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Women in rheumatology: A look back, a look forward
Jean Liew, MD, recalls the long list of women mentors who have guided her career in rheumatology.
It started during her residency, when Jennifer Barton, MD, at Oregon Health & Science University, Portland, exposed her to new ways of conducting clinical research on patient outcomes.
In fellowship, she met Lianne Gensler, MD, a leader in axial spondyloarthritis, at the annual meeting of the American College of Rheumatology. Through Dr. Gensler’s mentorship and sponsorship, she was introduced to Maureen Dubreuil, MD, at Boston University, whose research focuses on pharmacoepidemiologic approaches using large databases.
Dr. Liew currently practices rheumatology under the leadership of Tuhina Neogi, MD, a world-renowned expert in osteoarthritis and gout. “She’s my research mentor,” Dr. Liew, an assistant professor of medicine at Boston University, said in an interview.
Her academic timeline reflects the powerful network and influence of women rheumatologists, who represent half of the adult rheumatology workforce in the United States. “In the research arena, many experts are women and they serve as role models and mentors to many,” Dr. Liew said.
But there’s more work to do, she and others acknowledged.
Rheumatology faces ongoing workforce shortages while struggling with a gender gap that’s closing but not as quickly as many women rheumatologists would like to see.
The gap persists, despite overall gains in the field of medicine, Vaneet Sandhu, MD, a rheumatologist with Loma Linda (Calif.) University, said in an interview. Women have exceeded men as enrollees in medical colleges, reported the Association of American Medical Colleges. And yet, “our colleagues reported last year that, in academic rheumatology, women are less likely to be full or associate professors than men,” she said.
The odds of being a fellowship program director or division director is similar in both males and females. “So, we’ve had some gains, but there’s always room for more,” Dr. Sandhu said.
Too few physicians
The next 10 years forecasts a dearth in American physicians.
AAMC projects a shortage of 124,000 doctors in the United States by 2034. Following on a similar trajectory, the ACR in 2015 anticipated a 25% drop in the supply of rheumatology clinical providers by 2030, with demand exceeding supply by more than 4,100 clinical employees.
The ACR’s workforce study projected that more women would come into rheumatology, noted Marcy Bolster, MD, director of the rheumatology fellowship training program at Massachusetts General Hospital, Boston. Women make up at least 50% of the workforce and 66% of fellows If these numbers hold, “we’ll definitely see an increase in the percent of women in the workforce” moving forward, Dr. Bolster said in an interview.
Women have helped the shortage to a great extent, said Nilanjana Bose, MD, a rheumatologist at Lonestar Rheumatology, Houston.
The work-life balance that rheumatology offers, combined with its focus on the cognitive part of internal medicine, explains why the field has attracted so many women. Rheumatology provides flexible work options. Women “get to teach or do rounds in the hospital or have a private practice where you’re mostly outpatient with some hospital work,” Dr. Bose said in an interview.
With anticipated shortages looming over the next decade, the profession needs to be cognizant of the different demands women face in their careers and how it can accommodate the workforce to meet the needs of its providers and maintain access for patients, Dr. Bolster said.
There are many innovative ways to match the demand for access. One thought is to create shared positions. Instead of employing four full-time physicians and one person part time, have two people who are working part time, Dr. Bolster suggested. “It is also important to not only expand our workforce with advanced practice providers, but to ensure their retention in the rheumatology workforce, to improve access to care for those with rheumatic diseases.”
Increasing the number of residency positions is another step toward addressing the shortage, Dr. Sandhu offered.
Women rheumatologists should make their voices heard by contacting members of Congress to support legislation that advocates for workforce shortage solutions, “in addition to generally supporting women’s rights and growth in the workplace,” she said.
The gender divide continues
Rosalind Ramsey-Goldman, MD, DrPH, remembers being the only woman in a group of five during her fellowship in the mid-1980s. Few women role models existed within the ACR, especially those in academic careers. “Now, most fellowships have more than 50% women, reflecting the number of women going to medical school,” said Dr. Ramsey-Goldman, Gallagher Research Professor in Rheumatology at Northwestern University and Northwestern Medicine, Chicago.
As more women enter the profession, women rheumatologists in academic rheumatology have started to outpace men in recent years. Some research suggests they’ve made headway in gaining leadership spots at institutions.
One recent paper, a cross-sectional national study of more than 6,100 rheumatologists, found that women had similar odds of attaining fellowship program or division director positions as men. As directors of training programs, women in rheumatology “instill this collaborative and growth mindset that encourages learners to self-reflect and work as a team,” Dr. Sandhu said.
Women bring a different perspective to training, and how curriculum works, Dr. Bose said. Studies have shown that women tend to be more empathic. They ask more questions. “That’s not to say men aren’t good. Women just have an inborn ability for connecting,” and this perspective helps to enrich the educational experience for trainees.
Women who lead training programs are also attuned to realities that female trainees confront, such as dealing with the challenges of achieving the best possible education while also raising a family, noted Graciela S. Alarcón, MD, MPH, who holds emeritus positions at the University of Alabama at Birmingham and the Universidad Peruana Cayetano Heredia in Lima, Peru.
“These program directors cultivate the ability to relate to women trainees in a very personal manner, supporting them in their efforts to achieve a balance between their training demands and their family/personal responsibilities,” she said.
Other research suggests the gender gap hasn’t gone away. Women continue to have lower odds of holding a higher-level professorship, receiving a federal grant, or speaking at academic conferences. They are also less likely to serve as first authors on rheumatology guidelines or recommendations.
Some studies suggest that women see fewer patients and earn less than their male counterparts. At peak difference, men can earn up to $100,000+ more than women. “My own impression is that it takes more efforts for women to reach the same level of recognition than men, and although overt discrimination is rare nowadays, subtle discrimination still occurs,” according to Dr. Alarcón.
Over a lifetime, female physicians can expect to earn less than their male counterparts, with clear implications for different retirement income levels, she said.
Fixing a leaky academic pipeline
The reality is the academic pipeline, and especially the physician-scientist pipeline, “continues to be leaky,” Dr. Liew said. “We know that caregivers to young children have larger barriers to surmount in academics and in research, and that there is a gender disparity present.” The toll of academic medicine on early career women who are parents is especially pronounced. While the pandemic has intensified this problem, it was around pre-COVID, she added.
Women who start in academia as academic clinicians or clinician researchers aren’t always able to meet their goals for promotion within the appropriate time frame. This is because of inequities in the system and lack of support related to maternity leave, childcare, and other issues. As a result, they leave academia and go into private practice or industry, Dr. Liew said.
The ACR in its 2015 survey projected that more women would be seeking part-time positions.
The good news is many academic institutions are taking a more equitable view about different career paths, offering equal parental leave to both men and women, Dr. Bolster noted. “It is essential that workforce planning encompasses the changing responsibilities within families and account for more parental leave by both men and women.” If certain projections come true, with 50% of the profession retiring between 2015 and 2030, combined with more men and women working part time, “it is requisite that workforce strategies plan for this.”
When Dr. Ramsey-Goldman was a trainee and junior faculty, there were no formal maternity leave policies.
Now, this benefit is available, she said. In another critical change, the ACR has made childcare services and a lactation room available for young mothers during its annual meeting. “Virtual meetings afford further ways to interact with colleagues,” she added.
Whether women choose to stay in academia or go into clinical practice is a very personal decision. “But it is also fair that, in some programs, training directors and faculty members can encourage trainees toward academia and its fascinating research possibilities,” Dr. Alarcón offered.
Making gains in research
Women are increasingly driving groundbreaking rheumatology research at all levels, Dr. Sandhu said. “And women empower women. Not infrequently, our female leaders, veterans in rheumatology research, seek younger female rheumatologists to help them grow in their niches. This has been one of the most beautiful things of the sisterhood in rheumatology that I have been blessed to be part of.”
In pediatric rheumatology, young female researchers are leading global research efforts. Some standouts include Kate Webb, MD, a pediatric rheumatologist in Cape Town, South Africa, and scientist who has worked on multisystem inflammatory syndrome during the pandemic. Sheila Angeles-Han, MD, who works on uveitis in juvenile idiopathic arthritis, had a role in recent ACR guidelines. Laura Lewandowski, MD, has also contributed to global rheumatology efforts, especially in low- and middle-income countries, Dr. Liew said.
The 2021 ACR annual meeting highlighted the research efforts of women rheumatologists from around the world. A global rheumatology summit at the meeting featured many women voices, including Dzifa Dey, MD, from Ghana, who received the ACR Distinguished International Rheumatology Professional Award. Ashira Blazer, MD, and Irene Blanco, MD, have spearheaded the ACR’s diversity, equity, and inclusion initiatives.
Women researchers have many opportunities to study rheumatologic diseases that disproportionately affect women, Dr. Alarcón said.
Lupus, for example, affects women in a much higher proportion than men (90% vs. 10%). This may be an attractive target for the best and brightest among future women researchers, Dr. Alarcón suggested. “It is a fact that publications related to lupus in leading internal medicine and rheumatology journals often include women either as first or senior authors. In that context, it can be said that several advances in the study of lupus worldwide can be attributed to women.”
This applies to disparities in social determinants of health that account for extremely complex outcomes in lupus among women of color, compared with White women, in addition to the costs associated with the disease and its impact on morbidity, mortality, and quality of life.
Women rheumatologists have advanced the work in reproductive management of rheumatic diseases, including a recent ACR-endorsed publication that provides formal guidance on managing reproductive health in women with rheumatic disease, Dr. Sandhu said. “One thing is clear: Without women, the work on reproductive diseases in rheumatology to date would not likely be where it is.”
Dr. Ramsey-Goldman added that “this critical work will not only set the stage for clinical care of both women and men regarding their reproductive health but will also inform education strategies for trainees and future research activities, and help direct policy regarding access to care, medication development, and costs of treatment.”
Obtaining grant funding to support salaries and researcher endeavors remains a challenge, Dr. Liew said. “It takes working evenings, weekends, and holidays to meet those goals within a set time frame. So you can see why a female faculty member with children might be disadvantaged, compared to a male counterpart without children.”
Competition for grant funding remains fierce as budgets become tighter, she added.
“We will lose a lot more brilliant and compassionate rheumatologists (clinicians, physician-scientists, and scientists alike) if we do not think of ways to make things more equitable or do not acknowledge the privileges that support some to continued career successes and leave others behind,” Dr. Liew said.
Women who choose a research field should seek out mentor and financial support that will allow them enough protected time to balance out research with other clinical activities, such as teaching and patient care, Dr. Alarcón said.
Training directors, mentors, and faculty should prioritize the needs of current and future women researchers, she said. “The guidance provided to young female trainees toward a successful research career is a formidable challenge that may provide, in turn, enormous satisfaction. There are established avenues to seek funding as new investigators.”
Progress in diversity
Rheumatology as a field is attracting more candidates and all races and genders, Dr. Bose said. “I think in the coming years we will see more and more women from minorities being incorporated into the rheumatology workforce.”
Others would like to see further improvements in diversity and attracting women from historically excluded backgrounds. Patients will benefit from rheumatologists who are able to connect with them through shared languages, cultures, and other life experiences, Dr. Liew said. “It is imperative that we work on recruitment, mentorship, and retention in this regard.”
While the representation of women of color is still inadequate, there has been some progress, Dr. Sandhu said. The number of female Hispanic, Latinx, and Black or African American graduates from medical school has seen a steady rise since 2017. And, AAMC has established task forces such as the Women of Color Initiative to identify strategies for furthering the careers of women of color in academic medicine.
“There’s still a lot of room to grow. I am, however, proud to say we will finally have a woman of color as the president of ACR in 2023,” said Dr. Sandhu, referring to Deborah Dyett Desir, MD.
Dr. Desir discussed the importance of diversifying the ACR in a recent interview.
All rheumatologists know that there is a place for them in the ACR, she stressed. “The demographics of our membership should reflect that of our population.”
As growth in diverse representation occurs, so will recruitment, retention, and a greater awareness and distribution of knowledge and means to address implicit biases and microaggressions, Dr. Sandhu said. “We will see a greater quality of health care, where patients may feel more connected to someone they can identify with.”
Looking ahead
Dr. Alarcón expects women to continue to play a major role in rheumatology, not just in research, education, and patient care but in leadership of academic societies and professional organizations.
“Women in rheumatology have come a long way – a piece of history that I have been fortunate to witness from my beginnings in the early 1970s. We have, I think, paved the way for the next generations of leaders in our beloved specialty field.”
Dr. Bolster is a member of the ACR board of directors and board liaison of the ACR Workforce Solutions Committee. Dr. Ramsey-Goldman has been a GlaxoSmithKline consultant for lupus studies, a consultant and site investigator with Exagen Diagnostics for lupus biomarker studies, and a site investigator for Xencor and Horizon Pharma lupus trials. Dr. Sandhu serves on the ACR’s Committee on Rheumatology Training and Workforce Issues.
Related article
Pioneer days of rheumatology: One veteran looks back
Patricia Woo, CBE, FMedSci, FRCP, has seen it all.
As a member of the British Rheumatology Society and fellow of the Royal College of Physicians, she presented the case for and obtained official training approval for pediatric rheumatology in the 1990s. She also set the wheels in motion to form the Paediatric Rheumatology International Trials Organisation and the Paediatric Rheumatology European Society.
Now 74, Dr. Woo remembers the discrimination she faced in the 1970s. “I was told I couldn’t become an investigator or consultant if I were to marry or have children.” Around the same time, she found out a male clinician researcher didn’t want to work with her, not because of her qualifications, but because she was a woman.
That wouldn’t happen now with all the antidiscrimination laws in place, noted Dr. Woo, an emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. Looking at the advances made by women in rheumatology, “there’s a major difference between 3 decades ago and today. If anyone discriminates today, they are called out.”
As the founding president of the Paediatric Rheumatology European Society, Dr. Woo is one of many early trailblazers who weathered many changes and made gains in the profession.
It’s important to recognize the work of Barbara Ansell, MD, the founder of pediatric rheumatology in the Canadian Red Cross Memorial Hospital, said Dr. Woo. Back in the 1960s, this wasn’t even a subspecialty. “Sick kids in general were taken either to pediatricians who didn’t know much about undescribed rheumatological conditions, and rheumatologists who didn’t know or have facilities for pediatric care.”
Dr. Ansell started this work, and Dr. Woo took over when she retired. With her colleagues, she set up a syllabus for pediatric rheumatology to formalize training for all junior doctors. This established a model of multidisciplinary clinical care and research. “Over the years, more women doctors have been attracted to pediatric rheumatology and have done well,” she said.
The rise of female leaders in rheumatology over the past few decades has been exponential, she continued. Women have become presidents of rheumatologic societies. Some established themselves as leaders in specific disciplines.
Carol Black, MD, from the United Kingdom is renowned for her international collaborative work in scleroderma research and clinical care. Patience White, MD in Washington, D.C., started research on the process of transitioning from childhood to adolescent to adult clinical care, a discipline that now has a strong international presence, Dr. Woo said.
The European Alliance of Associations for Rheumatology, which created a task force on gender equity in academic rheumatology, is evolving, she continued. The Academy of Medical Sciences in the United Kingdom also has active gender equality and mentoring programs, including a program to boost the careers of all researchers.
It’s also much easier now for women to become lead authors on papers since many are heads of lab or clinical services, Dr. Woo continued. “I don’t think there’s much discrimination if you’re a good clinician, and/or a good scientist. If women do their work well, they get the appropriate acknowledgment.”
Jean Liew, MD, recalls the long list of women mentors who have guided her career in rheumatology.
It started during her residency, when Jennifer Barton, MD, at Oregon Health & Science University, Portland, exposed her to new ways of conducting clinical research on patient outcomes.
In fellowship, she met Lianne Gensler, MD, a leader in axial spondyloarthritis, at the annual meeting of the American College of Rheumatology. Through Dr. Gensler’s mentorship and sponsorship, she was introduced to Maureen Dubreuil, MD, at Boston University, whose research focuses on pharmacoepidemiologic approaches using large databases.
Dr. Liew currently practices rheumatology under the leadership of Tuhina Neogi, MD, a world-renowned expert in osteoarthritis and gout. “She’s my research mentor,” Dr. Liew, an assistant professor of medicine at Boston University, said in an interview.
Her academic timeline reflects the powerful network and influence of women rheumatologists, who represent half of the adult rheumatology workforce in the United States. “In the research arena, many experts are women and they serve as role models and mentors to many,” Dr. Liew said.
But there’s more work to do, she and others acknowledged.
Rheumatology faces ongoing workforce shortages while struggling with a gender gap that’s closing but not as quickly as many women rheumatologists would like to see.
The gap persists, despite overall gains in the field of medicine, Vaneet Sandhu, MD, a rheumatologist with Loma Linda (Calif.) University, said in an interview. Women have exceeded men as enrollees in medical colleges, reported the Association of American Medical Colleges. And yet, “our colleagues reported last year that, in academic rheumatology, women are less likely to be full or associate professors than men,” she said.
The odds of being a fellowship program director or division director is similar in both males and females. “So, we’ve had some gains, but there’s always room for more,” Dr. Sandhu said.
Too few physicians
The next 10 years forecasts a dearth in American physicians.
AAMC projects a shortage of 124,000 doctors in the United States by 2034. Following on a similar trajectory, the ACR in 2015 anticipated a 25% drop in the supply of rheumatology clinical providers by 2030, with demand exceeding supply by more than 4,100 clinical employees.
The ACR’s workforce study projected that more women would come into rheumatology, noted Marcy Bolster, MD, director of the rheumatology fellowship training program at Massachusetts General Hospital, Boston. Women make up at least 50% of the workforce and 66% of fellows If these numbers hold, “we’ll definitely see an increase in the percent of women in the workforce” moving forward, Dr. Bolster said in an interview.
Women have helped the shortage to a great extent, said Nilanjana Bose, MD, a rheumatologist at Lonestar Rheumatology, Houston.
The work-life balance that rheumatology offers, combined with its focus on the cognitive part of internal medicine, explains why the field has attracted so many women. Rheumatology provides flexible work options. Women “get to teach or do rounds in the hospital or have a private practice where you’re mostly outpatient with some hospital work,” Dr. Bose said in an interview.
With anticipated shortages looming over the next decade, the profession needs to be cognizant of the different demands women face in their careers and how it can accommodate the workforce to meet the needs of its providers and maintain access for patients, Dr. Bolster said.
There are many innovative ways to match the demand for access. One thought is to create shared positions. Instead of employing four full-time physicians and one person part time, have two people who are working part time, Dr. Bolster suggested. “It is also important to not only expand our workforce with advanced practice providers, but to ensure their retention in the rheumatology workforce, to improve access to care for those with rheumatic diseases.”
Increasing the number of residency positions is another step toward addressing the shortage, Dr. Sandhu offered.
Women rheumatologists should make their voices heard by contacting members of Congress to support legislation that advocates for workforce shortage solutions, “in addition to generally supporting women’s rights and growth in the workplace,” she said.
The gender divide continues
Rosalind Ramsey-Goldman, MD, DrPH, remembers being the only woman in a group of five during her fellowship in the mid-1980s. Few women role models existed within the ACR, especially those in academic careers. “Now, most fellowships have more than 50% women, reflecting the number of women going to medical school,” said Dr. Ramsey-Goldman, Gallagher Research Professor in Rheumatology at Northwestern University and Northwestern Medicine, Chicago.
As more women enter the profession, women rheumatologists in academic rheumatology have started to outpace men in recent years. Some research suggests they’ve made headway in gaining leadership spots at institutions.
One recent paper, a cross-sectional national study of more than 6,100 rheumatologists, found that women had similar odds of attaining fellowship program or division director positions as men. As directors of training programs, women in rheumatology “instill this collaborative and growth mindset that encourages learners to self-reflect and work as a team,” Dr. Sandhu said.
Women bring a different perspective to training, and how curriculum works, Dr. Bose said. Studies have shown that women tend to be more empathic. They ask more questions. “That’s not to say men aren’t good. Women just have an inborn ability for connecting,” and this perspective helps to enrich the educational experience for trainees.
Women who lead training programs are also attuned to realities that female trainees confront, such as dealing with the challenges of achieving the best possible education while also raising a family, noted Graciela S. Alarcón, MD, MPH, who holds emeritus positions at the University of Alabama at Birmingham and the Universidad Peruana Cayetano Heredia in Lima, Peru.
“These program directors cultivate the ability to relate to women trainees in a very personal manner, supporting them in their efforts to achieve a balance between their training demands and their family/personal responsibilities,” she said.
Other research suggests the gender gap hasn’t gone away. Women continue to have lower odds of holding a higher-level professorship, receiving a federal grant, or speaking at academic conferences. They are also less likely to serve as first authors on rheumatology guidelines or recommendations.
Some studies suggest that women see fewer patients and earn less than their male counterparts. At peak difference, men can earn up to $100,000+ more than women. “My own impression is that it takes more efforts for women to reach the same level of recognition than men, and although overt discrimination is rare nowadays, subtle discrimination still occurs,” according to Dr. Alarcón.
Over a lifetime, female physicians can expect to earn less than their male counterparts, with clear implications for different retirement income levels, she said.
Fixing a leaky academic pipeline
The reality is the academic pipeline, and especially the physician-scientist pipeline, “continues to be leaky,” Dr. Liew said. “We know that caregivers to young children have larger barriers to surmount in academics and in research, and that there is a gender disparity present.” The toll of academic medicine on early career women who are parents is especially pronounced. While the pandemic has intensified this problem, it was around pre-COVID, she added.
Women who start in academia as academic clinicians or clinician researchers aren’t always able to meet their goals for promotion within the appropriate time frame. This is because of inequities in the system and lack of support related to maternity leave, childcare, and other issues. As a result, they leave academia and go into private practice or industry, Dr. Liew said.
The ACR in its 2015 survey projected that more women would be seeking part-time positions.
The good news is many academic institutions are taking a more equitable view about different career paths, offering equal parental leave to both men and women, Dr. Bolster noted. “It is essential that workforce planning encompasses the changing responsibilities within families and account for more parental leave by both men and women.” If certain projections come true, with 50% of the profession retiring between 2015 and 2030, combined with more men and women working part time, “it is requisite that workforce strategies plan for this.”
When Dr. Ramsey-Goldman was a trainee and junior faculty, there were no formal maternity leave policies.
Now, this benefit is available, she said. In another critical change, the ACR has made childcare services and a lactation room available for young mothers during its annual meeting. “Virtual meetings afford further ways to interact with colleagues,” she added.
Whether women choose to stay in academia or go into clinical practice is a very personal decision. “But it is also fair that, in some programs, training directors and faculty members can encourage trainees toward academia and its fascinating research possibilities,” Dr. Alarcón offered.
Making gains in research
Women are increasingly driving groundbreaking rheumatology research at all levels, Dr. Sandhu said. “And women empower women. Not infrequently, our female leaders, veterans in rheumatology research, seek younger female rheumatologists to help them grow in their niches. This has been one of the most beautiful things of the sisterhood in rheumatology that I have been blessed to be part of.”
In pediatric rheumatology, young female researchers are leading global research efforts. Some standouts include Kate Webb, MD, a pediatric rheumatologist in Cape Town, South Africa, and scientist who has worked on multisystem inflammatory syndrome during the pandemic. Sheila Angeles-Han, MD, who works on uveitis in juvenile idiopathic arthritis, had a role in recent ACR guidelines. Laura Lewandowski, MD, has also contributed to global rheumatology efforts, especially in low- and middle-income countries, Dr. Liew said.
The 2021 ACR annual meeting highlighted the research efforts of women rheumatologists from around the world. A global rheumatology summit at the meeting featured many women voices, including Dzifa Dey, MD, from Ghana, who received the ACR Distinguished International Rheumatology Professional Award. Ashira Blazer, MD, and Irene Blanco, MD, have spearheaded the ACR’s diversity, equity, and inclusion initiatives.
Women researchers have many opportunities to study rheumatologic diseases that disproportionately affect women, Dr. Alarcón said.
Lupus, for example, affects women in a much higher proportion than men (90% vs. 10%). This may be an attractive target for the best and brightest among future women researchers, Dr. Alarcón suggested. “It is a fact that publications related to lupus in leading internal medicine and rheumatology journals often include women either as first or senior authors. In that context, it can be said that several advances in the study of lupus worldwide can be attributed to women.”
This applies to disparities in social determinants of health that account for extremely complex outcomes in lupus among women of color, compared with White women, in addition to the costs associated with the disease and its impact on morbidity, mortality, and quality of life.
Women rheumatologists have advanced the work in reproductive management of rheumatic diseases, including a recent ACR-endorsed publication that provides formal guidance on managing reproductive health in women with rheumatic disease, Dr. Sandhu said. “One thing is clear: Without women, the work on reproductive diseases in rheumatology to date would not likely be where it is.”
Dr. Ramsey-Goldman added that “this critical work will not only set the stage for clinical care of both women and men regarding their reproductive health but will also inform education strategies for trainees and future research activities, and help direct policy regarding access to care, medication development, and costs of treatment.”
Obtaining grant funding to support salaries and researcher endeavors remains a challenge, Dr. Liew said. “It takes working evenings, weekends, and holidays to meet those goals within a set time frame. So you can see why a female faculty member with children might be disadvantaged, compared to a male counterpart without children.”
Competition for grant funding remains fierce as budgets become tighter, she added.
“We will lose a lot more brilliant and compassionate rheumatologists (clinicians, physician-scientists, and scientists alike) if we do not think of ways to make things more equitable or do not acknowledge the privileges that support some to continued career successes and leave others behind,” Dr. Liew said.
Women who choose a research field should seek out mentor and financial support that will allow them enough protected time to balance out research with other clinical activities, such as teaching and patient care, Dr. Alarcón said.
Training directors, mentors, and faculty should prioritize the needs of current and future women researchers, she said. “The guidance provided to young female trainees toward a successful research career is a formidable challenge that may provide, in turn, enormous satisfaction. There are established avenues to seek funding as new investigators.”
Progress in diversity
Rheumatology as a field is attracting more candidates and all races and genders, Dr. Bose said. “I think in the coming years we will see more and more women from minorities being incorporated into the rheumatology workforce.”
Others would like to see further improvements in diversity and attracting women from historically excluded backgrounds. Patients will benefit from rheumatologists who are able to connect with them through shared languages, cultures, and other life experiences, Dr. Liew said. “It is imperative that we work on recruitment, mentorship, and retention in this regard.”
While the representation of women of color is still inadequate, there has been some progress, Dr. Sandhu said. The number of female Hispanic, Latinx, and Black or African American graduates from medical school has seen a steady rise since 2017. And, AAMC has established task forces such as the Women of Color Initiative to identify strategies for furthering the careers of women of color in academic medicine.
“There’s still a lot of room to grow. I am, however, proud to say we will finally have a woman of color as the president of ACR in 2023,” said Dr. Sandhu, referring to Deborah Dyett Desir, MD.
Dr. Desir discussed the importance of diversifying the ACR in a recent interview.
All rheumatologists know that there is a place for them in the ACR, she stressed. “The demographics of our membership should reflect that of our population.”
As growth in diverse representation occurs, so will recruitment, retention, and a greater awareness and distribution of knowledge and means to address implicit biases and microaggressions, Dr. Sandhu said. “We will see a greater quality of health care, where patients may feel more connected to someone they can identify with.”
Looking ahead
Dr. Alarcón expects women to continue to play a major role in rheumatology, not just in research, education, and patient care but in leadership of academic societies and professional organizations.
“Women in rheumatology have come a long way – a piece of history that I have been fortunate to witness from my beginnings in the early 1970s. We have, I think, paved the way for the next generations of leaders in our beloved specialty field.”
Dr. Bolster is a member of the ACR board of directors and board liaison of the ACR Workforce Solutions Committee. Dr. Ramsey-Goldman has been a GlaxoSmithKline consultant for lupus studies, a consultant and site investigator with Exagen Diagnostics for lupus biomarker studies, and a site investigator for Xencor and Horizon Pharma lupus trials. Dr. Sandhu serves on the ACR’s Committee on Rheumatology Training and Workforce Issues.
Related article
Pioneer days of rheumatology: One veteran looks back
Patricia Woo, CBE, FMedSci, FRCP, has seen it all.
As a member of the British Rheumatology Society and fellow of the Royal College of Physicians, she presented the case for and obtained official training approval for pediatric rheumatology in the 1990s. She also set the wheels in motion to form the Paediatric Rheumatology International Trials Organisation and the Paediatric Rheumatology European Society.
Now 74, Dr. Woo remembers the discrimination she faced in the 1970s. “I was told I couldn’t become an investigator or consultant if I were to marry or have children.” Around the same time, she found out a male clinician researcher didn’t want to work with her, not because of her qualifications, but because she was a woman.
That wouldn’t happen now with all the antidiscrimination laws in place, noted Dr. Woo, an emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. Looking at the advances made by women in rheumatology, “there’s a major difference between 3 decades ago and today. If anyone discriminates today, they are called out.”
As the founding president of the Paediatric Rheumatology European Society, Dr. Woo is one of many early trailblazers who weathered many changes and made gains in the profession.
It’s important to recognize the work of Barbara Ansell, MD, the founder of pediatric rheumatology in the Canadian Red Cross Memorial Hospital, said Dr. Woo. Back in the 1960s, this wasn’t even a subspecialty. “Sick kids in general were taken either to pediatricians who didn’t know much about undescribed rheumatological conditions, and rheumatologists who didn’t know or have facilities for pediatric care.”
Dr. Ansell started this work, and Dr. Woo took over when she retired. With her colleagues, she set up a syllabus for pediatric rheumatology to formalize training for all junior doctors. This established a model of multidisciplinary clinical care and research. “Over the years, more women doctors have been attracted to pediatric rheumatology and have done well,” she said.
The rise of female leaders in rheumatology over the past few decades has been exponential, she continued. Women have become presidents of rheumatologic societies. Some established themselves as leaders in specific disciplines.
Carol Black, MD, from the United Kingdom is renowned for her international collaborative work in scleroderma research and clinical care. Patience White, MD in Washington, D.C., started research on the process of transitioning from childhood to adolescent to adult clinical care, a discipline that now has a strong international presence, Dr. Woo said.
The European Alliance of Associations for Rheumatology, which created a task force on gender equity in academic rheumatology, is evolving, she continued. The Academy of Medical Sciences in the United Kingdom also has active gender equality and mentoring programs, including a program to boost the careers of all researchers.
It’s also much easier now for women to become lead authors on papers since many are heads of lab or clinical services, Dr. Woo continued. “I don’t think there’s much discrimination if you’re a good clinician, and/or a good scientist. If women do their work well, they get the appropriate acknowledgment.”
Jean Liew, MD, recalls the long list of women mentors who have guided her career in rheumatology.
It started during her residency, when Jennifer Barton, MD, at Oregon Health & Science University, Portland, exposed her to new ways of conducting clinical research on patient outcomes.
In fellowship, she met Lianne Gensler, MD, a leader in axial spondyloarthritis, at the annual meeting of the American College of Rheumatology. Through Dr. Gensler’s mentorship and sponsorship, she was introduced to Maureen Dubreuil, MD, at Boston University, whose research focuses on pharmacoepidemiologic approaches using large databases.
Dr. Liew currently practices rheumatology under the leadership of Tuhina Neogi, MD, a world-renowned expert in osteoarthritis and gout. “She’s my research mentor,” Dr. Liew, an assistant professor of medicine at Boston University, said in an interview.
Her academic timeline reflects the powerful network and influence of women rheumatologists, who represent half of the adult rheumatology workforce in the United States. “In the research arena, many experts are women and they serve as role models and mentors to many,” Dr. Liew said.
But there’s more work to do, she and others acknowledged.
Rheumatology faces ongoing workforce shortages while struggling with a gender gap that’s closing but not as quickly as many women rheumatologists would like to see.
The gap persists, despite overall gains in the field of medicine, Vaneet Sandhu, MD, a rheumatologist with Loma Linda (Calif.) University, said in an interview. Women have exceeded men as enrollees in medical colleges, reported the Association of American Medical Colleges. And yet, “our colleagues reported last year that, in academic rheumatology, women are less likely to be full or associate professors than men,” she said.
The odds of being a fellowship program director or division director is similar in both males and females. “So, we’ve had some gains, but there’s always room for more,” Dr. Sandhu said.
Too few physicians
The next 10 years forecasts a dearth in American physicians.
AAMC projects a shortage of 124,000 doctors in the United States by 2034. Following on a similar trajectory, the ACR in 2015 anticipated a 25% drop in the supply of rheumatology clinical providers by 2030, with demand exceeding supply by more than 4,100 clinical employees.
The ACR’s workforce study projected that more women would come into rheumatology, noted Marcy Bolster, MD, director of the rheumatology fellowship training program at Massachusetts General Hospital, Boston. Women make up at least 50% of the workforce and 66% of fellows If these numbers hold, “we’ll definitely see an increase in the percent of women in the workforce” moving forward, Dr. Bolster said in an interview.
Women have helped the shortage to a great extent, said Nilanjana Bose, MD, a rheumatologist at Lonestar Rheumatology, Houston.
The work-life balance that rheumatology offers, combined with its focus on the cognitive part of internal medicine, explains why the field has attracted so many women. Rheumatology provides flexible work options. Women “get to teach or do rounds in the hospital or have a private practice where you’re mostly outpatient with some hospital work,” Dr. Bose said in an interview.
With anticipated shortages looming over the next decade, the profession needs to be cognizant of the different demands women face in their careers and how it can accommodate the workforce to meet the needs of its providers and maintain access for patients, Dr. Bolster said.
There are many innovative ways to match the demand for access. One thought is to create shared positions. Instead of employing four full-time physicians and one person part time, have two people who are working part time, Dr. Bolster suggested. “It is also important to not only expand our workforce with advanced practice providers, but to ensure their retention in the rheumatology workforce, to improve access to care for those with rheumatic diseases.”
Increasing the number of residency positions is another step toward addressing the shortage, Dr. Sandhu offered.
Women rheumatologists should make their voices heard by contacting members of Congress to support legislation that advocates for workforce shortage solutions, “in addition to generally supporting women’s rights and growth in the workplace,” she said.
The gender divide continues
Rosalind Ramsey-Goldman, MD, DrPH, remembers being the only woman in a group of five during her fellowship in the mid-1980s. Few women role models existed within the ACR, especially those in academic careers. “Now, most fellowships have more than 50% women, reflecting the number of women going to medical school,” said Dr. Ramsey-Goldman, Gallagher Research Professor in Rheumatology at Northwestern University and Northwestern Medicine, Chicago.
As more women enter the profession, women rheumatologists in academic rheumatology have started to outpace men in recent years. Some research suggests they’ve made headway in gaining leadership spots at institutions.
One recent paper, a cross-sectional national study of more than 6,100 rheumatologists, found that women had similar odds of attaining fellowship program or division director positions as men. As directors of training programs, women in rheumatology “instill this collaborative and growth mindset that encourages learners to self-reflect and work as a team,” Dr. Sandhu said.
Women bring a different perspective to training, and how curriculum works, Dr. Bose said. Studies have shown that women tend to be more empathic. They ask more questions. “That’s not to say men aren’t good. Women just have an inborn ability for connecting,” and this perspective helps to enrich the educational experience for trainees.
Women who lead training programs are also attuned to realities that female trainees confront, such as dealing with the challenges of achieving the best possible education while also raising a family, noted Graciela S. Alarcón, MD, MPH, who holds emeritus positions at the University of Alabama at Birmingham and the Universidad Peruana Cayetano Heredia in Lima, Peru.
“These program directors cultivate the ability to relate to women trainees in a very personal manner, supporting them in their efforts to achieve a balance between their training demands and their family/personal responsibilities,” she said.
Other research suggests the gender gap hasn’t gone away. Women continue to have lower odds of holding a higher-level professorship, receiving a federal grant, or speaking at academic conferences. They are also less likely to serve as first authors on rheumatology guidelines or recommendations.
Some studies suggest that women see fewer patients and earn less than their male counterparts. At peak difference, men can earn up to $100,000+ more than women. “My own impression is that it takes more efforts for women to reach the same level of recognition than men, and although overt discrimination is rare nowadays, subtle discrimination still occurs,” according to Dr. Alarcón.
Over a lifetime, female physicians can expect to earn less than their male counterparts, with clear implications for different retirement income levels, she said.
Fixing a leaky academic pipeline
The reality is the academic pipeline, and especially the physician-scientist pipeline, “continues to be leaky,” Dr. Liew said. “We know that caregivers to young children have larger barriers to surmount in academics and in research, and that there is a gender disparity present.” The toll of academic medicine on early career women who are parents is especially pronounced. While the pandemic has intensified this problem, it was around pre-COVID, she added.
Women who start in academia as academic clinicians or clinician researchers aren’t always able to meet their goals for promotion within the appropriate time frame. This is because of inequities in the system and lack of support related to maternity leave, childcare, and other issues. As a result, they leave academia and go into private practice or industry, Dr. Liew said.
The ACR in its 2015 survey projected that more women would be seeking part-time positions.
The good news is many academic institutions are taking a more equitable view about different career paths, offering equal parental leave to both men and women, Dr. Bolster noted. “It is essential that workforce planning encompasses the changing responsibilities within families and account for more parental leave by both men and women.” If certain projections come true, with 50% of the profession retiring between 2015 and 2030, combined with more men and women working part time, “it is requisite that workforce strategies plan for this.”
When Dr. Ramsey-Goldman was a trainee and junior faculty, there were no formal maternity leave policies.
Now, this benefit is available, she said. In another critical change, the ACR has made childcare services and a lactation room available for young mothers during its annual meeting. “Virtual meetings afford further ways to interact with colleagues,” she added.
Whether women choose to stay in academia or go into clinical practice is a very personal decision. “But it is also fair that, in some programs, training directors and faculty members can encourage trainees toward academia and its fascinating research possibilities,” Dr. Alarcón offered.
Making gains in research
Women are increasingly driving groundbreaking rheumatology research at all levels, Dr. Sandhu said. “And women empower women. Not infrequently, our female leaders, veterans in rheumatology research, seek younger female rheumatologists to help them grow in their niches. This has been one of the most beautiful things of the sisterhood in rheumatology that I have been blessed to be part of.”
In pediatric rheumatology, young female researchers are leading global research efforts. Some standouts include Kate Webb, MD, a pediatric rheumatologist in Cape Town, South Africa, and scientist who has worked on multisystem inflammatory syndrome during the pandemic. Sheila Angeles-Han, MD, who works on uveitis in juvenile idiopathic arthritis, had a role in recent ACR guidelines. Laura Lewandowski, MD, has also contributed to global rheumatology efforts, especially in low- and middle-income countries, Dr. Liew said.
The 2021 ACR annual meeting highlighted the research efforts of women rheumatologists from around the world. A global rheumatology summit at the meeting featured many women voices, including Dzifa Dey, MD, from Ghana, who received the ACR Distinguished International Rheumatology Professional Award. Ashira Blazer, MD, and Irene Blanco, MD, have spearheaded the ACR’s diversity, equity, and inclusion initiatives.
Women researchers have many opportunities to study rheumatologic diseases that disproportionately affect women, Dr. Alarcón said.
Lupus, for example, affects women in a much higher proportion than men (90% vs. 10%). This may be an attractive target for the best and brightest among future women researchers, Dr. Alarcón suggested. “It is a fact that publications related to lupus in leading internal medicine and rheumatology journals often include women either as first or senior authors. In that context, it can be said that several advances in the study of lupus worldwide can be attributed to women.”
This applies to disparities in social determinants of health that account for extremely complex outcomes in lupus among women of color, compared with White women, in addition to the costs associated with the disease and its impact on morbidity, mortality, and quality of life.
Women rheumatologists have advanced the work in reproductive management of rheumatic diseases, including a recent ACR-endorsed publication that provides formal guidance on managing reproductive health in women with rheumatic disease, Dr. Sandhu said. “One thing is clear: Without women, the work on reproductive diseases in rheumatology to date would not likely be where it is.”
Dr. Ramsey-Goldman added that “this critical work will not only set the stage for clinical care of both women and men regarding their reproductive health but will also inform education strategies for trainees and future research activities, and help direct policy regarding access to care, medication development, and costs of treatment.”
Obtaining grant funding to support salaries and researcher endeavors remains a challenge, Dr. Liew said. “It takes working evenings, weekends, and holidays to meet those goals within a set time frame. So you can see why a female faculty member with children might be disadvantaged, compared to a male counterpart without children.”
Competition for grant funding remains fierce as budgets become tighter, she added.
“We will lose a lot more brilliant and compassionate rheumatologists (clinicians, physician-scientists, and scientists alike) if we do not think of ways to make things more equitable or do not acknowledge the privileges that support some to continued career successes and leave others behind,” Dr. Liew said.
Women who choose a research field should seek out mentor and financial support that will allow them enough protected time to balance out research with other clinical activities, such as teaching and patient care, Dr. Alarcón said.
Training directors, mentors, and faculty should prioritize the needs of current and future women researchers, she said. “The guidance provided to young female trainees toward a successful research career is a formidable challenge that may provide, in turn, enormous satisfaction. There are established avenues to seek funding as new investigators.”
Progress in diversity
Rheumatology as a field is attracting more candidates and all races and genders, Dr. Bose said. “I think in the coming years we will see more and more women from minorities being incorporated into the rheumatology workforce.”
Others would like to see further improvements in diversity and attracting women from historically excluded backgrounds. Patients will benefit from rheumatologists who are able to connect with them through shared languages, cultures, and other life experiences, Dr. Liew said. “It is imperative that we work on recruitment, mentorship, and retention in this regard.”
While the representation of women of color is still inadequate, there has been some progress, Dr. Sandhu said. The number of female Hispanic, Latinx, and Black or African American graduates from medical school has seen a steady rise since 2017. And, AAMC has established task forces such as the Women of Color Initiative to identify strategies for furthering the careers of women of color in academic medicine.
“There’s still a lot of room to grow. I am, however, proud to say we will finally have a woman of color as the president of ACR in 2023,” said Dr. Sandhu, referring to Deborah Dyett Desir, MD.
Dr. Desir discussed the importance of diversifying the ACR in a recent interview.
All rheumatologists know that there is a place for them in the ACR, she stressed. “The demographics of our membership should reflect that of our population.”
As growth in diverse representation occurs, so will recruitment, retention, and a greater awareness and distribution of knowledge and means to address implicit biases and microaggressions, Dr. Sandhu said. “We will see a greater quality of health care, where patients may feel more connected to someone they can identify with.”
Looking ahead
Dr. Alarcón expects women to continue to play a major role in rheumatology, not just in research, education, and patient care but in leadership of academic societies and professional organizations.
“Women in rheumatology have come a long way – a piece of history that I have been fortunate to witness from my beginnings in the early 1970s. We have, I think, paved the way for the next generations of leaders in our beloved specialty field.”
Dr. Bolster is a member of the ACR board of directors and board liaison of the ACR Workforce Solutions Committee. Dr. Ramsey-Goldman has been a GlaxoSmithKline consultant for lupus studies, a consultant and site investigator with Exagen Diagnostics for lupus biomarker studies, and a site investigator for Xencor and Horizon Pharma lupus trials. Dr. Sandhu serves on the ACR’s Committee on Rheumatology Training and Workforce Issues.
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Pioneer days of rheumatology: One veteran looks back
Patricia Woo, CBE, FMedSci, FRCP, has seen it all.
As a member of the British Rheumatology Society and fellow of the Royal College of Physicians, she presented the case for and obtained official training approval for pediatric rheumatology in the 1990s. She also set the wheels in motion to form the Paediatric Rheumatology International Trials Organisation and the Paediatric Rheumatology European Society.
Now 74, Dr. Woo remembers the discrimination she faced in the 1970s. “I was told I couldn’t become an investigator or consultant if I were to marry or have children.” Around the same time, she found out a male clinician researcher didn’t want to work with her, not because of her qualifications, but because she was a woman.
That wouldn’t happen now with all the antidiscrimination laws in place, noted Dr. Woo, an emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. Looking at the advances made by women in rheumatology, “there’s a major difference between 3 decades ago and today. If anyone discriminates today, they are called out.”
As the founding president of the Paediatric Rheumatology European Society, Dr. Woo is one of many early trailblazers who weathered many changes and made gains in the profession.
It’s important to recognize the work of Barbara Ansell, MD, the founder of pediatric rheumatology in the Canadian Red Cross Memorial Hospital, said Dr. Woo. Back in the 1960s, this wasn’t even a subspecialty. “Sick kids in general were taken either to pediatricians who didn’t know much about undescribed rheumatological conditions, and rheumatologists who didn’t know or have facilities for pediatric care.”
Dr. Ansell started this work, and Dr. Woo took over when she retired. With her colleagues, she set up a syllabus for pediatric rheumatology to formalize training for all junior doctors. This established a model of multidisciplinary clinical care and research. “Over the years, more women doctors have been attracted to pediatric rheumatology and have done well,” she said.
The rise of female leaders in rheumatology over the past few decades has been exponential, she continued. Women have become presidents of rheumatologic societies. Some established themselves as leaders in specific disciplines.
Carol Black, MD, from the United Kingdom is renowned for her international collaborative work in scleroderma research and clinical care. Patience White, MD in Washington, D.C., started research on the process of transitioning from childhood to adolescent to adult clinical care, a discipline that now has a strong international presence, Dr. Woo said.
The European Alliance of Associations for Rheumatology, which created a task force on gender equity in academic rheumatology, is evolving, she continued. The Academy of Medical Sciences in the United Kingdom also has active gender equality and mentoring programs, including a program to boost the careers of all researchers.
It’s also much easier now for women to become lead authors on papers since many are heads of lab or clinical services, Dr. Woo continued. “I don’t think there’s much discrimination if you’re a good clinician, and/or a good scientist. If women do their work well, they get the appropriate acknowledgment.”
Med school to pay $1.2 million to students in refunds and debt cancellation in FTC settlement
Although it disputed the allegations, The complaint referenced the school’s medical license exam test pass rate and residency matches along with violations of rules that protect consumers, including those dealing with credit contracts.
The school, based in the Caribbean with operations in Illinois, agreed to pay $1.2 million toward refunds and debt cancellation for students harmed by the marketing in the past 5 years.
“While we strongly disagree with the FTC’s approach to this matter, we did not want a lengthy legal process to distract from our mission of providing a quality medical education at an affordable cost,” Kaushik Guha, executive vice president of the parent of the school, Human Resources Development Services, said in a YouTube statement posted on the school’s website.
“Saint James lured students by lying about their chances of success,” Samuel Levine, director of the FTC’s Bureau of Consumer Protection, said in a press release. The settlement agreement was with HRDS, which bills itself as providing students from “non-traditional backgrounds the opportunity to pursue a medical degree and practice in the U.S. or Canada,” according to the school’s statement.
The complaint alleges that, since at least April 2018, the school, HRDS, and its operator Mr. Guha has lured students using “phony claims about the standardized test pass rate and students’ residency or job prospects. They lured consumers with false guarantees of student success at passing a critical medical school standardized test, the United States Medical Licensing Examination Step 1 Exam.”
For example, a brochure distributed at open houses claimed a first-time Step 1 pass rate of about 96.8%. The brochure further claimed: “Saint James is the first and only medical school to offer a USMLE Step 1 Pass Guarantee,” according to the FTC complaint.
The FTC said the USMLE rate is lower than touted and lower than reported by other U.S. and Canadian medical schools. “Since 2017, only 35% of Saint James students who have completed the necessary coursework to take the USMLE Step 1 exam passed the test.”
The school also misrepresented the residency match rate as “the same” as American medical schools, according to the complaint. For example, the school instructed telemarketers to tell consumers that the match rate for the school’s students was 85%-90%. The school stated on its website that the residency match rate for Saint James students was 83%. “In fact, the match rate for SJSM students is lower than touted and lower than that reported by U.S. medical schools. Since 2018, defendants’ average match rate has been 63%.”
The FTC also claims the school used illegal credit contracts when marketing financing for tuition and living expenses for students. “The financing contracts contained language attempting to waive consumers’ rights under federal law and omit legally mandated disclosures.”
Saint James’ tuition ranges from about $6,650 to $9,859 per trimester, depending on campus and course study, the complaint states. Between 2016 and 2020, about 1,300 students were enrolled each year in Saint James’ schools. Students who attended the schools between 2016 and 2022 are eligible for a refund under the settlement.
Saint James is required to notify consumers whose debts are being canceled through Delta Financial Solutions, Saint James’ financing partner. The debt will also be deleted from consumers’ credit reports.
“We have chosen to settle with the FTC over its allegations that disclosures on our website and in Delta’s loan agreements were insufficient,” Mr. Guha stated on the school website. “However, we have added additional language and clarifications any time the USMLE pass rate and placement rates are mentioned.”
He said he hopes the school will be “an industry leader for transparency and accountability” and that the school’s “efforts will lead to lasting change throughout the for-profit educational industry.”
Mr. Guha added that more than 600 of the school’s alumni are serving as doctors, including many “working to bridge the health equity gap in underserved areas in North America.”
The FTC has been cracking down on deceptive practices by for-profit institutions. In October, the FTC put 70 for-profit colleges on notice that it would investigate false promises the schools make about their graduates’ job prospects, expected earnings, and other educational outcomes and would levy significant financial penalties against violators. Saint James was not on that list, which included several of the largest for-profit universities in the nation, including Capella University, DeVry University, Strayer University, and Walden University.
A version of this article first appeared on Medscape.com.
Although it disputed the allegations, The complaint referenced the school’s medical license exam test pass rate and residency matches along with violations of rules that protect consumers, including those dealing with credit contracts.
The school, based in the Caribbean with operations in Illinois, agreed to pay $1.2 million toward refunds and debt cancellation for students harmed by the marketing in the past 5 years.
“While we strongly disagree with the FTC’s approach to this matter, we did not want a lengthy legal process to distract from our mission of providing a quality medical education at an affordable cost,” Kaushik Guha, executive vice president of the parent of the school, Human Resources Development Services, said in a YouTube statement posted on the school’s website.
“Saint James lured students by lying about their chances of success,” Samuel Levine, director of the FTC’s Bureau of Consumer Protection, said in a press release. The settlement agreement was with HRDS, which bills itself as providing students from “non-traditional backgrounds the opportunity to pursue a medical degree and practice in the U.S. or Canada,” according to the school’s statement.
The complaint alleges that, since at least April 2018, the school, HRDS, and its operator Mr. Guha has lured students using “phony claims about the standardized test pass rate and students’ residency or job prospects. They lured consumers with false guarantees of student success at passing a critical medical school standardized test, the United States Medical Licensing Examination Step 1 Exam.”
For example, a brochure distributed at open houses claimed a first-time Step 1 pass rate of about 96.8%. The brochure further claimed: “Saint James is the first and only medical school to offer a USMLE Step 1 Pass Guarantee,” according to the FTC complaint.
The FTC said the USMLE rate is lower than touted and lower than reported by other U.S. and Canadian medical schools. “Since 2017, only 35% of Saint James students who have completed the necessary coursework to take the USMLE Step 1 exam passed the test.”
The school also misrepresented the residency match rate as “the same” as American medical schools, according to the complaint. For example, the school instructed telemarketers to tell consumers that the match rate for the school’s students was 85%-90%. The school stated on its website that the residency match rate for Saint James students was 83%. “In fact, the match rate for SJSM students is lower than touted and lower than that reported by U.S. medical schools. Since 2018, defendants’ average match rate has been 63%.”
The FTC also claims the school used illegal credit contracts when marketing financing for tuition and living expenses for students. “The financing contracts contained language attempting to waive consumers’ rights under federal law and omit legally mandated disclosures.”
Saint James’ tuition ranges from about $6,650 to $9,859 per trimester, depending on campus and course study, the complaint states. Between 2016 and 2020, about 1,300 students were enrolled each year in Saint James’ schools. Students who attended the schools between 2016 and 2022 are eligible for a refund under the settlement.
Saint James is required to notify consumers whose debts are being canceled through Delta Financial Solutions, Saint James’ financing partner. The debt will also be deleted from consumers’ credit reports.
“We have chosen to settle with the FTC over its allegations that disclosures on our website and in Delta’s loan agreements were insufficient,” Mr. Guha stated on the school website. “However, we have added additional language and clarifications any time the USMLE pass rate and placement rates are mentioned.”
He said he hopes the school will be “an industry leader for transparency and accountability” and that the school’s “efforts will lead to lasting change throughout the for-profit educational industry.”
Mr. Guha added that more than 600 of the school’s alumni are serving as doctors, including many “working to bridge the health equity gap in underserved areas in North America.”
The FTC has been cracking down on deceptive practices by for-profit institutions. In October, the FTC put 70 for-profit colleges on notice that it would investigate false promises the schools make about their graduates’ job prospects, expected earnings, and other educational outcomes and would levy significant financial penalties against violators. Saint James was not on that list, which included several of the largest for-profit universities in the nation, including Capella University, DeVry University, Strayer University, and Walden University.
A version of this article first appeared on Medscape.com.
Although it disputed the allegations, The complaint referenced the school’s medical license exam test pass rate and residency matches along with violations of rules that protect consumers, including those dealing with credit contracts.
The school, based in the Caribbean with operations in Illinois, agreed to pay $1.2 million toward refunds and debt cancellation for students harmed by the marketing in the past 5 years.
“While we strongly disagree with the FTC’s approach to this matter, we did not want a lengthy legal process to distract from our mission of providing a quality medical education at an affordable cost,” Kaushik Guha, executive vice president of the parent of the school, Human Resources Development Services, said in a YouTube statement posted on the school’s website.
“Saint James lured students by lying about their chances of success,” Samuel Levine, director of the FTC’s Bureau of Consumer Protection, said in a press release. The settlement agreement was with HRDS, which bills itself as providing students from “non-traditional backgrounds the opportunity to pursue a medical degree and practice in the U.S. or Canada,” according to the school’s statement.
The complaint alleges that, since at least April 2018, the school, HRDS, and its operator Mr. Guha has lured students using “phony claims about the standardized test pass rate and students’ residency or job prospects. They lured consumers with false guarantees of student success at passing a critical medical school standardized test, the United States Medical Licensing Examination Step 1 Exam.”
For example, a brochure distributed at open houses claimed a first-time Step 1 pass rate of about 96.8%. The brochure further claimed: “Saint James is the first and only medical school to offer a USMLE Step 1 Pass Guarantee,” according to the FTC complaint.
The FTC said the USMLE rate is lower than touted and lower than reported by other U.S. and Canadian medical schools. “Since 2017, only 35% of Saint James students who have completed the necessary coursework to take the USMLE Step 1 exam passed the test.”
The school also misrepresented the residency match rate as “the same” as American medical schools, according to the complaint. For example, the school instructed telemarketers to tell consumers that the match rate for the school’s students was 85%-90%. The school stated on its website that the residency match rate for Saint James students was 83%. “In fact, the match rate for SJSM students is lower than touted and lower than that reported by U.S. medical schools. Since 2018, defendants’ average match rate has been 63%.”
The FTC also claims the school used illegal credit contracts when marketing financing for tuition and living expenses for students. “The financing contracts contained language attempting to waive consumers’ rights under federal law and omit legally mandated disclosures.”
Saint James’ tuition ranges from about $6,650 to $9,859 per trimester, depending on campus and course study, the complaint states. Between 2016 and 2020, about 1,300 students were enrolled each year in Saint James’ schools. Students who attended the schools between 2016 and 2022 are eligible for a refund under the settlement.
Saint James is required to notify consumers whose debts are being canceled through Delta Financial Solutions, Saint James’ financing partner. The debt will also be deleted from consumers’ credit reports.
“We have chosen to settle with the FTC over its allegations that disclosures on our website and in Delta’s loan agreements were insufficient,” Mr. Guha stated on the school website. “However, we have added additional language and clarifications any time the USMLE pass rate and placement rates are mentioned.”
He said he hopes the school will be “an industry leader for transparency and accountability” and that the school’s “efforts will lead to lasting change throughout the for-profit educational industry.”
Mr. Guha added that more than 600 of the school’s alumni are serving as doctors, including many “working to bridge the health equity gap in underserved areas in North America.”
The FTC has been cracking down on deceptive practices by for-profit institutions. In October, the FTC put 70 for-profit colleges on notice that it would investigate false promises the schools make about their graduates’ job prospects, expected earnings, and other educational outcomes and would levy significant financial penalties against violators. Saint James was not on that list, which included several of the largest for-profit universities in the nation, including Capella University, DeVry University, Strayer University, and Walden University.
A version of this article first appeared on Medscape.com.
Real-world data suggest coprescribing PDE5 inhibitors and nitrates may be safe
The authors of the new research specifically examined how frequently phosphodiesterase type 5 (PDE5) inhibitors, such as Viagra, were prescribed. The U.S. Food and Drug Administration and the European Medicines Agency have warned that these drugs for erectile dysfunction are contraindicated for use with nitrates because of concerns about cardiovascular risks.
“Small, randomized, pharmacologic studies have reported an amplified decrease in blood pressure during controlled coexposure with nitrates and [phosphodiesterase type 5 inhibitors], both in healthy participants and in participants with IHD,” wrote lead author Anders Holt, MD, of Copenhagen University Hospital–Herlev and Gentofte and colleagues, in Annals of Internal Medicine. “Potentially, this increases the risk for vascular ischemic events including myocardial infarction and stroke.”
But there is a scarcity of real-world data showing that using both types of drugs together increase these risks, the researchers noted.
To address this knowledge gap, Dr. Holt and colleagues conducted a retrospective study involving 249,541 Danish men with IHD. In this overall population, from 2000 to 2018, prescriptions for PDE5 inhibitors increased 10-fold, from 3.1 to 30.9 prescriptions per 100 persons per year. Within a subgroup of 42,073 patients continuously prescribed oral organic nitrates, PDE5-inhibitor prescriptions jumped twice that magnitude, from 0.9 to 19.7 prescriptions per 100 persons per year.
Despite this surge in coprescribing, the investigators did not observe a significant increase in either of two composite measures of cardiovascular adverse events. The first composite included ischemic stroke, shock, cardiac arrest, myocardial infarction, or acute coronary arteriography (odds ratio, 0.58; 95% confidence interval, 0.28-1.13). The second composite included drug-related adverse events, angina pectoris, or syncope (OR, 0.73; CI, 0.40-1.32).
Lead author speculates on reasons for findings
“I propose several explanations [for these findings],” Dr. Holt said in an interview, “but I want to emphasize that our study does not contain any data to back it up. It is just speculation. First, the observed drop in blood pressure may not cause a condition for which patients seek a hospital. A drop in blood pressure has been shown in pharmacologic trials, but it might not translate to a real-life risk for cardiovascular outcomes. Second, patients could be well informed and adherent to guidance that the prescribing physician has provided. For example, patients are aware of the recommended pause in nitrate treatment before PDE5-inhibitor use and follow these recommendations. Third, nitrates are often taken in the morning, and with the careful assumption that most PDE5-inhibitor activities take place in the evening, the nitrates could be metabolized to a degree such that the synergistic interaction is negligible.”
Dr. Holt went on to suggest a novel clinical approach based on the new findings.
“Coadministration should still be contraindicated due to the proven drop in blood pressure,” he said. “However, perhaps physicians can allow for coprescription if patients are adequately informed.”
A qualitative study is needed to determine how patients and physicians discuss coprescription, including avoidance of coadministration, Dr. Holt added.
Findings call for a reassessment of whether the contraindication is warranted
Robert A. Kloner, MD, PhD, chief science officer at the Huntington Medical Research Institutes in Pasadena, Calif., and professor of medicine at University of Southern California, Los Angeles, previously conducted research exploring drug interactions with PDE5 inhibitors, and in 2018, coauthored a literature review that concluded that PDE5 inhibitors and nitrates are contraindicated.
But now, considering these new findings, Dr. Kloner is offering a fresh perspective.
“This study is reassuring,” Dr. Kloner said in an interview. “I think that it’s time to reassess whether there should be an absolute contraindication, or this should be more of like a warning.”
He noted that in controlled studies, like the ones he previously conducted, PDE5 inhibitors and nitrates were administered “very close to each other, on purpose,” yet this probably doesn’t reflect typical practice, in which clinicians can guide usage based on durations of drug metabolism.
“I think that physicians might be more comfortable now prescribing the drugs at the same time, but then telling patients that they shouldn’t take the two drugs simultaneously; they should wait and take the nitrate 24 hours after the last Viagra, or the nitrate 48 hours after the last Cialis,” Dr. Kloner said. “I suspect that that is happening. I suspect also the fact that people would be more likely to take the nitrate in the morning and the PDE5 inhibitor at night probably also contributes to the safety findings.”
Dr. Kloner noted that blood pressures vary throughout the day based on circadian rhythm, and that the body can adapt to some fluctuations without negative effects.
There could still be some people who experience a drop in blood pressure and get sick from it from the two drugs interacting, but that’s probably not that common, he said.
The study was supported by several grants. The investigators disclosed relationships with Merck, BMS, Bayer, and others. Dr. Kloner consults for Sanofi.
The authors of the new research specifically examined how frequently phosphodiesterase type 5 (PDE5) inhibitors, such as Viagra, were prescribed. The U.S. Food and Drug Administration and the European Medicines Agency have warned that these drugs for erectile dysfunction are contraindicated for use with nitrates because of concerns about cardiovascular risks.
“Small, randomized, pharmacologic studies have reported an amplified decrease in blood pressure during controlled coexposure with nitrates and [phosphodiesterase type 5 inhibitors], both in healthy participants and in participants with IHD,” wrote lead author Anders Holt, MD, of Copenhagen University Hospital–Herlev and Gentofte and colleagues, in Annals of Internal Medicine. “Potentially, this increases the risk for vascular ischemic events including myocardial infarction and stroke.”
But there is a scarcity of real-world data showing that using both types of drugs together increase these risks, the researchers noted.
To address this knowledge gap, Dr. Holt and colleagues conducted a retrospective study involving 249,541 Danish men with IHD. In this overall population, from 2000 to 2018, prescriptions for PDE5 inhibitors increased 10-fold, from 3.1 to 30.9 prescriptions per 100 persons per year. Within a subgroup of 42,073 patients continuously prescribed oral organic nitrates, PDE5-inhibitor prescriptions jumped twice that magnitude, from 0.9 to 19.7 prescriptions per 100 persons per year.
Despite this surge in coprescribing, the investigators did not observe a significant increase in either of two composite measures of cardiovascular adverse events. The first composite included ischemic stroke, shock, cardiac arrest, myocardial infarction, or acute coronary arteriography (odds ratio, 0.58; 95% confidence interval, 0.28-1.13). The second composite included drug-related adverse events, angina pectoris, or syncope (OR, 0.73; CI, 0.40-1.32).
Lead author speculates on reasons for findings
“I propose several explanations [for these findings],” Dr. Holt said in an interview, “but I want to emphasize that our study does not contain any data to back it up. It is just speculation. First, the observed drop in blood pressure may not cause a condition for which patients seek a hospital. A drop in blood pressure has been shown in pharmacologic trials, but it might not translate to a real-life risk for cardiovascular outcomes. Second, patients could be well informed and adherent to guidance that the prescribing physician has provided. For example, patients are aware of the recommended pause in nitrate treatment before PDE5-inhibitor use and follow these recommendations. Third, nitrates are often taken in the morning, and with the careful assumption that most PDE5-inhibitor activities take place in the evening, the nitrates could be metabolized to a degree such that the synergistic interaction is negligible.”
Dr. Holt went on to suggest a novel clinical approach based on the new findings.
“Coadministration should still be contraindicated due to the proven drop in blood pressure,” he said. “However, perhaps physicians can allow for coprescription if patients are adequately informed.”
A qualitative study is needed to determine how patients and physicians discuss coprescription, including avoidance of coadministration, Dr. Holt added.
Findings call for a reassessment of whether the contraindication is warranted
Robert A. Kloner, MD, PhD, chief science officer at the Huntington Medical Research Institutes in Pasadena, Calif., and professor of medicine at University of Southern California, Los Angeles, previously conducted research exploring drug interactions with PDE5 inhibitors, and in 2018, coauthored a literature review that concluded that PDE5 inhibitors and nitrates are contraindicated.
But now, considering these new findings, Dr. Kloner is offering a fresh perspective.
“This study is reassuring,” Dr. Kloner said in an interview. “I think that it’s time to reassess whether there should be an absolute contraindication, or this should be more of like a warning.”
He noted that in controlled studies, like the ones he previously conducted, PDE5 inhibitors and nitrates were administered “very close to each other, on purpose,” yet this probably doesn’t reflect typical practice, in which clinicians can guide usage based on durations of drug metabolism.
“I think that physicians might be more comfortable now prescribing the drugs at the same time, but then telling patients that they shouldn’t take the two drugs simultaneously; they should wait and take the nitrate 24 hours after the last Viagra, or the nitrate 48 hours after the last Cialis,” Dr. Kloner said. “I suspect that that is happening. I suspect also the fact that people would be more likely to take the nitrate in the morning and the PDE5 inhibitor at night probably also contributes to the safety findings.”
Dr. Kloner noted that blood pressures vary throughout the day based on circadian rhythm, and that the body can adapt to some fluctuations without negative effects.
There could still be some people who experience a drop in blood pressure and get sick from it from the two drugs interacting, but that’s probably not that common, he said.
The study was supported by several grants. The investigators disclosed relationships with Merck, BMS, Bayer, and others. Dr. Kloner consults for Sanofi.
The authors of the new research specifically examined how frequently phosphodiesterase type 5 (PDE5) inhibitors, such as Viagra, were prescribed. The U.S. Food and Drug Administration and the European Medicines Agency have warned that these drugs for erectile dysfunction are contraindicated for use with nitrates because of concerns about cardiovascular risks.
“Small, randomized, pharmacologic studies have reported an amplified decrease in blood pressure during controlled coexposure with nitrates and [phosphodiesterase type 5 inhibitors], both in healthy participants and in participants with IHD,” wrote lead author Anders Holt, MD, of Copenhagen University Hospital–Herlev and Gentofte and colleagues, in Annals of Internal Medicine. “Potentially, this increases the risk for vascular ischemic events including myocardial infarction and stroke.”
But there is a scarcity of real-world data showing that using both types of drugs together increase these risks, the researchers noted.
To address this knowledge gap, Dr. Holt and colleagues conducted a retrospective study involving 249,541 Danish men with IHD. In this overall population, from 2000 to 2018, prescriptions for PDE5 inhibitors increased 10-fold, from 3.1 to 30.9 prescriptions per 100 persons per year. Within a subgroup of 42,073 patients continuously prescribed oral organic nitrates, PDE5-inhibitor prescriptions jumped twice that magnitude, from 0.9 to 19.7 prescriptions per 100 persons per year.
Despite this surge in coprescribing, the investigators did not observe a significant increase in either of two composite measures of cardiovascular adverse events. The first composite included ischemic stroke, shock, cardiac arrest, myocardial infarction, or acute coronary arteriography (odds ratio, 0.58; 95% confidence interval, 0.28-1.13). The second composite included drug-related adverse events, angina pectoris, or syncope (OR, 0.73; CI, 0.40-1.32).
Lead author speculates on reasons for findings
“I propose several explanations [for these findings],” Dr. Holt said in an interview, “but I want to emphasize that our study does not contain any data to back it up. It is just speculation. First, the observed drop in blood pressure may not cause a condition for which patients seek a hospital. A drop in blood pressure has been shown in pharmacologic trials, but it might not translate to a real-life risk for cardiovascular outcomes. Second, patients could be well informed and adherent to guidance that the prescribing physician has provided. For example, patients are aware of the recommended pause in nitrate treatment before PDE5-inhibitor use and follow these recommendations. Third, nitrates are often taken in the morning, and with the careful assumption that most PDE5-inhibitor activities take place in the evening, the nitrates could be metabolized to a degree such that the synergistic interaction is negligible.”
Dr. Holt went on to suggest a novel clinical approach based on the new findings.
“Coadministration should still be contraindicated due to the proven drop in blood pressure,” he said. “However, perhaps physicians can allow for coprescription if patients are adequately informed.”
A qualitative study is needed to determine how patients and physicians discuss coprescription, including avoidance of coadministration, Dr. Holt added.
Findings call for a reassessment of whether the contraindication is warranted
Robert A. Kloner, MD, PhD, chief science officer at the Huntington Medical Research Institutes in Pasadena, Calif., and professor of medicine at University of Southern California, Los Angeles, previously conducted research exploring drug interactions with PDE5 inhibitors, and in 2018, coauthored a literature review that concluded that PDE5 inhibitors and nitrates are contraindicated.
But now, considering these new findings, Dr. Kloner is offering a fresh perspective.
“This study is reassuring,” Dr. Kloner said in an interview. “I think that it’s time to reassess whether there should be an absolute contraindication, or this should be more of like a warning.”
He noted that in controlled studies, like the ones he previously conducted, PDE5 inhibitors and nitrates were administered “very close to each other, on purpose,” yet this probably doesn’t reflect typical practice, in which clinicians can guide usage based on durations of drug metabolism.
“I think that physicians might be more comfortable now prescribing the drugs at the same time, but then telling patients that they shouldn’t take the two drugs simultaneously; they should wait and take the nitrate 24 hours after the last Viagra, or the nitrate 48 hours after the last Cialis,” Dr. Kloner said. “I suspect that that is happening. I suspect also the fact that people would be more likely to take the nitrate in the morning and the PDE5 inhibitor at night probably also contributes to the safety findings.”
Dr. Kloner noted that blood pressures vary throughout the day based on circadian rhythm, and that the body can adapt to some fluctuations without negative effects.
There could still be some people who experience a drop in blood pressure and get sick from it from the two drugs interacting, but that’s probably not that common, he said.
The study was supported by several grants. The investigators disclosed relationships with Merck, BMS, Bayer, and others. Dr. Kloner consults for Sanofi.
FROM ANNALS OF INTERNAL MEDICINE
Meta-analysis confirms neuroprotective benefit of metformin
Key takeaways
, according to a systematic review and meta-analysis of longitudinal data.
However, the heterogeneity between the available studies and the potential heterogeneity of diagnostic criteria may mean that validation studies are needed.
Why is this important?
Data suggest that metformin, the most commonly prescribed antidiabetic drug, may be neuroprotective, while diabetes is associated with an excess risk of neurodegenerative disease. Results of studies conducted specifically to investigate the benefit of the antidiabetic drug on cognitive prognosis have been unclear. A meta-analysis was published in 2020, but it included cross-sectional and case-control studies. Given the long observation period needed to measure such an outcome, only cohort studies conducted over several years can provide reliable results. This new meta-analysis attempts to circumvent this limitation.
Methods
The meta-analysis was conducted using studies published up to March 2021 that met the inclusion criteria (population-based cohort studies published in English in which the administration of metformin and associated risk of exposure were reported).
Main results
Twelve studies were included in this analysis, of which eight were retrospective and 11 were considered to be of good methodologic quality. In total, 194,792 patients were included.
Pooled data showed that the relative risk associated with onset of neurodegenerative disease was 0.77 (95% CI, 0.67-0.88) for patients with diabetes taking metformin versus those not taking metformin. However, heterogeneity between studies was high (I2; 78.8%; P < .001).
The effect was greater with longer metformin use, with an RR of 0.29 (95% CI, 0.13-0.44) for those who took metformin for 4 years or more. Similarly, the studies conducted in Asian countries versus other locations suggested an added benefit for this population (RR, 0.69; 95% CI, 0.64-0.74).
Sensitivity analyses confirmed these results, and subtype analyses showed no difference according to the nature of the neurodegenerative disease.
A version of this article first appeared on Univadis.
Key takeaways
, according to a systematic review and meta-analysis of longitudinal data.
However, the heterogeneity between the available studies and the potential heterogeneity of diagnostic criteria may mean that validation studies are needed.
Why is this important?
Data suggest that metformin, the most commonly prescribed antidiabetic drug, may be neuroprotective, while diabetes is associated with an excess risk of neurodegenerative disease. Results of studies conducted specifically to investigate the benefit of the antidiabetic drug on cognitive prognosis have been unclear. A meta-analysis was published in 2020, but it included cross-sectional and case-control studies. Given the long observation period needed to measure such an outcome, only cohort studies conducted over several years can provide reliable results. This new meta-analysis attempts to circumvent this limitation.
Methods
The meta-analysis was conducted using studies published up to March 2021 that met the inclusion criteria (population-based cohort studies published in English in which the administration of metformin and associated risk of exposure were reported).
Main results
Twelve studies were included in this analysis, of which eight were retrospective and 11 were considered to be of good methodologic quality. In total, 194,792 patients were included.
Pooled data showed that the relative risk associated with onset of neurodegenerative disease was 0.77 (95% CI, 0.67-0.88) for patients with diabetes taking metformin versus those not taking metformin. However, heterogeneity between studies was high (I2; 78.8%; P < .001).
The effect was greater with longer metformin use, with an RR of 0.29 (95% CI, 0.13-0.44) for those who took metformin for 4 years or more. Similarly, the studies conducted in Asian countries versus other locations suggested an added benefit for this population (RR, 0.69; 95% CI, 0.64-0.74).
Sensitivity analyses confirmed these results, and subtype analyses showed no difference according to the nature of the neurodegenerative disease.
A version of this article first appeared on Univadis.
Key takeaways
, according to a systematic review and meta-analysis of longitudinal data.
However, the heterogeneity between the available studies and the potential heterogeneity of diagnostic criteria may mean that validation studies are needed.
Why is this important?
Data suggest that metformin, the most commonly prescribed antidiabetic drug, may be neuroprotective, while diabetes is associated with an excess risk of neurodegenerative disease. Results of studies conducted specifically to investigate the benefit of the antidiabetic drug on cognitive prognosis have been unclear. A meta-analysis was published in 2020, but it included cross-sectional and case-control studies. Given the long observation period needed to measure such an outcome, only cohort studies conducted over several years can provide reliable results. This new meta-analysis attempts to circumvent this limitation.
Methods
The meta-analysis was conducted using studies published up to March 2021 that met the inclusion criteria (population-based cohort studies published in English in which the administration of metformin and associated risk of exposure were reported).
Main results
Twelve studies were included in this analysis, of which eight were retrospective and 11 were considered to be of good methodologic quality. In total, 194,792 patients were included.
Pooled data showed that the relative risk associated with onset of neurodegenerative disease was 0.77 (95% CI, 0.67-0.88) for patients with diabetes taking metformin versus those not taking metformin. However, heterogeneity between studies was high (I2; 78.8%; P < .001).
The effect was greater with longer metformin use, with an RR of 0.29 (95% CI, 0.13-0.44) for those who took metformin for 4 years or more. Similarly, the studies conducted in Asian countries versus other locations suggested an added benefit for this population (RR, 0.69; 95% CI, 0.64-0.74).
Sensitivity analyses confirmed these results, and subtype analyses showed no difference according to the nature of the neurodegenerative disease.
A version of this article first appeared on Univadis.
Blistering Lesions in a Newborn
The Diagnosis: Epidermolysis Bullosa
Our patient was found to have epidermolysis bullosa (EB), a rare genetic disease in which the superficial layers of the skin separate to form vesicles or bullae due to a mutation in the keratin 14 gene, KRT14. Separation of the skin occurs due to cleavage of various proteins that connect the epidermis to the dermis. A genetic mutation in KRT14, one of the more common genetic mutations associated with EB, results in cleavage at the basal epidermal protein keratin 14. The skin of individuals with EB typically is fragile and cannot tolerate friction or manipulation due to the risk for new bullae formation.1 Epidermolysis bullosa is rare, affecting approximately 20 children per 1 million births in the United States, and is not commonly seen by most general adult dermatologists.2
In our patient, the differential diagnoses included staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), herpes simplex virus (HSV), and bullous pemphigoid (BP). Symptoms of SSSS can range from mild and localized to full-body exfoliation of the skin. Although SSSS can resemble other bullous disorders, its etiology arises from the Staphylococcus exotoxin targeting desmoglein in the stratum granulosum— the layer of the epidermis between the stratum corneum and stratum spinosum.3 Lesions start on the face, neck, and body folds, which was consistent with our patient’s presentation. However, bullae continued to develop in our patient despite antibiotic therapy, which reduced the likelihood of SSSS. Stevens-Johnson syndrome/toxic epidermal necrolysis develops rapidly and often involves the mucosa, which our patient initially did not have. In children, SJS/TEN can develop secondary to infection, whereas in adults it more commonly is associated with medication administration.4 Although the mother tested negative for HSV, the infant was started on acyclovir, which ultimately was discontinued due to low clinical suspicion. The clinical presentation of HSV (ie, clustered vesicles) was not consistent with our patient’s presentation. Bullous pemphigoid is a subepithelial blistering disease seen in older adults. Tense, fluidfilled blisters primarily are seen on the trunk and flexures. Although infantile BP can occur, it usually does not present in the neonatal period but rather at approximately 3 to 5 months of age.5
High clinical suspicion for EB due to the common characteristics of bullae location and formation following skin manipulation led to genetic testing in our patient. Mild forms of EB simplex typically appear on the upper and lower extremities with sparing of the trunk. In more severe cases of EB simplex, truncal and mucosal involvement may occur.6 In our case, the infant had a classic distribution of arm and leg blisters with truncal sparing. Epidermolysis bullosa may not be diagnosed in the neonatal period because of its similarities to other more common diseases, such as HSV or bullous impetigo, or other genetic blistering diseases, such as epidermolytic ichthyosis and incontinentia pigmenti.6
Epidermolysis bullosa can be inherited in an autosomal-dominant or autosomal-recessive fashion or with de novo mutations and is classified based on the location of cleavage in the skin. The 4 classical subtypes— simplex, junctional, dystrophic, and Kindler—have now been further subclassified. Epidermolysis bullosa simplex (intraepidermal split) is now separated into basal and suprabasal, with further subclassification including the distribution of blisters (generalized or localized) and the severity of cutaneous or extracutaneous involvement.7
In our case, the infant was found to have intraepidermal EB (simplex) due to a KRT14 mutation (missense mutation).6KRT14 (17q21.2) and KRT5 (12q13.3) are the 2 most common mutations causing cleavage at the basal intraepidermal layer. Thickening of the palms, soles, and nails can be seen; however, blisters heal well without scarring, as seen in our patient. Junctional EB due to cleavage at the intralamina lucida often involves mutations in laminin 332, plectin, and α6β4 integrin. Infants with junctional EB often die from severe infection, dehydration, or malnutrition due to mucosal involvement. Dystrophic EB occurs due to a collagen VII mutation in the dermis, leading to blisters at the sublamina densa and more severe symptoms in the recessive form.7
Newborn management for infants with EB differs from normal newborn care due to increased skin fragility with physical manipulation. Minimal skin manipulation and proper wound care are essential from the first day of life. For new bullae formation, bullae should be ruptured with a needle at the base of the blister and drained. The remaining skin overlying the wound should remain in place as a natural wound barrier. Patients with EB should not have tape or adhesive bandages applied directly to the skin. Instead, nonadhesive dressings can be placed directly on wounds and covered in soft wraps circumferentially. Dressings can be taped together without involving the skin. The cost for supplies for families to manage bullae is expensive. Fortunately, there are resources available for supplies and support for families, including the EB Research Partnership (https://www.ebresearch.org/) and DEBRA of America (https://www.debra.org/).
Currently, there is no cure for EB. Current treatment involves wound care, prevention, and symptomatic relief. Prevention includes avoiding activities that may result in increased friction of the skin and ensuring careful manipulation. Children with EB may have pain or itching from their blisters, which can be treated with oral acetaminophen or ibuprofen and diphenhydramine, respectively. Other complications of EB include anemia, dehydration, constipation, infection, and malnutrition. In more severe forms of EB, complications including eye problems, mucosal strictures, and skin cancer may occur.8 Future treatment directions include gene therapy, bone marrow transplantation, protein replacement therapies, and cell-based therapies. Prognosis for infants with EB due to KRT14 mutation is good, as it is a milder subtype of EB with a full life expectancy and improvement of blistering skin with age. The most at-risk time for early death is during infancy due to increased risk for infection.8 In this case, our patient showed full healing with no scar formation, which suggested a reassuring prognosis.
- Fine JD, Bruckner-Tuderman L, Eady RAJ, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70:1103-1126.
- Wolff K, Johnson RA, Saavedra AP, et al. Hereditary epidermolysis bullosa. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 8th ed. McGraw-Hill Education; 2017:94-99.
- Ross A, Shoff HW. Staphylococcus scalded skin syndrome. In: StatPearls. StatPearls Publishing; 2020:1-20.
- Alerhand S, Cassella C, Koyfman A. Steven-Johnson syndrome and toxic epidermal necrolysis in the pediatric population. Pediatr Emerg Care. 2016;32:472-476.
- Schwieger-Briel A, Moellmann C, Mattulat B, et al. Bullous pemphigoid in infants: characteristics, diagnosis and treatment. Orphanet J Rare Dis. 2014;9:185.
- Gonzalez ME. Evaluation and treatment of the newborn with epidermolysis bullosa. Semin Perinatol. 2013;37:32-39.
- Has C, Bauer JW, Bodemer C, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183:614-627.
- Watkins J. Diagnosis, treatment and management of epidermolysis bullosa. Br J Nurs. 2016;25:428-431.
The Diagnosis: Epidermolysis Bullosa
Our patient was found to have epidermolysis bullosa (EB), a rare genetic disease in which the superficial layers of the skin separate to form vesicles or bullae due to a mutation in the keratin 14 gene, KRT14. Separation of the skin occurs due to cleavage of various proteins that connect the epidermis to the dermis. A genetic mutation in KRT14, one of the more common genetic mutations associated with EB, results in cleavage at the basal epidermal protein keratin 14. The skin of individuals with EB typically is fragile and cannot tolerate friction or manipulation due to the risk for new bullae formation.1 Epidermolysis bullosa is rare, affecting approximately 20 children per 1 million births in the United States, and is not commonly seen by most general adult dermatologists.2
In our patient, the differential diagnoses included staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), herpes simplex virus (HSV), and bullous pemphigoid (BP). Symptoms of SSSS can range from mild and localized to full-body exfoliation of the skin. Although SSSS can resemble other bullous disorders, its etiology arises from the Staphylococcus exotoxin targeting desmoglein in the stratum granulosum— the layer of the epidermis between the stratum corneum and stratum spinosum.3 Lesions start on the face, neck, and body folds, which was consistent with our patient’s presentation. However, bullae continued to develop in our patient despite antibiotic therapy, which reduced the likelihood of SSSS. Stevens-Johnson syndrome/toxic epidermal necrolysis develops rapidly and often involves the mucosa, which our patient initially did not have. In children, SJS/TEN can develop secondary to infection, whereas in adults it more commonly is associated with medication administration.4 Although the mother tested negative for HSV, the infant was started on acyclovir, which ultimately was discontinued due to low clinical suspicion. The clinical presentation of HSV (ie, clustered vesicles) was not consistent with our patient’s presentation. Bullous pemphigoid is a subepithelial blistering disease seen in older adults. Tense, fluidfilled blisters primarily are seen on the trunk and flexures. Although infantile BP can occur, it usually does not present in the neonatal period but rather at approximately 3 to 5 months of age.5
High clinical suspicion for EB due to the common characteristics of bullae location and formation following skin manipulation led to genetic testing in our patient. Mild forms of EB simplex typically appear on the upper and lower extremities with sparing of the trunk. In more severe cases of EB simplex, truncal and mucosal involvement may occur.6 In our case, the infant had a classic distribution of arm and leg blisters with truncal sparing. Epidermolysis bullosa may not be diagnosed in the neonatal period because of its similarities to other more common diseases, such as HSV or bullous impetigo, or other genetic blistering diseases, such as epidermolytic ichthyosis and incontinentia pigmenti.6
Epidermolysis bullosa can be inherited in an autosomal-dominant or autosomal-recessive fashion or with de novo mutations and is classified based on the location of cleavage in the skin. The 4 classical subtypes— simplex, junctional, dystrophic, and Kindler—have now been further subclassified. Epidermolysis bullosa simplex (intraepidermal split) is now separated into basal and suprabasal, with further subclassification including the distribution of blisters (generalized or localized) and the severity of cutaneous or extracutaneous involvement.7
In our case, the infant was found to have intraepidermal EB (simplex) due to a KRT14 mutation (missense mutation).6KRT14 (17q21.2) and KRT5 (12q13.3) are the 2 most common mutations causing cleavage at the basal intraepidermal layer. Thickening of the palms, soles, and nails can be seen; however, blisters heal well without scarring, as seen in our patient. Junctional EB due to cleavage at the intralamina lucida often involves mutations in laminin 332, plectin, and α6β4 integrin. Infants with junctional EB often die from severe infection, dehydration, or malnutrition due to mucosal involvement. Dystrophic EB occurs due to a collagen VII mutation in the dermis, leading to blisters at the sublamina densa and more severe symptoms in the recessive form.7
Newborn management for infants with EB differs from normal newborn care due to increased skin fragility with physical manipulation. Minimal skin manipulation and proper wound care are essential from the first day of life. For new bullae formation, bullae should be ruptured with a needle at the base of the blister and drained. The remaining skin overlying the wound should remain in place as a natural wound barrier. Patients with EB should not have tape or adhesive bandages applied directly to the skin. Instead, nonadhesive dressings can be placed directly on wounds and covered in soft wraps circumferentially. Dressings can be taped together without involving the skin. The cost for supplies for families to manage bullae is expensive. Fortunately, there are resources available for supplies and support for families, including the EB Research Partnership (https://www.ebresearch.org/) and DEBRA of America (https://www.debra.org/).
Currently, there is no cure for EB. Current treatment involves wound care, prevention, and symptomatic relief. Prevention includes avoiding activities that may result in increased friction of the skin and ensuring careful manipulation. Children with EB may have pain or itching from their blisters, which can be treated with oral acetaminophen or ibuprofen and diphenhydramine, respectively. Other complications of EB include anemia, dehydration, constipation, infection, and malnutrition. In more severe forms of EB, complications including eye problems, mucosal strictures, and skin cancer may occur.8 Future treatment directions include gene therapy, bone marrow transplantation, protein replacement therapies, and cell-based therapies. Prognosis for infants with EB due to KRT14 mutation is good, as it is a milder subtype of EB with a full life expectancy and improvement of blistering skin with age. The most at-risk time for early death is during infancy due to increased risk for infection.8 In this case, our patient showed full healing with no scar formation, which suggested a reassuring prognosis.
The Diagnosis: Epidermolysis Bullosa
Our patient was found to have epidermolysis bullosa (EB), a rare genetic disease in which the superficial layers of the skin separate to form vesicles or bullae due to a mutation in the keratin 14 gene, KRT14. Separation of the skin occurs due to cleavage of various proteins that connect the epidermis to the dermis. A genetic mutation in KRT14, one of the more common genetic mutations associated with EB, results in cleavage at the basal epidermal protein keratin 14. The skin of individuals with EB typically is fragile and cannot tolerate friction or manipulation due to the risk for new bullae formation.1 Epidermolysis bullosa is rare, affecting approximately 20 children per 1 million births in the United States, and is not commonly seen by most general adult dermatologists.2
In our patient, the differential diagnoses included staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), herpes simplex virus (HSV), and bullous pemphigoid (BP). Symptoms of SSSS can range from mild and localized to full-body exfoliation of the skin. Although SSSS can resemble other bullous disorders, its etiology arises from the Staphylococcus exotoxin targeting desmoglein in the stratum granulosum— the layer of the epidermis between the stratum corneum and stratum spinosum.3 Lesions start on the face, neck, and body folds, which was consistent with our patient’s presentation. However, bullae continued to develop in our patient despite antibiotic therapy, which reduced the likelihood of SSSS. Stevens-Johnson syndrome/toxic epidermal necrolysis develops rapidly and often involves the mucosa, which our patient initially did not have. In children, SJS/TEN can develop secondary to infection, whereas in adults it more commonly is associated with medication administration.4 Although the mother tested negative for HSV, the infant was started on acyclovir, which ultimately was discontinued due to low clinical suspicion. The clinical presentation of HSV (ie, clustered vesicles) was not consistent with our patient’s presentation. Bullous pemphigoid is a subepithelial blistering disease seen in older adults. Tense, fluidfilled blisters primarily are seen on the trunk and flexures. Although infantile BP can occur, it usually does not present in the neonatal period but rather at approximately 3 to 5 months of age.5
High clinical suspicion for EB due to the common characteristics of bullae location and formation following skin manipulation led to genetic testing in our patient. Mild forms of EB simplex typically appear on the upper and lower extremities with sparing of the trunk. In more severe cases of EB simplex, truncal and mucosal involvement may occur.6 In our case, the infant had a classic distribution of arm and leg blisters with truncal sparing. Epidermolysis bullosa may not be diagnosed in the neonatal period because of its similarities to other more common diseases, such as HSV or bullous impetigo, or other genetic blistering diseases, such as epidermolytic ichthyosis and incontinentia pigmenti.6
Epidermolysis bullosa can be inherited in an autosomal-dominant or autosomal-recessive fashion or with de novo mutations and is classified based on the location of cleavage in the skin. The 4 classical subtypes— simplex, junctional, dystrophic, and Kindler—have now been further subclassified. Epidermolysis bullosa simplex (intraepidermal split) is now separated into basal and suprabasal, with further subclassification including the distribution of blisters (generalized or localized) and the severity of cutaneous or extracutaneous involvement.7
In our case, the infant was found to have intraepidermal EB (simplex) due to a KRT14 mutation (missense mutation).6KRT14 (17q21.2) and KRT5 (12q13.3) are the 2 most common mutations causing cleavage at the basal intraepidermal layer. Thickening of the palms, soles, and nails can be seen; however, blisters heal well without scarring, as seen in our patient. Junctional EB due to cleavage at the intralamina lucida often involves mutations in laminin 332, plectin, and α6β4 integrin. Infants with junctional EB often die from severe infection, dehydration, or malnutrition due to mucosal involvement. Dystrophic EB occurs due to a collagen VII mutation in the dermis, leading to blisters at the sublamina densa and more severe symptoms in the recessive form.7
Newborn management for infants with EB differs from normal newborn care due to increased skin fragility with physical manipulation. Minimal skin manipulation and proper wound care are essential from the first day of life. For new bullae formation, bullae should be ruptured with a needle at the base of the blister and drained. The remaining skin overlying the wound should remain in place as a natural wound barrier. Patients with EB should not have tape or adhesive bandages applied directly to the skin. Instead, nonadhesive dressings can be placed directly on wounds and covered in soft wraps circumferentially. Dressings can be taped together without involving the skin. The cost for supplies for families to manage bullae is expensive. Fortunately, there are resources available for supplies and support for families, including the EB Research Partnership (https://www.ebresearch.org/) and DEBRA of America (https://www.debra.org/).
Currently, there is no cure for EB. Current treatment involves wound care, prevention, and symptomatic relief. Prevention includes avoiding activities that may result in increased friction of the skin and ensuring careful manipulation. Children with EB may have pain or itching from their blisters, which can be treated with oral acetaminophen or ibuprofen and diphenhydramine, respectively. Other complications of EB include anemia, dehydration, constipation, infection, and malnutrition. In more severe forms of EB, complications including eye problems, mucosal strictures, and skin cancer may occur.8 Future treatment directions include gene therapy, bone marrow transplantation, protein replacement therapies, and cell-based therapies. Prognosis for infants with EB due to KRT14 mutation is good, as it is a milder subtype of EB with a full life expectancy and improvement of blistering skin with age. The most at-risk time for early death is during infancy due to increased risk for infection.8 In this case, our patient showed full healing with no scar formation, which suggested a reassuring prognosis.
- Fine JD, Bruckner-Tuderman L, Eady RAJ, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70:1103-1126.
- Wolff K, Johnson RA, Saavedra AP, et al. Hereditary epidermolysis bullosa. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 8th ed. McGraw-Hill Education; 2017:94-99.
- Ross A, Shoff HW. Staphylococcus scalded skin syndrome. In: StatPearls. StatPearls Publishing; 2020:1-20.
- Alerhand S, Cassella C, Koyfman A. Steven-Johnson syndrome and toxic epidermal necrolysis in the pediatric population. Pediatr Emerg Care. 2016;32:472-476.
- Schwieger-Briel A, Moellmann C, Mattulat B, et al. Bullous pemphigoid in infants: characteristics, diagnosis and treatment. Orphanet J Rare Dis. 2014;9:185.
- Gonzalez ME. Evaluation and treatment of the newborn with epidermolysis bullosa. Semin Perinatol. 2013;37:32-39.
- Has C, Bauer JW, Bodemer C, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183:614-627.
- Watkins J. Diagnosis, treatment and management of epidermolysis bullosa. Br J Nurs. 2016;25:428-431.
- Fine JD, Bruckner-Tuderman L, Eady RAJ, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70:1103-1126.
- Wolff K, Johnson RA, Saavedra AP, et al. Hereditary epidermolysis bullosa. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 8th ed. McGraw-Hill Education; 2017:94-99.
- Ross A, Shoff HW. Staphylococcus scalded skin syndrome. In: StatPearls. StatPearls Publishing; 2020:1-20.
- Alerhand S, Cassella C, Koyfman A. Steven-Johnson syndrome and toxic epidermal necrolysis in the pediatric population. Pediatr Emerg Care. 2016;32:472-476.
- Schwieger-Briel A, Moellmann C, Mattulat B, et al. Bullous pemphigoid in infants: characteristics, diagnosis and treatment. Orphanet J Rare Dis. 2014;9:185.
- Gonzalez ME. Evaluation and treatment of the newborn with epidermolysis bullosa. Semin Perinatol. 2013;37:32-39.
- Has C, Bauer JW, Bodemer C, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183:614-627.
- Watkins J. Diagnosis, treatment and management of epidermolysis bullosa. Br J Nurs. 2016;25:428-431.
A 4-day-old infant boy presented with blisters on the skin. He was born at 36 weeks’ gestation by cesarean delivery to a nulliparous mother who received appropriate prenatal care. On day 2 of life, the patient developed bullae with breakdown of the skin on the bilateral heels and on the skin surrounding intravenous injection sites. Similar blisters subsequently developed on the fingers (top), thighs, groin, and toes (bottom), sparing the oral mucosa and trunk. He remained afebrile and stable and was started on ampicillin, gentamicin, and acyclovir with continued development of blisters. Two weeks later he developed painful ulcers on the tongue that bled upon scraping.
Age and ferritin levels may predict MIS-C severity
, according to a Canadian multicenter cohort study.
The adjusted absolute risk for admission to an intensive care unit was 43.6% among children aged 6 years and older and 46.2% in children aged 13 to 17 years, compared with 18.4% in children aged 5 years or younger.
“We do not understand why teens get more severe MIS-C than younger children,” senior author Joan Robinson, MD, of the University of Alberta, Edmonton, told this news organization. “It is possible that more exposures to other coronaviruses in the past result in them having a more robust immune response to SARS-CoV-2, which results in more inflammation.”
The data were published in the Canadian Medical Association Journal.
A multinational study
The study included data on 232 children admitted with probable or confirmed MIS-C at 15 hospitals in Canada, Iran, and Costa Rica between March 1, 2020, and March 7, 2021. The median age of the children was 5.8 years, 56.0% were boys, and 21.6% had comorbidities.
Although cardiac involvement was common (58.6%), and almost one-third of the cohort (31.5%) was admitted to an ICU, “recovery was typically rapid, with 85% of patients discharged within 10 days,” said Dr. Robinson, for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC).
Older age as a risk
The results suggest that older age is associated with increased risk of severe MIS-C. “However, one would then predict that adults would be at even higher risk than teens, whereas the same syndrome in adults (MIS-A) is very, very rare,” said Dr. Robinson.
The study also found that children admitted with ferritin levels greater than 500 μg/L, signaling greater inflammation, also had an increased risk for ICU admission, compared with those with lower levels (adjusted risk difference, 18.4%; relative risk, 1.69). “This is presumably because the more inflammation that the child has, the more likely they are to have inflammation of the heart, which can lead to low blood pressure,” said Dr. Robinson.
Features of MIS-C
Among all patients with MIS-C, gastrointestinal involvement was common (89.2%), as were mucocutaneous findings (84.5%). Children with MIS-C had fever for a median duration of 6 days. “Clinicians who see children in their practice commonly have to determine why a child is febrile. Our study shows that one mainly has to consider MIS-C if febrile children have a rash and one or more of vomiting, diarrhea, or abdominal pain,” said Dr. Robinson.
The study also found that patients with MIS-C who were admitted to the hospital in the latter part of the study period (Nov. 1, 2020, to March 7, 2021) were slightly more likely to require ICU admission, compared with those admitted between March 1 and Oct. 31, 2020. “We cannot provide a clear explanation [for this],” the authors noted. “The features of severe MIS-C were widely publicized by May 2020, so it seems unlikely that severe cases were missed early in the study period. SARS-CoV-2 variants of concern have replaced the wild-type virus. It is possible that the immune response to circulating variants alters the severity of COVID-19 and MIS-C, when compared with wild-type virus.”
Despite initial concerns that pediatric COVID-19 vaccines might cause MIS-C, Dr. Robinson says data suggest this is rarely, if ever, the case, and that vaccines actually prevent the syndrome. She says further studies will be needed to assess MIS-C risk following reinfection with SARS-CoV-2. “I am an optimistic person, and it is my hope that MIS-C following reinfection is rare,” she said. “If this is the case, perhaps we will see very few cases once almost all children have been immunized and/or had SARS-CoV-2 infection.”
‘Differences across countries’
Adrienne Randolph, MD, a pediatrician at Harvard Medical School, Boston, and senior author of a large case series of patients with MIS-C, said that the Canadian study is valuable because it includes children from three countries. “It’s very interesting that there are differences across countries,” she said. “The patients in Iran had the highest percentage (58.7%) going into the ICU, whereas Costa Rica had the lowest percentage (9.2%), and the percentage going to the ICU in Canada (34.7%) was less than the percentages we see in the U.S. – which is pretty consistently about 60% to 70% of MIS-C patients going into the ICU.” Dr. Randolph was not involved in the current study.
Reasons for differences in the rates of ICU visits will be important to explore in the effort to standardize diagnostic criteria, stratification of severity, and recommendations for treatment of MIS-C, said Dr. Randolph.
“What is consistent is that the younger kids, zero to 5 years, in general are less ill,” she said. “That’s been consistent across multiple countries.” It’s unclear whether the cause of this difference is that parents observe younger patients more closely than they do teenagers, or whether other aspects of adolescence, such as prevalence of obesity and attendant inflammation, are at work, said Dr. Randolph.
What is also unclear is why hospitalized patients with MIS-C had higher percentages of ICU admission in the latter part of the study period, compared with the earlier period. “Did the patients change, or did practice change as we got to understand the disease process?” asked Dr. Randolph. “It could be that they got better at the diagnosis and were weeding out some of the patients who they realized didn’t need to be hospitalized. At the very beginning, we had a very low threshold to admit patients, because we didn’t know, and then, over time, people understood what was going on and felt more comfortable monitoring them as outpatients.”
This study was partially funded by a Janeway Foundation Research Grant to support data collection. Dr. Robinson disclosed no conflicts of interest. Dr. Randolph reported receiving royalties from UpToDate and personal fees from the La Jolla Pharmaceutical Company.
A version of this article first appeared on Medscape.com.
, according to a Canadian multicenter cohort study.
The adjusted absolute risk for admission to an intensive care unit was 43.6% among children aged 6 years and older and 46.2% in children aged 13 to 17 years, compared with 18.4% in children aged 5 years or younger.
“We do not understand why teens get more severe MIS-C than younger children,” senior author Joan Robinson, MD, of the University of Alberta, Edmonton, told this news organization. “It is possible that more exposures to other coronaviruses in the past result in them having a more robust immune response to SARS-CoV-2, which results in more inflammation.”
The data were published in the Canadian Medical Association Journal.
A multinational study
The study included data on 232 children admitted with probable or confirmed MIS-C at 15 hospitals in Canada, Iran, and Costa Rica between March 1, 2020, and March 7, 2021. The median age of the children was 5.8 years, 56.0% were boys, and 21.6% had comorbidities.
Although cardiac involvement was common (58.6%), and almost one-third of the cohort (31.5%) was admitted to an ICU, “recovery was typically rapid, with 85% of patients discharged within 10 days,” said Dr. Robinson, for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC).
Older age as a risk
The results suggest that older age is associated with increased risk of severe MIS-C. “However, one would then predict that adults would be at even higher risk than teens, whereas the same syndrome in adults (MIS-A) is very, very rare,” said Dr. Robinson.
The study also found that children admitted with ferritin levels greater than 500 μg/L, signaling greater inflammation, also had an increased risk for ICU admission, compared with those with lower levels (adjusted risk difference, 18.4%; relative risk, 1.69). “This is presumably because the more inflammation that the child has, the more likely they are to have inflammation of the heart, which can lead to low blood pressure,” said Dr. Robinson.
Features of MIS-C
Among all patients with MIS-C, gastrointestinal involvement was common (89.2%), as were mucocutaneous findings (84.5%). Children with MIS-C had fever for a median duration of 6 days. “Clinicians who see children in their practice commonly have to determine why a child is febrile. Our study shows that one mainly has to consider MIS-C if febrile children have a rash and one or more of vomiting, diarrhea, or abdominal pain,” said Dr. Robinson.
The study also found that patients with MIS-C who were admitted to the hospital in the latter part of the study period (Nov. 1, 2020, to March 7, 2021) were slightly more likely to require ICU admission, compared with those admitted between March 1 and Oct. 31, 2020. “We cannot provide a clear explanation [for this],” the authors noted. “The features of severe MIS-C were widely publicized by May 2020, so it seems unlikely that severe cases were missed early in the study period. SARS-CoV-2 variants of concern have replaced the wild-type virus. It is possible that the immune response to circulating variants alters the severity of COVID-19 and MIS-C, when compared with wild-type virus.”
Despite initial concerns that pediatric COVID-19 vaccines might cause MIS-C, Dr. Robinson says data suggest this is rarely, if ever, the case, and that vaccines actually prevent the syndrome. She says further studies will be needed to assess MIS-C risk following reinfection with SARS-CoV-2. “I am an optimistic person, and it is my hope that MIS-C following reinfection is rare,” she said. “If this is the case, perhaps we will see very few cases once almost all children have been immunized and/or had SARS-CoV-2 infection.”
‘Differences across countries’
Adrienne Randolph, MD, a pediatrician at Harvard Medical School, Boston, and senior author of a large case series of patients with MIS-C, said that the Canadian study is valuable because it includes children from three countries. “It’s very interesting that there are differences across countries,” she said. “The patients in Iran had the highest percentage (58.7%) going into the ICU, whereas Costa Rica had the lowest percentage (9.2%), and the percentage going to the ICU in Canada (34.7%) was less than the percentages we see in the U.S. – which is pretty consistently about 60% to 70% of MIS-C patients going into the ICU.” Dr. Randolph was not involved in the current study.
Reasons for differences in the rates of ICU visits will be important to explore in the effort to standardize diagnostic criteria, stratification of severity, and recommendations for treatment of MIS-C, said Dr. Randolph.
“What is consistent is that the younger kids, zero to 5 years, in general are less ill,” she said. “That’s been consistent across multiple countries.” It’s unclear whether the cause of this difference is that parents observe younger patients more closely than they do teenagers, or whether other aspects of adolescence, such as prevalence of obesity and attendant inflammation, are at work, said Dr. Randolph.
What is also unclear is why hospitalized patients with MIS-C had higher percentages of ICU admission in the latter part of the study period, compared with the earlier period. “Did the patients change, or did practice change as we got to understand the disease process?” asked Dr. Randolph. “It could be that they got better at the diagnosis and were weeding out some of the patients who they realized didn’t need to be hospitalized. At the very beginning, we had a very low threshold to admit patients, because we didn’t know, and then, over time, people understood what was going on and felt more comfortable monitoring them as outpatients.”
This study was partially funded by a Janeway Foundation Research Grant to support data collection. Dr. Robinson disclosed no conflicts of interest. Dr. Randolph reported receiving royalties from UpToDate and personal fees from the La Jolla Pharmaceutical Company.
A version of this article first appeared on Medscape.com.
, according to a Canadian multicenter cohort study.
The adjusted absolute risk for admission to an intensive care unit was 43.6% among children aged 6 years and older and 46.2% in children aged 13 to 17 years, compared with 18.4% in children aged 5 years or younger.
“We do not understand why teens get more severe MIS-C than younger children,” senior author Joan Robinson, MD, of the University of Alberta, Edmonton, told this news organization. “It is possible that more exposures to other coronaviruses in the past result in them having a more robust immune response to SARS-CoV-2, which results in more inflammation.”
The data were published in the Canadian Medical Association Journal.
A multinational study
The study included data on 232 children admitted with probable or confirmed MIS-C at 15 hospitals in Canada, Iran, and Costa Rica between March 1, 2020, and March 7, 2021. The median age of the children was 5.8 years, 56.0% were boys, and 21.6% had comorbidities.
Although cardiac involvement was common (58.6%), and almost one-third of the cohort (31.5%) was admitted to an ICU, “recovery was typically rapid, with 85% of patients discharged within 10 days,” said Dr. Robinson, for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC).
Older age as a risk
The results suggest that older age is associated with increased risk of severe MIS-C. “However, one would then predict that adults would be at even higher risk than teens, whereas the same syndrome in adults (MIS-A) is very, very rare,” said Dr. Robinson.
The study also found that children admitted with ferritin levels greater than 500 μg/L, signaling greater inflammation, also had an increased risk for ICU admission, compared with those with lower levels (adjusted risk difference, 18.4%; relative risk, 1.69). “This is presumably because the more inflammation that the child has, the more likely they are to have inflammation of the heart, which can lead to low blood pressure,” said Dr. Robinson.
Features of MIS-C
Among all patients with MIS-C, gastrointestinal involvement was common (89.2%), as were mucocutaneous findings (84.5%). Children with MIS-C had fever for a median duration of 6 days. “Clinicians who see children in their practice commonly have to determine why a child is febrile. Our study shows that one mainly has to consider MIS-C if febrile children have a rash and one or more of vomiting, diarrhea, or abdominal pain,” said Dr. Robinson.
The study also found that patients with MIS-C who were admitted to the hospital in the latter part of the study period (Nov. 1, 2020, to March 7, 2021) were slightly more likely to require ICU admission, compared with those admitted between March 1 and Oct. 31, 2020. “We cannot provide a clear explanation [for this],” the authors noted. “The features of severe MIS-C were widely publicized by May 2020, so it seems unlikely that severe cases were missed early in the study period. SARS-CoV-2 variants of concern have replaced the wild-type virus. It is possible that the immune response to circulating variants alters the severity of COVID-19 and MIS-C, when compared with wild-type virus.”
Despite initial concerns that pediatric COVID-19 vaccines might cause MIS-C, Dr. Robinson says data suggest this is rarely, if ever, the case, and that vaccines actually prevent the syndrome. She says further studies will be needed to assess MIS-C risk following reinfection with SARS-CoV-2. “I am an optimistic person, and it is my hope that MIS-C following reinfection is rare,” she said. “If this is the case, perhaps we will see very few cases once almost all children have been immunized and/or had SARS-CoV-2 infection.”
‘Differences across countries’
Adrienne Randolph, MD, a pediatrician at Harvard Medical School, Boston, and senior author of a large case series of patients with MIS-C, said that the Canadian study is valuable because it includes children from three countries. “It’s very interesting that there are differences across countries,” she said. “The patients in Iran had the highest percentage (58.7%) going into the ICU, whereas Costa Rica had the lowest percentage (9.2%), and the percentage going to the ICU in Canada (34.7%) was less than the percentages we see in the U.S. – which is pretty consistently about 60% to 70% of MIS-C patients going into the ICU.” Dr. Randolph was not involved in the current study.
Reasons for differences in the rates of ICU visits will be important to explore in the effort to standardize diagnostic criteria, stratification of severity, and recommendations for treatment of MIS-C, said Dr. Randolph.
“What is consistent is that the younger kids, zero to 5 years, in general are less ill,” she said. “That’s been consistent across multiple countries.” It’s unclear whether the cause of this difference is that parents observe younger patients more closely than they do teenagers, or whether other aspects of adolescence, such as prevalence of obesity and attendant inflammation, are at work, said Dr. Randolph.
What is also unclear is why hospitalized patients with MIS-C had higher percentages of ICU admission in the latter part of the study period, compared with the earlier period. “Did the patients change, or did practice change as we got to understand the disease process?” asked Dr. Randolph. “It could be that they got better at the diagnosis and were weeding out some of the patients who they realized didn’t need to be hospitalized. At the very beginning, we had a very low threshold to admit patients, because we didn’t know, and then, over time, people understood what was going on and felt more comfortable monitoring them as outpatients.”
This study was partially funded by a Janeway Foundation Research Grant to support data collection. Dr. Robinson disclosed no conflicts of interest. Dr. Randolph reported receiving royalties from UpToDate and personal fees from the La Jolla Pharmaceutical Company.
A version of this article first appeared on Medscape.com.
Bariatric surgery cuts cardiovascular events, even in seniors
Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years suggests.
Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction), compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation, Ohio, and colleagues.
The results were published in the Journal of the American College of Cardiology.
Previous studies on bariatric surgery outcomes have primarily focused on individuals from select health care networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues in an accompanying editorial.
Moreover, other long-term and observational studies have shown that bariatric surgery can decrease the risk of myocardial infarction, death, and stroke in young and middle-aged patients with obesity, but the evidence is less clear for older patients and those without diabetes, noted Dr. Mentias in a phone interview.
“To date, this is one of the first studies to support bariatric surgery for CVD risk reduction in patients older than 65 years, a population at highest risk for developing heart failure,” the editorial points out.
“We should consider referring patients who qualify for bariatric surgery based on BMI; it really should be considered as a treatment option for patients with class 3 obesity, especially with a body mass index over 40 kg/m2,” Dr. Powell-Wiley told this news organization.
“We know that patients are generally under-referred for bariatric surgery, and this highlights the need to refer patients for bariatric surgery,” she added.
“There should be discussion about expanding insurance coverage to include bariatric surgery for eligible patients,” Dr. Mentias added.
Contemporary cohort of patients
“A lot of the studies showed long-term outcomes outside of the U.S., specifically in Europe,” Dr. Mentias added.
The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.
Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.
The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Female patients comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.
The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.
Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.
More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:
- Myocardial infarction (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68)
- Stroke (HR, 0.71; 95% CI, 0.65-0.79)
- New-onset heart failure (HR, 0.46; 95% CI, 0.44-0.49)
- Reduced risk of death (9.2 vs. 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60-0.66)
Findings for those over the age of 65 were similar – lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.
The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.
An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.
“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.
This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr. Milind Y. Desai’s research. Dr. Mentias has disclosed no relevant financial relationships. Dr. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years suggests.
Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction), compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation, Ohio, and colleagues.
The results were published in the Journal of the American College of Cardiology.
Previous studies on bariatric surgery outcomes have primarily focused on individuals from select health care networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues in an accompanying editorial.
Moreover, other long-term and observational studies have shown that bariatric surgery can decrease the risk of myocardial infarction, death, and stroke in young and middle-aged patients with obesity, but the evidence is less clear for older patients and those without diabetes, noted Dr. Mentias in a phone interview.
“To date, this is one of the first studies to support bariatric surgery for CVD risk reduction in patients older than 65 years, a population at highest risk for developing heart failure,” the editorial points out.
“We should consider referring patients who qualify for bariatric surgery based on BMI; it really should be considered as a treatment option for patients with class 3 obesity, especially with a body mass index over 40 kg/m2,” Dr. Powell-Wiley told this news organization.
“We know that patients are generally under-referred for bariatric surgery, and this highlights the need to refer patients for bariatric surgery,” she added.
“There should be discussion about expanding insurance coverage to include bariatric surgery for eligible patients,” Dr. Mentias added.
Contemporary cohort of patients
“A lot of the studies showed long-term outcomes outside of the U.S., specifically in Europe,” Dr. Mentias added.
The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.
Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.
The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Female patients comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.
The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.
Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.
More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:
- Myocardial infarction (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68)
- Stroke (HR, 0.71; 95% CI, 0.65-0.79)
- New-onset heart failure (HR, 0.46; 95% CI, 0.44-0.49)
- Reduced risk of death (9.2 vs. 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60-0.66)
Findings for those over the age of 65 were similar – lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.
The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.
An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.
“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.
This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr. Milind Y. Desai’s research. Dr. Mentias has disclosed no relevant financial relationships. Dr. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years suggests.
Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction), compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation, Ohio, and colleagues.
The results were published in the Journal of the American College of Cardiology.
Previous studies on bariatric surgery outcomes have primarily focused on individuals from select health care networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues in an accompanying editorial.
Moreover, other long-term and observational studies have shown that bariatric surgery can decrease the risk of myocardial infarction, death, and stroke in young and middle-aged patients with obesity, but the evidence is less clear for older patients and those without diabetes, noted Dr. Mentias in a phone interview.
“To date, this is one of the first studies to support bariatric surgery for CVD risk reduction in patients older than 65 years, a population at highest risk for developing heart failure,” the editorial points out.
“We should consider referring patients who qualify for bariatric surgery based on BMI; it really should be considered as a treatment option for patients with class 3 obesity, especially with a body mass index over 40 kg/m2,” Dr. Powell-Wiley told this news organization.
“We know that patients are generally under-referred for bariatric surgery, and this highlights the need to refer patients for bariatric surgery,” she added.
“There should be discussion about expanding insurance coverage to include bariatric surgery for eligible patients,” Dr. Mentias added.
Contemporary cohort of patients
“A lot of the studies showed long-term outcomes outside of the U.S., specifically in Europe,” Dr. Mentias added.
The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.
Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.
The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Female patients comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.
The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.
Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.
More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:
- Myocardial infarction (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68)
- Stroke (HR, 0.71; 95% CI, 0.65-0.79)
- New-onset heart failure (HR, 0.46; 95% CI, 0.44-0.49)
- Reduced risk of death (9.2 vs. 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60-0.66)
Findings for those over the age of 65 were similar – lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.
The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.
An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.
“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.
This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr. Milind Y. Desai’s research. Dr. Mentias has disclosed no relevant financial relationships. Dr. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
PD-L1 test debated in gastroesophageal cancer immunotherapy
on whether measuring programmed death–ligand 1 (PD-L1) is essential before prescribing checkpoint inhibitors for gastroesophageal cancer.
“In the last couple of years, the incorporation of PD-1 antibodies is really changing our standard of care and international guidelines in this disease,” said Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital, London.
He moderated a debate at the 2022 Gastrointestinal Cancers Symposium on the importance of measuring PD-L1 expression levels before administering immune checkpoint inhibitor therapy.
Tumor cells can use PD-1 signaling to deactivate the response of T cells that would otherwise destroy them, and several new drugs are designed to block that signaling.
Multiple randomized controlled trials have shown the benefit of adding such checkpoint inhibitors to chemotherapy for gastroesophageal cancer and currently, chemotherapy plus a checkpoint inhibitor is standard care, Dr. Chau said.
PD-1–blocking antibodies include pembrolizumab (Keytruda, Merck) for colorectal cancer, gastric cancer, esophageal cancer, hepatocellular carcinoma, and renal cell carcinoma, among other cancers. And, nivolumab (Opdivo, Bristol-Myers Squibb) approved for renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma, among other cancers.
Regulators differ on whether these treatments should be limited to patients whose expression level of PD-L1 reaches a defined threshold. The FDA has not required the measurement of any biomarker before starting therapy with either of these drugs. However, the EMA requires a PD-L1 combined positive score (CPS) of at least 10 for pembrolizumab and at least 5 for nivolumab.
In a poll conducted before the start of the debate, 83% of physician attendees said they favor of the EMA position, while 17% disagreed.
Florian Lordick, MD, PhD, director of the University of Leipzig (Germany) Cancer Center, argued that tests for PD-L1 expression are accurate. About half of patients have CPS of at least 1. And, pathologists are in agreement in interpreting the tests about 97% of the time.
Pivotal decision-making clinical trials
The EMA requires a PD-L1 assay primarily based on its interpretation of the data from KEYNOTE-590 and CheckMate-648.
KEYNOTE-590 included 749 patients with esophageal carcinoma who were randomized to receive either pembrolizumab with standard of care chemotherapy, or placebo and standard of care chemotherapy. Patients receiving pembrolizumab who had PD-L1 CPS scores of 10 or more survived a few months longer on average. But in a post hoc analysis, the investigators found that, in patients with PD-L1 CPS scores less than 10, the difference between the treatment and placebo groups was not statistically significant.
In CheckMate-648, 970 patients with esophageal carcinoma were randomized to receive nivolumab with ipilimumab, nivolumab with chemotherapy, or chemotherapy alone. Investigators used a slightly different measurement of PD-L1 tumor proportion score (TPS), in comparing chemotherapy plus nivolumab to chemotherapy alone for advanced esophageal squamous cell carcinoma.
The median survival time of patients with TPS of at least 1% was 15.4 months in the nivolumab group and 9.2 months in the control group. But among patients with a TPS of less than 1%, the median overall survival was 12.0 months in the nivolumab group and 12.2 in the control group. CPS thresholds of 5 or 1 resulted in similar effects.
Dr. Lordick cited a systematic review of four studies in press at ESMO Open. Hazard ratios for three of the studies favored immunotherapy only in patients with CPS of at least 10.
Deciding which patients to treat matters because these drugs are expensive, he said. A single dose of 240 mg nivolumab costs $7,228.70, and treatment for 1 year can cost $173,488.80 in addition to costs for hospitalization because of immune-related adverse events, labs, imaging, colonoscopy, and other related costs.
“This is a lot of money, isn’t it? It’s the same price the hospital pay for two registered nurses in the U.S., at least when we are talking about the average price. I’m not sure I want to spend this money for a drug that does not work,” Dr. Lordick said.
Aaron Scott, MD, an oncologist with the University of Arizona Cancer Center, Tucson, said that “patients and clinicians want and need options” because there may be other factors that should be considered.
“PD-L1 has shown inconsistent results. And while I agree it is the best that we have for predictive biomarker in the space, it is far from perfect. PD-L1 has not been predictive for response in a variety of settings and trials. In first-line, second-line, third-line trials we have examples where it does not predict response,” he said.
JUPITER06 compared toripalimab or placebo with paclitaxel and cisplatin for patients with esophageal squamous cell carcinoma. Patients who received toripalimab lived longer than patients who received the placebo, but within the toripalimab group, there was no difference in median overall survival between those patients above and those below the threshold of CPS 1.
ORIENT-15 compared sintilimab or placebo with chemotherapy as first-line therapy for patients with esophageal squamous cell carcinoma. Although the treatment group fared better, survival rates were the same whether patients were above or below the CPS 10 threshold.
Dr. Scott cited three other trials in which PD-L1 was not predictive of response to checkpoint inhibitors.
The differences among studies could be attributed to different assays, he said. “Where you biopsy and when you biopsy seems to matter.”
In a second opinion poll conducted after the presentations, the proportion of physician attendees saying PD-L1 was essential before initiating checkpoint inhibitors, dropped to about two-thirds.
Dr. Chau reported financial relationships with Bristol-Myers Squibb, Merck Serono, and other pharmaceutical companies. Dr. Lordick reported financial relationships Bristol-Myers Squibb, Merck Sharp & Dohme, Merck, and other pharmaceutical companies.
on whether measuring programmed death–ligand 1 (PD-L1) is essential before prescribing checkpoint inhibitors for gastroesophageal cancer.
“In the last couple of years, the incorporation of PD-1 antibodies is really changing our standard of care and international guidelines in this disease,” said Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital, London.
He moderated a debate at the 2022 Gastrointestinal Cancers Symposium on the importance of measuring PD-L1 expression levels before administering immune checkpoint inhibitor therapy.
Tumor cells can use PD-1 signaling to deactivate the response of T cells that would otherwise destroy them, and several new drugs are designed to block that signaling.
Multiple randomized controlled trials have shown the benefit of adding such checkpoint inhibitors to chemotherapy for gastroesophageal cancer and currently, chemotherapy plus a checkpoint inhibitor is standard care, Dr. Chau said.
PD-1–blocking antibodies include pembrolizumab (Keytruda, Merck) for colorectal cancer, gastric cancer, esophageal cancer, hepatocellular carcinoma, and renal cell carcinoma, among other cancers. And, nivolumab (Opdivo, Bristol-Myers Squibb) approved for renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma, among other cancers.
Regulators differ on whether these treatments should be limited to patients whose expression level of PD-L1 reaches a defined threshold. The FDA has not required the measurement of any biomarker before starting therapy with either of these drugs. However, the EMA requires a PD-L1 combined positive score (CPS) of at least 10 for pembrolizumab and at least 5 for nivolumab.
In a poll conducted before the start of the debate, 83% of physician attendees said they favor of the EMA position, while 17% disagreed.
Florian Lordick, MD, PhD, director of the University of Leipzig (Germany) Cancer Center, argued that tests for PD-L1 expression are accurate. About half of patients have CPS of at least 1. And, pathologists are in agreement in interpreting the tests about 97% of the time.
Pivotal decision-making clinical trials
The EMA requires a PD-L1 assay primarily based on its interpretation of the data from KEYNOTE-590 and CheckMate-648.
KEYNOTE-590 included 749 patients with esophageal carcinoma who were randomized to receive either pembrolizumab with standard of care chemotherapy, or placebo and standard of care chemotherapy. Patients receiving pembrolizumab who had PD-L1 CPS scores of 10 or more survived a few months longer on average. But in a post hoc analysis, the investigators found that, in patients with PD-L1 CPS scores less than 10, the difference between the treatment and placebo groups was not statistically significant.
In CheckMate-648, 970 patients with esophageal carcinoma were randomized to receive nivolumab with ipilimumab, nivolumab with chemotherapy, or chemotherapy alone. Investigators used a slightly different measurement of PD-L1 tumor proportion score (TPS), in comparing chemotherapy plus nivolumab to chemotherapy alone for advanced esophageal squamous cell carcinoma.
The median survival time of patients with TPS of at least 1% was 15.4 months in the nivolumab group and 9.2 months in the control group. But among patients with a TPS of less than 1%, the median overall survival was 12.0 months in the nivolumab group and 12.2 in the control group. CPS thresholds of 5 or 1 resulted in similar effects.
Dr. Lordick cited a systematic review of four studies in press at ESMO Open. Hazard ratios for three of the studies favored immunotherapy only in patients with CPS of at least 10.
Deciding which patients to treat matters because these drugs are expensive, he said. A single dose of 240 mg nivolumab costs $7,228.70, and treatment for 1 year can cost $173,488.80 in addition to costs for hospitalization because of immune-related adverse events, labs, imaging, colonoscopy, and other related costs.
“This is a lot of money, isn’t it? It’s the same price the hospital pay for two registered nurses in the U.S., at least when we are talking about the average price. I’m not sure I want to spend this money for a drug that does not work,” Dr. Lordick said.
Aaron Scott, MD, an oncologist with the University of Arizona Cancer Center, Tucson, said that “patients and clinicians want and need options” because there may be other factors that should be considered.
“PD-L1 has shown inconsistent results. And while I agree it is the best that we have for predictive biomarker in the space, it is far from perfect. PD-L1 has not been predictive for response in a variety of settings and trials. In first-line, second-line, third-line trials we have examples where it does not predict response,” he said.
JUPITER06 compared toripalimab or placebo with paclitaxel and cisplatin for patients with esophageal squamous cell carcinoma. Patients who received toripalimab lived longer than patients who received the placebo, but within the toripalimab group, there was no difference in median overall survival between those patients above and those below the threshold of CPS 1.
ORIENT-15 compared sintilimab or placebo with chemotherapy as first-line therapy for patients with esophageal squamous cell carcinoma. Although the treatment group fared better, survival rates were the same whether patients were above or below the CPS 10 threshold.
Dr. Scott cited three other trials in which PD-L1 was not predictive of response to checkpoint inhibitors.
The differences among studies could be attributed to different assays, he said. “Where you biopsy and when you biopsy seems to matter.”
In a second opinion poll conducted after the presentations, the proportion of physician attendees saying PD-L1 was essential before initiating checkpoint inhibitors, dropped to about two-thirds.
Dr. Chau reported financial relationships with Bristol-Myers Squibb, Merck Serono, and other pharmaceutical companies. Dr. Lordick reported financial relationships Bristol-Myers Squibb, Merck Sharp & Dohme, Merck, and other pharmaceutical companies.
on whether measuring programmed death–ligand 1 (PD-L1) is essential before prescribing checkpoint inhibitors for gastroesophageal cancer.
“In the last couple of years, the incorporation of PD-1 antibodies is really changing our standard of care and international guidelines in this disease,” said Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital, London.
He moderated a debate at the 2022 Gastrointestinal Cancers Symposium on the importance of measuring PD-L1 expression levels before administering immune checkpoint inhibitor therapy.
Tumor cells can use PD-1 signaling to deactivate the response of T cells that would otherwise destroy them, and several new drugs are designed to block that signaling.
Multiple randomized controlled trials have shown the benefit of adding such checkpoint inhibitors to chemotherapy for gastroesophageal cancer and currently, chemotherapy plus a checkpoint inhibitor is standard care, Dr. Chau said.
PD-1–blocking antibodies include pembrolizumab (Keytruda, Merck) for colorectal cancer, gastric cancer, esophageal cancer, hepatocellular carcinoma, and renal cell carcinoma, among other cancers. And, nivolumab (Opdivo, Bristol-Myers Squibb) approved for renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma, among other cancers.
Regulators differ on whether these treatments should be limited to patients whose expression level of PD-L1 reaches a defined threshold. The FDA has not required the measurement of any biomarker before starting therapy with either of these drugs. However, the EMA requires a PD-L1 combined positive score (CPS) of at least 10 for pembrolizumab and at least 5 for nivolumab.
In a poll conducted before the start of the debate, 83% of physician attendees said they favor of the EMA position, while 17% disagreed.
Florian Lordick, MD, PhD, director of the University of Leipzig (Germany) Cancer Center, argued that tests for PD-L1 expression are accurate. About half of patients have CPS of at least 1. And, pathologists are in agreement in interpreting the tests about 97% of the time.
Pivotal decision-making clinical trials
The EMA requires a PD-L1 assay primarily based on its interpretation of the data from KEYNOTE-590 and CheckMate-648.
KEYNOTE-590 included 749 patients with esophageal carcinoma who were randomized to receive either pembrolizumab with standard of care chemotherapy, or placebo and standard of care chemotherapy. Patients receiving pembrolizumab who had PD-L1 CPS scores of 10 or more survived a few months longer on average. But in a post hoc analysis, the investigators found that, in patients with PD-L1 CPS scores less than 10, the difference between the treatment and placebo groups was not statistically significant.
In CheckMate-648, 970 patients with esophageal carcinoma were randomized to receive nivolumab with ipilimumab, nivolumab with chemotherapy, or chemotherapy alone. Investigators used a slightly different measurement of PD-L1 tumor proportion score (TPS), in comparing chemotherapy plus nivolumab to chemotherapy alone for advanced esophageal squamous cell carcinoma.
The median survival time of patients with TPS of at least 1% was 15.4 months in the nivolumab group and 9.2 months in the control group. But among patients with a TPS of less than 1%, the median overall survival was 12.0 months in the nivolumab group and 12.2 in the control group. CPS thresholds of 5 or 1 resulted in similar effects.
Dr. Lordick cited a systematic review of four studies in press at ESMO Open. Hazard ratios for three of the studies favored immunotherapy only in patients with CPS of at least 10.
Deciding which patients to treat matters because these drugs are expensive, he said. A single dose of 240 mg nivolumab costs $7,228.70, and treatment for 1 year can cost $173,488.80 in addition to costs for hospitalization because of immune-related adverse events, labs, imaging, colonoscopy, and other related costs.
“This is a lot of money, isn’t it? It’s the same price the hospital pay for two registered nurses in the U.S., at least when we are talking about the average price. I’m not sure I want to spend this money for a drug that does not work,” Dr. Lordick said.
Aaron Scott, MD, an oncologist with the University of Arizona Cancer Center, Tucson, said that “patients and clinicians want and need options” because there may be other factors that should be considered.
“PD-L1 has shown inconsistent results. And while I agree it is the best that we have for predictive biomarker in the space, it is far from perfect. PD-L1 has not been predictive for response in a variety of settings and trials. In first-line, second-line, third-line trials we have examples where it does not predict response,” he said.
JUPITER06 compared toripalimab or placebo with paclitaxel and cisplatin for patients with esophageal squamous cell carcinoma. Patients who received toripalimab lived longer than patients who received the placebo, but within the toripalimab group, there was no difference in median overall survival between those patients above and those below the threshold of CPS 1.
ORIENT-15 compared sintilimab or placebo with chemotherapy as first-line therapy for patients with esophageal squamous cell carcinoma. Although the treatment group fared better, survival rates were the same whether patients were above or below the CPS 10 threshold.
Dr. Scott cited three other trials in which PD-L1 was not predictive of response to checkpoint inhibitors.
The differences among studies could be attributed to different assays, he said. “Where you biopsy and when you biopsy seems to matter.”
In a second opinion poll conducted after the presentations, the proportion of physician attendees saying PD-L1 was essential before initiating checkpoint inhibitors, dropped to about two-thirds.
Dr. Chau reported financial relationships with Bristol-Myers Squibb, Merck Serono, and other pharmaceutical companies. Dr. Lordick reported financial relationships Bristol-Myers Squibb, Merck Sharp & Dohme, Merck, and other pharmaceutical companies.
FROM ASCO GI 2022
Zanubrutinib shows worth against standard CLL drugs
MANCHESTER, ENGLAND – A new treatment option may soon be available for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Zanubrutinib (Brukinsa), an irreversible, next-generation Bruton tyrosine kinase (BTK) inhibitor, is designed to minimize the off-target cardiovascular toxicities, such as atrial fibrillation and hypertension, seen with the first-generation ibrutinib (Imbruvica).
Zanubrutinib is already approved for use in mantle cell and marginal zone lymphomas and Waldenström’s macroglobulinemia.
Now it has also shown efficacy in CLL.
However, experts question whether the drug will find its place in an increasingly crowded space for the management of CLL.
Data from two phase 3 trials
The new data from two phase 3 clinical trials were presented recently at the British Society for Haematology 62nd annual scientific meeting, held in Manchester, England.
The ALPINE trial compared zanubrutinib with ibrutinib in 415 patients with CLL/SLL and showed that the novel drug was associated with a significant improvement in overall response rate, at 78% versus 63%.
This first interim analysis also showed that there was an increase in progression-free survival (PFS) with zanubrutinib, and crucially, it was associated with a lower atrial fibrillation/flutter rate than ibrutinib.
“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” said lead author Peter Hillmen, MBChB, FRCP, PhD, St. James’s University Hospital, Leeds, England.
The SEQUOIA study looked at zanubrutinib versus bendamustine plus rituximab in patients with untreated CLL/SLL with a 17p deletion and showed that PFS was improved with zanubrutinib by 58%.
Zanubrutinib was also associated with improved overall response rates and was well tolerated.
The results therefore “support the potential utility of zanubrutinib in the frontline management of patients with previously untreated CLL/SLL,” said lead author Talha Munir, MBBS, also of St. James’s University Hospital.
Improvement over ibrutinib
Ibrutinib, the first BTK inhibitor, “truly revolutionized the way we treat CLL,” commented Renata Walewska, MRCP, PhD, consultant hematologist at the Royal Bournemouth (England) Hospital and chair of the UKCLL Forum.
“But it has got quite a lot of, especially cardiac, problems, with atrial fibrillation and hypertension,” she said in an interview. The problem is that it acts not only as an inhibitor of Bruton kinase, but also affects other kinases, she explained.
Zanubrutinib is “much cleaner,” continued Dr. Walewska, who was lead author of the recently published British Society of Haematology guideline for the treatment of CLL.
However, the drug “is not that groundbreaking,” she commented, as acalabrutinib (Calquence), another next-generation BTK inhibitor, is already available for use in the clinic.
“We’re really lucky in CLL,” Dr. Walewska said, “we’ve got so many new drugs available, and it’s getting quite crowded. Trying to find a place for zanubrutinib is going be tricky.”
Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, commented that he “gives a lot of credit” to BeiGene, the company behind zanubrutinib, for “taking on these big studies.”
He said that, with the improvements in PFS and reduced atrial fibrillation with the drug, “there will be many clinicians paying attention to this and zanubrutinib could be preferred over conventional options.”
However, he agreed that it will have to compete with acalabrutinib, adding that, beyond BTK inhibitors, there are “a lot of options” for patients with CLL.
“That makes it very difficult for physicians to figure out what is the best type of therapy” to use in these patients, he added.
Dr. Greenberger told this news organization that further studies will need to demonstrate that zanubrutinib is associated with extended survival, which is “just not possible to show” at the moment with the current follow-up period.
He also noted that, in 10 years, ibrutinib will be off-patent, but zanubrutinib will not, at which point the “substantial” cost of the medication, which is a source of “hardship to patients,” will be increasingly relevant.
Study details
The phase 3 ALPINE study involved 415 adults with CLL/SLL refractory to one or more prior systemic therapies and measurable lymphadenopathy on imaging.
They were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or withdrawal from the study.
Most patients had Binet stage A/B or Ann Arbor stage I/II disease, and 7.3% of patients treated with zanubrutinib and 10.1% of those assigned to ibrutinib had received more than three prior lines of therapy.
Over 60% of patients were aged 65 years or older and around 70% were men, with no significant differences between treatment groups.
Patients were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or study withdrawal.
After a median follow-up of 15 months, the overall response rate was significantly higher with zanubrutinib than ibrutinib, at 78.3% versus 62.5% (P = .0006).
Subgroup analysis confirmed that the effect was seen regardless of age, sex, disease stage, number of prior lines of therapy, mutation status, or bulky disease.
Over a median follow-up of 14 months, the investigator-assessed 12-month PFS was 94.9% for zanubrutinib and 84.0% for ibrutinib (P = .0007). Overall survival at 12 months was 97% versus 92.7%, but the difference was not significant (P = .1081).
Patients treated with zanubrutinib experienced more grade 3 or higher adverse events than those given ibrutinib, at 55.9% versus 51.2%, although they had fewer adverse events leading to treatment discontinuation, at 7.8% versus 13.0%.
More importantly, there were fewer cardiac disorders of any grade with zanubrutinib versus ibrutinib, and any-grade atrial fibrillation was significantly less common, at 2.5% versus 10.1% (P = .0014).
Rates of hypertension and hemorrhage were similar between the two treatments, while rates of neutropenia were higher with zanubrutinib versus ibrutinib, at 28.4% versus 21.7%.
The phase 3 SEQUOIA study looked at an earlier stage of disease and included patients with previously untreated CLL/SLL (without 17p depletion) who were unsuitable for treatment with fludarabine, cyclophosphamide, and rituximab.
This trial involved 479 patients randomized to zanubrutinib or bendamustine (days 1 and 2) plus rituximab for six cycles of 28 days each (B+R).
The median age of patients was 70 years, and approximately 80% were at least 65 years old. Just over 60% were men and most (over 70%) were from Europe.
After a median of 26.2 months, independent review committee–assessed PFS was significantly longer with zanubrutinib versus B+R (hazard ratio, 0.42; P < .0001), with an estimated 24-month PFS of 85.5% versus 69.5%.
These results held whether patients were stratified by age, Binet stage, bulky disease, or 11q deletion status, and for patients with an unmutated, but not mutated, immunoglobulin heavy chain gene.
The overall response rate with zanubrutinib was 94.6% versus 85.3% with B+R, and estimated 24-month overall survival was 94.3% versus 94.6%.
Rates of adverse events of any grade were similar between the two treatment groups, although B+R was associated with a higher (grade ≥ 3) adverse event rate, at 79.7%, versus 52.5% for zanubrutinib, and a higher rate of treatment discontinuation because of adverse events, at 13.7% versus 8.3%.
Interestingly, any-grade hypertension was more common with zanubrutinib versus B+R, at 14.2% versus 10.6%, but much lower rates of neutropenia were more common with zanubrutinib, at 15.8% versus 56.8%.
The studies were sponsored by BeiGene. Dr. Hillmen has reported relationships with Janssen, AbbVie, Pharmacyclics, Roche, Gilead, AstraZeneca, SOBI, and BeiGene. Dr. Munir has reported relationships with AbbVie, AstraZeneca, Roche, Alexion, Janssen, MorphoSys, and SOBI. Other authors have also declared numerous relationships.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND – A new treatment option may soon be available for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Zanubrutinib (Brukinsa), an irreversible, next-generation Bruton tyrosine kinase (BTK) inhibitor, is designed to minimize the off-target cardiovascular toxicities, such as atrial fibrillation and hypertension, seen with the first-generation ibrutinib (Imbruvica).
Zanubrutinib is already approved for use in mantle cell and marginal zone lymphomas and Waldenström’s macroglobulinemia.
Now it has also shown efficacy in CLL.
However, experts question whether the drug will find its place in an increasingly crowded space for the management of CLL.
Data from two phase 3 trials
The new data from two phase 3 clinical trials were presented recently at the British Society for Haematology 62nd annual scientific meeting, held in Manchester, England.
The ALPINE trial compared zanubrutinib with ibrutinib in 415 patients with CLL/SLL and showed that the novel drug was associated with a significant improvement in overall response rate, at 78% versus 63%.
This first interim analysis also showed that there was an increase in progression-free survival (PFS) with zanubrutinib, and crucially, it was associated with a lower atrial fibrillation/flutter rate than ibrutinib.
“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” said lead author Peter Hillmen, MBChB, FRCP, PhD, St. James’s University Hospital, Leeds, England.
The SEQUOIA study looked at zanubrutinib versus bendamustine plus rituximab in patients with untreated CLL/SLL with a 17p deletion and showed that PFS was improved with zanubrutinib by 58%.
Zanubrutinib was also associated with improved overall response rates and was well tolerated.
The results therefore “support the potential utility of zanubrutinib in the frontline management of patients with previously untreated CLL/SLL,” said lead author Talha Munir, MBBS, also of St. James’s University Hospital.
Improvement over ibrutinib
Ibrutinib, the first BTK inhibitor, “truly revolutionized the way we treat CLL,” commented Renata Walewska, MRCP, PhD, consultant hematologist at the Royal Bournemouth (England) Hospital and chair of the UKCLL Forum.
“But it has got quite a lot of, especially cardiac, problems, with atrial fibrillation and hypertension,” she said in an interview. The problem is that it acts not only as an inhibitor of Bruton kinase, but also affects other kinases, she explained.
Zanubrutinib is “much cleaner,” continued Dr. Walewska, who was lead author of the recently published British Society of Haematology guideline for the treatment of CLL.
However, the drug “is not that groundbreaking,” she commented, as acalabrutinib (Calquence), another next-generation BTK inhibitor, is already available for use in the clinic.
“We’re really lucky in CLL,” Dr. Walewska said, “we’ve got so many new drugs available, and it’s getting quite crowded. Trying to find a place for zanubrutinib is going be tricky.”
Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, commented that he “gives a lot of credit” to BeiGene, the company behind zanubrutinib, for “taking on these big studies.”
He said that, with the improvements in PFS and reduced atrial fibrillation with the drug, “there will be many clinicians paying attention to this and zanubrutinib could be preferred over conventional options.”
However, he agreed that it will have to compete with acalabrutinib, adding that, beyond BTK inhibitors, there are “a lot of options” for patients with CLL.
“That makes it very difficult for physicians to figure out what is the best type of therapy” to use in these patients, he added.
Dr. Greenberger told this news organization that further studies will need to demonstrate that zanubrutinib is associated with extended survival, which is “just not possible to show” at the moment with the current follow-up period.
He also noted that, in 10 years, ibrutinib will be off-patent, but zanubrutinib will not, at which point the “substantial” cost of the medication, which is a source of “hardship to patients,” will be increasingly relevant.
Study details
The phase 3 ALPINE study involved 415 adults with CLL/SLL refractory to one or more prior systemic therapies and measurable lymphadenopathy on imaging.
They were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or withdrawal from the study.
Most patients had Binet stage A/B or Ann Arbor stage I/II disease, and 7.3% of patients treated with zanubrutinib and 10.1% of those assigned to ibrutinib had received more than three prior lines of therapy.
Over 60% of patients were aged 65 years or older and around 70% were men, with no significant differences between treatment groups.
Patients were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or study withdrawal.
After a median follow-up of 15 months, the overall response rate was significantly higher with zanubrutinib than ibrutinib, at 78.3% versus 62.5% (P = .0006).
Subgroup analysis confirmed that the effect was seen regardless of age, sex, disease stage, number of prior lines of therapy, mutation status, or bulky disease.
Over a median follow-up of 14 months, the investigator-assessed 12-month PFS was 94.9% for zanubrutinib and 84.0% for ibrutinib (P = .0007). Overall survival at 12 months was 97% versus 92.7%, but the difference was not significant (P = .1081).
Patients treated with zanubrutinib experienced more grade 3 or higher adverse events than those given ibrutinib, at 55.9% versus 51.2%, although they had fewer adverse events leading to treatment discontinuation, at 7.8% versus 13.0%.
More importantly, there were fewer cardiac disorders of any grade with zanubrutinib versus ibrutinib, and any-grade atrial fibrillation was significantly less common, at 2.5% versus 10.1% (P = .0014).
Rates of hypertension and hemorrhage were similar between the two treatments, while rates of neutropenia were higher with zanubrutinib versus ibrutinib, at 28.4% versus 21.7%.
The phase 3 SEQUOIA study looked at an earlier stage of disease and included patients with previously untreated CLL/SLL (without 17p depletion) who were unsuitable for treatment with fludarabine, cyclophosphamide, and rituximab.
This trial involved 479 patients randomized to zanubrutinib or bendamustine (days 1 and 2) plus rituximab for six cycles of 28 days each (B+R).
The median age of patients was 70 years, and approximately 80% were at least 65 years old. Just over 60% were men and most (over 70%) were from Europe.
After a median of 26.2 months, independent review committee–assessed PFS was significantly longer with zanubrutinib versus B+R (hazard ratio, 0.42; P < .0001), with an estimated 24-month PFS of 85.5% versus 69.5%.
These results held whether patients were stratified by age, Binet stage, bulky disease, or 11q deletion status, and for patients with an unmutated, but not mutated, immunoglobulin heavy chain gene.
The overall response rate with zanubrutinib was 94.6% versus 85.3% with B+R, and estimated 24-month overall survival was 94.3% versus 94.6%.
Rates of adverse events of any grade were similar between the two treatment groups, although B+R was associated with a higher (grade ≥ 3) adverse event rate, at 79.7%, versus 52.5% for zanubrutinib, and a higher rate of treatment discontinuation because of adverse events, at 13.7% versus 8.3%.
Interestingly, any-grade hypertension was more common with zanubrutinib versus B+R, at 14.2% versus 10.6%, but much lower rates of neutropenia were more common with zanubrutinib, at 15.8% versus 56.8%.
The studies were sponsored by BeiGene. Dr. Hillmen has reported relationships with Janssen, AbbVie, Pharmacyclics, Roche, Gilead, AstraZeneca, SOBI, and BeiGene. Dr. Munir has reported relationships with AbbVie, AstraZeneca, Roche, Alexion, Janssen, MorphoSys, and SOBI. Other authors have also declared numerous relationships.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND – A new treatment option may soon be available for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Zanubrutinib (Brukinsa), an irreversible, next-generation Bruton tyrosine kinase (BTK) inhibitor, is designed to minimize the off-target cardiovascular toxicities, such as atrial fibrillation and hypertension, seen with the first-generation ibrutinib (Imbruvica).
Zanubrutinib is already approved for use in mantle cell and marginal zone lymphomas and Waldenström’s macroglobulinemia.
Now it has also shown efficacy in CLL.
However, experts question whether the drug will find its place in an increasingly crowded space for the management of CLL.
Data from two phase 3 trials
The new data from two phase 3 clinical trials were presented recently at the British Society for Haematology 62nd annual scientific meeting, held in Manchester, England.
The ALPINE trial compared zanubrutinib with ibrutinib in 415 patients with CLL/SLL and showed that the novel drug was associated with a significant improvement in overall response rate, at 78% versus 63%.
This first interim analysis also showed that there was an increase in progression-free survival (PFS) with zanubrutinib, and crucially, it was associated with a lower atrial fibrillation/flutter rate than ibrutinib.
“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” said lead author Peter Hillmen, MBChB, FRCP, PhD, St. James’s University Hospital, Leeds, England.
The SEQUOIA study looked at zanubrutinib versus bendamustine plus rituximab in patients with untreated CLL/SLL with a 17p deletion and showed that PFS was improved with zanubrutinib by 58%.
Zanubrutinib was also associated with improved overall response rates and was well tolerated.
The results therefore “support the potential utility of zanubrutinib in the frontline management of patients with previously untreated CLL/SLL,” said lead author Talha Munir, MBBS, also of St. James’s University Hospital.
Improvement over ibrutinib
Ibrutinib, the first BTK inhibitor, “truly revolutionized the way we treat CLL,” commented Renata Walewska, MRCP, PhD, consultant hematologist at the Royal Bournemouth (England) Hospital and chair of the UKCLL Forum.
“But it has got quite a lot of, especially cardiac, problems, with atrial fibrillation and hypertension,” she said in an interview. The problem is that it acts not only as an inhibitor of Bruton kinase, but also affects other kinases, she explained.
Zanubrutinib is “much cleaner,” continued Dr. Walewska, who was lead author of the recently published British Society of Haematology guideline for the treatment of CLL.
However, the drug “is not that groundbreaking,” she commented, as acalabrutinib (Calquence), another next-generation BTK inhibitor, is already available for use in the clinic.
“We’re really lucky in CLL,” Dr. Walewska said, “we’ve got so many new drugs available, and it’s getting quite crowded. Trying to find a place for zanubrutinib is going be tricky.”
Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, commented that he “gives a lot of credit” to BeiGene, the company behind zanubrutinib, for “taking on these big studies.”
He said that, with the improvements in PFS and reduced atrial fibrillation with the drug, “there will be many clinicians paying attention to this and zanubrutinib could be preferred over conventional options.”
However, he agreed that it will have to compete with acalabrutinib, adding that, beyond BTK inhibitors, there are “a lot of options” for patients with CLL.
“That makes it very difficult for physicians to figure out what is the best type of therapy” to use in these patients, he added.
Dr. Greenberger told this news organization that further studies will need to demonstrate that zanubrutinib is associated with extended survival, which is “just not possible to show” at the moment with the current follow-up period.
He also noted that, in 10 years, ibrutinib will be off-patent, but zanubrutinib will not, at which point the “substantial” cost of the medication, which is a source of “hardship to patients,” will be increasingly relevant.
Study details
The phase 3 ALPINE study involved 415 adults with CLL/SLL refractory to one or more prior systemic therapies and measurable lymphadenopathy on imaging.
They were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or withdrawal from the study.
Most patients had Binet stage A/B or Ann Arbor stage I/II disease, and 7.3% of patients treated with zanubrutinib and 10.1% of those assigned to ibrutinib had received more than three prior lines of therapy.
Over 60% of patients were aged 65 years or older and around 70% were men, with no significant differences between treatment groups.
Patients were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or study withdrawal.
After a median follow-up of 15 months, the overall response rate was significantly higher with zanubrutinib than ibrutinib, at 78.3% versus 62.5% (P = .0006).
Subgroup analysis confirmed that the effect was seen regardless of age, sex, disease stage, number of prior lines of therapy, mutation status, or bulky disease.
Over a median follow-up of 14 months, the investigator-assessed 12-month PFS was 94.9% for zanubrutinib and 84.0% for ibrutinib (P = .0007). Overall survival at 12 months was 97% versus 92.7%, but the difference was not significant (P = .1081).
Patients treated with zanubrutinib experienced more grade 3 or higher adverse events than those given ibrutinib, at 55.9% versus 51.2%, although they had fewer adverse events leading to treatment discontinuation, at 7.8% versus 13.0%.
More importantly, there were fewer cardiac disorders of any grade with zanubrutinib versus ibrutinib, and any-grade atrial fibrillation was significantly less common, at 2.5% versus 10.1% (P = .0014).
Rates of hypertension and hemorrhage were similar between the two treatments, while rates of neutropenia were higher with zanubrutinib versus ibrutinib, at 28.4% versus 21.7%.
The phase 3 SEQUOIA study looked at an earlier stage of disease and included patients with previously untreated CLL/SLL (without 17p depletion) who were unsuitable for treatment with fludarabine, cyclophosphamide, and rituximab.
This trial involved 479 patients randomized to zanubrutinib or bendamustine (days 1 and 2) plus rituximab for six cycles of 28 days each (B+R).
The median age of patients was 70 years, and approximately 80% were at least 65 years old. Just over 60% were men and most (over 70%) were from Europe.
After a median of 26.2 months, independent review committee–assessed PFS was significantly longer with zanubrutinib versus B+R (hazard ratio, 0.42; P < .0001), with an estimated 24-month PFS of 85.5% versus 69.5%.
These results held whether patients were stratified by age, Binet stage, bulky disease, or 11q deletion status, and for patients with an unmutated, but not mutated, immunoglobulin heavy chain gene.
The overall response rate with zanubrutinib was 94.6% versus 85.3% with B+R, and estimated 24-month overall survival was 94.3% versus 94.6%.
Rates of adverse events of any grade were similar between the two treatment groups, although B+R was associated with a higher (grade ≥ 3) adverse event rate, at 79.7%, versus 52.5% for zanubrutinib, and a higher rate of treatment discontinuation because of adverse events, at 13.7% versus 8.3%.
Interestingly, any-grade hypertension was more common with zanubrutinib versus B+R, at 14.2% versus 10.6%, but much lower rates of neutropenia were more common with zanubrutinib, at 15.8% versus 56.8%.
The studies were sponsored by BeiGene. Dr. Hillmen has reported relationships with Janssen, AbbVie, Pharmacyclics, Roche, Gilead, AstraZeneca, SOBI, and BeiGene. Dr. Munir has reported relationships with AbbVie, AstraZeneca, Roche, Alexion, Janssen, MorphoSys, and SOBI. Other authors have also declared numerous relationships.
A version of this article first appeared on Medscape.com.
Cancer diet studies: Veggies get another rave, while red meat’s busted again
Researchers report that high consumption of vegetables – especially lettuce, legumes, and cruciferous varieties – appears to lower the risk of liver cancer/liver disease. A separate team suggests that high consumption of red meat, organ meats, and processed meats boosts the risk of gastric cancer.
The findings of the latter study “reinforce the idea that avoidance of red meat and processed meat is probably good beyond [the prevention of] colorectal cancer,” said corresponding author and epidemiologist Paolo Boffetta, MD, MPH, of Stony Brook University Cancer Center, New York, in an interview. “The possible carcinogenic effect may extend beyond the colon.”
Both studies were released at the annual meeting of the American Association for Cancer Research.
For the red meat study, researchers examined statistics from the Golestan cohort study, which is prospectively tracking 50,045 people aged 40-75 from northeastern Iran. The study focuses on esophageal cancer due to the region’s high rate of the disease.
Red meat consumption is fairly rare in the region, where residents typically prefer chicken, said study lead author Giulia Collatuzzo, MD, a resident physician in occupational medicine at the University of Bologna, Italy, in an interview. On average, participants reported eating 18.4 grams daily of red meat and 72.1 grams daily of white meat.
The researchers tracked study participants for a median 12-year follow-up, during which 369 developed esophageal cancer and 368 developed gastric cancer. Red meat was only linked to more esophageal cancer in women (hazard ratio, 1.13, 95% confidence interval, 1.00-1.18, for each quintile increase in consumption).
Overall red meat consumption (including red meat, organ meat, and processed meat) was linked to higher rates of gastric cancer (HR, 1.08, 95% CI, 1.00-1.17) for each quartile increase in consumption, as was consumption of the red meat subtype alone (HR, 1.09, 95% CI, 1.00-1.18).
According to Dr. Collatuzzo, the findings suggest that those in the highest quartile of overall red meat consumption may have around a 25% increase in risk, compared with the lowest quartile.
Overall, she said, the study findings aren’t surprising. The lack of a connection between red meat consumption and esophageal cancer may be due to the fact that meat only temporarily transits through the esophagus, she said.
For the liver cancer/liver disease study, researchers examined the medical records of 470,653 subjects in the NIH-AARP Diet and Health Study. They were recruited in 1995-1996 when they were 50-71 years old. Over a median follow-up of 15.5 years, 899 developed liver cancer, and 934 died of chronic liver disease.
The median intakes of vegetables in quintile 5 (highest) and quintile 1 (lowest) were 3.7 cups daily and 1.0 cups daily, respectively, said study lead author Long-Gang Zhao, MS, a graduate student at Harvard University.
After adjusting for possible cofounders, those in the highest quintile of vegetable consumption were a third less likely to develop liver cancer, compared with the lowest quintile (HR, 0.66, 95% CI, 0.53-0.82, P < 0.01). Several types of vegetables appeared to be the strongest cancer fighters: cruciferous (broccoli, cauliflower), lettuce, legumes, and carrots. These kinds of vegetables were also linked to lower rates of chronic liver disease mortality (all P < 0.01), as was total vegetable intake for the top quintile versus the lowest quintile (HR, 0.60, 95% CI, 0.49-0.74, P = < 0.01).
“A one-cup increase (8 oz or 225 g) in vegetable intake was associated with about 20% decreased risk of liver cancer incidence and chronic liver mortality,” Zhao said.
There was no statistically significant link between fruit consumption and liver cancer or chronic liver disease mortality.
The findings provide more insight into diet and liver disease, Zhao said. “Chronic liver disease, which predisposes to liver cancer, is the tenth cause of death worldwide, causing two million deaths each year. It shares some etiological processes with liver cancer. Therefore, examining both chronic liver disease mortality and liver cancer incidence in our study may provide a more general picture for the prevention of liver diseases.”
As for limitations, both studies are based on self-reports about food consumption, which can be unreliable, and the subjects in the fruit/vegetable analysis were mainly of European origin.
The authors of both studies report no relevant disclosures. No funding is reported for either study.
Researchers report that high consumption of vegetables – especially lettuce, legumes, and cruciferous varieties – appears to lower the risk of liver cancer/liver disease. A separate team suggests that high consumption of red meat, organ meats, and processed meats boosts the risk of gastric cancer.
The findings of the latter study “reinforce the idea that avoidance of red meat and processed meat is probably good beyond [the prevention of] colorectal cancer,” said corresponding author and epidemiologist Paolo Boffetta, MD, MPH, of Stony Brook University Cancer Center, New York, in an interview. “The possible carcinogenic effect may extend beyond the colon.”
Both studies were released at the annual meeting of the American Association for Cancer Research.
For the red meat study, researchers examined statistics from the Golestan cohort study, which is prospectively tracking 50,045 people aged 40-75 from northeastern Iran. The study focuses on esophageal cancer due to the region’s high rate of the disease.
Red meat consumption is fairly rare in the region, where residents typically prefer chicken, said study lead author Giulia Collatuzzo, MD, a resident physician in occupational medicine at the University of Bologna, Italy, in an interview. On average, participants reported eating 18.4 grams daily of red meat and 72.1 grams daily of white meat.
The researchers tracked study participants for a median 12-year follow-up, during which 369 developed esophageal cancer and 368 developed gastric cancer. Red meat was only linked to more esophageal cancer in women (hazard ratio, 1.13, 95% confidence interval, 1.00-1.18, for each quintile increase in consumption).
Overall red meat consumption (including red meat, organ meat, and processed meat) was linked to higher rates of gastric cancer (HR, 1.08, 95% CI, 1.00-1.17) for each quartile increase in consumption, as was consumption of the red meat subtype alone (HR, 1.09, 95% CI, 1.00-1.18).
According to Dr. Collatuzzo, the findings suggest that those in the highest quartile of overall red meat consumption may have around a 25% increase in risk, compared with the lowest quartile.
Overall, she said, the study findings aren’t surprising. The lack of a connection between red meat consumption and esophageal cancer may be due to the fact that meat only temporarily transits through the esophagus, she said.
For the liver cancer/liver disease study, researchers examined the medical records of 470,653 subjects in the NIH-AARP Diet and Health Study. They were recruited in 1995-1996 when they were 50-71 years old. Over a median follow-up of 15.5 years, 899 developed liver cancer, and 934 died of chronic liver disease.
The median intakes of vegetables in quintile 5 (highest) and quintile 1 (lowest) were 3.7 cups daily and 1.0 cups daily, respectively, said study lead author Long-Gang Zhao, MS, a graduate student at Harvard University.
After adjusting for possible cofounders, those in the highest quintile of vegetable consumption were a third less likely to develop liver cancer, compared with the lowest quintile (HR, 0.66, 95% CI, 0.53-0.82, P < 0.01). Several types of vegetables appeared to be the strongest cancer fighters: cruciferous (broccoli, cauliflower), lettuce, legumes, and carrots. These kinds of vegetables were also linked to lower rates of chronic liver disease mortality (all P < 0.01), as was total vegetable intake for the top quintile versus the lowest quintile (HR, 0.60, 95% CI, 0.49-0.74, P = < 0.01).
“A one-cup increase (8 oz or 225 g) in vegetable intake was associated with about 20% decreased risk of liver cancer incidence and chronic liver mortality,” Zhao said.
There was no statistically significant link between fruit consumption and liver cancer or chronic liver disease mortality.
The findings provide more insight into diet and liver disease, Zhao said. “Chronic liver disease, which predisposes to liver cancer, is the tenth cause of death worldwide, causing two million deaths each year. It shares some etiological processes with liver cancer. Therefore, examining both chronic liver disease mortality and liver cancer incidence in our study may provide a more general picture for the prevention of liver diseases.”
As for limitations, both studies are based on self-reports about food consumption, which can be unreliable, and the subjects in the fruit/vegetable analysis were mainly of European origin.
The authors of both studies report no relevant disclosures. No funding is reported for either study.
Researchers report that high consumption of vegetables – especially lettuce, legumes, and cruciferous varieties – appears to lower the risk of liver cancer/liver disease. A separate team suggests that high consumption of red meat, organ meats, and processed meats boosts the risk of gastric cancer.
The findings of the latter study “reinforce the idea that avoidance of red meat and processed meat is probably good beyond [the prevention of] colorectal cancer,” said corresponding author and epidemiologist Paolo Boffetta, MD, MPH, of Stony Brook University Cancer Center, New York, in an interview. “The possible carcinogenic effect may extend beyond the colon.”
Both studies were released at the annual meeting of the American Association for Cancer Research.
For the red meat study, researchers examined statistics from the Golestan cohort study, which is prospectively tracking 50,045 people aged 40-75 from northeastern Iran. The study focuses on esophageal cancer due to the region’s high rate of the disease.
Red meat consumption is fairly rare in the region, where residents typically prefer chicken, said study lead author Giulia Collatuzzo, MD, a resident physician in occupational medicine at the University of Bologna, Italy, in an interview. On average, participants reported eating 18.4 grams daily of red meat and 72.1 grams daily of white meat.
The researchers tracked study participants for a median 12-year follow-up, during which 369 developed esophageal cancer and 368 developed gastric cancer. Red meat was only linked to more esophageal cancer in women (hazard ratio, 1.13, 95% confidence interval, 1.00-1.18, for each quintile increase in consumption).
Overall red meat consumption (including red meat, organ meat, and processed meat) was linked to higher rates of gastric cancer (HR, 1.08, 95% CI, 1.00-1.17) for each quartile increase in consumption, as was consumption of the red meat subtype alone (HR, 1.09, 95% CI, 1.00-1.18).
According to Dr. Collatuzzo, the findings suggest that those in the highest quartile of overall red meat consumption may have around a 25% increase in risk, compared with the lowest quartile.
Overall, she said, the study findings aren’t surprising. The lack of a connection between red meat consumption and esophageal cancer may be due to the fact that meat only temporarily transits through the esophagus, she said.
For the liver cancer/liver disease study, researchers examined the medical records of 470,653 subjects in the NIH-AARP Diet and Health Study. They were recruited in 1995-1996 when they were 50-71 years old. Over a median follow-up of 15.5 years, 899 developed liver cancer, and 934 died of chronic liver disease.
The median intakes of vegetables in quintile 5 (highest) and quintile 1 (lowest) were 3.7 cups daily and 1.0 cups daily, respectively, said study lead author Long-Gang Zhao, MS, a graduate student at Harvard University.
After adjusting for possible cofounders, those in the highest quintile of vegetable consumption were a third less likely to develop liver cancer, compared with the lowest quintile (HR, 0.66, 95% CI, 0.53-0.82, P < 0.01). Several types of vegetables appeared to be the strongest cancer fighters: cruciferous (broccoli, cauliflower), lettuce, legumes, and carrots. These kinds of vegetables were also linked to lower rates of chronic liver disease mortality (all P < 0.01), as was total vegetable intake for the top quintile versus the lowest quintile (HR, 0.60, 95% CI, 0.49-0.74, P = < 0.01).
“A one-cup increase (8 oz or 225 g) in vegetable intake was associated with about 20% decreased risk of liver cancer incidence and chronic liver mortality,” Zhao said.
There was no statistically significant link between fruit consumption and liver cancer or chronic liver disease mortality.
The findings provide more insight into diet and liver disease, Zhao said. “Chronic liver disease, which predisposes to liver cancer, is the tenth cause of death worldwide, causing two million deaths each year. It shares some etiological processes with liver cancer. Therefore, examining both chronic liver disease mortality and liver cancer incidence in our study may provide a more general picture for the prevention of liver diseases.”
As for limitations, both studies are based on self-reports about food consumption, which can be unreliable, and the subjects in the fruit/vegetable analysis were mainly of European origin.
The authors of both studies report no relevant disclosures. No funding is reported for either study.
FROM AACR 2022