with GI groups and societies, and learn endoscopy techniques, including “unique approaches ... [that] overcome the challenges of standard scope sizes and accessibility.” At the institutional level, opportunities to affect positive changes for women trainees include “formal education on the benefits of hands-on learning and encouraging explicit and open communication between parties regarding invitation to, comfort with, and type of physical contact prior to a case.”

After fellowship, early-career gastroenterologists should scrutinize contracts for details on pay and research support, and they should ideally join a practice that either already has many women physicians on staff, or that ensures salary transparency and has “parental leave policies that are compatible with [applicants’] personal and professional goals.” But the experts advocated caution about part-time positions, which may purport to offer more flexibility but turn into full-time work for part-time pay and can preclude participation in practice management.

The experts recommended midcareer female gastroenterologists call out their own achievements rather than waiting for recognition, “actively seek promotion and tenure,” negotiate their salaries (as men tend to do routinely), and think twice before accepting professional roles that are uncompensated or do not clearly promote career advancement.

Senior gastroenterologists have unique opportunities to spearhead changes in institutional policies and practices, according to the experts. Specific examples include “explicitly stating [in job listings] that salary is negotiable, creating transparent written compensation plans, and conducting audits of job offers” to help mitigate any inequities in pay or hiring practices. In addition, senior women gastroenterologists can mentor individual women in the field, implement formal trainings on implicit bias, ensure that their practice or department tracks the gender of gastroenterologists who join, leave, or are promoted.

The experts did not report receiving funding for the work. They reported having no conflicts of interest.

Experts assessed different chemopreventive agents meant to reduce the incidence of colorectal neoplasia and associated mortality based on whether these agents were effective and safe, but they found few fit both criteria, according to a new clinical practice update from the American Gastroenterological Association.

That said, the update does advise that clinicians use low-dose aspirin therapy in patients who are younger than 70 years with at least a 10-year life expectancy, are not at high risk for bleeding, and have at least a 10% cardiovascular disease risk over the next decade.

This best practice advice statement reflects “high-quality trial data” for this patient population and also echoes U.S. Preventive Services Task Force recommendations, wrote Peter S. Liang, MD, MPH, and his associates on behalf of the American Gastroenterological Association. However, they note that low-dose aspirin therapy has shown inconsistent results for older patients and that its chemopreventive benefits always should be weighed against an individual’s bleeding risk.

Published in Clinical Gastroenterology and Hepatology, the clinical practice update also recommends considering low-dose aspirin therapy for patients with a history of colorectal neoplasia, based on data from several trials in which daily doses of 81-325 mg were associated with a significantly lower likelihood of recurrence of earlier-stage adenomas (the findings did not extend to patients with more advanced lesions). Evidence on sessile serrated polyps is sparser, but there is some indication for a benefit in this setting, the experts noted.

Their best-practice advice also covers nonaspirin nonsteroidal anti-inflammatory drugs, metformin, calcium, vitamin D, folic acid, and statins. Among these agents, only metformin receives even a conditional green light. “Because of the results of a large number of observational studies, a small adenoma trial, as well as a favorable safety profile, metformin may be considered for chemoprevention against colorectal neoplasia in individuals with diabetes,” the experts concluded. Support for this best-practice advice includes a meta-analysis of colorectal cancer–specific survival in 17 observational studies, a meta-analysis of colorectal cancer incidence in 14 observational studies, and a randomized, placebo-controlled trial in which 250 mg daily metformin was safe and associated with a 40% lower risk of recurrent adenoma.

For calcium, study findings have been mixed, and a recent large clinical trial found no overall benefit for adenoma prevention. Because high-dose calcium has been linked to kidney toxicity, hypercalcemia, and prostate cancer, its risks likely outweigh any benefits, the experts concluded. Vitamin D (as monotherapy or with calcium) also has shown no overall benefit for preventing adenomas or sessile serrated lesions. A large ongoing, randomized trial will examine colorectal cancer incidence among adults receiving 5 years of oral vitamin D or placebo, but its results will not be available until at least 2025.

Nonsteroidal anti-inflammatory drugs are not recommended to prevent colorectal neoplasia among average-risk individuals. Cyclooxygenase-2 inhibitors pose “substantial cardiovascular risks,” while nonselective NSAIDs are associated with a significantly increased risk for gastrointestinal bleeding. Meta-analyses have shown no benefit of folic acid for preventing colorectal neoplasia, and observational studies on statins have produced only mixed results.

No funding sources were reported. The experts reported having no conflicts of interest.

Experts assessed different chemopreventive agents meant to reduce the incidence of colorectal neoplasia and associated mortality based on whether these agents were effective and safe, but they found few fit both criteria, according to a new clinical practice update from the American Gastroenterological Association.

That said, the update does advise that clinicians use low-dose aspirin therapy in patients who are younger than 70 years with at least a 10-year life expectancy, are not at high risk for bleeding, and have at least a 10% cardiovascular disease risk over the next decade.

This best practice advice statement reflects “high-quality trial data” for this patient population and also echoes U.S. Preventive Services Task Force recommendations, wrote Peter S. Liang, MD, MPH, and his associates on behalf of the American Gastroenterological Association. However, they note that low-dose aspirin therapy has shown inconsistent results for older patients and that its chemopreventive benefits always should be weighed against an individual’s bleeding risk.

Published in Clinical Gastroenterology and Hepatology, the clinical practice update also recommends considering low-dose aspirin therapy for patients with a history of colorectal neoplasia, based on data from several trials in which daily doses of 81-325 mg were associated with a significantly lower likelihood of recurrence of earlier-stage adenomas (the findings did not extend to patients with more advanced lesions). Evidence on sessile serrated polyps is sparser, but there is some indication for a benefit in this setting, the experts noted.

Their best-practice advice also covers nonaspirin nonsteroidal anti-inflammatory drugs, metformin, calcium, vitamin D, folic acid, and statins. Among these agents, only metformin receives even a conditional green light. “Because of the results of a large number of observational studies, a small adenoma trial, as well as a favorable safety profile, metformin may be considered for chemoprevention against colorectal neoplasia in individuals with diabetes,” the experts concluded. Support for this best-practice advice includes a meta-analysis of colorectal cancer–specific survival in 17 observational studies, a meta-analysis of colorectal cancer incidence in 14 observational studies, and a randomized, placebo-controlled trial in which 250 mg daily metformin was safe and associated with a 40% lower risk of recurrent adenoma.

For calcium, study findings have been mixed, and a recent large clinical trial found no overall benefit for adenoma prevention. Because high-dose calcium has been linked to kidney toxicity, hypercalcemia, and prostate cancer, its risks likely outweigh any benefits, the experts concluded. Vitamin D (as monotherapy or with calcium) also has shown no overall benefit for preventing adenomas or sessile serrated lesions. A large ongoing, randomized trial will examine colorectal cancer incidence among adults receiving 5 years of oral vitamin D or placebo, but its results will not be available until at least 2025.

Nonsteroidal anti-inflammatory drugs are not recommended to prevent colorectal neoplasia among average-risk individuals. Cyclooxygenase-2 inhibitors pose “substantial cardiovascular risks,” while nonselective NSAIDs are associated with a significantly increased risk for gastrointestinal bleeding. Meta-analyses have shown no benefit of folic acid for preventing colorectal neoplasia, and observational studies on statins have produced only mixed results.

No funding sources were reported. The experts reported having no conflicts of interest.

Experts assessed different chemopreventive agents meant to reduce the incidence of colorectal neoplasia and associated mortality based on whether these agents were effective and safe, but they found few fit both criteria, according to a new clinical practice update from the American Gastroenterological Association.

That said, the update does advise that clinicians use low-dose aspirin therapy in patients who are younger than 70 years with at least a 10-year life expectancy, are not at high risk for bleeding, and have at least a 10% cardiovascular disease risk over the next decade.

This best practice advice statement reflects “high-quality trial data” for this patient population and also echoes U.S. Preventive Services Task Force recommendations, wrote Peter S. Liang, MD, MPH, and his associates on behalf of the American Gastroenterological Association. However, they note that low-dose aspirin therapy has shown inconsistent results for older patients and that its chemopreventive benefits always should be weighed against an individual’s bleeding risk.

Published in Clinical Gastroenterology and Hepatology, the clinical practice update also recommends considering low-dose aspirin therapy for patients with a history of colorectal neoplasia, based on data from several trials in which daily doses of 81-325 mg were associated with a significantly lower likelihood of recurrence of earlier-stage adenomas (the findings did not extend to patients with more advanced lesions). Evidence on sessile serrated polyps is sparser, but there is some indication for a benefit in this setting, the experts noted.

Their best-practice advice also covers nonaspirin nonsteroidal anti-inflammatory drugs, metformin, calcium, vitamin D, folic acid, and statins. Among these agents, only metformin receives even a conditional green light. “Because of the results of a large number of observational studies, a small adenoma trial, as well as a favorable safety profile, metformin may be considered for chemoprevention against colorectal neoplasia in individuals with diabetes,” the experts concluded. Support for this best-practice advice includes a meta-analysis of colorectal cancer–specific survival in 17 observational studies, a meta-analysis of colorectal cancer incidence in 14 observational studies, and a randomized, placebo-controlled trial in which 250 mg daily metformin was safe and associated with a 40% lower risk of recurrent adenoma.

For calcium, study findings have been mixed, and a recent large clinical trial found no overall benefit for adenoma prevention. Because high-dose calcium has been linked to kidney toxicity, hypercalcemia, and prostate cancer, its risks likely outweigh any benefits, the experts concluded. Vitamin D (as monotherapy or with calcium) also has shown no overall benefit for preventing adenomas or sessile serrated lesions. A large ongoing, randomized trial will examine colorectal cancer incidence among adults receiving 5 years of oral vitamin D or placebo, but its results will not be available until at least 2025.

Nonsteroidal anti-inflammatory drugs are not recommended to prevent colorectal neoplasia among average-risk individuals. Cyclooxygenase-2 inhibitors pose “substantial cardiovascular risks,” while nonselective NSAIDs are associated with a significantly increased risk for gastrointestinal bleeding. Meta-analyses have shown no benefit of folic acid for preventing colorectal neoplasia, and observational studies on statins have produced only mixed results.

No funding sources were reported. The experts reported having no conflicts of interest.

The gender gap in gastroenterology persists – currently, women constitute 39% of fellows, but only 22% of senior AGA members and less than 18% of all practicing gastroenterologists – and it has gained even greater significance within the “current historical moment” of the COVID pandemic and growing cognizance of systemic sexism and racism, according to experts.

During the pandemic, women have been more likely to stay home to care for ill family members and children affected by school closures, which increases their already disproportionate share of unpaid work, wrote Jessica Bernica, MD, of Baylor College of Medicine in Houston with her associates in Techniques and Innovations in Gastrointestinal Endoscopy. They noted that, according to one study, this “holds true for female physicians, who despite their more privileged positions, also experience higher demands at home, impacting their ability to contribute to teaching, service, and research.”

At the same time, the pandemic has brought into focus which jobs are “truly essential” – and that they are “overwhelmingly [held] by women and people of color, who are often underpaid and undervalued,” the experts wrote. The growing focus on systemic racism has also increased awareness of the chronic gender discrimination faced by female minorities, as well as by women in general, they added. In the field of gastroenterology, inherent gender bias – both systemic and self-directed – can bar women from advancing beginning as early as medical school.

To help address these issues, the experts outlined key opportunities for change as women navigate professional “forks in the road” throughout their careers.
 

Throughout their careers

During medical school and residency, women can specifically request gastroenterology rotations (“ideally with both inpatient and outpatient exposure”), attend society conferences, participate in research themselves, and join a research track or serve as chief medical resident. When applying for gastroenterology fellowships, they can prioritize programs with female faculty, which were recently found to be more likely to hire female fellows.

During fellowship, women can avail themselves of female mentors, who can help them strategize about ways to address gender bias, connect with GI groups and societies, and learn endoscopy techniques, including “unique approaches ... [that] overcome the challenges of standard scope sizes and accessibility.” At the institutional level, opportunities to affect positive changes for women trainees include “formal education on the benefits of hands-on learning and encouraging explicit and open communication between parties regarding invitation to, comfort with, and type of physical contact prior to a case.”

After fellowship, early-career gastroenterologists should scrutinize contracts for details on pay and research support, and they should ideally join a practice that either already has many women physicians on staff, or that ensures salary transparency and has “parental leave policies that are compatible with [applicants’] personal and professional goals.” But the experts advocated caution about part-time positions, which may purport to offer more flexibility but turn into full-time work for part-time pay and can preclude participation in practice management.

The experts recommended midcareer female gastroenterologists call out their own achievements rather than waiting for recognition, “actively seek promotion and tenure,” negotiate their salaries (as men tend to do routinely), and think twice before accepting professional roles that are uncompensated or do not clearly promote career advancement.

Senior gastroenterologists have unique opportunities to spearhead changes in institutional policies and practices, according to the experts. Specific examples include “explicitly stating [in job listings] that salary is negotiable, creating transparent written compensation plans, and conducting audits of job offers” to help mitigate any inequities in pay or hiring practices. In addition, senior women gastroenterologists can mentor individual women in the field, implement formal trainings on implicit bias, ensure that their practice or department tracks the gender of gastroenterologists who join, leave, or are promoted.

The experts did not report receiving funding for the work. They reported having no conflicts of interest.

The gender gap in gastroenterology persists – currently, women constitute 39% of fellows, but only 22% of senior AGA members and less than 18% of all practicing gastroenterologists – and it has gained even greater significance within the “current historical moment” of the COVID pandemic and growing cognizance of systemic sexism and racism, according to experts.

During the pandemic, women have been more likely to stay home to care for ill family members and children affected by school closures, which increases their already disproportionate share of unpaid work, wrote Jessica Bernica, MD, of Baylor College of Medicine in Houston with her associates in Techniques and Innovations in Gastrointestinal Endoscopy. They noted that, according to one study, this “holds true for female physicians, who despite their more privileged positions, also experience higher demands at home, impacting their ability to contribute to teaching, service, and research.”

At the same time, the pandemic has brought into focus which jobs are “truly essential” – and that they are “overwhelmingly [held] by women and people of color, who are often underpaid and undervalued,” the experts wrote. The growing focus on systemic racism has also increased awareness of the chronic gender discrimination faced by female minorities, as well as by women in general, they added. In the field of gastroenterology, inherent gender bias – both systemic and self-directed – can bar women from advancing beginning as early as medical school.

To help address these issues, the experts outlined key opportunities for change as women navigate professional “forks in the road” throughout their careers.
 

Throughout their careers

During medical school and residency, women can specifically request gastroenterology rotations (“ideally with both inpatient and outpatient exposure”), attend society conferences, participate in research themselves, and join a research track or serve as chief medical resident. When applying for gastroenterology fellowships, they can prioritize programs with female faculty, which were recently found to be more likely to hire female fellows.

During fellowship, women can avail themselves of female mentors, who can help them strategize about ways to address gender bias, connect with GI groups and societies, and learn endoscopy techniques, including “unique approaches ... [that] overcome the challenges of standard scope sizes and accessibility.” At the institutional level, opportunities to affect positive changes for women trainees include “formal education on the benefits of hands-on learning and encouraging explicit and open communication between parties regarding invitation to, comfort with, and type of physical contact prior to a case.”

After fellowship, early-career gastroenterologists should scrutinize contracts for details on pay and research support, and they should ideally join a practice that either already has many women physicians on staff, or that ensures salary transparency and has “parental leave policies that are compatible with [applicants’] personal and professional goals.” But the experts advocated caution about part-time positions, which may purport to offer more flexibility but turn into full-time work for part-time pay and can preclude participation in practice management.

The experts recommended midcareer female gastroenterologists call out their own achievements rather than waiting for recognition, “actively seek promotion and tenure,” negotiate their salaries (as men tend to do routinely), and think twice before accepting professional roles that are uncompensated or do not clearly promote career advancement.

Senior gastroenterologists have unique opportunities to spearhead changes in institutional policies and practices, according to the experts. Specific examples include “explicitly stating [in job listings] that salary is negotiable, creating transparent written compensation plans, and conducting audits of job offers” to help mitigate any inequities in pay or hiring practices. In addition, senior women gastroenterologists can mentor individual women in the field, implement formal trainings on implicit bias, ensure that their practice or department tracks the gender of gastroenterologists who join, leave, or are promoted.

The experts did not report receiving funding for the work. They reported having no conflicts of interest.

The gender gap in gastroenterology persists – currently, women constitute 39% of fellows, but only 22% of senior AGA members and less than 18% of all practicing gastroenterologists – and it has gained even greater significance within the “current historical moment” of the COVID pandemic and growing cognizance of systemic sexism and racism, according to experts.

During the pandemic, women have been more likely to stay home to care for ill family members and children affected by school closures, which increases their already disproportionate share of unpaid work, wrote Jessica Bernica, MD, of Baylor College of Medicine in Houston with her associates in Techniques and Innovations in Gastrointestinal Endoscopy. They noted that, according to one study, this “holds true for female physicians, who despite their more privileged positions, also experience higher demands at home, impacting their ability to contribute to teaching, service, and research.”

At the same time, the pandemic has brought into focus which jobs are “truly essential” – and that they are “overwhelmingly [held] by women and people of color, who are often underpaid and undervalued,” the experts wrote. The growing focus on systemic racism has also increased awareness of the chronic gender discrimination faced by female minorities, as well as by women in general, they added. In the field of gastroenterology, inherent gender bias – both systemic and self-directed – can bar women from advancing beginning as early as medical school.

To help address these issues, the experts outlined key opportunities for change as women navigate professional “forks in the road” throughout their careers.
 

Throughout their careers

During medical school and residency, women can specifically request gastroenterology rotations (“ideally with both inpatient and outpatient exposure”), attend society conferences, participate in research themselves, and join a research track or serve as chief medical resident. When applying for gastroenterology fellowships, they can prioritize programs with female faculty, which were recently found to be more likely to hire female fellows.

During fellowship, women can avail themselves of female mentors, who can help them strategize about ways to address gender bias, connect with GI groups and societies, and learn endoscopy techniques, including “unique approaches ... [that] overcome the challenges of standard scope sizes and accessibility.” At the institutional level, opportunities to affect positive changes for women trainees include “formal education on the benefits of hands-on learning and encouraging explicit and open communication between parties regarding invitation to, comfort with, and type of physical contact prior to a case.”

After fellowship, early-career gastroenterologists should scrutinize contracts for details on pay and research support, and they should ideally join a practice that either already has many women physicians on staff, or that ensures salary transparency and has “parental leave policies that are compatible with [applicants’] personal and professional goals.” But the experts advocated caution about part-time positions, which may purport to offer more flexibility but turn into full-time work for part-time pay and can preclude participation in practice management.

The experts recommended midcareer female gastroenterologists call out their own achievements rather than waiting for recognition, “actively seek promotion and tenure,” negotiate their salaries (as men tend to do routinely), and think twice before accepting professional roles that are uncompensated or do not clearly promote career advancement.

Senior gastroenterologists have unique opportunities to spearhead changes in institutional policies and practices, according to the experts. Specific examples include “explicitly stating [in job listings] that salary is negotiable, creating transparent written compensation plans, and conducting audits of job offers” to help mitigate any inequities in pay or hiring practices. In addition, senior women gastroenterologists can mentor individual women in the field, implement formal trainings on implicit bias, ensure that their practice or department tracks the gender of gastroenterologists who join, leave, or are promoted.

The experts did not report receiving funding for the work. They reported having no conflicts of interest.

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

As bleeding disorders are increasingly recognized as a national health priority, hematologists are focusing on how the patient-centered medical home – a widely accepted concept in primary care and in some specialties – can improve outcomes and quality life for their patients.

Courtesy of Dr. Shapiro

The patient-centered medical home is a model of health care delivery in which patients receive comprehensive, accessible care that is fully integrated across all providers and elements of a healthcare system.¹ The concept emerged in the 1960s among pediatricians seeking to better coordinate care for children with complex medical needs. Since then, the patient-centered medical home has become a globally recognized standard – not only in primary care, but also in specialties such as endocrinology, oncology, and geriatric medicine. The movement to establish medical homes for patients with bleeding disorders is more recent and is receiving national attention.

Why a medical home?

The advent of prophylactic therapies for bleeding disorders has vastly improved the outlook for many patients compared to just a few decades ago. However, treatment options remain limited, and patients who have severe disease or complications – such as an inadequate treatment response or the development of inhibitory antibodies to replacement clotting factors – are at risk for recurrent breakthrough bleeding that can lead to synovitis and ultimately culminate in progressive, irreversible joint damage. The resulting pain and limitation of motion greatly compromises patients’ quality of life across physical, psychological, and social domains, undermines their ability to live and work independently, and greatly increases treatment costs.^2-4 Family members, too, face high stress and lower quality of life when they struggle to obtain and manage treatment while caring for loved ones with bleeding disorders.⁵

For patients with bleeding disorders, a patient-centered medical home can help address or surmount these challenges, said Amy Shapiro, MD, medical director of the Indiana Hemophilia and Thrombosis Center in Indianapolis, Ind., which was the first hemophilia treatment center in the country to be formally certified as a medical home.

Dr. Shapiro explained that a patient-centered medical home leverages the care of an integrated multidisciplinary team to help optimize therapies and patient outcomes across all domains of life. She sees the medical home concept as a natural fit for patients with bleeding disorders, given the complexity of their needs and the number of specialties involved. “When you have hemophilia, you don’t just need a hematologist to manage your care. You need nurses, physical therapists, and social workers. You need coordinated care for genetic counseling. You also need to coordinate dental hygiene and surgical interventions, if these are required. Patients need nutrition counseling, and they may need assistance with education or career options if too many days are missed from work or school. Patients or their families may need counseling on choosing the right insurance program so they don’t choose a plan that may create more hardships for them because of their chronic disorder.”

Meeting these needs requires the help of an integrated care team, which many individuals with bleeding disorders lack. “If you are just out there in the community and you have medical issues that need to be dealt with, often the individuals themselves have to coordinate their own care, including their medications and their appointments with different specialists,” said Dr. Shapiro. “For example, a care provider may tell a patient that they need a physical therapist and give them some names, and then the patient has to take it from there and not only find the provider, but also determine if their insurance provides coverage.”

A medical home takes a completely different approach, she explained. “At my center, when we say you need a physical therapist, we have a physical therapist on staff. Our therapist provides an assessment and determines the need for ongoing PT and whether that can be done at home with a plan and intermittent oversight, or whether the patient needs a referral, and whether the person the patient is referred to needs education on how to provide PT for someone with hemophilia. A medical home provides all this in one place. It is a place where patients know they will receive either direct services, or support to shepherd their care and outcomes, and oversight of that support as well.”

Few studies have directly assessed the medical home model in the setting of bleeding disorders, but a number have evaluated the impact of integrated care, a more general term for the practice of coordinating multidisciplinary care to improve access and outcomes while eliminating redundancies and unnecessary costs. In a recent systematic review and meta-analysis of 27 nonrandomized studies of patients with hemophilia, integrated care was linked to lower mortality, fewer emergency room visits and hospitalizations, shorter lengths of stay in the hospital, and fewer missed days of school and work.⁶ Such findings, combined with promising outcomes data from studies of patient-centered medical homes in other disease settings, suggest that the patient-centered medical home can significantly benefit patients with bleeding disorders and their families and caregivers.
 

Creating a medical home

Establishing a patient-centered medical home can be challenging, involving a plethora of stakeholders and a considerable investment of time, energy, and resources. Organizations such as the National Committee for Quality Assurance and the Accreditation Association for Ambulatory Health Care have formal certification programs to help ensure that an inpatient or outpatient center that calls itself a medical home truly is one.^7-8

The certification process requires centers to document activities in areas such as patients’ rights and responsibilities, administration and governance, patient and care team relationships, clinical records and other health information, and quality, comprehensiveness, continuity, and accessibility.⁷ Achieving certification is rigorous, often requiring centers to document compliance with more than 100 policies, procedures, and standards.

For the Indiana Hemophilia and Thrombosis Center, becoming certified as a medical home “was a multiyear process and an ongoing process,” said Dr. Shapiro. “It involves documentation of quality improvement initiatives, obtaining input from patients to document their satisfaction, and looking at all types of systems within our center and how we integrate care so that all those systems function together. It’s a difficult process, but treatment centers are a medical home for patients with bleeding disorders, and this is an effort to provide some documentation on a national level of how we’re doing everything that we are doing.”

She noted that the process of obtaining medical home certification may require an even higher level of commitment if a bleeding disorder (hemophilia) treatment center is embedded in a university or academic medical center. In this case, more stakeholders are involved, and more hoops may need to be jumped through to implement processes that meet medical home standards while still adhering to any requirements at the organizational level.

Certification programs for patient-centered medical homes are not designed around specific disorders or diseases, but a closer look at their compliance metrics underscores how medical homes can benefit patients with bleeding disorders. For example, to receive medical home certification from the Accreditation Association for Ambulatory Health Care, a center needs to be able to document that patients’ care is not transferred without first making arrangements with a receiving health care provider, that the quality improvement programs are peer-led, and that these programs assess and address diverse measures of clinical performance, cost-effectiveness, and administrative functioning.^7-9

Medical homes, the NHPCC, and Healthy People 2030

Creating patient-centered medical homes for patients with bleeding disorders is now a quality improvement objective of the National Hemophilia Program Coordinating Center, or NHPCC. Established in 2012 and funded by the federal Health Resources and Services Administration, the NHPCC partners with the eight regional hemophilia networks and more than 140 federally funded hemophilia treatment centers across the United States to identify gaps, standardize and improve access to care, and share and promote best practices for the treatment and management of blood disorders.¹⁰

In the United States, receiving care in a hemophilia treatment center (which, despite its name, typically offers care for other disorders such as von Willebrand disease) has been linked to lower mortality and fewer hospitalizations related to bleeding complications.¹¹ To continue to improve on these outcomes, the NHPCC, regional networks, and hemophilia treatment centers are prioritizing medical homes and ranking their establishments alongside core objectives such as bettering patient and family engagement and improving the transition from pediatric to adult care.¹²

As part of this quality improvement work, the NHPCC, regional leadership, and hemophilia treatment centers meet regularly to identify needs and priorities, plan programs, and ensure that each center is meeting the goals and objectives set out by its federal grant.¹³ Such partnerships help improve and integrate care within a coordinated national framework, Dr. Shapiro said. “We all are charged with this same mission,” she added. “That doesn’t mean that every treatment center looks exactly the same, has the same number of staff, or does everything the same way, but we all have the same mission, and we know what that is. That is the work of the NHPCC, to determine and document that and help level and improve care throughout the country.”

The NHPCC also engages other stakeholders, including consumer agencies and professional organizations. Recent achievements have included a first-ever national patient needs assessment, a tandem technical needs assessment of hemophilia treatment centers, an educational outreach program for genetic counselors, a webinar on transitioning care for adolescents, a national survey of the federal 340B Drug Pricing Program, and a survey of minority patients to identify and characterize problems such as language and insurance barriers, the lack of culturally appropriate educational materials on blood disorders, and difficulties getting transportation to treatment centers or educational programs.¹⁴

In part because of this advocacy work, the U.S. Department of Health and Human Services recently included hemophilia for the first time in Healthy People, its evidence-based set of decade-long objectives aimed at improving the health of all Americans. In Healthy People 2030, the specific objective for hemophilia is to reduce the proportion of patients with severe disease who experience more than four joint bleeds per year to 13.3% (the current estimate is 16.9%).¹⁵

For Healthy People to prioritize hemophilia for the first time alongside much more common conditions such as diabetes and heart disease reflects the challenges of managing bleeding disorders and the efforts by the NHPCC and other stakeholders to raise awareness about current needs. To track progress in meeting the Healthy People 2030 objective, the NHPCC will work with federal partners to analyze patient-level data gathered through the Centers for Disease Control’s Community Counts Registry for Bleeding Disorders Surveillance program, which collects data from hemophilia treatment centers across the United States and includes patients with all levels of disease severity.

“The inclusion of bleeding disorders in Healthy People 2030 is really very significant,” said Dr. Shapiro. “These are disorders that affect less than 200,000 Americans, which is the definition of a rare disease in this context. To have hemophilia considered as a national priority is very important, not only for hemophilia, but also for other rare diseases that may in the future also be considered as being as of national importance in this way.”
 

References

1. Rodriguez-Saldana J. 2019. The Patient-Centered Medical Home, Primary Care, and Diabetes. In: Rodriguez-Saldana J. (eds) The Diabetes Textbook. Springer, Cham.

2. J Comorb. 2011;1:51-59.

3. Eur J Haematol. 2018 Apr;100 Suppl 1:5-13.

4. Blood. 2003;102(7):2358-63.

5. Haemophilia. 2014 Jul;20(4):541-9.

6. Haemophilia. 2016;22(Suppl 3):31-40.

7. AAAHC. Medical Home.

8. NCQA. Patient-centered medical home (PCMH).

9. AAAHC, 2013. Medical Home On-Site Certification Handbook.

10. Centers for Disease Control and Prevention. HTC Population Profile.

11. Blood Transfus. 2014;12 Suppl 3(Suppl 3):e542-e548.

12. American Thrombosis and Hemostasis Network.

13. The Great Lakes Regional Hemophilia Network.

14. American Thrombosis and Hemostasis Network. What the NHPCC does.

15. U.S. Department of Health and Human Services. Healthy People 2030: Blood Disorders.

As bleeding disorders are increasingly recognized as a national health priority, hematologists are focusing on how the patient-centered medical home – a widely accepted concept in primary care and in some specialties – can improve outcomes and quality life for their patients.

Courtesy of Dr. Shapiro

The patient-centered medical home is a model of health care delivery in which patients receive comprehensive, accessible care that is fully integrated across all providers and elements of a healthcare system.¹ The concept emerged in the 1960s among pediatricians seeking to better coordinate care for children with complex medical needs. Since then, the patient-centered medical home has become a globally recognized standard – not only in primary care, but also in specialties such as endocrinology, oncology, and geriatric medicine. The movement to establish medical homes for patients with bleeding disorders is more recent and is receiving national attention.

Why a medical home?

The advent of prophylactic therapies for bleeding disorders has vastly improved the outlook for many patients compared to just a few decades ago. However, treatment options remain limited, and patients who have severe disease or complications – such as an inadequate treatment response or the development of inhibitory antibodies to replacement clotting factors – are at risk for recurrent breakthrough bleeding that can lead to synovitis and ultimately culminate in progressive, irreversible joint damage. The resulting pain and limitation of motion greatly compromises patients’ quality of life across physical, psychological, and social domains, undermines their ability to live and work independently, and greatly increases treatment costs.^2-4 Family members, too, face high stress and lower quality of life when they struggle to obtain and manage treatment while caring for loved ones with bleeding disorders.⁵

For patients with bleeding disorders, a patient-centered medical home can help address or surmount these challenges, said Amy Shapiro, MD, medical director of the Indiana Hemophilia and Thrombosis Center in Indianapolis, Ind., which was the first hemophilia treatment center in the country to be formally certified as a medical home.

Dr. Shapiro explained that a patient-centered medical home leverages the care of an integrated multidisciplinary team to help optimize therapies and patient outcomes across all domains of life. She sees the medical home concept as a natural fit for patients with bleeding disorders, given the complexity of their needs and the number of specialties involved. “When you have hemophilia, you don’t just need a hematologist to manage your care. You need nurses, physical therapists, and social workers. You need coordinated care for genetic counseling. You also need to coordinate dental hygiene and surgical interventions, if these are required. Patients need nutrition counseling, and they may need assistance with education or career options if too many days are missed from work or school. Patients or their families may need counseling on choosing the right insurance program so they don’t choose a plan that may create more hardships for them because of their chronic disorder.”

Meeting these needs requires the help of an integrated care team, which many individuals with bleeding disorders lack. “If you are just out there in the community and you have medical issues that need to be dealt with, often the individuals themselves have to coordinate their own care, including their medications and their appointments with different specialists,” said Dr. Shapiro. “For example, a care provider may tell a patient that they need a physical therapist and give them some names, and then the patient has to take it from there and not only find the provider, but also determine if their insurance provides coverage.”

A medical home takes a completely different approach, she explained. “At my center, when we say you need a physical therapist, we have a physical therapist on staff. Our therapist provides an assessment and determines the need for ongoing PT and whether that can be done at home with a plan and intermittent oversight, or whether the patient needs a referral, and whether the person the patient is referred to needs education on how to provide PT for someone with hemophilia. A medical home provides all this in one place. It is a place where patients know they will receive either direct services, or support to shepherd their care and outcomes, and oversight of that support as well.”

Few studies have directly assessed the medical home model in the setting of bleeding disorders, but a number have evaluated the impact of integrated care, a more general term for the practice of coordinating multidisciplinary care to improve access and outcomes while eliminating redundancies and unnecessary costs. In a recent systematic review and meta-analysis of 27 nonrandomized studies of patients with hemophilia, integrated care was linked to lower mortality, fewer emergency room visits and hospitalizations, shorter lengths of stay in the hospital, and fewer missed days of school and work.⁶ Such findings, combined with promising outcomes data from studies of patient-centered medical homes in other disease settings, suggest that the patient-centered medical home can significantly benefit patients with bleeding disorders and their families and caregivers.
 

Creating a medical home

Establishing a patient-centered medical home can be challenging, involving a plethora of stakeholders and a considerable investment of time, energy, and resources. Organizations such as the National Committee for Quality Assurance and the Accreditation Association for Ambulatory Health Care have formal certification programs to help ensure that an inpatient or outpatient center that calls itself a medical home truly is one.^7-8

The certification process requires centers to document activities in areas such as patients’ rights and responsibilities, administration and governance, patient and care team relationships, clinical records and other health information, and quality, comprehensiveness, continuity, and accessibility.⁷ Achieving certification is rigorous, often requiring centers to document compliance with more than 100 policies, procedures, and standards.

For the Indiana Hemophilia and Thrombosis Center, becoming certified as a medical home “was a multiyear process and an ongoing process,” said Dr. Shapiro. “It involves documentation of quality improvement initiatives, obtaining input from patients to document their satisfaction, and looking at all types of systems within our center and how we integrate care so that all those systems function together. It’s a difficult process, but treatment centers are a medical home for patients with bleeding disorders, and this is an effort to provide some documentation on a national level of how we’re doing everything that we are doing.”

She noted that the process of obtaining medical home certification may require an even higher level of commitment if a bleeding disorder (hemophilia) treatment center is embedded in a university or academic medical center. In this case, more stakeholders are involved, and more hoops may need to be jumped through to implement processes that meet medical home standards while still adhering to any requirements at the organizational level.

Certification programs for patient-centered medical homes are not designed around specific disorders or diseases, but a closer look at their compliance metrics underscores how medical homes can benefit patients with bleeding disorders. For example, to receive medical home certification from the Accreditation Association for Ambulatory Health Care, a center needs to be able to document that patients’ care is not transferred without first making arrangements with a receiving health care provider, that the quality improvement programs are peer-led, and that these programs assess and address diverse measures of clinical performance, cost-effectiveness, and administrative functioning.^7-9

Medical homes, the NHPCC, and Healthy People 2030

Creating patient-centered medical homes for patients with bleeding disorders is now a quality improvement objective of the National Hemophilia Program Coordinating Center, or NHPCC. Established in 2012 and funded by the federal Health Resources and Services Administration, the NHPCC partners with the eight regional hemophilia networks and more than 140 federally funded hemophilia treatment centers across the United States to identify gaps, standardize and improve access to care, and share and promote best practices for the treatment and management of blood disorders.¹⁰

In the United States, receiving care in a hemophilia treatment center (which, despite its name, typically offers care for other disorders such as von Willebrand disease) has been linked to lower mortality and fewer hospitalizations related to bleeding complications.¹¹ To continue to improve on these outcomes, the NHPCC, regional networks, and hemophilia treatment centers are prioritizing medical homes and ranking their establishments alongside core objectives such as bettering patient and family engagement and improving the transition from pediatric to adult care.¹²

As part of this quality improvement work, the NHPCC, regional leadership, and hemophilia treatment centers meet regularly to identify needs and priorities, plan programs, and ensure that each center is meeting the goals and objectives set out by its federal grant.¹³ Such partnerships help improve and integrate care within a coordinated national framework, Dr. Shapiro said. “We all are charged with this same mission,” she added. “That doesn’t mean that every treatment center looks exactly the same, has the same number of staff, or does everything the same way, but we all have the same mission, and we know what that is. That is the work of the NHPCC, to determine and document that and help level and improve care throughout the country.”

The NHPCC also engages other stakeholders, including consumer agencies and professional organizations. Recent achievements have included a first-ever national patient needs assessment, a tandem technical needs assessment of hemophilia treatment centers, an educational outreach program for genetic counselors, a webinar on transitioning care for adolescents, a national survey of the federal 340B Drug Pricing Program, and a survey of minority patients to identify and characterize problems such as language and insurance barriers, the lack of culturally appropriate educational materials on blood disorders, and difficulties getting transportation to treatment centers or educational programs.¹⁴

In part because of this advocacy work, the U.S. Department of Health and Human Services recently included hemophilia for the first time in Healthy People, its evidence-based set of decade-long objectives aimed at improving the health of all Americans. In Healthy People 2030, the specific objective for hemophilia is to reduce the proportion of patients with severe disease who experience more than four joint bleeds per year to 13.3% (the current estimate is 16.9%).¹⁵

For Healthy People to prioritize hemophilia for the first time alongside much more common conditions such as diabetes and heart disease reflects the challenges of managing bleeding disorders and the efforts by the NHPCC and other stakeholders to raise awareness about current needs. To track progress in meeting the Healthy People 2030 objective, the NHPCC will work with federal partners to analyze patient-level data gathered through the Centers for Disease Control’s Community Counts Registry for Bleeding Disorders Surveillance program, which collects data from hemophilia treatment centers across the United States and includes patients with all levels of disease severity.

“The inclusion of bleeding disorders in Healthy People 2030 is really very significant,” said Dr. Shapiro. “These are disorders that affect less than 200,000 Americans, which is the definition of a rare disease in this context. To have hemophilia considered as a national priority is very important, not only for hemophilia, but also for other rare diseases that may in the future also be considered as being as of national importance in this way.”
 

References

1. Rodriguez-Saldana J. 2019. The Patient-Centered Medical Home, Primary Care, and Diabetes. In: Rodriguez-Saldana J. (eds) The Diabetes Textbook. Springer, Cham.

2. J Comorb. 2011;1:51-59.

3. Eur J Haematol. 2018 Apr;100 Suppl 1:5-13.

4. Blood. 2003;102(7):2358-63.

5. Haemophilia. 2014 Jul;20(4):541-9.

6. Haemophilia. 2016;22(Suppl 3):31-40.

7. AAAHC. Medical Home.

8. NCQA. Patient-centered medical home (PCMH).

9. AAAHC, 2013. Medical Home On-Site Certification Handbook.

10. Centers for Disease Control and Prevention. HTC Population Profile.

11. Blood Transfus. 2014;12 Suppl 3(Suppl 3):e542-e548.

12. American Thrombosis and Hemostasis Network.

13. The Great Lakes Regional Hemophilia Network.

14. American Thrombosis and Hemostasis Network. What the NHPCC does.

15. U.S. Department of Health and Human Services. Healthy People 2030: Blood Disorders.

As bleeding disorders are increasingly recognized as a national health priority, hematologists are focusing on how the patient-centered medical home – a widely accepted concept in primary care and in some specialties – can improve outcomes and quality life for their patients.

Courtesy of Dr. Shapiro

The patient-centered medical home is a model of health care delivery in which patients receive comprehensive, accessible care that is fully integrated across all providers and elements of a healthcare system.¹ The concept emerged in the 1960s among pediatricians seeking to better coordinate care for children with complex medical needs. Since then, the patient-centered medical home has become a globally recognized standard – not only in primary care, but also in specialties such as endocrinology, oncology, and geriatric medicine. The movement to establish medical homes for patients with bleeding disorders is more recent and is receiving national attention.

Why a medical home?

The advent of prophylactic therapies for bleeding disorders has vastly improved the outlook for many patients compared to just a few decades ago. However, treatment options remain limited, and patients who have severe disease or complications – such as an inadequate treatment response or the development of inhibitory antibodies to replacement clotting factors – are at risk for recurrent breakthrough bleeding that can lead to synovitis and ultimately culminate in progressive, irreversible joint damage. The resulting pain and limitation of motion greatly compromises patients’ quality of life across physical, psychological, and social domains, undermines their ability to live and work independently, and greatly increases treatment costs.^2-4 Family members, too, face high stress and lower quality of life when they struggle to obtain and manage treatment while caring for loved ones with bleeding disorders.⁵

For patients with bleeding disorders, a patient-centered medical home can help address or surmount these challenges, said Amy Shapiro, MD, medical director of the Indiana Hemophilia and Thrombosis Center in Indianapolis, Ind., which was the first hemophilia treatment center in the country to be formally certified as a medical home.

Dr. Shapiro explained that a patient-centered medical home leverages the care of an integrated multidisciplinary team to help optimize therapies and patient outcomes across all domains of life. She sees the medical home concept as a natural fit for patients with bleeding disorders, given the complexity of their needs and the number of specialties involved. “When you have hemophilia, you don’t just need a hematologist to manage your care. You need nurses, physical therapists, and social workers. You need coordinated care for genetic counseling. You also need to coordinate dental hygiene and surgical interventions, if these are required. Patients need nutrition counseling, and they may need assistance with education or career options if too many days are missed from work or school. Patients or their families may need counseling on choosing the right insurance program so they don’t choose a plan that may create more hardships for them because of their chronic disorder.”

Meeting these needs requires the help of an integrated care team, which many individuals with bleeding disorders lack. “If you are just out there in the community and you have medical issues that need to be dealt with, often the individuals themselves have to coordinate their own care, including their medications and their appointments with different specialists,” said Dr. Shapiro. “For example, a care provider may tell a patient that they need a physical therapist and give them some names, and then the patient has to take it from there and not only find the provider, but also determine if their insurance provides coverage.”

A medical home takes a completely different approach, she explained. “At my center, when we say you need a physical therapist, we have a physical therapist on staff. Our therapist provides an assessment and determines the need for ongoing PT and whether that can be done at home with a plan and intermittent oversight, or whether the patient needs a referral, and whether the person the patient is referred to needs education on how to provide PT for someone with hemophilia. A medical home provides all this in one place. It is a place where patients know they will receive either direct services, or support to shepherd their care and outcomes, and oversight of that support as well.”

Few studies have directly assessed the medical home model in the setting of bleeding disorders, but a number have evaluated the impact of integrated care, a more general term for the practice of coordinating multidisciplinary care to improve access and outcomes while eliminating redundancies and unnecessary costs. In a recent systematic review and meta-analysis of 27 nonrandomized studies of patients with hemophilia, integrated care was linked to lower mortality, fewer emergency room visits and hospitalizations, shorter lengths of stay in the hospital, and fewer missed days of school and work.⁶ Such findings, combined with promising outcomes data from studies of patient-centered medical homes in other disease settings, suggest that the patient-centered medical home can significantly benefit patients with bleeding disorders and their families and caregivers.
 

Creating a medical home

Establishing a patient-centered medical home can be challenging, involving a plethora of stakeholders and a considerable investment of time, energy, and resources. Organizations such as the National Committee for Quality Assurance and the Accreditation Association for Ambulatory Health Care have formal certification programs to help ensure that an inpatient or outpatient center that calls itself a medical home truly is one.^7-8

The certification process requires centers to document activities in areas such as patients’ rights and responsibilities, administration and governance, patient and care team relationships, clinical records and other health information, and quality, comprehensiveness, continuity, and accessibility.⁷ Achieving certification is rigorous, often requiring centers to document compliance with more than 100 policies, procedures, and standards.

For the Indiana Hemophilia and Thrombosis Center, becoming certified as a medical home “was a multiyear process and an ongoing process,” said Dr. Shapiro. “It involves documentation of quality improvement initiatives, obtaining input from patients to document their satisfaction, and looking at all types of systems within our center and how we integrate care so that all those systems function together. It’s a difficult process, but treatment centers are a medical home for patients with bleeding disorders, and this is an effort to provide some documentation on a national level of how we’re doing everything that we are doing.”

She noted that the process of obtaining medical home certification may require an even higher level of commitment if a bleeding disorder (hemophilia) treatment center is embedded in a university or academic medical center. In this case, more stakeholders are involved, and more hoops may need to be jumped through to implement processes that meet medical home standards while still adhering to any requirements at the organizational level.

Certification programs for patient-centered medical homes are not designed around specific disorders or diseases, but a closer look at their compliance metrics underscores how medical homes can benefit patients with bleeding disorders. For example, to receive medical home certification from the Accreditation Association for Ambulatory Health Care, a center needs to be able to document that patients’ care is not transferred without first making arrangements with a receiving health care provider, that the quality improvement programs are peer-led, and that these programs assess and address diverse measures of clinical performance, cost-effectiveness, and administrative functioning.^7-9

Medical homes, the NHPCC, and Healthy People 2030

Creating patient-centered medical homes for patients with bleeding disorders is now a quality improvement objective of the National Hemophilia Program Coordinating Center, or NHPCC. Established in 2012 and funded by the federal Health Resources and Services Administration, the NHPCC partners with the eight regional hemophilia networks and more than 140 federally funded hemophilia treatment centers across the United States to identify gaps, standardize and improve access to care, and share and promote best practices for the treatment and management of blood disorders.¹⁰

In the United States, receiving care in a hemophilia treatment center (which, despite its name, typically offers care for other disorders such as von Willebrand disease) has been linked to lower mortality and fewer hospitalizations related to bleeding complications.¹¹ To continue to improve on these outcomes, the NHPCC, regional networks, and hemophilia treatment centers are prioritizing medical homes and ranking their establishments alongside core objectives such as bettering patient and family engagement and improving the transition from pediatric to adult care.¹²

As part of this quality improvement work, the NHPCC, regional leadership, and hemophilia treatment centers meet regularly to identify needs and priorities, plan programs, and ensure that each center is meeting the goals and objectives set out by its federal grant.¹³ Such partnerships help improve and integrate care within a coordinated national framework, Dr. Shapiro said. “We all are charged with this same mission,” she added. “That doesn’t mean that every treatment center looks exactly the same, has the same number of staff, or does everything the same way, but we all have the same mission, and we know what that is. That is the work of the NHPCC, to determine and document that and help level and improve care throughout the country.”

The NHPCC also engages other stakeholders, including consumer agencies and professional organizations. Recent achievements have included a first-ever national patient needs assessment, a tandem technical needs assessment of hemophilia treatment centers, an educational outreach program for genetic counselors, a webinar on transitioning care for adolescents, a national survey of the federal 340B Drug Pricing Program, and a survey of minority patients to identify and characterize problems such as language and insurance barriers, the lack of culturally appropriate educational materials on blood disorders, and difficulties getting transportation to treatment centers or educational programs.¹⁴

In part because of this advocacy work, the U.S. Department of Health and Human Services recently included hemophilia for the first time in Healthy People, its evidence-based set of decade-long objectives aimed at improving the health of all Americans. In Healthy People 2030, the specific objective for hemophilia is to reduce the proportion of patients with severe disease who experience more than four joint bleeds per year to 13.3% (the current estimate is 16.9%).¹⁵

For Healthy People to prioritize hemophilia for the first time alongside much more common conditions such as diabetes and heart disease reflects the challenges of managing bleeding disorders and the efforts by the NHPCC and other stakeholders to raise awareness about current needs. To track progress in meeting the Healthy People 2030 objective, the NHPCC will work with federal partners to analyze patient-level data gathered through the Centers for Disease Control’s Community Counts Registry for Bleeding Disorders Surveillance program, which collects data from hemophilia treatment centers across the United States and includes patients with all levels of disease severity.

“The inclusion of bleeding disorders in Healthy People 2030 is really very significant,” said Dr. Shapiro. “These are disorders that affect less than 200,000 Americans, which is the definition of a rare disease in this context. To have hemophilia considered as a national priority is very important, not only for hemophilia, but also for other rare diseases that may in the future also be considered as being as of national importance in this way.”
 

References

1. Rodriguez-Saldana J. 2019. The Patient-Centered Medical Home, Primary Care, and Diabetes. In: Rodriguez-Saldana J. (eds) The Diabetes Textbook. Springer, Cham.

2. J Comorb. 2011;1:51-59.

3. Eur J Haematol. 2018 Apr;100 Suppl 1:5-13.

4. Blood. 2003;102(7):2358-63.

5. Haemophilia. 2014 Jul;20(4):541-9.

6. Haemophilia. 2016;22(Suppl 3):31-40.

7. AAAHC. Medical Home.

8. NCQA. Patient-centered medical home (PCMH).

9. AAAHC, 2013. Medical Home On-Site Certification Handbook.

10. Centers for Disease Control and Prevention. HTC Population Profile.

11. Blood Transfus. 2014;12 Suppl 3(Suppl 3):e542-e548.

12. American Thrombosis and Hemostasis Network.

13. The Great Lakes Regional Hemophilia Network.

14. American Thrombosis and Hemostasis Network. What the NHPCC does.

15. U.S. Department of Health and Human Services. Healthy People 2030: Blood Disorders.

For patients with mild or remitted ulcerative colitis, a catered, low-fat, high-fiber diet improved quality of life and stool markers of dysbiosis and inflammation, according to the findings of a small crossover trial.

Lisovskaya/iStock/Getty Images

Patients with inflammatory bowel disease often ask what they should eat, but few studies have addressed that question, Julia Fritsch, of the University of Miami and her associates wrote in Clinical Gastroenterology and Hepatology. Building on previous findings that a high-fat diet may contribute to inflammatory bowel disease, they randomly assigned 38 adults whose ulcerative colitis was in remission or mild (with a flare within the past 18 months) to receive either a low-fat diet (with 10% of daily calories from fat and high amounts of fruit and vegetables) or an “improved American standard diet” (with 35%-40% of daily calories from fat but more fruit and vegetables than Americans typically eat). Each diet was catered, delivered to patients’ homes, and lasted 4 weeks, followed by a 2-week washout period, after which each participant switched to the other diet.

Of the 38 patients, 17 completed the study. Food recall surveys over 24 hours showed that both diets were healthier than what participants ate at baseline, and daily web-based food diaries (such as www.nutrihand.com/Static/index.html) confirmed that more than 94% of patients adhered to the amount of fat in each diet. Even though participants in both groups ate only about half of the provided fruits and vegetables, the primary outcome of quality of life based on the short inflammatory bowel disease questionnaire (SIBDQ) significantly improved from a median of 4.98 (interquartile range, 4.1-6.0) at baseline to 5.77 (IQR, 5-6.4) with the low-fat diet and 5.55 (IQR, 4.75-6.25) with the improved American standard diet. Both diets also produced significant improvements in quality of life as measured by the 36-Item Short Form Survey and in disease activity as measured by the partial Mayo score.

Notably, however, only the low-fat diet significantly reduced serum amyloid A, which is a marker of mucosal inflammation, and intestinal dysbiosis, which was quantified by 16S RNA ribosomal sequencing. “Of note, there were several variables that were associated with changes in the microbiota composition,” the researchers wrote. These included the SIBDQ, C-reactive protein, interleukin-6, interleukin-1 beta, and 32 dietary components such as protein, potassium, iron, and zinc.

“These data suggest that even patients in remission [from ulcerative colitis] could benefit from a healthier diet,” the investigators concluded. “Just as importantly, neither diet exacerbated symptoms, which is notable given the higher fiber in both catered diets.” They called catering “a feasible way to perform a diet intervention study with high adherence,” noting that “catering a diet for a patient with IBD for a year costs between $19,000 and $21,000 per patient. The cost of a patient on a biologic such as ustekinumab is approximately $130,752 to $261,504.”

The study was supported by the Crohn’s and Colitis Foundation Broad Medical Research Program, Micky and Madeleine Arison Family Foundation Crohn’s and Colitis Discovery Laboratory, and the Martin Kalser Chair. The senior author disclosed ties to Boehringer Ingelheim, Gilead, AbbVie, Seres Therapeutics, Shire, Landos, Pfizer, and several other pharmaceutical companies. The other researchers reported having no conflicts of interest.

For patients with mild or remitted ulcerative colitis, a catered, low-fat, high-fiber diet improved quality of life and stool markers of dysbiosis and inflammation, according to the findings of a small crossover trial.

Lisovskaya/iStock/Getty Images

Patients with inflammatory bowel disease often ask what they should eat, but few studies have addressed that question, Julia Fritsch, of the University of Miami and her associates wrote in Clinical Gastroenterology and Hepatology. Building on previous findings that a high-fat diet may contribute to inflammatory bowel disease, they randomly assigned 38 adults whose ulcerative colitis was in remission or mild (with a flare within the past 18 months) to receive either a low-fat diet (with 10% of daily calories from fat and high amounts of fruit and vegetables) or an “improved American standard diet” (with 35%-40% of daily calories from fat but more fruit and vegetables than Americans typically eat). Each diet was catered, delivered to patients’ homes, and lasted 4 weeks, followed by a 2-week washout period, after which each participant switched to the other diet.

Of the 38 patients, 17 completed the study. Food recall surveys over 24 hours showed that both diets were healthier than what participants ate at baseline, and daily web-based food diaries (such as www.nutrihand.com/Static/index.html) confirmed that more than 94% of patients adhered to the amount of fat in each diet. Even though participants in both groups ate only about half of the provided fruits and vegetables, the primary outcome of quality of life based on the short inflammatory bowel disease questionnaire (SIBDQ) significantly improved from a median of 4.98 (interquartile range, 4.1-6.0) at baseline to 5.77 (IQR, 5-6.4) with the low-fat diet and 5.55 (IQR, 4.75-6.25) with the improved American standard diet. Both diets also produced significant improvements in quality of life as measured by the 36-Item Short Form Survey and in disease activity as measured by the partial Mayo score.

Notably, however, only the low-fat diet significantly reduced serum amyloid A, which is a marker of mucosal inflammation, and intestinal dysbiosis, which was quantified by 16S RNA ribosomal sequencing. “Of note, there were several variables that were associated with changes in the microbiota composition,” the researchers wrote. These included the SIBDQ, C-reactive protein, interleukin-6, interleukin-1 beta, and 32 dietary components such as protein, potassium, iron, and zinc.

“These data suggest that even patients in remission [from ulcerative colitis] could benefit from a healthier diet,” the investigators concluded. “Just as importantly, neither diet exacerbated symptoms, which is notable given the higher fiber in both catered diets.” They called catering “a feasible way to perform a diet intervention study with high adherence,” noting that “catering a diet for a patient with IBD for a year costs between $19,000 and $21,000 per patient. The cost of a patient on a biologic such as ustekinumab is approximately $130,752 to $261,504.”

The study was supported by the Crohn’s and Colitis Foundation Broad Medical Research Program, Micky and Madeleine Arison Family Foundation Crohn’s and Colitis Discovery Laboratory, and the Martin Kalser Chair. The senior author disclosed ties to Boehringer Ingelheim, Gilead, AbbVie, Seres Therapeutics, Shire, Landos, Pfizer, and several other pharmaceutical companies. The other researchers reported having no conflicts of interest.

For patients with mild or remitted ulcerative colitis, a catered, low-fat, high-fiber diet improved quality of life and stool markers of dysbiosis and inflammation, according to the findings of a small crossover trial.

Lisovskaya/iStock/Getty Images

Patients with inflammatory bowel disease often ask what they should eat, but few studies have addressed that question, Julia Fritsch, of the University of Miami and her associates wrote in Clinical Gastroenterology and Hepatology. Building on previous findings that a high-fat diet may contribute to inflammatory bowel disease, they randomly assigned 38 adults whose ulcerative colitis was in remission or mild (with a flare within the past 18 months) to receive either a low-fat diet (with 10% of daily calories from fat and high amounts of fruit and vegetables) or an “improved American standard diet” (with 35%-40% of daily calories from fat but more fruit and vegetables than Americans typically eat). Each diet was catered, delivered to patients’ homes, and lasted 4 weeks, followed by a 2-week washout period, after which each participant switched to the other diet.

Of the 38 patients, 17 completed the study. Food recall surveys over 24 hours showed that both diets were healthier than what participants ate at baseline, and daily web-based food diaries (such as www.nutrihand.com/Static/index.html) confirmed that more than 94% of patients adhered to the amount of fat in each diet. Even though participants in both groups ate only about half of the provided fruits and vegetables, the primary outcome of quality of life based on the short inflammatory bowel disease questionnaire (SIBDQ) significantly improved from a median of 4.98 (interquartile range, 4.1-6.0) at baseline to 5.77 (IQR, 5-6.4) with the low-fat diet and 5.55 (IQR, 4.75-6.25) with the improved American standard diet. Both diets also produced significant improvements in quality of life as measured by the 36-Item Short Form Survey and in disease activity as measured by the partial Mayo score.

Notably, however, only the low-fat diet significantly reduced serum amyloid A, which is a marker of mucosal inflammation, and intestinal dysbiosis, which was quantified by 16S RNA ribosomal sequencing. “Of note, there were several variables that were associated with changes in the microbiota composition,” the researchers wrote. These included the SIBDQ, C-reactive protein, interleukin-6, interleukin-1 beta, and 32 dietary components such as protein, potassium, iron, and zinc.

“These data suggest that even patients in remission [from ulcerative colitis] could benefit from a healthier diet,” the investigators concluded. “Just as importantly, neither diet exacerbated symptoms, which is notable given the higher fiber in both catered diets.” They called catering “a feasible way to perform a diet intervention study with high adherence,” noting that “catering a diet for a patient with IBD for a year costs between $19,000 and $21,000 per patient. The cost of a patient on a biologic such as ustekinumab is approximately $130,752 to $261,504.”

The study was supported by the Crohn’s and Colitis Foundation Broad Medical Research Program, Micky and Madeleine Arison Family Foundation Crohn’s and Colitis Discovery Laboratory, and the Martin Kalser Chair. The senior author disclosed ties to Boehringer Ingelheim, Gilead, AbbVie, Seres Therapeutics, Shire, Landos, Pfizer, and several other pharmaceutical companies. The other researchers reported having no conflicts of interest.

The selective interleukin-6 (IL-6) trans-signaling inhibitor olamkicept was well tolerated and induced clinical remissions in 3 of 16 adults with moderately to severely active inflammatory bowel disease (IBD), and remission was associated with clear alterations in levels of phospho-STAT3 (pSTAT3) in the intestinal mucosa, researchers reported.

In a 12-week, open-label, prospective phase 2a trial, patients received up to seven infusions of 600-mg olamkicept (sgp130Fc) every 2 weeks. Clinical remissions occurred in two of nine patients with ulcerative colitis and one of seven patients with Crohn’s disease. The overall rate of clinical response was 44%, which included five patients with ulcerative colitis and two patients with Crohn’s disease. Transcriptome isolation and high-throughput RNA sequencing of mucosal tissue specimens showed that clinical remitters had a decrease from baseline to week 14 in the expression of TNF, IL-1A, REG1A, IL-8, IL-1B, and LILRA, a known composite molecular surrogate for mucosal inflammation. In addition, exposing whole-blood samples to a recombinant IL-6/IL-6R fusion protein mimicked physiologic IL-6 activity and demonstrated that pSTAT3 levels dropped within 4 hours of the first olamkicept infusion and throughout treatment. “Our overall finding of decreased pSTAT3-positive cells in remission patients indicates that STAT3 is crucially involved in the mechanism of action of olamkicept,” wrote Stefan Schreiber, MD, of University Medical Center Schleswig-Holstein, Campus Kiel (Germany) together with his associates. The study is published in Gastroenterology.

Blocking the IL-6/ILR receptor can induce IBD remissions but causes “profound immunosuppression,” the investigators noted. Building on prior findings that chronic proinflammatory IL-6 activity is primarily mediated by trans-signaling of a complex of IL-6 and soluble IL6R that engages the gp130 receptor, the researchers developed a “decoy protein,” sgp130Fc (now known as olamkicept), which “exclusively blocks” IL-6 proinflammatory trans-signaling. This decoy protein showed promise in preclinical studies, with no evidence of immunosuppression, they wrote. To further evaluate olamkicept, they recruited adults with moderately to severely active ulcerative colitis or Crohn’s disease from two centers in Germany. The primary clinical assessment was remission, defined as a Mayo score under 2, with a bleeding score of 0 and an endoscopy score of less than 1 for patients with ulcerative colitis, and a Crohn’s Disease Activity Index (CDAI) of less than 150 for patients with Crohn’s disease. The primary molecular outcome was change in the composite molecular surrogate score.

Of the 16 patients, 10 completed the trial. At week 14, endoscopic responses were observed in six patients, all of whom also had a clinical response, and all three patients with clinical remissions also had endoscopic remissions. “The drug was well tolerated in all 16 treated individuals, similar to the results of the [two prior] phase 1 trials,” the researchers wrote. Although significant immunosuppression and intestinal perforations were not seen, 13 patients developed adverse events, most commonly seasonal upper respiratory tract infections, recurrence of herpes labialis, and eczema or erythema. There were five serious adverse events, two of which were cardiac in nature. A larger placebo-controlled trial is underway to further evaluate safety. For now, the researchers wrote, it appears that IL-6 trans-signaling inhibition “might open up novel therapeutic avenues for the treatment of IBD.”

University Hospital Schleswig-Holstein sponsored the study. Ferring AG provided funding and donated the olamkicept. Analyses were funded by EU H2020 SYSCID and EU H2020 Innovative Medicines Initiative 2 Joint Undertaking. Dr. Schreiber reported having coinvented IP and having ties to Pfizer, Bristol Myers Squibb, and Roche. Four coinvestigators disclosed ties to Ferring, AbbVie, Chugai, Roche, Regeneron, Pfizer, Sanofi, Conaris, and Genentech Roche. The other researchers reported having no conflicts of interest.

The selective interleukin-6 (IL-6) trans-signaling inhibitor olamkicept was well tolerated and induced clinical remissions in 3 of 16 adults with moderately to severely active inflammatory bowel disease (IBD), and remission was associated with clear alterations in levels of phospho-STAT3 (pSTAT3) in the intestinal mucosa, researchers reported.

In a 12-week, open-label, prospective phase 2a trial, patients received up to seven infusions of 600-mg olamkicept (sgp130Fc) every 2 weeks. Clinical remissions occurred in two of nine patients with ulcerative colitis and one of seven patients with Crohn’s disease. The overall rate of clinical response was 44%, which included five patients with ulcerative colitis and two patients with Crohn’s disease. Transcriptome isolation and high-throughput RNA sequencing of mucosal tissue specimens showed that clinical remitters had a decrease from baseline to week 14 in the expression of TNF, IL-1A, REG1A, IL-8, IL-1B, and LILRA, a known composite molecular surrogate for mucosal inflammation. In addition, exposing whole-blood samples to a recombinant IL-6/IL-6R fusion protein mimicked physiologic IL-6 activity and demonstrated that pSTAT3 levels dropped within 4 hours of the first olamkicept infusion and throughout treatment. “Our overall finding of decreased pSTAT3-positive cells in remission patients indicates that STAT3 is crucially involved in the mechanism of action of olamkicept,” wrote Stefan Schreiber, MD, of University Medical Center Schleswig-Holstein, Campus Kiel (Germany) together with his associates. The study is published in Gastroenterology.

Blocking the IL-6/ILR receptor can induce IBD remissions but causes “profound immunosuppression,” the investigators noted. Building on prior findings that chronic proinflammatory IL-6 activity is primarily mediated by trans-signaling of a complex of IL-6 and soluble IL6R that engages the gp130 receptor, the researchers developed a “decoy protein,” sgp130Fc (now known as olamkicept), which “exclusively blocks” IL-6 proinflammatory trans-signaling. This decoy protein showed promise in preclinical studies, with no evidence of immunosuppression, they wrote. To further evaluate olamkicept, they recruited adults with moderately to severely active ulcerative colitis or Crohn’s disease from two centers in Germany. The primary clinical assessment was remission, defined as a Mayo score under 2, with a bleeding score of 0 and an endoscopy score of less than 1 for patients with ulcerative colitis, and a Crohn’s Disease Activity Index (CDAI) of less than 150 for patients with Crohn’s disease. The primary molecular outcome was change in the composite molecular surrogate score.

Of the 16 patients, 10 completed the trial. At week 14, endoscopic responses were observed in six patients, all of whom also had a clinical response, and all three patients with clinical remissions also had endoscopic remissions. “The drug was well tolerated in all 16 treated individuals, similar to the results of the [two prior] phase 1 trials,” the researchers wrote. Although significant immunosuppression and intestinal perforations were not seen, 13 patients developed adverse events, most commonly seasonal upper respiratory tract infections, recurrence of herpes labialis, and eczema or erythema. There were five serious adverse events, two of which were cardiac in nature. A larger placebo-controlled trial is underway to further evaluate safety. For now, the researchers wrote, it appears that IL-6 trans-signaling inhibition “might open up novel therapeutic avenues for the treatment of IBD.”

University Hospital Schleswig-Holstein sponsored the study. Ferring AG provided funding and donated the olamkicept. Analyses were funded by EU H2020 SYSCID and EU H2020 Innovative Medicines Initiative 2 Joint Undertaking. Dr. Schreiber reported having coinvented IP and having ties to Pfizer, Bristol Myers Squibb, and Roche. Four coinvestigators disclosed ties to Ferring, AbbVie, Chugai, Roche, Regeneron, Pfizer, Sanofi, Conaris, and Genentech Roche. The other researchers reported having no conflicts of interest.

The selective interleukin-6 (IL-6) trans-signaling inhibitor olamkicept was well tolerated and induced clinical remissions in 3 of 16 adults with moderately to severely active inflammatory bowel disease (IBD), and remission was associated with clear alterations in levels of phospho-STAT3 (pSTAT3) in the intestinal mucosa, researchers reported.

In a 12-week, open-label, prospective phase 2a trial, patients received up to seven infusions of 600-mg olamkicept (sgp130Fc) every 2 weeks. Clinical remissions occurred in two of nine patients with ulcerative colitis and one of seven patients with Crohn’s disease. The overall rate of clinical response was 44%, which included five patients with ulcerative colitis and two patients with Crohn’s disease. Transcriptome isolation and high-throughput RNA sequencing of mucosal tissue specimens showed that clinical remitters had a decrease from baseline to week 14 in the expression of TNF, IL-1A, REG1A, IL-8, IL-1B, and LILRA, a known composite molecular surrogate for mucosal inflammation. In addition, exposing whole-blood samples to a recombinant IL-6/IL-6R fusion protein mimicked physiologic IL-6 activity and demonstrated that pSTAT3 levels dropped within 4 hours of the first olamkicept infusion and throughout treatment. “Our overall finding of decreased pSTAT3-positive cells in remission patients indicates that STAT3 is crucially involved in the mechanism of action of olamkicept,” wrote Stefan Schreiber, MD, of University Medical Center Schleswig-Holstein, Campus Kiel (Germany) together with his associates. The study is published in Gastroenterology.

Blocking the IL-6/ILR receptor can induce IBD remissions but causes “profound immunosuppression,” the investigators noted. Building on prior findings that chronic proinflammatory IL-6 activity is primarily mediated by trans-signaling of a complex of IL-6 and soluble IL6R that engages the gp130 receptor, the researchers developed a “decoy protein,” sgp130Fc (now known as olamkicept), which “exclusively blocks” IL-6 proinflammatory trans-signaling. This decoy protein showed promise in preclinical studies, with no evidence of immunosuppression, they wrote. To further evaluate olamkicept, they recruited adults with moderately to severely active ulcerative colitis or Crohn’s disease from two centers in Germany. The primary clinical assessment was remission, defined as a Mayo score under 2, with a bleeding score of 0 and an endoscopy score of less than 1 for patients with ulcerative colitis, and a Crohn’s Disease Activity Index (CDAI) of less than 150 for patients with Crohn’s disease. The primary molecular outcome was change in the composite molecular surrogate score.

Of the 16 patients, 10 completed the trial. At week 14, endoscopic responses were observed in six patients, all of whom also had a clinical response, and all three patients with clinical remissions also had endoscopic remissions. “The drug was well tolerated in all 16 treated individuals, similar to the results of the [two prior] phase 1 trials,” the researchers wrote. Although significant immunosuppression and intestinal perforations were not seen, 13 patients developed adverse events, most commonly seasonal upper respiratory tract infections, recurrence of herpes labialis, and eczema or erythema. There were five serious adverse events, two of which were cardiac in nature. A larger placebo-controlled trial is underway to further evaluate safety. For now, the researchers wrote, it appears that IL-6 trans-signaling inhibition “might open up novel therapeutic avenues for the treatment of IBD.”

University Hospital Schleswig-Holstein sponsored the study. Ferring AG provided funding and donated the olamkicept. Analyses were funded by EU H2020 SYSCID and EU H2020 Innovative Medicines Initiative 2 Joint Undertaking. Dr. Schreiber reported having coinvented IP and having ties to Pfizer, Bristol Myers Squibb, and Roche. Four coinvestigators disclosed ties to Ferring, AbbVie, Chugai, Roche, Regeneron, Pfizer, Sanofi, Conaris, and Genentech Roche. The other researchers reported having no conflicts of interest.

For patients with mild or remitted ulcerative colitis, a catered, low-fat, high-fiber diet improved quality of life and stool markers of dysbiosis and inflammation, according to the findings of a small crossover trial.

Lisovskaya/iStock/Getty Images

Patients with inflammatory bowel disease often ask what they should eat, but few studies have addressed that question, Julia Fritsch, of the University of Miami and her associates wrote in Clinical Gastroenterology and Hepatology. Building on previous findings that a high-fat diet may contribute to inflammatory bowel disease, they randomly assigned 38 adults whose ulcerative colitis was in remission or mild (with a flare within the past 18 months) to receive either a low-fat diet (with 10% of daily calories from fat and high amounts of fruit and vegetables) or an “improved American standard diet” (with 35%-40% of daily calories from fat but more fruit and vegetables than Americans typically eat). Each diet was catered, delivered to patients’ homes, and lasted 4 weeks, followed by a 2-week washout period, after which each participant switched to the other diet.

Of the 38 patients, 17 completed the study. Food recall surveys over 24 hours showed that both diets were healthier than what participants ate at baseline, and daily web-based food diaries (such as www.nutrihand.com/Static/index.html) confirmed that more than 94% of patients adhered to the amount of fat in each diet. Even though participants in both groups ate only about half of the provided fruits and vegetables, the primary outcome of quality of life based on the short inflammatory bowel disease questionnaire (SIBDQ) significantly improved from a median of 4.98 (interquartile range, 4.1-6.0) at baseline to 5.77 (IQR, 5-6.4) with the low-fat diet and 5.55 (IQR, 4.75-6.25) with the improved American standard diet. Both diets also produced significant improvements in quality of life as measured by the 36-Item Short Form Survey and in disease activity as measured by the partial Mayo score.

Notably, however, only the low-fat diet significantly reduced serum amyloid A, which is a marker of mucosal inflammation, and intestinal dysbiosis, which was quantified by 16S RNA ribosomal sequencing. “Of note, there were several variables that were associated with changes in the microbiota composition,” the researchers wrote. These included the SIBDQ, C-reactive protein, interleukin-6, interleukin-1 beta, and 32 dietary components such as protein, potassium, iron, and zinc.

“These data suggest that even patients in remission [from ulcerative colitis] could benefit from a healthier diet,” the investigators concluded. “Just as importantly, neither diet exacerbated symptoms, which is notable given the higher fiber in both catered diets.” They called catering “a feasible way to perform a diet intervention study with high adherence,” noting that “catering a diet for a patient with IBD for a year costs between $19,000 and $21,000 per patient. The cost of a patient on a biologic such as ustekinumab is approximately $130,752 to $261,504.”

The study was supported by the Crohn’s and Colitis Foundation Broad Medical Research Program, Micky and Madeleine Arison Family Foundation Crohn’s and Colitis Discovery Laboratory, and the Martin Kalser Chair. The senior author disclosed ties to Boehringer Ingelheim, Gilead, AbbVie, Seres Therapeutics, Shire, Landos, Pfizer, and several other pharmaceutical companies. The other researchers reported having no conflicts of interest.

For patients with mild or remitted ulcerative colitis, a catered, low-fat, high-fiber diet improved quality of life and stool markers of dysbiosis and inflammation, according to the findings of a small crossover trial.

Lisovskaya/iStock/Getty Images

Patients with inflammatory bowel disease often ask what they should eat, but few studies have addressed that question, Julia Fritsch, of the University of Miami and her associates wrote in Clinical Gastroenterology and Hepatology. Building on previous findings that a high-fat diet may contribute to inflammatory bowel disease, they randomly assigned 38 adults whose ulcerative colitis was in remission or mild (with a flare within the past 18 months) to receive either a low-fat diet (with 10% of daily calories from fat and high amounts of fruit and vegetables) or an “improved American standard diet” (with 35%-40% of daily calories from fat but more fruit and vegetables than Americans typically eat). Each diet was catered, delivered to patients’ homes, and lasted 4 weeks, followed by a 2-week washout period, after which each participant switched to the other diet.

Of the 38 patients, 17 completed the study. Food recall surveys over 24 hours showed that both diets were healthier than what participants ate at baseline, and daily web-based food diaries (such as www.nutrihand.com/Static/index.html) confirmed that more than 94% of patients adhered to the amount of fat in each diet. Even though participants in both groups ate only about half of the provided fruits and vegetables, the primary outcome of quality of life based on the short inflammatory bowel disease questionnaire (SIBDQ) significantly improved from a median of 4.98 (interquartile range, 4.1-6.0) at baseline to 5.77 (IQR, 5-6.4) with the low-fat diet and 5.55 (IQR, 4.75-6.25) with the improved American standard diet. Both diets also produced significant improvements in quality of life as measured by the 36-Item Short Form Survey and in disease activity as measured by the partial Mayo score.

Notably, however, only the low-fat diet significantly reduced serum amyloid A, which is a marker of mucosal inflammation, and intestinal dysbiosis, which was quantified by 16S RNA ribosomal sequencing. “Of note, there were several variables that were associated with changes in the microbiota composition,” the researchers wrote. These included the SIBDQ, C-reactive protein, interleukin-6, interleukin-1 beta, and 32 dietary components such as protein, potassium, iron, and zinc.

“These data suggest that even patients in remission [from ulcerative colitis] could benefit from a healthier diet,” the investigators concluded. “Just as importantly, neither diet exacerbated symptoms, which is notable given the higher fiber in both catered diets.” They called catering “a feasible way to perform a diet intervention study with high adherence,” noting that “catering a diet for a patient with IBD for a year costs between $19,000 and $21,000 per patient. The cost of a patient on a biologic such as ustekinumab is approximately $130,752 to $261,504.”

The study was supported by the Crohn’s and Colitis Foundation Broad Medical Research Program, Micky and Madeleine Arison Family Foundation Crohn’s and Colitis Discovery Laboratory, and the Martin Kalser Chair. The senior author disclosed ties to Boehringer Ingelheim, Gilead, AbbVie, Seres Therapeutics, Shire, Landos, Pfizer, and several other pharmaceutical companies. The other researchers reported having no conflicts of interest.

For patients with mild or remitted ulcerative colitis, a catered, low-fat, high-fiber diet improved quality of life and stool markers of dysbiosis and inflammation, according to the findings of a small crossover trial.

Lisovskaya/iStock/Getty Images

Patients with inflammatory bowel disease often ask what they should eat, but few studies have addressed that question, Julia Fritsch, of the University of Miami and her associates wrote in Clinical Gastroenterology and Hepatology. Building on previous findings that a high-fat diet may contribute to inflammatory bowel disease, they randomly assigned 38 adults whose ulcerative colitis was in remission or mild (with a flare within the past 18 months) to receive either a low-fat diet (with 10% of daily calories from fat and high amounts of fruit and vegetables) or an “improved American standard diet” (with 35%-40% of daily calories from fat but more fruit and vegetables than Americans typically eat). Each diet was catered, delivered to patients’ homes, and lasted 4 weeks, followed by a 2-week washout period, after which each participant switched to the other diet.

Of the 38 patients, 17 completed the study. Food recall surveys over 24 hours showed that both diets were healthier than what participants ate at baseline, and daily web-based food diaries (such as www.nutrihand.com/Static/index.html) confirmed that more than 94% of patients adhered to the amount of fat in each diet. Even though participants in both groups ate only about half of the provided fruits and vegetables, the primary outcome of quality of life based on the short inflammatory bowel disease questionnaire (SIBDQ) significantly improved from a median of 4.98 (interquartile range, 4.1-6.0) at baseline to 5.77 (IQR, 5-6.4) with the low-fat diet and 5.55 (IQR, 4.75-6.25) with the improved American standard diet. Both diets also produced significant improvements in quality of life as measured by the 36-Item Short Form Survey and in disease activity as measured by the partial Mayo score.

Notably, however, only the low-fat diet significantly reduced serum amyloid A, which is a marker of mucosal inflammation, and intestinal dysbiosis, which was quantified by 16S RNA ribosomal sequencing. “Of note, there were several variables that were associated with changes in the microbiota composition,” the researchers wrote. These included the SIBDQ, C-reactive protein, interleukin-6, interleukin-1 beta, and 32 dietary components such as protein, potassium, iron, and zinc.

“These data suggest that even patients in remission [from ulcerative colitis] could benefit from a healthier diet,” the investigators concluded. “Just as importantly, neither diet exacerbated symptoms, which is notable given the higher fiber in both catered diets.” They called catering “a feasible way to perform a diet intervention study with high adherence,” noting that “catering a diet for a patient with IBD for a year costs between $19,000 and $21,000 per patient. The cost of a patient on a biologic such as ustekinumab is approximately $130,752 to $261,504.”

The study was supported by the Crohn’s and Colitis Foundation Broad Medical Research Program, Micky and Madeleine Arison Family Foundation Crohn’s and Colitis Discovery Laboratory, and the Martin Kalser Chair. The senior author disclosed ties to Boehringer Ingelheim, Gilead, AbbVie, Seres Therapeutics, Shire, Landos, Pfizer, and several other pharmaceutical companies. The other researchers reported having no conflicts of interest.

The selective interleukin-6 (IL-6) trans-signaling inhibitor olamkicept was well tolerated and induced clinical remissions in 3 of 16 adults with moderately to severely active inflammatory bowel disease (IBD), and remission was associated with clear alterations in levels of phospho-STAT3 (pSTAT3) in the intestinal mucosa, researchers reported.

In a 12-week, open-label, prospective phase 2a trial, patients received up to seven infusions of 600-mg olamkicept (sgp130Fc) every 2 weeks. Clinical remissions occurred in two of nine patients with ulcerative colitis and one of seven patients with Crohn’s disease. The overall rate of clinical response was 44%, which included five patients with ulcerative colitis and two patients with Crohn’s disease. Transcriptome isolation and high-throughput RNA sequencing of mucosal tissue specimens showed that clinical remitters had a decrease from baseline to week 14 in the expression of TNF, IL-1A, REG1A, IL-8, IL-1B, and LILRA, a known composite molecular surrogate for mucosal inflammation. In addition, exposing whole-blood samples to a recombinant IL-6/IL-6R fusion protein mimicked physiologic IL-6 activity and demonstrated that pSTAT3 levels dropped within 4 hours of the first olamkicept infusion and throughout treatment. “Our overall finding of decreased pSTAT3-positive cells in remission patients indicates that STAT3 is crucially involved in the mechanism of action of olamkicept,” wrote Stefan Schreiber, MD, of University Medical Center Schleswig-Holstein, Campus Kiel (Germany) together with his associates. The study is published in Gastroenterology.

Blocking the IL-6/ILR receptor can induce IBD remissions but causes “profound immunosuppression,” the investigators noted. Building on prior findings that chronic proinflammatory IL-6 activity is primarily mediated by trans-signaling of a complex of IL-6 and soluble IL6R that engages the gp130 receptor, the researchers developed a “decoy protein,” sgp130Fc (now known as olamkicept), which “exclusively blocks” IL-6 proinflammatory trans-signaling. This decoy protein showed promise in preclinical studies, with no evidence of immunosuppression, they wrote. To further evaluate olamkicept, they recruited adults with moderately to severely active ulcerative colitis or Crohn’s disease from two centers in Germany. The primary clinical assessment was remission, defined as a Mayo score under 2, with a bleeding score of 0 and an endoscopy score of less than 1 for patients with ulcerative colitis, and a Crohn’s Disease Activity Index (CDAI) of less than 150 for patients with Crohn’s disease. The primary molecular outcome was change in the composite molecular surrogate score.

Of the 16 patients, 10 completed the trial. At week 14, endoscopic responses were observed in six patients, all of whom also had a clinical response, and all three patients with clinical remissions also had endoscopic remissions. “The drug was well tolerated in all 16 treated individuals, similar to the results of the [two prior] phase 1 trials,” the researchers wrote. Although significant immunosuppression and intestinal perforations were not seen, 13 patients developed adverse events, most commonly seasonal upper respiratory tract infections, recurrence of herpes labialis, and eczema or erythema. There were five serious adverse events, two of which were cardiac in nature. A larger placebo-controlled trial is underway to further evaluate safety. For now, the researchers wrote, it appears that IL-6 trans-signaling inhibition “might open up novel therapeutic avenues for the treatment of IBD.”

University Hospital Schleswig-Holstein sponsored the study. Ferring AG provided funding and donated the olamkicept. Analyses were funded by EU H2020 SYSCID and EU H2020 Innovative Medicines Initiative 2 Joint Undertaking. Dr. Schreiber reported having coinvented IP and having ties to Pfizer, Bristol Myers Squibb, and Roche. Four coinvestigators disclosed ties to Ferring, AbbVie, Chugai, Roche, Regeneron, Pfizer, Sanofi, Conaris, and Genentech Roche. The other researchers reported having no conflicts of interest.

The selective interleukin-6 (IL-6) trans-signaling inhibitor olamkicept was well tolerated and induced clinical remissions in 3 of 16 adults with moderately to severely active inflammatory bowel disease (IBD), and remission was associated with clear alterations in levels of phospho-STAT3 (pSTAT3) in the intestinal mucosa, researchers reported.

In a 12-week, open-label, prospective phase 2a trial, patients received up to seven infusions of 600-mg olamkicept (sgp130Fc) every 2 weeks. Clinical remissions occurred in two of nine patients with ulcerative colitis and one of seven patients with Crohn’s disease. The overall rate of clinical response was 44%, which included five patients with ulcerative colitis and two patients with Crohn’s disease. Transcriptome isolation and high-throughput RNA sequencing of mucosal tissue specimens showed that clinical remitters had a decrease from baseline to week 14 in the expression of TNF, IL-1A, REG1A, IL-8, IL-1B, and LILRA, a known composite molecular surrogate for mucosal inflammation. In addition, exposing whole-blood samples to a recombinant IL-6/IL-6R fusion protein mimicked physiologic IL-6 activity and demonstrated that pSTAT3 levels dropped within 4 hours of the first olamkicept infusion and throughout treatment. “Our overall finding of decreased pSTAT3-positive cells in remission patients indicates that STAT3 is crucially involved in the mechanism of action of olamkicept,” wrote Stefan Schreiber, MD, of University Medical Center Schleswig-Holstein, Campus Kiel (Germany) together with his associates. The study is published in Gastroenterology.

Blocking the IL-6/ILR receptor can induce IBD remissions but causes “profound immunosuppression,” the investigators noted. Building on prior findings that chronic proinflammatory IL-6 activity is primarily mediated by trans-signaling of a complex of IL-6 and soluble IL6R that engages the gp130 receptor, the researchers developed a “decoy protein,” sgp130Fc (now known as olamkicept), which “exclusively blocks” IL-6 proinflammatory trans-signaling. This decoy protein showed promise in preclinical studies, with no evidence of immunosuppression, they wrote. To further evaluate olamkicept, they recruited adults with moderately to severely active ulcerative colitis or Crohn’s disease from two centers in Germany. The primary clinical assessment was remission, defined as a Mayo score under 2, with a bleeding score of 0 and an endoscopy score of less than 1 for patients with ulcerative colitis, and a Crohn’s Disease Activity Index (CDAI) of less than 150 for patients with Crohn’s disease. The primary molecular outcome was change in the composite molecular surrogate score.

Of the 16 patients, 10 completed the trial. At week 14, endoscopic responses were observed in six patients, all of whom also had a clinical response, and all three patients with clinical remissions also had endoscopic remissions. “The drug was well tolerated in all 16 treated individuals, similar to the results of the [two prior] phase 1 trials,” the researchers wrote. Although significant immunosuppression and intestinal perforations were not seen, 13 patients developed adverse events, most commonly seasonal upper respiratory tract infections, recurrence of herpes labialis, and eczema or erythema. There were five serious adverse events, two of which were cardiac in nature. A larger placebo-controlled trial is underway to further evaluate safety. For now, the researchers wrote, it appears that IL-6 trans-signaling inhibition “might open up novel therapeutic avenues for the treatment of IBD.”

University Hospital Schleswig-Holstein sponsored the study. Ferring AG provided funding and donated the olamkicept. Analyses were funded by EU H2020 SYSCID and EU H2020 Innovative Medicines Initiative 2 Joint Undertaking. Dr. Schreiber reported having coinvented IP and having ties to Pfizer, Bristol Myers Squibb, and Roche. Four coinvestigators disclosed ties to Ferring, AbbVie, Chugai, Roche, Regeneron, Pfizer, Sanofi, Conaris, and Genentech Roche. The other researchers reported having no conflicts of interest.

The selective interleukin-6 (IL-6) trans-signaling inhibitor olamkicept was well tolerated and induced clinical remissions in 3 of 16 adults with moderately to severely active inflammatory bowel disease (IBD), and remission was associated with clear alterations in levels of phospho-STAT3 (pSTAT3) in the intestinal mucosa, researchers reported.

In a 12-week, open-label, prospective phase 2a trial, patients received up to seven infusions of 600-mg olamkicept (sgp130Fc) every 2 weeks. Clinical remissions occurred in two of nine patients with ulcerative colitis and one of seven patients with Crohn’s disease. The overall rate of clinical response was 44%, which included five patients with ulcerative colitis and two patients with Crohn’s disease. Transcriptome isolation and high-throughput RNA sequencing of mucosal tissue specimens showed that clinical remitters had a decrease from baseline to week 14 in the expression of TNF, IL-1A, REG1A, IL-8, IL-1B, and LILRA, a known composite molecular surrogate for mucosal inflammation. In addition, exposing whole-blood samples to a recombinant IL-6/IL-6R fusion protein mimicked physiologic IL-6 activity and demonstrated that pSTAT3 levels dropped within 4 hours of the first olamkicept infusion and throughout treatment. “Our overall finding of decreased pSTAT3-positive cells in remission patients indicates that STAT3 is crucially involved in the mechanism of action of olamkicept,” wrote Stefan Schreiber, MD, of University Medical Center Schleswig-Holstein, Campus Kiel (Germany) together with his associates. The study is published in Gastroenterology.

Blocking the IL-6/ILR receptor can induce IBD remissions but causes “profound immunosuppression,” the investigators noted. Building on prior findings that chronic proinflammatory IL-6 activity is primarily mediated by trans-signaling of a complex of IL-6 and soluble IL6R that engages the gp130 receptor, the researchers developed a “decoy protein,” sgp130Fc (now known as olamkicept), which “exclusively blocks” IL-6 proinflammatory trans-signaling. This decoy protein showed promise in preclinical studies, with no evidence of immunosuppression, they wrote. To further evaluate olamkicept, they recruited adults with moderately to severely active ulcerative colitis or Crohn’s disease from two centers in Germany. The primary clinical assessment was remission, defined as a Mayo score under 2, with a bleeding score of 0 and an endoscopy score of less than 1 for patients with ulcerative colitis, and a Crohn’s Disease Activity Index (CDAI) of less than 150 for patients with Crohn’s disease. The primary molecular outcome was change in the composite molecular surrogate score.

Of the 16 patients, 10 completed the trial. At week 14, endoscopic responses were observed in six patients, all of whom also had a clinical response, and all three patients with clinical remissions also had endoscopic remissions. “The drug was well tolerated in all 16 treated individuals, similar to the results of the [two prior] phase 1 trials,” the researchers wrote. Although significant immunosuppression and intestinal perforations were not seen, 13 patients developed adverse events, most commonly seasonal upper respiratory tract infections, recurrence of herpes labialis, and eczema or erythema. There were five serious adverse events, two of which were cardiac in nature. A larger placebo-controlled trial is underway to further evaluate safety. For now, the researchers wrote, it appears that IL-6 trans-signaling inhibition “might open up novel therapeutic avenues for the treatment of IBD.”

University Hospital Schleswig-Holstein sponsored the study. Ferring AG provided funding and donated the olamkicept. Analyses were funded by EU H2020 SYSCID and EU H2020 Innovative Medicines Initiative 2 Joint Undertaking. Dr. Schreiber reported having coinvented IP and having ties to Pfizer, Bristol Myers Squibb, and Roche. Four coinvestigators disclosed ties to Ferring, AbbVie, Chugai, Roche, Regeneron, Pfizer, Sanofi, Conaris, and Genentech Roche. The other researchers reported having no conflicts of interest.

When classifying gastric varices during endoscopy, experts suggest not only describing their location but also their size and whether any high-risk stigmata, such as discolorations and platelet plugs, are present.

In a clinical practice update from the American Gastroenterological Association, Zachary Henry, MD, of the University of Virginia, Charlottesville, and associates also proposed an alternative nomenclature for locating gastric varices (GV). “In practice, most gastroenterologists use the Sarin classification with the main distinction being cardiofundal versus lesser curvature GV. However, the vascular supply and corresponding therapy for GV and esophageal varices are often different, so a merged classification, such as Sarin’s, can be problematic for therapeutic planning purposes,” they wrote in Clinical Gastroenterology and Hepatology, referring to the classification system published by Shiv K. Sarin, MD, DM, and colleagues. They suggested that a merged classification, such as Sarin’s, can be “problematic for therapeutic and planning purposes” because “the vascular supply and corresponding therapy for GV and [esophageal varices] are often different.” Instead, they advised that an “alternative nomenclature based on location within the stomach is clearer and facilitates correlation with vascular imaging.” Another approach is to add risk factors for bleeding, such as an estimate of variceal size and high-risk stigmata (discolored marks, platelet plugs), to Sarin classification.

Diagnosis and treatment of bleeding GV are complex, and multidisciplinary management by hepatologists, interventional radiologists, and interventional endoscopists is optimal, the experts wrote. Data and clinical guidelines do not support primary prophylaxis to prevent bleeding of GV. The authors offered an algorithm for initial management of suspected portal hypertensive GV bleeding based on both endoscopic and vascular anatomy; it includes assessment of circulatory and respiratory status, vasoactive drug administration, antibiotic prophylaxis, and more.

An early goal is confirming bleeding source and attempting to classify the bleeding site; this can be complicated by presence of intragastric blood that obscures the cardia and fundus and underlying GV. Further steps may include temporizing: “Temporizing measures to halt active bleeding are often not the definitive treatment of choice to prevent rebleeding from GV, whereas definitive measures such as endoscopic cyanoacrylate injection (ECI) or endovascular treatments are often not feasible in the acute, diagnostic setting.”

When definitive endoscopic treatment is preferred, ECI of bleeding GV is the therapy of choice because other approaches may be complicated by location and bleeding risk of GV, although band ligation may be appropriate in lesser curve GV. Specific ECI techniques have not been compared directly in studies, according to the update authors; however, “the specific cyanoacrylate agent should favor the fastest polymerization time to avoid embolization and inducing GV bleeding.” This has meant 4-carbon (butyl) preparations are preferred to 8-carbon (octyl) preparations, they noted.

After treatment, endoscopy is performed every 2-4 weeks so that the ECI can be repeated as needed until obliteration is complete. The experts suggested that, after eradication of GV, an endoscopic reevaluation within 3-6 months should be scheduled, then annually thereafter. Any de novo or recurrent GV during the long-term follow-up may require additional imaging and multidisciplinary exploration to determine potential mechanisms and need for alternative treatments, the authors advised.

According to the practice update, transjugular intrahepatic portosystemic shunt can be used when the GV is receiving significant inflow from the coronary vein or the patient has significant complications from portal hypertension. When TIPS is used, the experts suggest also performing endovascular sclerosis or direct embolization of GV, if possible. For patients with a gastrorenal shunt, balloon-occluded retrograde transvenous obliteration (BRTO) of bleeding GV is considered optimal if local expertise is available and the patient lacks severe complications from portal hypertension. Endoscopy should be performed within 48 hours after BRTO to confirm obliteration of the vascular flow. If residual flow is detected, “cyanoacrylate injection should be performed,” the experts wrote. To confirm that GV are obliterated and check for any vascular complications, they suggest performing CT or MR within 4-6 weeks after BRTO and then as clinically indicated. In addition, surveillance endoscopy is important to identify and treat any esophageal varices that could have been worsened by increased portal pressures.

No funding sources were reported. The experts reported having no conflicts of interest.

When classifying gastric varices during endoscopy, experts suggest not only describing their location but also their size and whether any high-risk stigmata, such as discolorations and platelet plugs, are present.

In a clinical practice update from the American Gastroenterological Association, Zachary Henry, MD, of the University of Virginia, Charlottesville, and associates also proposed an alternative nomenclature for locating gastric varices (GV). “In practice, most gastroenterologists use the Sarin classification with the main distinction being cardiofundal versus lesser curvature GV. However, the vascular supply and corresponding therapy for GV and esophageal varices are often different, so a merged classification, such as Sarin’s, can be problematic for therapeutic planning purposes,” they wrote in Clinical Gastroenterology and Hepatology, referring to the classification system published by Shiv K. Sarin, MD, DM, and colleagues. They suggested that a merged classification, such as Sarin’s, can be “problematic for therapeutic and planning purposes” because “the vascular supply and corresponding therapy for GV and [esophageal varices] are often different.” Instead, they advised that an “alternative nomenclature based on location within the stomach is clearer and facilitates correlation with vascular imaging.” Another approach is to add risk factors for bleeding, such as an estimate of variceal size and high-risk stigmata (discolored marks, platelet plugs), to Sarin classification.

Diagnosis and treatment of bleeding GV are complex, and multidisciplinary management by hepatologists, interventional radiologists, and interventional endoscopists is optimal, the experts wrote. Data and clinical guidelines do not support primary prophylaxis to prevent bleeding of GV. The authors offered an algorithm for initial management of suspected portal hypertensive GV bleeding based on both endoscopic and vascular anatomy; it includes assessment of circulatory and respiratory status, vasoactive drug administration, antibiotic prophylaxis, and more.

An early goal is confirming bleeding source and attempting to classify the bleeding site; this can be complicated by presence of intragastric blood that obscures the cardia and fundus and underlying GV. Further steps may include temporizing: “Temporizing measures to halt active bleeding are often not the definitive treatment of choice to prevent rebleeding from GV, whereas definitive measures such as endoscopic cyanoacrylate injection (ECI) or endovascular treatments are often not feasible in the acute, diagnostic setting.”

When definitive endoscopic treatment is preferred, ECI of bleeding GV is the therapy of choice because other approaches may be complicated by location and bleeding risk of GV, although band ligation may be appropriate in lesser curve GV. Specific ECI techniques have not been compared directly in studies, according to the update authors; however, “the specific cyanoacrylate agent should favor the fastest polymerization time to avoid embolization and inducing GV bleeding.” This has meant 4-carbon (butyl) preparations are preferred to 8-carbon (octyl) preparations, they noted.

After treatment, endoscopy is performed every 2-4 weeks so that the ECI can be repeated as needed until obliteration is complete. The experts suggested that, after eradication of GV, an endoscopic reevaluation within 3-6 months should be scheduled, then annually thereafter. Any de novo or recurrent GV during the long-term follow-up may require additional imaging and multidisciplinary exploration to determine potential mechanisms and need for alternative treatments, the authors advised.

According to the practice update, transjugular intrahepatic portosystemic shunt can be used when the GV is receiving significant inflow from the coronary vein or the patient has significant complications from portal hypertension. When TIPS is used, the experts suggest also performing endovascular sclerosis or direct embolization of GV, if possible. For patients with a gastrorenal shunt, balloon-occluded retrograde transvenous obliteration (BRTO) of bleeding GV is considered optimal if local expertise is available and the patient lacks severe complications from portal hypertension. Endoscopy should be performed within 48 hours after BRTO to confirm obliteration of the vascular flow. If residual flow is detected, “cyanoacrylate injection should be performed,” the experts wrote. To confirm that GV are obliterated and check for any vascular complications, they suggest performing CT or MR within 4-6 weeks after BRTO and then as clinically indicated. In addition, surveillance endoscopy is important to identify and treat any esophageal varices that could have been worsened by increased portal pressures.

No funding sources were reported. The experts reported having no conflicts of interest.

When classifying gastric varices during endoscopy, experts suggest not only describing their location but also their size and whether any high-risk stigmata, such as discolorations and platelet plugs, are present.

In a clinical practice update from the American Gastroenterological Association, Zachary Henry, MD, of the University of Virginia, Charlottesville, and associates also proposed an alternative nomenclature for locating gastric varices (GV). “In practice, most gastroenterologists use the Sarin classification with the main distinction being cardiofundal versus lesser curvature GV. However, the vascular supply and corresponding therapy for GV and esophageal varices are often different, so a merged classification, such as Sarin’s, can be problematic for therapeutic planning purposes,” they wrote in Clinical Gastroenterology and Hepatology, referring to the classification system published by Shiv K. Sarin, MD, DM, and colleagues. They suggested that a merged classification, such as Sarin’s, can be “problematic for therapeutic and planning purposes” because “the vascular supply and corresponding therapy for GV and [esophageal varices] are often different.” Instead, they advised that an “alternative nomenclature based on location within the stomach is clearer and facilitates correlation with vascular imaging.” Another approach is to add risk factors for bleeding, such as an estimate of variceal size and high-risk stigmata (discolored marks, platelet plugs), to Sarin classification.

Diagnosis and treatment of bleeding GV are complex, and multidisciplinary management by hepatologists, interventional radiologists, and interventional endoscopists is optimal, the experts wrote. Data and clinical guidelines do not support primary prophylaxis to prevent bleeding of GV. The authors offered an algorithm for initial management of suspected portal hypertensive GV bleeding based on both endoscopic and vascular anatomy; it includes assessment of circulatory and respiratory status, vasoactive drug administration, antibiotic prophylaxis, and more.

An early goal is confirming bleeding source and attempting to classify the bleeding site; this can be complicated by presence of intragastric blood that obscures the cardia and fundus and underlying GV. Further steps may include temporizing: “Temporizing measures to halt active bleeding are often not the definitive treatment of choice to prevent rebleeding from GV, whereas definitive measures such as endoscopic cyanoacrylate injection (ECI) or endovascular treatments are often not feasible in the acute, diagnostic setting.”

When definitive endoscopic treatment is preferred, ECI of bleeding GV is the therapy of choice because other approaches may be complicated by location and bleeding risk of GV, although band ligation may be appropriate in lesser curve GV. Specific ECI techniques have not been compared directly in studies, according to the update authors; however, “the specific cyanoacrylate agent should favor the fastest polymerization time to avoid embolization and inducing GV bleeding.” This has meant 4-carbon (butyl) preparations are preferred to 8-carbon (octyl) preparations, they noted.

After treatment, endoscopy is performed every 2-4 weeks so that the ECI can be repeated as needed until obliteration is complete. The experts suggested that, after eradication of GV, an endoscopic reevaluation within 3-6 months should be scheduled, then annually thereafter. Any de novo or recurrent GV during the long-term follow-up may require additional imaging and multidisciplinary exploration to determine potential mechanisms and need for alternative treatments, the authors advised.

According to the practice update, transjugular intrahepatic portosystemic shunt can be used when the GV is receiving significant inflow from the coronary vein or the patient has significant complications from portal hypertension. When TIPS is used, the experts suggest also performing endovascular sclerosis or direct embolization of GV, if possible. For patients with a gastrorenal shunt, balloon-occluded retrograde transvenous obliteration (BRTO) of bleeding GV is considered optimal if local expertise is available and the patient lacks severe complications from portal hypertension. Endoscopy should be performed within 48 hours after BRTO to confirm obliteration of the vascular flow. If residual flow is detected, “cyanoacrylate injection should be performed,” the experts wrote. To confirm that GV are obliterated and check for any vascular complications, they suggest performing CT or MR within 4-6 weeks after BRTO and then as clinically indicated. In addition, surveillance endoscopy is important to identify and treat any esophageal varices that could have been worsened by increased portal pressures.

No funding sources were reported. The experts reported having no conflicts of interest.