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Ovarian cancer prevention: How patients decide on surgery
Investigators interviewed 24 premenopausal women with BRCA mutations who were considering prophylactic surgery. Responses showed that women who prioritized cancer risk reduction opted for risk-reducing salpingo-oophorectomy (RRSO), while those who were more concerned about the effects of surgical menopause opted for risk-reducing early salpingectomy with delayed oophorectomy (RRESDO). Factors such as past surgical experience influenced patients’ decisions as well.
The women were participants in the PROTECTOR trial, which was designed to determine the impact of RRESDO on sexual function by comparing RRESDO, RRSO, and no surgery. Study participants made their own decisions regarding surgery, and the interviews with 24 participants provided insight into how patients made their decisions.
Faiza Gaba, MBBS, PhD, of Queen Mary University of London, and colleagues reviewed the results in the Journal of Medical Genetics.
“I think what is most important is that even though this is a tough decision women are being given, they are being given options that allow them to make up their own minds with support from health care providers,” said Barbara A. Goff, MD, of the University of Washington, Seattle, when asked to comment on this research.
Study details and results
The investigators interviewed 24 women aged 34-46 years. Fourteen patients were BRCA1 carriers, and 10 were BRCA2 carriers. Twenty-two women were White, and two were Asian. Nineteen women were married, and four were nulliparous.
The interviews lasted a mean of 55 minutes and were conducted with a predeveloped topic guide.
Eleven of the women interviewed opted for RRESDO, seven opted for RRSO, and six decided against prophylactic surgery. Four women who had previous breast cancer all opted for ovarian cancer prevention surgery.
Among the 18 women who chose surgery, 16 had completed childbearing, and 2 didn’t want children. Among the six women who decided against surgery, four had not completed childbearing, one was unsure of which procedure to choose, and the sixth had strong feelings against removing healthy tissue.
The 11 women who chose RRESDO did so because of concerns about early menopause following oophorectomy, particularly low mood, sexual dysfunction, and poorer quality of life. They were also more likely to have had a previous positive surgical experience, so they were not as concerned about a two-step surgery.
Women who chose RRSO were motivated by a strong family history of ovarian cancer, fear of dying, concurrent benign gynecological issues, lack of screening for ovarian cancer, and physician advice.
Nine women also opted for risk-reducing mastectomy (RRM), which was deemed a more difficult decision than prophylactic ovarian cancer surgery.
Women who decided against RRM did so because they hadn’t completed childbearing, they were concerned about recovery time and the psychological effects of the surgery, or they had confidence in breast cancer screening and treatment.
Among women who chose RRM, two highlighted lack of health care professional support for deciding against reconstruction. One interviewee regretted opting for flap reconstruction due to the resultant cosmetic appearance and chronic pain but did not regret RRM.
Fifteen women said they would have preferred combined RRM and ovarian cancer prevention in one surgery, due to less anxiety, less waiting, fewer appointments, less time off work, and a single surgical recovery.
The women advised fellow BRCA carriers to avoid time pressure with surgical decision-making, talk to other BRCA carriers, do personal research, and ask for second opinions if not satisfied. They also said the opportunity to ask experts questions and meet other BRCA carriers face-to-face was more helpful than online support groups. Women managed in specialist settings said they received better care, better access to hormone replacement therapy, and were more satisfied.
High-risk women need to be supported by a multidisciplinary team of geneticists, gynecologists/oncologists, oncoplastic surgeons, menopause specialists, fertility specialists, psychologists, and specialist nurses, the investigators wrote.
This study was funded by the Rosetrees Trust and Barts Charity. The authors disclosed relationships with AstraZeneca, Merck, Cancer Research UK, The Eve Appeal, Israel National Institute for Health Policy Research, and the UK National Health Service. Dr. Goff has no relevant disclosures.
Investigators interviewed 24 premenopausal women with BRCA mutations who were considering prophylactic surgery. Responses showed that women who prioritized cancer risk reduction opted for risk-reducing salpingo-oophorectomy (RRSO), while those who were more concerned about the effects of surgical menopause opted for risk-reducing early salpingectomy with delayed oophorectomy (RRESDO). Factors such as past surgical experience influenced patients’ decisions as well.
The women were participants in the PROTECTOR trial, which was designed to determine the impact of RRESDO on sexual function by comparing RRESDO, RRSO, and no surgery. Study participants made their own decisions regarding surgery, and the interviews with 24 participants provided insight into how patients made their decisions.
Faiza Gaba, MBBS, PhD, of Queen Mary University of London, and colleagues reviewed the results in the Journal of Medical Genetics.
“I think what is most important is that even though this is a tough decision women are being given, they are being given options that allow them to make up their own minds with support from health care providers,” said Barbara A. Goff, MD, of the University of Washington, Seattle, when asked to comment on this research.
Study details and results
The investigators interviewed 24 women aged 34-46 years. Fourteen patients were BRCA1 carriers, and 10 were BRCA2 carriers. Twenty-two women were White, and two were Asian. Nineteen women were married, and four were nulliparous.
The interviews lasted a mean of 55 minutes and were conducted with a predeveloped topic guide.
Eleven of the women interviewed opted for RRESDO, seven opted for RRSO, and six decided against prophylactic surgery. Four women who had previous breast cancer all opted for ovarian cancer prevention surgery.
Among the 18 women who chose surgery, 16 had completed childbearing, and 2 didn’t want children. Among the six women who decided against surgery, four had not completed childbearing, one was unsure of which procedure to choose, and the sixth had strong feelings against removing healthy tissue.
The 11 women who chose RRESDO did so because of concerns about early menopause following oophorectomy, particularly low mood, sexual dysfunction, and poorer quality of life. They were also more likely to have had a previous positive surgical experience, so they were not as concerned about a two-step surgery.
Women who chose RRSO were motivated by a strong family history of ovarian cancer, fear of dying, concurrent benign gynecological issues, lack of screening for ovarian cancer, and physician advice.
Nine women also opted for risk-reducing mastectomy (RRM), which was deemed a more difficult decision than prophylactic ovarian cancer surgery.
Women who decided against RRM did so because they hadn’t completed childbearing, they were concerned about recovery time and the psychological effects of the surgery, or they had confidence in breast cancer screening and treatment.
Among women who chose RRM, two highlighted lack of health care professional support for deciding against reconstruction. One interviewee regretted opting for flap reconstruction due to the resultant cosmetic appearance and chronic pain but did not regret RRM.
Fifteen women said they would have preferred combined RRM and ovarian cancer prevention in one surgery, due to less anxiety, less waiting, fewer appointments, less time off work, and a single surgical recovery.
The women advised fellow BRCA carriers to avoid time pressure with surgical decision-making, talk to other BRCA carriers, do personal research, and ask for second opinions if not satisfied. They also said the opportunity to ask experts questions and meet other BRCA carriers face-to-face was more helpful than online support groups. Women managed in specialist settings said they received better care, better access to hormone replacement therapy, and were more satisfied.
High-risk women need to be supported by a multidisciplinary team of geneticists, gynecologists/oncologists, oncoplastic surgeons, menopause specialists, fertility specialists, psychologists, and specialist nurses, the investigators wrote.
This study was funded by the Rosetrees Trust and Barts Charity. The authors disclosed relationships with AstraZeneca, Merck, Cancer Research UK, The Eve Appeal, Israel National Institute for Health Policy Research, and the UK National Health Service. Dr. Goff has no relevant disclosures.
Investigators interviewed 24 premenopausal women with BRCA mutations who were considering prophylactic surgery. Responses showed that women who prioritized cancer risk reduction opted for risk-reducing salpingo-oophorectomy (RRSO), while those who were more concerned about the effects of surgical menopause opted for risk-reducing early salpingectomy with delayed oophorectomy (RRESDO). Factors such as past surgical experience influenced patients’ decisions as well.
The women were participants in the PROTECTOR trial, which was designed to determine the impact of RRESDO on sexual function by comparing RRESDO, RRSO, and no surgery. Study participants made their own decisions regarding surgery, and the interviews with 24 participants provided insight into how patients made their decisions.
Faiza Gaba, MBBS, PhD, of Queen Mary University of London, and colleagues reviewed the results in the Journal of Medical Genetics.
“I think what is most important is that even though this is a tough decision women are being given, they are being given options that allow them to make up their own minds with support from health care providers,” said Barbara A. Goff, MD, of the University of Washington, Seattle, when asked to comment on this research.
Study details and results
The investigators interviewed 24 women aged 34-46 years. Fourteen patients were BRCA1 carriers, and 10 were BRCA2 carriers. Twenty-two women were White, and two were Asian. Nineteen women were married, and four were nulliparous.
The interviews lasted a mean of 55 minutes and were conducted with a predeveloped topic guide.
Eleven of the women interviewed opted for RRESDO, seven opted for RRSO, and six decided against prophylactic surgery. Four women who had previous breast cancer all opted for ovarian cancer prevention surgery.
Among the 18 women who chose surgery, 16 had completed childbearing, and 2 didn’t want children. Among the six women who decided against surgery, four had not completed childbearing, one was unsure of which procedure to choose, and the sixth had strong feelings against removing healthy tissue.
The 11 women who chose RRESDO did so because of concerns about early menopause following oophorectomy, particularly low mood, sexual dysfunction, and poorer quality of life. They were also more likely to have had a previous positive surgical experience, so they were not as concerned about a two-step surgery.
Women who chose RRSO were motivated by a strong family history of ovarian cancer, fear of dying, concurrent benign gynecological issues, lack of screening for ovarian cancer, and physician advice.
Nine women also opted for risk-reducing mastectomy (RRM), which was deemed a more difficult decision than prophylactic ovarian cancer surgery.
Women who decided against RRM did so because they hadn’t completed childbearing, they were concerned about recovery time and the psychological effects of the surgery, or they had confidence in breast cancer screening and treatment.
Among women who chose RRM, two highlighted lack of health care professional support for deciding against reconstruction. One interviewee regretted opting for flap reconstruction due to the resultant cosmetic appearance and chronic pain but did not regret RRM.
Fifteen women said they would have preferred combined RRM and ovarian cancer prevention in one surgery, due to less anxiety, less waiting, fewer appointments, less time off work, and a single surgical recovery.
The women advised fellow BRCA carriers to avoid time pressure with surgical decision-making, talk to other BRCA carriers, do personal research, and ask for second opinions if not satisfied. They also said the opportunity to ask experts questions and meet other BRCA carriers face-to-face was more helpful than online support groups. Women managed in specialist settings said they received better care, better access to hormone replacement therapy, and were more satisfied.
High-risk women need to be supported by a multidisciplinary team of geneticists, gynecologists/oncologists, oncoplastic surgeons, menopause specialists, fertility specialists, psychologists, and specialist nurses, the investigators wrote.
This study was funded by the Rosetrees Trust and Barts Charity. The authors disclosed relationships with AstraZeneca, Merck, Cancer Research UK, The Eve Appeal, Israel National Institute for Health Policy Research, and the UK National Health Service. Dr. Goff has no relevant disclosures.
FROM THE JOURNAL OF MEDICAL GENETICS
Owning all aspects of patient care: Bridget McGrath, PA-C, FHM
Editor’s note: This profile is part of the Society of Hospital Medicine’s celebration of National Hospitalist Day on March 4. National Hospitalist Day occurs the first Thursday in March annually and celebrates the fastest growing specialty in modern medicine and hospitalists’ enduring contributions to the evolving health care landscape.
Bridget McGrath, PA-C, FHM, is a physician assistant and director of the nurse practitioner/physician assistant service line for the section of hospital medicine at the University of Chicago. She is a cochair of SHM’s NP/PA Special Interest Group.
Where did you receive your PA education/training? Was your intention always to be a PA?
I graduated from the PA program at Butler University, Indianapolis, in 2014. In college, whenever I shadowed a PA, I was always impressed that each one loved their job and said they would never change it. That universal passion for the PA profession really made an impression on me.
At what point in your PA education/training did you decide to practice hospital medicine? What about it appealed to you?
That occurred during my clinical rotation year at Butler. I had always thought I wanted to practice neonatology, but during my clinical rotation I really fell in love with adult medicine. I recall that during my clinical rotation, the preceptor said to me that the goal was not to have me understand every aspect of medicine, but to learn how to exist in a hospital setting. I was exposed to the breadth of hospital medicine practice and I fell in love with the complexity, the variety, and the environment itself.
I initially accepted a job as a med-peds hospitalist PA – which brought both of my passions together at that time – at Schneck Medical Center in Seymour, Ind. During that time, Schneck was a 100-bed rural community hospital which had recently been the recipient of the Malcolm Baldrige National Quality Award. It was there that I was able to practice with a phenomenal group of physicians, nurses, and social workers who really took me under their wing and taught me how to be a hospitalist PA. I practiced at Schneck for 3 years, and then moved to the University of Chicago in 2017.
I am now the director of NP/PA services for the section of hospital medicine, overseeing a group of seven on our NP/PA team, within a larger group of about 60 physicians.
What are your favorite areas of clinical practice?
Like many hospitalists, I enjoy the variety of medicine that hospitalists practice. One area that I find especially rewarding is my time in our transplant comanagement services. To be able to walk with patients on their transplant journey is very rewarding, and I am very appreciative of the mentoring I have received from some of my colleagues with a deeper understanding of transplant medicine.
In my administrative role, I have the privilege of helping to expand the professional education and training of my colleagues. I have a passion for medical education, and we have been working to develop interprofessional educational opportunities within our section. I have had time to think about the imprint of NPs and PAs in academic medicine, and how we can continue to meet the professional educational needs of our section while improving the care of our patients.
What are the most challenging aspects of practicing hospital medicine?
The volume of diagnoses that we are expected to manage on a daily basis can be challenging. This challenges you to continue learning. The complexity of discharge planning, particularly for patients in underserved communities, can also be challenging. You have to make sure your patients are ready mentally, physically and emotionally for discharge. As a hospitalist, you are continuously thinking about how to optimize patients to leave your care. For example, patients have different insurance situations, different access to care at home – you are always managing the medical needs of your patient in the context of these other issues.
How does a hospitalist PA work differently from a PA in other care settings?
We are meant to be generalists. We serve as the main provider in owning our patients’ care. A hospitalist PA serves as a cog in the wheel, with connections to specialists, consultants, nurses, social workers, pharmacists, etc., and we are tasked with synthesizing all aspects of patient care to ensure the best outcome.
What has your experience taught you about how NPs and PAs can best fit into hospital medicine groups?
Each hospital medicine group will know how to best integrate their NPs and PAs based on the skillsets of their NPs and PAs, and the needs of the section and the hospital. I personally feel that the best way to utilize NPs and PAs is to allow them to own all aspects of patient care and work at the highest scope of practice. By doing this you empower the NP or PA to continue to develop their skill set and set a precedent of collaboration and respect for interprofessional care models within your section’s culture.
Scope of practice for an NP or PA is going to be based on a conglomeration of roles and bylaws. We are certified nationally, and our scope of practice is determined at the state level and the hospital by level. For the individual NP and PA, it really depends on the hospital medicine group, and how well a practice incorporates a sense of collegiality.
What kind of resources do hospitalist PAs need to succeed, either from SHM or from their own institutions?
There are a few key things that need to happen in order for hospital medicine groups to set up their NPs and PAs for success. The first is for PAs to have exposure to inpatient rotations during clinical rotations. A hospital medicine group also should have a very intentional onboarding process for NPs and PAs. They should also establish a culture of acceptance. To do this, they should utilize resources like SHM’s NP/PA Hospital Medicine Onboarding Toolkit and the SHM/American Academy of Physician Assistants Hospitalist Bootcamp On Demand.
Mentoring is also remarkably important. I have been incredibly blessed to have mentors that helped make me into the PA that I am. I could not have done what I did in the field without people taking a chance on me, and it is important to pass that on to the next generation of PAs.
How has COVID-19 changed the practice of hospital medicine, specifically for advanced practice providers?
The pandemic has demonstrated opportunities for teamwork and utilization of NPs and PAs. The COVID pandemic forced everyone to reflect on why they originally got into medicine – to help patients. I think there will be many doors opening for NPs and PAs, and many pathways for leadership.
The hospitalist leadership at the University of Chicago truly identified that we needed to make wellness a main priority during the beginning of the pandemic. We developed a wellness work group that I have been coleading.
What’s on the horizon for NPs and PAs in hospital medicine?
We are seeing significant increases in hospitalist program utilization, so this is a time where NPs and PAs can be advocates for our profession and articulate how we can use our backgrounds and training to build better care models in order to meet the needs of our patients.
I hope we will see more NPs and PAs assuming leadership roles to ensure that our voices are heard. We should also be advocating for more collaboration and teamwork with our MD and DO colleagues.
Do you have any advice for PA students interested in hospital medicine?
I always tell my students that they should be sponges – you are not expected to know everything as a hospitalist PA, but you are expected to continue learning in order to develop into the best PA you can be. Always be open to where your career path can take you. Hospital medicine is a relatively young field within medicine, and the diversity of our field is very exciting looking forward.
Editor’s note: This profile is part of the Society of Hospital Medicine’s celebration of National Hospitalist Day on March 4. National Hospitalist Day occurs the first Thursday in March annually and celebrates the fastest growing specialty in modern medicine and hospitalists’ enduring contributions to the evolving health care landscape.
Bridget McGrath, PA-C, FHM, is a physician assistant and director of the nurse practitioner/physician assistant service line for the section of hospital medicine at the University of Chicago. She is a cochair of SHM’s NP/PA Special Interest Group.
Where did you receive your PA education/training? Was your intention always to be a PA?
I graduated from the PA program at Butler University, Indianapolis, in 2014. In college, whenever I shadowed a PA, I was always impressed that each one loved their job and said they would never change it. That universal passion for the PA profession really made an impression on me.
At what point in your PA education/training did you decide to practice hospital medicine? What about it appealed to you?
That occurred during my clinical rotation year at Butler. I had always thought I wanted to practice neonatology, but during my clinical rotation I really fell in love with adult medicine. I recall that during my clinical rotation, the preceptor said to me that the goal was not to have me understand every aspect of medicine, but to learn how to exist in a hospital setting. I was exposed to the breadth of hospital medicine practice and I fell in love with the complexity, the variety, and the environment itself.
I initially accepted a job as a med-peds hospitalist PA – which brought both of my passions together at that time – at Schneck Medical Center in Seymour, Ind. During that time, Schneck was a 100-bed rural community hospital which had recently been the recipient of the Malcolm Baldrige National Quality Award. It was there that I was able to practice with a phenomenal group of physicians, nurses, and social workers who really took me under their wing and taught me how to be a hospitalist PA. I practiced at Schneck for 3 years, and then moved to the University of Chicago in 2017.
I am now the director of NP/PA services for the section of hospital medicine, overseeing a group of seven on our NP/PA team, within a larger group of about 60 physicians.
What are your favorite areas of clinical practice?
Like many hospitalists, I enjoy the variety of medicine that hospitalists practice. One area that I find especially rewarding is my time in our transplant comanagement services. To be able to walk with patients on their transplant journey is very rewarding, and I am very appreciative of the mentoring I have received from some of my colleagues with a deeper understanding of transplant medicine.
In my administrative role, I have the privilege of helping to expand the professional education and training of my colleagues. I have a passion for medical education, and we have been working to develop interprofessional educational opportunities within our section. I have had time to think about the imprint of NPs and PAs in academic medicine, and how we can continue to meet the professional educational needs of our section while improving the care of our patients.
What are the most challenging aspects of practicing hospital medicine?
The volume of diagnoses that we are expected to manage on a daily basis can be challenging. This challenges you to continue learning. The complexity of discharge planning, particularly for patients in underserved communities, can also be challenging. You have to make sure your patients are ready mentally, physically and emotionally for discharge. As a hospitalist, you are continuously thinking about how to optimize patients to leave your care. For example, patients have different insurance situations, different access to care at home – you are always managing the medical needs of your patient in the context of these other issues.
How does a hospitalist PA work differently from a PA in other care settings?
We are meant to be generalists. We serve as the main provider in owning our patients’ care. A hospitalist PA serves as a cog in the wheel, with connections to specialists, consultants, nurses, social workers, pharmacists, etc., and we are tasked with synthesizing all aspects of patient care to ensure the best outcome.
What has your experience taught you about how NPs and PAs can best fit into hospital medicine groups?
Each hospital medicine group will know how to best integrate their NPs and PAs based on the skillsets of their NPs and PAs, and the needs of the section and the hospital. I personally feel that the best way to utilize NPs and PAs is to allow them to own all aspects of patient care and work at the highest scope of practice. By doing this you empower the NP or PA to continue to develop their skill set and set a precedent of collaboration and respect for interprofessional care models within your section’s culture.
Scope of practice for an NP or PA is going to be based on a conglomeration of roles and bylaws. We are certified nationally, and our scope of practice is determined at the state level and the hospital by level. For the individual NP and PA, it really depends on the hospital medicine group, and how well a practice incorporates a sense of collegiality.
What kind of resources do hospitalist PAs need to succeed, either from SHM or from their own institutions?
There are a few key things that need to happen in order for hospital medicine groups to set up their NPs and PAs for success. The first is for PAs to have exposure to inpatient rotations during clinical rotations. A hospital medicine group also should have a very intentional onboarding process for NPs and PAs. They should also establish a culture of acceptance. To do this, they should utilize resources like SHM’s NP/PA Hospital Medicine Onboarding Toolkit and the SHM/American Academy of Physician Assistants Hospitalist Bootcamp On Demand.
Mentoring is also remarkably important. I have been incredibly blessed to have mentors that helped make me into the PA that I am. I could not have done what I did in the field without people taking a chance on me, and it is important to pass that on to the next generation of PAs.
How has COVID-19 changed the practice of hospital medicine, specifically for advanced practice providers?
The pandemic has demonstrated opportunities for teamwork and utilization of NPs and PAs. The COVID pandemic forced everyone to reflect on why they originally got into medicine – to help patients. I think there will be many doors opening for NPs and PAs, and many pathways for leadership.
The hospitalist leadership at the University of Chicago truly identified that we needed to make wellness a main priority during the beginning of the pandemic. We developed a wellness work group that I have been coleading.
What’s on the horizon for NPs and PAs in hospital medicine?
We are seeing significant increases in hospitalist program utilization, so this is a time where NPs and PAs can be advocates for our profession and articulate how we can use our backgrounds and training to build better care models in order to meet the needs of our patients.
I hope we will see more NPs and PAs assuming leadership roles to ensure that our voices are heard. We should also be advocating for more collaboration and teamwork with our MD and DO colleagues.
Do you have any advice for PA students interested in hospital medicine?
I always tell my students that they should be sponges – you are not expected to know everything as a hospitalist PA, but you are expected to continue learning in order to develop into the best PA you can be. Always be open to where your career path can take you. Hospital medicine is a relatively young field within medicine, and the diversity of our field is very exciting looking forward.
Editor’s note: This profile is part of the Society of Hospital Medicine’s celebration of National Hospitalist Day on March 4. National Hospitalist Day occurs the first Thursday in March annually and celebrates the fastest growing specialty in modern medicine and hospitalists’ enduring contributions to the evolving health care landscape.
Bridget McGrath, PA-C, FHM, is a physician assistant and director of the nurse practitioner/physician assistant service line for the section of hospital medicine at the University of Chicago. She is a cochair of SHM’s NP/PA Special Interest Group.
Where did you receive your PA education/training? Was your intention always to be a PA?
I graduated from the PA program at Butler University, Indianapolis, in 2014. In college, whenever I shadowed a PA, I was always impressed that each one loved their job and said they would never change it. That universal passion for the PA profession really made an impression on me.
At what point in your PA education/training did you decide to practice hospital medicine? What about it appealed to you?
That occurred during my clinical rotation year at Butler. I had always thought I wanted to practice neonatology, but during my clinical rotation I really fell in love with adult medicine. I recall that during my clinical rotation, the preceptor said to me that the goal was not to have me understand every aspect of medicine, but to learn how to exist in a hospital setting. I was exposed to the breadth of hospital medicine practice and I fell in love with the complexity, the variety, and the environment itself.
I initially accepted a job as a med-peds hospitalist PA – which brought both of my passions together at that time – at Schneck Medical Center in Seymour, Ind. During that time, Schneck was a 100-bed rural community hospital which had recently been the recipient of the Malcolm Baldrige National Quality Award. It was there that I was able to practice with a phenomenal group of physicians, nurses, and social workers who really took me under their wing and taught me how to be a hospitalist PA. I practiced at Schneck for 3 years, and then moved to the University of Chicago in 2017.
I am now the director of NP/PA services for the section of hospital medicine, overseeing a group of seven on our NP/PA team, within a larger group of about 60 physicians.
What are your favorite areas of clinical practice?
Like many hospitalists, I enjoy the variety of medicine that hospitalists practice. One area that I find especially rewarding is my time in our transplant comanagement services. To be able to walk with patients on their transplant journey is very rewarding, and I am very appreciative of the mentoring I have received from some of my colleagues with a deeper understanding of transplant medicine.
In my administrative role, I have the privilege of helping to expand the professional education and training of my colleagues. I have a passion for medical education, and we have been working to develop interprofessional educational opportunities within our section. I have had time to think about the imprint of NPs and PAs in academic medicine, and how we can continue to meet the professional educational needs of our section while improving the care of our patients.
What are the most challenging aspects of practicing hospital medicine?
The volume of diagnoses that we are expected to manage on a daily basis can be challenging. This challenges you to continue learning. The complexity of discharge planning, particularly for patients in underserved communities, can also be challenging. You have to make sure your patients are ready mentally, physically and emotionally for discharge. As a hospitalist, you are continuously thinking about how to optimize patients to leave your care. For example, patients have different insurance situations, different access to care at home – you are always managing the medical needs of your patient in the context of these other issues.
How does a hospitalist PA work differently from a PA in other care settings?
We are meant to be generalists. We serve as the main provider in owning our patients’ care. A hospitalist PA serves as a cog in the wheel, with connections to specialists, consultants, nurses, social workers, pharmacists, etc., and we are tasked with synthesizing all aspects of patient care to ensure the best outcome.
What has your experience taught you about how NPs and PAs can best fit into hospital medicine groups?
Each hospital medicine group will know how to best integrate their NPs and PAs based on the skillsets of their NPs and PAs, and the needs of the section and the hospital. I personally feel that the best way to utilize NPs and PAs is to allow them to own all aspects of patient care and work at the highest scope of practice. By doing this you empower the NP or PA to continue to develop their skill set and set a precedent of collaboration and respect for interprofessional care models within your section’s culture.
Scope of practice for an NP or PA is going to be based on a conglomeration of roles and bylaws. We are certified nationally, and our scope of practice is determined at the state level and the hospital by level. For the individual NP and PA, it really depends on the hospital medicine group, and how well a practice incorporates a sense of collegiality.
What kind of resources do hospitalist PAs need to succeed, either from SHM or from their own institutions?
There are a few key things that need to happen in order for hospital medicine groups to set up their NPs and PAs for success. The first is for PAs to have exposure to inpatient rotations during clinical rotations. A hospital medicine group also should have a very intentional onboarding process for NPs and PAs. They should also establish a culture of acceptance. To do this, they should utilize resources like SHM’s NP/PA Hospital Medicine Onboarding Toolkit and the SHM/American Academy of Physician Assistants Hospitalist Bootcamp On Demand.
Mentoring is also remarkably important. I have been incredibly blessed to have mentors that helped make me into the PA that I am. I could not have done what I did in the field without people taking a chance on me, and it is important to pass that on to the next generation of PAs.
How has COVID-19 changed the practice of hospital medicine, specifically for advanced practice providers?
The pandemic has demonstrated opportunities for teamwork and utilization of NPs and PAs. The COVID pandemic forced everyone to reflect on why they originally got into medicine – to help patients. I think there will be many doors opening for NPs and PAs, and many pathways for leadership.
The hospitalist leadership at the University of Chicago truly identified that we needed to make wellness a main priority during the beginning of the pandemic. We developed a wellness work group that I have been coleading.
What’s on the horizon for NPs and PAs in hospital medicine?
We are seeing significant increases in hospitalist program utilization, so this is a time where NPs and PAs can be advocates for our profession and articulate how we can use our backgrounds and training to build better care models in order to meet the needs of our patients.
I hope we will see more NPs and PAs assuming leadership roles to ensure that our voices are heard. We should also be advocating for more collaboration and teamwork with our MD and DO colleagues.
Do you have any advice for PA students interested in hospital medicine?
I always tell my students that they should be sponges – you are not expected to know everything as a hospitalist PA, but you are expected to continue learning in order to develop into the best PA you can be. Always be open to where your career path can take you. Hospital medicine is a relatively young field within medicine, and the diversity of our field is very exciting looking forward.
Maribavir seen as superior to other antivirals for CMV clearance post transplant
Maribavir, an investigational antiviral agent with a novel mechanism of action, was superior to other antiviral strategies at clearing cytomegalovirus (CMV) viremia and controlling symptoms in hematopoietic cell or solid-organ transplant recipients, results of a phase 3 clinical trial showed.
CMV viremia clearance at study week 8 was seen in 55.7% of all patients randomized to receive maribavir, compared with 23.9% for patients assigned to receive investigator-assigned therapy (IAT), Francisco Marty, MD, from the Dana-Farber Cancer Institute in Boston reported at the Transplant & Cellular Therapies Meetings.
“Maribavir’s benefit was driven by lower incidence of treatment-limiting toxicities, compared with IAT,” he said a late-breaking abstract session during the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
“Available anti-CMV antivirals are limited by development of resistance and toxicities, particularly myelosuppression with the use of valganciclovir and nephrotoxicity with the use of foscarnet and cidofovir. Alternative treatment options are required to address this unmet medical need,” he said.
Maribavir inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.
Details of trial
In the phase 3 SHP620-30e trial (NCT02931539), Dr. Marty and colleagues enrolled patients with relapsed or refractory CMV infections after hematopoietic cell transplant (HCT) or solid-organ transplant (SOT) and after stratification by transplant type and screening CMV DNA level randomly assigned them on a 2:1 basis to receive either maribavir 400 mg twice daily (235 patients) or IAT (117 patients), consisting of either ganciclovir/valganciclovir, foscarnet, cidofovir, or combined foscarnet and val/ganciclovir.
The primary endpoint of viremia clearance at 8 weeks was defined as plasma CMV DNA less than 137 IU/mL in two consecutive tests at a central laboratory at least 5 days apart beginning at the end of week 8.
The trial met its primary endpoint, with a viremia clearance rate of 55.7% with maribavir versus 23.9% with IAT.
The viremia clearance rates were similar in each of the transplant groups: 55.9% versus 20.8%, respectively, in patients who underwent HCT, and 55.6% versus 26.1% in patients who underwent SOT (P < .001).
Clearance rates among patients with CMV DNA below 9,100 IU/mL at baseline were 62.1% with maribavir versus 24.7% with IAT. Among patients with baseline CMV DNA of 9100 IU/mL or above, the respective rates were 43.9% versus 21.9%.
CMV viremia clearance continued from week 8 to week 16 in 18.7% of patients assigned to maribavir and to 10.3% of patients randomized to IAT (P < .013).
The median time to first CMV viremia clearance as 22 days with maribavir versus 27 days with IAT (P = .039).
All-cause mortality was similar between the groups, at 11.5% versus 11.1%, respectively.
The incidences of serious and severe treatment-emergent adverse events (TEAE) were 38.5% and 32.1%, respectively, in the maribavir group, and 37.1% and 37.9% in the IAT group.
Any TEAE leading to study drug discontinuation was less common with maribavir, occurring in 13.2% of patients, compared with 31.9% of patients on IAT. Serious TEAEs leading to drug discontinuation occurred in 8.5% versus 14.7%, respectively.
Serious TEAEs leading to death occurred in 6.8% of patients on maribavir versus 5.2% of those on IAT.
Role of letermovir
In the question-and-answer session following the presentation, comoderator Monalisa Ghosh, MD, from the University of Michigan, Ann Arbor, asked whether any patients in the study were currently on letermovir (Prevymis) prophylaxis, and whether any patients had previously been treated with letermovir but had CMV reactivation and were then treated on study.
Dr. Marty noted that the trial was designed before letermovir was approved for CMV prophylaxis in adults who have undergone an allogeneic HCT.
“Nobody was on letermovir at the beginning of the trial,” he replied, but noted that some patients who were enrolled and had infections that were refractory or resistant to valganciclovir, foscarnet, or a combination of the two received letermovir as secondary prophylaxis.
“I haven’t got the data to tell you how often [letermovir] was used; I think part of the lack of mortality benefit [with maribavir] may be due to the fact that people jumped into secondary prophylaxis with letermovir to minimize the toxicities that we saw,” he said.
Although maribavir has not as of this writing received Food and Drug Administration approval, the drug may be available to some patients through a compassionate-use program from Takeda, Dr. Marty noted.
The study was funded by Shire ViroPharma. Dr. Marty disclosed research funding from Shire and from others. Dr. Ghosh had no relevant disclosures.
Maribavir, an investigational antiviral agent with a novel mechanism of action, was superior to other antiviral strategies at clearing cytomegalovirus (CMV) viremia and controlling symptoms in hematopoietic cell or solid-organ transplant recipients, results of a phase 3 clinical trial showed.
CMV viremia clearance at study week 8 was seen in 55.7% of all patients randomized to receive maribavir, compared with 23.9% for patients assigned to receive investigator-assigned therapy (IAT), Francisco Marty, MD, from the Dana-Farber Cancer Institute in Boston reported at the Transplant & Cellular Therapies Meetings.
“Maribavir’s benefit was driven by lower incidence of treatment-limiting toxicities, compared with IAT,” he said a late-breaking abstract session during the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
“Available anti-CMV antivirals are limited by development of resistance and toxicities, particularly myelosuppression with the use of valganciclovir and nephrotoxicity with the use of foscarnet and cidofovir. Alternative treatment options are required to address this unmet medical need,” he said.
Maribavir inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.
Details of trial
In the phase 3 SHP620-30e trial (NCT02931539), Dr. Marty and colleagues enrolled patients with relapsed or refractory CMV infections after hematopoietic cell transplant (HCT) or solid-organ transplant (SOT) and after stratification by transplant type and screening CMV DNA level randomly assigned them on a 2:1 basis to receive either maribavir 400 mg twice daily (235 patients) or IAT (117 patients), consisting of either ganciclovir/valganciclovir, foscarnet, cidofovir, or combined foscarnet and val/ganciclovir.
The primary endpoint of viremia clearance at 8 weeks was defined as plasma CMV DNA less than 137 IU/mL in two consecutive tests at a central laboratory at least 5 days apart beginning at the end of week 8.
The trial met its primary endpoint, with a viremia clearance rate of 55.7% with maribavir versus 23.9% with IAT.
The viremia clearance rates were similar in each of the transplant groups: 55.9% versus 20.8%, respectively, in patients who underwent HCT, and 55.6% versus 26.1% in patients who underwent SOT (P < .001).
Clearance rates among patients with CMV DNA below 9,100 IU/mL at baseline were 62.1% with maribavir versus 24.7% with IAT. Among patients with baseline CMV DNA of 9100 IU/mL or above, the respective rates were 43.9% versus 21.9%.
CMV viremia clearance continued from week 8 to week 16 in 18.7% of patients assigned to maribavir and to 10.3% of patients randomized to IAT (P < .013).
The median time to first CMV viremia clearance as 22 days with maribavir versus 27 days with IAT (P = .039).
All-cause mortality was similar between the groups, at 11.5% versus 11.1%, respectively.
The incidences of serious and severe treatment-emergent adverse events (TEAE) were 38.5% and 32.1%, respectively, in the maribavir group, and 37.1% and 37.9% in the IAT group.
Any TEAE leading to study drug discontinuation was less common with maribavir, occurring in 13.2% of patients, compared with 31.9% of patients on IAT. Serious TEAEs leading to drug discontinuation occurred in 8.5% versus 14.7%, respectively.
Serious TEAEs leading to death occurred in 6.8% of patients on maribavir versus 5.2% of those on IAT.
Role of letermovir
In the question-and-answer session following the presentation, comoderator Monalisa Ghosh, MD, from the University of Michigan, Ann Arbor, asked whether any patients in the study were currently on letermovir (Prevymis) prophylaxis, and whether any patients had previously been treated with letermovir but had CMV reactivation and were then treated on study.
Dr. Marty noted that the trial was designed before letermovir was approved for CMV prophylaxis in adults who have undergone an allogeneic HCT.
“Nobody was on letermovir at the beginning of the trial,” he replied, but noted that some patients who were enrolled and had infections that were refractory or resistant to valganciclovir, foscarnet, or a combination of the two received letermovir as secondary prophylaxis.
“I haven’t got the data to tell you how often [letermovir] was used; I think part of the lack of mortality benefit [with maribavir] may be due to the fact that people jumped into secondary prophylaxis with letermovir to minimize the toxicities that we saw,” he said.
Although maribavir has not as of this writing received Food and Drug Administration approval, the drug may be available to some patients through a compassionate-use program from Takeda, Dr. Marty noted.
The study was funded by Shire ViroPharma. Dr. Marty disclosed research funding from Shire and from others. Dr. Ghosh had no relevant disclosures.
Maribavir, an investigational antiviral agent with a novel mechanism of action, was superior to other antiviral strategies at clearing cytomegalovirus (CMV) viremia and controlling symptoms in hematopoietic cell or solid-organ transplant recipients, results of a phase 3 clinical trial showed.
CMV viremia clearance at study week 8 was seen in 55.7% of all patients randomized to receive maribavir, compared with 23.9% for patients assigned to receive investigator-assigned therapy (IAT), Francisco Marty, MD, from the Dana-Farber Cancer Institute in Boston reported at the Transplant & Cellular Therapies Meetings.
“Maribavir’s benefit was driven by lower incidence of treatment-limiting toxicities, compared with IAT,” he said a late-breaking abstract session during the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
“Available anti-CMV antivirals are limited by development of resistance and toxicities, particularly myelosuppression with the use of valganciclovir and nephrotoxicity with the use of foscarnet and cidofovir. Alternative treatment options are required to address this unmet medical need,” he said.
Maribavir inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.
Details of trial
In the phase 3 SHP620-30e trial (NCT02931539), Dr. Marty and colleagues enrolled patients with relapsed or refractory CMV infections after hematopoietic cell transplant (HCT) or solid-organ transplant (SOT) and after stratification by transplant type and screening CMV DNA level randomly assigned them on a 2:1 basis to receive either maribavir 400 mg twice daily (235 patients) or IAT (117 patients), consisting of either ganciclovir/valganciclovir, foscarnet, cidofovir, or combined foscarnet and val/ganciclovir.
The primary endpoint of viremia clearance at 8 weeks was defined as plasma CMV DNA less than 137 IU/mL in two consecutive tests at a central laboratory at least 5 days apart beginning at the end of week 8.
The trial met its primary endpoint, with a viremia clearance rate of 55.7% with maribavir versus 23.9% with IAT.
The viremia clearance rates were similar in each of the transplant groups: 55.9% versus 20.8%, respectively, in patients who underwent HCT, and 55.6% versus 26.1% in patients who underwent SOT (P < .001).
Clearance rates among patients with CMV DNA below 9,100 IU/mL at baseline were 62.1% with maribavir versus 24.7% with IAT. Among patients with baseline CMV DNA of 9100 IU/mL or above, the respective rates were 43.9% versus 21.9%.
CMV viremia clearance continued from week 8 to week 16 in 18.7% of patients assigned to maribavir and to 10.3% of patients randomized to IAT (P < .013).
The median time to first CMV viremia clearance as 22 days with maribavir versus 27 days with IAT (P = .039).
All-cause mortality was similar between the groups, at 11.5% versus 11.1%, respectively.
The incidences of serious and severe treatment-emergent adverse events (TEAE) were 38.5% and 32.1%, respectively, in the maribavir group, and 37.1% and 37.9% in the IAT group.
Any TEAE leading to study drug discontinuation was less common with maribavir, occurring in 13.2% of patients, compared with 31.9% of patients on IAT. Serious TEAEs leading to drug discontinuation occurred in 8.5% versus 14.7%, respectively.
Serious TEAEs leading to death occurred in 6.8% of patients on maribavir versus 5.2% of those on IAT.
Role of letermovir
In the question-and-answer session following the presentation, comoderator Monalisa Ghosh, MD, from the University of Michigan, Ann Arbor, asked whether any patients in the study were currently on letermovir (Prevymis) prophylaxis, and whether any patients had previously been treated with letermovir but had CMV reactivation and were then treated on study.
Dr. Marty noted that the trial was designed before letermovir was approved for CMV prophylaxis in adults who have undergone an allogeneic HCT.
“Nobody was on letermovir at the beginning of the trial,” he replied, but noted that some patients who were enrolled and had infections that were refractory or resistant to valganciclovir, foscarnet, or a combination of the two received letermovir as secondary prophylaxis.
“I haven’t got the data to tell you how often [letermovir] was used; I think part of the lack of mortality benefit [with maribavir] may be due to the fact that people jumped into secondary prophylaxis with letermovir to minimize the toxicities that we saw,” he said.
Although maribavir has not as of this writing received Food and Drug Administration approval, the drug may be available to some patients through a compassionate-use program from Takeda, Dr. Marty noted.
The study was funded by Shire ViroPharma. Dr. Marty disclosed research funding from Shire and from others. Dr. Ghosh had no relevant disclosures.
FROM TCT 2021
Recent psoriasis pathophysiology insights carry treatment implications
at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.
Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Our understanding of the pathophysiology of psoriasis is still a work in progress,” the dermatologist observed.
Immunoregulatory deficits in mild vs. severe psoriasis
Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.
The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.
Dr. Gordon concurs.
“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”
The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.
Autoimmunity in psoriasis
“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.
That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.
He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.
“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.
Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.
Growing clinical relevance of IL-19
It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.
In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.
Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.
Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.
MedscapeLive and this news organization are owned by the same parent company.
at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.
Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Our understanding of the pathophysiology of psoriasis is still a work in progress,” the dermatologist observed.
Immunoregulatory deficits in mild vs. severe psoriasis
Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.
The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.
Dr. Gordon concurs.
“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”
The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.
Autoimmunity in psoriasis
“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.
That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.
He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.
“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.
Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.
Growing clinical relevance of IL-19
It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.
In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.
Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.
Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.
MedscapeLive and this news organization are owned by the same parent company.
at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually.
Among these unexpected developments was the startling finding that skin inflammation in mild psoriasis is at least as great as in severe disease; evidence that psoriasis may actually be an autoimmune disease rather than a nonspecific immune-mediated disease; and the newly appreciated importance of interleukin-19 (IL-19) in keratinocyte proliferation, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Our understanding of the pathophysiology of psoriasis is still a work in progress,” the dermatologist observed.
Immunoregulatory deficits in mild vs. severe psoriasis
Conventional wisdom has held that mild psoriasis as defined by limited affected body surface area involves less skin inflammation than more extensive severe psoriasis, so less-potent topical therapies are appropriate. Not so, according to Dr. Gordon, who highlighted work by James G. Krueger, MD, PhD, head of the laboratory of investigative dermatology at Rockefeller University, New York, and coinvestigators. They demonstrated that overall skin inflammation expressed as the sum of T-cell activation and IL-19-mediated epidermal responses didn’t differ in lesions of mild as compared with severe psoriasis. Indeed, mild skin lesions featured a greater number of T-cells, stronger expression of proinflammatory cytokine IL-17A, and greater expression of the central psoriasis transcriptome. The big difference between skin lesions of mild versus severe psoriasis was that severe psoriasis was characterized by strikingly weaker expression of immunoregulatory genes, including programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), than that of mild lesions.
The implication is that IL-17-targeted therapies may be of benefit in a much larger segment of the psoriatic population: namely, those with mild disease, who comprise the majority of psoriasis patients by a wide margin, according to the investigators.
Dr. Gordon concurs.
“The primary problem in psoriasis is not so much the inflammatory activity, but the ability to turn off the activity,” he explained. “That implies that if a patient wants to get clear or have significant improvement in disease, you can’t use a less effective medication just because they have less amount of disease. You’re going to need to treat it just as aggressively because the great majority of our medications block the proinflammatory pathways.”
The deficit in immunoregulatory action identified by Dr. Krueger and colleagues in patients with severe disease could provide a novel therapeutic target. If the deficient immunoregulation could be boosted, it might achieve disease control without need for continuous anti-inflammatory therapy.
Autoimmunity in psoriasis
“When I started work in psoriasis, we always thought there would be a common antigen for the immune process in the disease. We never found it. So for that reason, we sort of put it aside and called psoriasis a nonspecific immune-mediated disease,” Dr. Gordon recalled.
That view is being reexamined. “While we’re not completely certain, there is now some evidence that there might be autoimmunity in psoriasis,” he said.
He cited work by an international team of investigators who identified the cathelicidin antimicrobial peptide LL37 as being overexpressed in psoriatic skin, where it appears to serve as a T-cell autoantigen. LL37-specific CD4+ and CD8+ T-cells are skin homing: They can infiltrate lesional skin, where they produce interferon-gamma and proinflammatory Th17 cytokines. The investigators reported that levels of circulating LL37-specific T cells correlated with disease activity such that they were found in three-quarters of patients with moderate to severe plaque psoriasis.
“As LL37 is able to activate innate immune cells and break innate tolerance to self-nucleic acids, it represents an even more appealing target to treat psoriasis. Therapeutic targeting of LL37-specific T cells may provide new avenues to prevent or treat psoriasis without inducing indiscriminate immunosuppression,” the investigators concluded.
Similarly, German investigators have identified ADAMTS-like protein 5 (ADAMTSL5) as an autoantigen specific for melanocytes in psoriasis patients who possess the central psoriasis risk gene, known as HLA-C*06:02, which is present in two-thirds of patients with psoriasis. They proposed that their newly recognized autoimmune pathway may explain how HLA-C*06.02 predisposes to psoriasis.
Growing clinical relevance of IL-19
It’s now well-established that IL-17 is the pivotal force driving the changes in keratinocytes that define the visible expressions of psoriasis, including plaque scale and thickness, which are due to abnormal keratinocyte maturation and proliferation, respectively. Less well appreciated is the fact that IL-17-activated keratinocytes produce IL-19, which feeds back and further stimulates keratinocyte proliferation.
In light of mounting evidence that IL-19 plays an important role in the pathogenesis of psoriasis and that naked eye assessment of visible psoriasis may not reflect the true extent of inflammation, Brian J. Nickoloff, MD, PhD, and coworkers at Lilly Research Laboratories have developed a novel serum IL-19 immunoassay that appears to provide a much-needed objective biomarker of disease activity in psoriasis patients. They demonstrated that serum IL-19 levels correlated with Psoriasis Area and Severity Index scores, and that treatment with the anti-IL-17A biologic ixekizumab (Taltz) led to rapid reduction of IL-19 down to a normal level.
Moreover, following withdrawal of ixekizumab, IL-19 levels rose prior to clinical relapse, then dropped again in response to retreatment. The hope is that this assay will serve as an accurate tool for assessment of response to therapy.
Dr. Gordon reported receiving research funding and/or honoraria from more than a dozen pharmaceutical companies involved in psoriasis therapy.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
CAR-T in children branching out to solid tumors
Although the only pediatric indication for chimeric antigen receptor T-cell therapy currently approved by the Food and Drug Administration is B-lineage acute lymphoblastic leukemia (ALL) that is refractory to at least two frontline induction attempts or is in second or later relapse, clinical trials of CAR-T therapy for pediatric solid tumors are also currently in progress, said Gregory Yanik, MD, from the CS Mott Children’s Hospital at the University of Michigan, Ann Arbor, at the Transplant & Cellular Therapies Meetings.
In his presentation, Dr. Yanik discussed progress in solid tumor studies as well as some issues involving the current use of CAR-T therapy for ALL.
Solid tumor studies
Malignancies such as sarcomas, brain tumors, and neuroblastomas pose unique challenges, “In contrast to hematologic malignancies, the protein we’re targeting may not be present on the cell surface of all the tumor cells. There are lower-expression profiles, and this is a problem. In fact, many people have postulated that with CAR-T for pediatric solid tumors we’ll have to do repeated cycles, almost like we do with chemotherapy,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
There are currently 14 studies of CAR-T for central nervous system tumors in children, targeting either epidermal growth factor receptor (EGFR) in glioblastoma multiforme and high-grade gliomas, HER2 in a variety of CNS tumors, the GD2 antigen on pontine gliomas, and the checkpoint molecular B7H3 in medulloblastomas and pontine gliomas.
“In sarcomas in kids there are currently 12 trials in progress. Most of the targeting epitopes are targeting either HER2 or GD2. Repetitive CAR-T infusions are being used in several of these trials in sarcomas.
For neuroblastomas there are currently 13 studies in progress, nearly all of which target GD2. Some of the trials include combining CAR-T with immune checkpoint inhibitors or C7R, an engineered cytokine driver designed to prevent T-cell exhaustion.
In addition, several trials of tumor pulsed dendritic cell vaccines are underway for treatment of children with Wilms tumor, Dr. Yanik noted.
Unresolved procedural questions
It’s still early days in CAR-T therapy, and there are several still unanswered questions regarding optimal therapy for and management of patients undergoing CAR-T procedures, Dr. Yanik said.
For example, the optimal time to collect T cells during apheresis is still unclear, he said. Collecting prior to reinduction therapy raises the risk of transducing leukemic cells, while collecting after reinduction may result in inadequate quantity or quality of cells. Regardless of when cells are collected, apheresis should be performed only when the absolute lymphocyte count is above 500/mcL or the CD3 count is above 150/mcL at the time of apheresis.
In the case tisagenlecleucel (Kymriah), his center typically collects 1x109 CD3 cells regardless of age or weight.
The number of CAR T-cells infused also appears to matter, as responses are improved at CAR-T doses above 1.5x106/kg, while risk for higher-grade cytokine release syndrome (CRS) occurs at higher infusion doses.
Blinatumomab or inotuzumab?
Along with CAR-T, two other agents, the bispecific T-cell engager blinatumomab (Blincyto) and the antibody conjugate inotuzumab ozogamicin (Besponsa) are also approved for the treatment of patients with relapsed/refractory B-cell ALL.
Like CAR-T therapy, the primary toxicities associated with blinatumomab are CRS and neurologic adverse events, whereas at inotuzumab is largely associated with hematologic and hepatic toxicities.
The logistics of therapy differ widely, with a 28-day infusion required for blinatumomab, compared with weekly dosing of inotuzumab, and the multiple visits for apheresis and infusion required for CAR-T.
Blinatumomab is approved for both children and adults with relapsed/refractory ALL, but inotuzumab is approved only for adults, and CAR-T with tisagenlecleucel is approved only for children in this indication.
CD-19 expression
There is evidence to suggest that CD19 expression prior to CAR-T has an effect on outcomes, Dr. Yanik said.
“Does blinatumomab pre–CAR-T impact outcome? The answer is probably yes,” he said.
He referred to a study by investigators at the Children’s Hospital of Philadelphia showing that, “if you’re giving blinatumomab prior to CAR-T therapy, you’re potentially reducing the cell-surface expression of CD19 on your leukemic blasts, and now while you’re bringing these patients in for CAR-T therapy, you’re getting a much higher population of dim CD19 expressers, and this is associated with a higher relapse rate and lower remission rate.”
Predicting relapse
Dr. Yanik referred to a study, currently unpublished, which will show that next-generation sequencing (NGS) is more sensitive than flow cytometry for detection of minimal residual disease (MRD), and that MRD analysis of marrow was more sensitive than analysis of peripheral blood.
“Poor outcomes were seen post CAR-T for patients who were in morphologic remission on day 28 or day 100, but had positive MRD. This especially held true if it was next-gen sequencing MRD-positive at day 100, for which relapse rates were over 95%,” he said.
The absence of B-cells is a surrogate marker for the persistence of CAR-T, and conversely, the recovery of CD19-positive B cells may be a predictor for relapse, especially if the B-cell recovery occurs within the first 6 months following CAR-T infusion.
Transplant after CAR-T?
Bone marrow transplant after CAR-T is recommend for patients with high risk of relapse, including those with B-cell recovery within the first 6 months after CAR-T, patients with MRD positivity at days 28 or 100, and patients with mixed lineage leukemia.
“Should we transplant good-risk patients, meaning, if you have NGS-MRD negative patients, is there a role for transplant? You have to look at the risk versus benefit there. These patients may have a cure rate that’s in the 80%-plus range, could we potentially optimize that even more if we consolidate them with an allo[geneic] transplant,” Dr. Yank said.
Move CAR-T up front?
A Children’s Oncology Group study is currently examining whether giving CAR-T therapy to patients with MRD of 0.01% or greater following first consolidation could result in lower tumor burden, fewer relapse, and less CRS with CAR-T.
Dr. Yanik reported that he had no conflicts of interest to disclose.
Although the only pediatric indication for chimeric antigen receptor T-cell therapy currently approved by the Food and Drug Administration is B-lineage acute lymphoblastic leukemia (ALL) that is refractory to at least two frontline induction attempts or is in second or later relapse, clinical trials of CAR-T therapy for pediatric solid tumors are also currently in progress, said Gregory Yanik, MD, from the CS Mott Children’s Hospital at the University of Michigan, Ann Arbor, at the Transplant & Cellular Therapies Meetings.
In his presentation, Dr. Yanik discussed progress in solid tumor studies as well as some issues involving the current use of CAR-T therapy for ALL.
Solid tumor studies
Malignancies such as sarcomas, brain tumors, and neuroblastomas pose unique challenges, “In contrast to hematologic malignancies, the protein we’re targeting may not be present on the cell surface of all the tumor cells. There are lower-expression profiles, and this is a problem. In fact, many people have postulated that with CAR-T for pediatric solid tumors we’ll have to do repeated cycles, almost like we do with chemotherapy,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
There are currently 14 studies of CAR-T for central nervous system tumors in children, targeting either epidermal growth factor receptor (EGFR) in glioblastoma multiforme and high-grade gliomas, HER2 in a variety of CNS tumors, the GD2 antigen on pontine gliomas, and the checkpoint molecular B7H3 in medulloblastomas and pontine gliomas.
“In sarcomas in kids there are currently 12 trials in progress. Most of the targeting epitopes are targeting either HER2 or GD2. Repetitive CAR-T infusions are being used in several of these trials in sarcomas.
For neuroblastomas there are currently 13 studies in progress, nearly all of which target GD2. Some of the trials include combining CAR-T with immune checkpoint inhibitors or C7R, an engineered cytokine driver designed to prevent T-cell exhaustion.
In addition, several trials of tumor pulsed dendritic cell vaccines are underway for treatment of children with Wilms tumor, Dr. Yanik noted.
Unresolved procedural questions
It’s still early days in CAR-T therapy, and there are several still unanswered questions regarding optimal therapy for and management of patients undergoing CAR-T procedures, Dr. Yanik said.
For example, the optimal time to collect T cells during apheresis is still unclear, he said. Collecting prior to reinduction therapy raises the risk of transducing leukemic cells, while collecting after reinduction may result in inadequate quantity or quality of cells. Regardless of when cells are collected, apheresis should be performed only when the absolute lymphocyte count is above 500/mcL or the CD3 count is above 150/mcL at the time of apheresis.
In the case tisagenlecleucel (Kymriah), his center typically collects 1x109 CD3 cells regardless of age or weight.
The number of CAR T-cells infused also appears to matter, as responses are improved at CAR-T doses above 1.5x106/kg, while risk for higher-grade cytokine release syndrome (CRS) occurs at higher infusion doses.
Blinatumomab or inotuzumab?
Along with CAR-T, two other agents, the bispecific T-cell engager blinatumomab (Blincyto) and the antibody conjugate inotuzumab ozogamicin (Besponsa) are also approved for the treatment of patients with relapsed/refractory B-cell ALL.
Like CAR-T therapy, the primary toxicities associated with blinatumomab are CRS and neurologic adverse events, whereas at inotuzumab is largely associated with hematologic and hepatic toxicities.
The logistics of therapy differ widely, with a 28-day infusion required for blinatumomab, compared with weekly dosing of inotuzumab, and the multiple visits for apheresis and infusion required for CAR-T.
Blinatumomab is approved for both children and adults with relapsed/refractory ALL, but inotuzumab is approved only for adults, and CAR-T with tisagenlecleucel is approved only for children in this indication.
CD-19 expression
There is evidence to suggest that CD19 expression prior to CAR-T has an effect on outcomes, Dr. Yanik said.
“Does blinatumomab pre–CAR-T impact outcome? The answer is probably yes,” he said.
He referred to a study by investigators at the Children’s Hospital of Philadelphia showing that, “if you’re giving blinatumomab prior to CAR-T therapy, you’re potentially reducing the cell-surface expression of CD19 on your leukemic blasts, and now while you’re bringing these patients in for CAR-T therapy, you’re getting a much higher population of dim CD19 expressers, and this is associated with a higher relapse rate and lower remission rate.”
Predicting relapse
Dr. Yanik referred to a study, currently unpublished, which will show that next-generation sequencing (NGS) is more sensitive than flow cytometry for detection of minimal residual disease (MRD), and that MRD analysis of marrow was more sensitive than analysis of peripheral blood.
“Poor outcomes were seen post CAR-T for patients who were in morphologic remission on day 28 or day 100, but had positive MRD. This especially held true if it was next-gen sequencing MRD-positive at day 100, for which relapse rates were over 95%,” he said.
The absence of B-cells is a surrogate marker for the persistence of CAR-T, and conversely, the recovery of CD19-positive B cells may be a predictor for relapse, especially if the B-cell recovery occurs within the first 6 months following CAR-T infusion.
Transplant after CAR-T?
Bone marrow transplant after CAR-T is recommend for patients with high risk of relapse, including those with B-cell recovery within the first 6 months after CAR-T, patients with MRD positivity at days 28 or 100, and patients with mixed lineage leukemia.
“Should we transplant good-risk patients, meaning, if you have NGS-MRD negative patients, is there a role for transplant? You have to look at the risk versus benefit there. These patients may have a cure rate that’s in the 80%-plus range, could we potentially optimize that even more if we consolidate them with an allo[geneic] transplant,” Dr. Yank said.
Move CAR-T up front?
A Children’s Oncology Group study is currently examining whether giving CAR-T therapy to patients with MRD of 0.01% or greater following first consolidation could result in lower tumor burden, fewer relapse, and less CRS with CAR-T.
Dr. Yanik reported that he had no conflicts of interest to disclose.
Although the only pediatric indication for chimeric antigen receptor T-cell therapy currently approved by the Food and Drug Administration is B-lineage acute lymphoblastic leukemia (ALL) that is refractory to at least two frontline induction attempts or is in second or later relapse, clinical trials of CAR-T therapy for pediatric solid tumors are also currently in progress, said Gregory Yanik, MD, from the CS Mott Children’s Hospital at the University of Michigan, Ann Arbor, at the Transplant & Cellular Therapies Meetings.
In his presentation, Dr. Yanik discussed progress in solid tumor studies as well as some issues involving the current use of CAR-T therapy for ALL.
Solid tumor studies
Malignancies such as sarcomas, brain tumors, and neuroblastomas pose unique challenges, “In contrast to hematologic malignancies, the protein we’re targeting may not be present on the cell surface of all the tumor cells. There are lower-expression profiles, and this is a problem. In fact, many people have postulated that with CAR-T for pediatric solid tumors we’ll have to do repeated cycles, almost like we do with chemotherapy,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
There are currently 14 studies of CAR-T for central nervous system tumors in children, targeting either epidermal growth factor receptor (EGFR) in glioblastoma multiforme and high-grade gliomas, HER2 in a variety of CNS tumors, the GD2 antigen on pontine gliomas, and the checkpoint molecular B7H3 in medulloblastomas and pontine gliomas.
“In sarcomas in kids there are currently 12 trials in progress. Most of the targeting epitopes are targeting either HER2 or GD2. Repetitive CAR-T infusions are being used in several of these trials in sarcomas.
For neuroblastomas there are currently 13 studies in progress, nearly all of which target GD2. Some of the trials include combining CAR-T with immune checkpoint inhibitors or C7R, an engineered cytokine driver designed to prevent T-cell exhaustion.
In addition, several trials of tumor pulsed dendritic cell vaccines are underway for treatment of children with Wilms tumor, Dr. Yanik noted.
Unresolved procedural questions
It’s still early days in CAR-T therapy, and there are several still unanswered questions regarding optimal therapy for and management of patients undergoing CAR-T procedures, Dr. Yanik said.
For example, the optimal time to collect T cells during apheresis is still unclear, he said. Collecting prior to reinduction therapy raises the risk of transducing leukemic cells, while collecting after reinduction may result in inadequate quantity or quality of cells. Regardless of when cells are collected, apheresis should be performed only when the absolute lymphocyte count is above 500/mcL or the CD3 count is above 150/mcL at the time of apheresis.
In the case tisagenlecleucel (Kymriah), his center typically collects 1x109 CD3 cells regardless of age or weight.
The number of CAR T-cells infused also appears to matter, as responses are improved at CAR-T doses above 1.5x106/kg, while risk for higher-grade cytokine release syndrome (CRS) occurs at higher infusion doses.
Blinatumomab or inotuzumab?
Along with CAR-T, two other agents, the bispecific T-cell engager blinatumomab (Blincyto) and the antibody conjugate inotuzumab ozogamicin (Besponsa) are also approved for the treatment of patients with relapsed/refractory B-cell ALL.
Like CAR-T therapy, the primary toxicities associated with blinatumomab are CRS and neurologic adverse events, whereas at inotuzumab is largely associated with hematologic and hepatic toxicities.
The logistics of therapy differ widely, with a 28-day infusion required for blinatumomab, compared with weekly dosing of inotuzumab, and the multiple visits for apheresis and infusion required for CAR-T.
Blinatumomab is approved for both children and adults with relapsed/refractory ALL, but inotuzumab is approved only for adults, and CAR-T with tisagenlecleucel is approved only for children in this indication.
CD-19 expression
There is evidence to suggest that CD19 expression prior to CAR-T has an effect on outcomes, Dr. Yanik said.
“Does blinatumomab pre–CAR-T impact outcome? The answer is probably yes,” he said.
He referred to a study by investigators at the Children’s Hospital of Philadelphia showing that, “if you’re giving blinatumomab prior to CAR-T therapy, you’re potentially reducing the cell-surface expression of CD19 on your leukemic blasts, and now while you’re bringing these patients in for CAR-T therapy, you’re getting a much higher population of dim CD19 expressers, and this is associated with a higher relapse rate and lower remission rate.”
Predicting relapse
Dr. Yanik referred to a study, currently unpublished, which will show that next-generation sequencing (NGS) is more sensitive than flow cytometry for detection of minimal residual disease (MRD), and that MRD analysis of marrow was more sensitive than analysis of peripheral blood.
“Poor outcomes were seen post CAR-T for patients who were in morphologic remission on day 28 or day 100, but had positive MRD. This especially held true if it was next-gen sequencing MRD-positive at day 100, for which relapse rates were over 95%,” he said.
The absence of B-cells is a surrogate marker for the persistence of CAR-T, and conversely, the recovery of CD19-positive B cells may be a predictor for relapse, especially if the B-cell recovery occurs within the first 6 months following CAR-T infusion.
Transplant after CAR-T?
Bone marrow transplant after CAR-T is recommend for patients with high risk of relapse, including those with B-cell recovery within the first 6 months after CAR-T, patients with MRD positivity at days 28 or 100, and patients with mixed lineage leukemia.
“Should we transplant good-risk patients, meaning, if you have NGS-MRD negative patients, is there a role for transplant? You have to look at the risk versus benefit there. These patients may have a cure rate that’s in the 80%-plus range, could we potentially optimize that even more if we consolidate them with an allo[geneic] transplant,” Dr. Yank said.
Move CAR-T up front?
A Children’s Oncology Group study is currently examining whether giving CAR-T therapy to patients with MRD of 0.01% or greater following first consolidation could result in lower tumor burden, fewer relapse, and less CRS with CAR-T.
Dr. Yanik reported that he had no conflicts of interest to disclose.
FROM TCT 2021
Roundtable discussion: The Pluripotent Hospitalist
In honor of National Hospitalist Day, the Society of Hospital Medicine and the Explore the Space podcast are teaming up to bring you a roundtable discussion, featuring a diverse group of hospitalists from all stages in their careers, on Thursday, March 4, at 7 p.m. ET / 4 p.m. PT.
Registration is required. Sign up here.
Hosted by Mark Shapiro, MD, hospitalist and founder, producer, and host of Explore the Space, the roundtable will include:
- Gurpreet Dhaliwal, MD, a clinician-educator and professor of medicine at the University of California, San Francisco. He studies, writes, and speaks about how doctors think – how they make diagnoses, how they develop diagnostic expertise, and what motivates them to improve their practice and the systems in which they work.
- Anika Kumar, MD, FHM, a clinical assistant professor of pediatrics at the Cleveland Clinic Lerner College of Medicine, and a pediatric hospitalist at Cleveland Clinic Children’s. She also serves as the pediatric editor of the Hospitalist, SHM’s monthly news magazine.
- Maylyn S. Martinez, MD, a clinician-researcher and clinical associate at the University of Chicago. Her research focuses on hospital-associated disability and she recently authored a perspectives piece in the Journal of Hospital Medicine with her mentor, Vineet Arora, MD, MHM, on why the COVID-19 pandemic might exacerbate this problem.
- Ndidi Unaka, MD, MEd, an associate professor in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center. Dr. Unaka has served as the associate program director of the pediatric residency program since 2011. She is also the medical director of an inpatient unit that serves as the primary home.
For more information about SHM, please visit hospitalmedicine.org. To learn more about Explore the Space, please visit explorethespaceshow.com.
Register now.
In honor of National Hospitalist Day, the Society of Hospital Medicine and the Explore the Space podcast are teaming up to bring you a roundtable discussion, featuring a diverse group of hospitalists from all stages in their careers, on Thursday, March 4, at 7 p.m. ET / 4 p.m. PT.
Registration is required. Sign up here.
Hosted by Mark Shapiro, MD, hospitalist and founder, producer, and host of Explore the Space, the roundtable will include:
- Gurpreet Dhaliwal, MD, a clinician-educator and professor of medicine at the University of California, San Francisco. He studies, writes, and speaks about how doctors think – how they make diagnoses, how they develop diagnostic expertise, and what motivates them to improve their practice and the systems in which they work.
- Anika Kumar, MD, FHM, a clinical assistant professor of pediatrics at the Cleveland Clinic Lerner College of Medicine, and a pediatric hospitalist at Cleveland Clinic Children’s. She also serves as the pediatric editor of the Hospitalist, SHM’s monthly news magazine.
- Maylyn S. Martinez, MD, a clinician-researcher and clinical associate at the University of Chicago. Her research focuses on hospital-associated disability and she recently authored a perspectives piece in the Journal of Hospital Medicine with her mentor, Vineet Arora, MD, MHM, on why the COVID-19 pandemic might exacerbate this problem.
- Ndidi Unaka, MD, MEd, an associate professor in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center. Dr. Unaka has served as the associate program director of the pediatric residency program since 2011. She is also the medical director of an inpatient unit that serves as the primary home.
For more information about SHM, please visit hospitalmedicine.org. To learn more about Explore the Space, please visit explorethespaceshow.com.
Register now.
In honor of National Hospitalist Day, the Society of Hospital Medicine and the Explore the Space podcast are teaming up to bring you a roundtable discussion, featuring a diverse group of hospitalists from all stages in their careers, on Thursday, March 4, at 7 p.m. ET / 4 p.m. PT.
Registration is required. Sign up here.
Hosted by Mark Shapiro, MD, hospitalist and founder, producer, and host of Explore the Space, the roundtable will include:
- Gurpreet Dhaliwal, MD, a clinician-educator and professor of medicine at the University of California, San Francisco. He studies, writes, and speaks about how doctors think – how they make diagnoses, how they develop diagnostic expertise, and what motivates them to improve their practice and the systems in which they work.
- Anika Kumar, MD, FHM, a clinical assistant professor of pediatrics at the Cleveland Clinic Lerner College of Medicine, and a pediatric hospitalist at Cleveland Clinic Children’s. She also serves as the pediatric editor of the Hospitalist, SHM’s monthly news magazine.
- Maylyn S. Martinez, MD, a clinician-researcher and clinical associate at the University of Chicago. Her research focuses on hospital-associated disability and she recently authored a perspectives piece in the Journal of Hospital Medicine with her mentor, Vineet Arora, MD, MHM, on why the COVID-19 pandemic might exacerbate this problem.
- Ndidi Unaka, MD, MEd, an associate professor in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center. Dr. Unaka has served as the associate program director of the pediatric residency program since 2011. She is also the medical director of an inpatient unit that serves as the primary home.
For more information about SHM, please visit hospitalmedicine.org. To learn more about Explore the Space, please visit explorethespaceshow.com.
Register now.
Rough lesion on the thigh
A shave biopsy was performed and revealed a well-differentiated, invasive squamous cell carcinoma (SCC). Complete excision was performed with a 4-mm margin.
In the United States, SCC is the most common skin cancer in Black patients, as well as the second most common skin cancer overall. A history of UV exposure from the sun or artificial tanning beds is the most significant risk factor.1 Radiation, carcinogenic chemical exposure, longstanding inflammation caused by burns, and immunosuppression are also risk factors for SCC.
When caring for a patient with SCC, the best initial work-up is a biopsy. A punch, shave, or excisional biopsy may all be appropriate if the dermis is adequately sampled. However, with a shave or shallow punch biopsy, thick keratin debris can unintentionally lead to a superficial sampling.
Cutaneous SCC should be treated by excision with 4- to 6-mm margins or Mohs microsurgery. Tumors that are smaller than 2 cm, lack aggressive histologic features, and are located in low-risk areas (eg, trunk or extremities) may be treated with standard excision. Larger tumors, recurrent tumors, higher risk histologic subtypes, and tumors on the head, neck, genitals, hands, or feet are candidates for Mohs surgery.
This patient was counseled to practice sun protection and to schedule regular follow-up visits every 6 months for the next 2 years.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).
1. Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68:957-966. doi: 10.1016/j.jaad.2012.11.037
A shave biopsy was performed and revealed a well-differentiated, invasive squamous cell carcinoma (SCC). Complete excision was performed with a 4-mm margin.
In the United States, SCC is the most common skin cancer in Black patients, as well as the second most common skin cancer overall. A history of UV exposure from the sun or artificial tanning beds is the most significant risk factor.1 Radiation, carcinogenic chemical exposure, longstanding inflammation caused by burns, and immunosuppression are also risk factors for SCC.
When caring for a patient with SCC, the best initial work-up is a biopsy. A punch, shave, or excisional biopsy may all be appropriate if the dermis is adequately sampled. However, with a shave or shallow punch biopsy, thick keratin debris can unintentionally lead to a superficial sampling.
Cutaneous SCC should be treated by excision with 4- to 6-mm margins or Mohs microsurgery. Tumors that are smaller than 2 cm, lack aggressive histologic features, and are located in low-risk areas (eg, trunk or extremities) may be treated with standard excision. Larger tumors, recurrent tumors, higher risk histologic subtypes, and tumors on the head, neck, genitals, hands, or feet are candidates for Mohs surgery.
This patient was counseled to practice sun protection and to schedule regular follow-up visits every 6 months for the next 2 years.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).
A shave biopsy was performed and revealed a well-differentiated, invasive squamous cell carcinoma (SCC). Complete excision was performed with a 4-mm margin.
In the United States, SCC is the most common skin cancer in Black patients, as well as the second most common skin cancer overall. A history of UV exposure from the sun or artificial tanning beds is the most significant risk factor.1 Radiation, carcinogenic chemical exposure, longstanding inflammation caused by burns, and immunosuppression are also risk factors for SCC.
When caring for a patient with SCC, the best initial work-up is a biopsy. A punch, shave, or excisional biopsy may all be appropriate if the dermis is adequately sampled. However, with a shave or shallow punch biopsy, thick keratin debris can unintentionally lead to a superficial sampling.
Cutaneous SCC should be treated by excision with 4- to 6-mm margins or Mohs microsurgery. Tumors that are smaller than 2 cm, lack aggressive histologic features, and are located in low-risk areas (eg, trunk or extremities) may be treated with standard excision. Larger tumors, recurrent tumors, higher risk histologic subtypes, and tumors on the head, neck, genitals, hands, or feet are candidates for Mohs surgery.
This patient was counseled to practice sun protection and to schedule regular follow-up visits every 6 months for the next 2 years.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).
1. Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68:957-966. doi: 10.1016/j.jaad.2012.11.037
1. Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68:957-966. doi: 10.1016/j.jaad.2012.11.037
Acute care of migraine and cluster headaches: Mainstay treatments and emerging strategies
Acute migraine headache attacks
A recent review in the Journal of Neuro-Ophthalmology by Konstantinos Spingos and colleagues (including me as the senior author) details typical and new treatments for migraine. We all know about the longstanding options, including the 7 triptans and ergots, as well as over-the-counter analgesics, which can be combined with caffeine, nonsteroidal anti-inflammatory drugs; and many use the 2 categories of medication that I no longer use for migraine, butalbital-containing medications, and opioids.
Now 2 gepants are available—small molecule calcitonin gene-related peptide (CGRP) receptor antagonists. These medications are thought to be a useful alternative for those in whom triptans do not work or are relatively contraindicated due to coronary and cerebrovascular problems and other cardiac risk factors like obesity, smoking, lack of exercise, high cholesterol, and diabetes. Ubrogepant was approved by the FDA in 2019, and rimegepant soon followed in 2020.
- Ubrogepant: In the ACHIEVE trials, approximately 1 in 5 participants who received the 50 mg dose were pain-free at 2 hours. Moreover, nearly 40% of individuals who received it said their worst migraine symptom was resolved at 2 hours. Pain relief at 2 hours was 59%
- Rimegepant: Like ubrogepant, about 20% of trial participants who received the 75 mg melt tablet dose of rimegepant were pain-free at 2 hours. Thirty-seven percent reported that their worst migraine symptom was gone at 2 hours. Patients began to return to normal functioning in 15 minutes.
In addition to gepants, there is 1 ditan approved, which stimulates 5-HT1F receptors. Lasmiditan is the first medication in this class to be FDA-approved. It, too, is considered an alternative in patients in whom triptans are ineffective or when patients should not take a vasoconstrictor. In the most recent phase 3 study, the percentage of individuals who received lasmiditan and were pain-free at 2 hours were 28% (50 mg), 31% (100 mg) and 39% (200 mg). Relief from the migraine sufferers’ most bothersome symptom at 2 hours occurred in 41%, 44%, and 49% of patients, respectively. Lasmiditan is a Class V controlled substance. It has 18% dizziness in clinical trials. After administration, patients should not drive for 8 hours, and it should only be used once in a 24-hour period.
Non-pharmaceutical treatment options for acute migraine include nerve stimulation using electrical and magnetic stimulation devices, and behavioral approaches such as biofeedback training and mindfulness. The Nerivio device for the upper arm is controlled by a smart phone app and seems to work as well as a triptan in some patients with almost no adverse events. Just approved in February is the Relivion device which is worn like a tiara on the head and stimulates the frontal branches of the trigeminal nerve as well as the 2 occipital nerves in the back of the head.
Acute care of cluster headache attacks
In 2011, Ashkenazi and Schwedt published a comprehensive table in Headache outlining the treatment options for acute cluster headache. More recently, a review in CNS Drugs by Brandt and colleagues presented the choices with level 1 evidence for efficacy. They include:
- Sumatriptan, 6 mg subcutaneous injection, or 20 mg nasal spray
- Zolmitriptan, 5 or 10 mg nasal spray
- Oxygen, 100%, 7 to 12 liters per minute via a mask over the nose and mouth
The authors recommend subcutaneous sumatriptan 6 mg and/or high-flow oxygen at 9- to 12- liters per minute for 15 minutes. Subcutaneous sumatriptan, they note, has been shown to achieve pain relief within 15 minutes in 75% of patients who receive it. Moreover, one-third report pain freedom. Oxygen’s efficacy has long been established, and relief comes with no adverse events. As for mask type, though no significant differences have been observed in studies, patients appear to express a preference for the demand valve oxygen type, which allows a high flow rate and is dependent on the user’s breathing rate.
Lidocaine intranasally has been found to be effective when triptans or oxygen do not work, according to a review in The Lancet Neurology by Hoffman and May. The medication is dripped or sprayed into the ipsilateral nostril at a concentration of between 4% and 10%. Pain relief is typically achieved within 10 minutes. This review also reports efficacy with percutaneous vagus nerve stimulation with the gammaCore device and neurostimulation of the sphenopalatine ganglion, though the mechanisms of these approaches are poorly understood.
Evolving therapies for acute cluster headache include the aforementioned CGRP receptor-antagonists. Additionally, intranasal ketamine hydrochloride is under investigation in an open-label, proof-of-concept study; and a zolmitriptan patch is being evaluated in a double-blind, placebo-controlled trial.
Attacks of migraine occur in 12% of the adult population, 3 times more in women than men and are painful and debilitating. Cluster attacks are even more painful and occur in about 0.1% of the population, somewhat more in men. Both types of headache have a variety of effective treatment as detailed above.
Acute migraine headache attacks
A recent review in the Journal of Neuro-Ophthalmology by Konstantinos Spingos and colleagues (including me as the senior author) details typical and new treatments for migraine. We all know about the longstanding options, including the 7 triptans and ergots, as well as over-the-counter analgesics, which can be combined with caffeine, nonsteroidal anti-inflammatory drugs; and many use the 2 categories of medication that I no longer use for migraine, butalbital-containing medications, and opioids.
Now 2 gepants are available—small molecule calcitonin gene-related peptide (CGRP) receptor antagonists. These medications are thought to be a useful alternative for those in whom triptans do not work or are relatively contraindicated due to coronary and cerebrovascular problems and other cardiac risk factors like obesity, smoking, lack of exercise, high cholesterol, and diabetes. Ubrogepant was approved by the FDA in 2019, and rimegepant soon followed in 2020.
- Ubrogepant: In the ACHIEVE trials, approximately 1 in 5 participants who received the 50 mg dose were pain-free at 2 hours. Moreover, nearly 40% of individuals who received it said their worst migraine symptom was resolved at 2 hours. Pain relief at 2 hours was 59%
- Rimegepant: Like ubrogepant, about 20% of trial participants who received the 75 mg melt tablet dose of rimegepant were pain-free at 2 hours. Thirty-seven percent reported that their worst migraine symptom was gone at 2 hours. Patients began to return to normal functioning in 15 minutes.
In addition to gepants, there is 1 ditan approved, which stimulates 5-HT1F receptors. Lasmiditan is the first medication in this class to be FDA-approved. It, too, is considered an alternative in patients in whom triptans are ineffective or when patients should not take a vasoconstrictor. In the most recent phase 3 study, the percentage of individuals who received lasmiditan and were pain-free at 2 hours were 28% (50 mg), 31% (100 mg) and 39% (200 mg). Relief from the migraine sufferers’ most bothersome symptom at 2 hours occurred in 41%, 44%, and 49% of patients, respectively. Lasmiditan is a Class V controlled substance. It has 18% dizziness in clinical trials. After administration, patients should not drive for 8 hours, and it should only be used once in a 24-hour period.
Non-pharmaceutical treatment options for acute migraine include nerve stimulation using electrical and magnetic stimulation devices, and behavioral approaches such as biofeedback training and mindfulness. The Nerivio device for the upper arm is controlled by a smart phone app and seems to work as well as a triptan in some patients with almost no adverse events. Just approved in February is the Relivion device which is worn like a tiara on the head and stimulates the frontal branches of the trigeminal nerve as well as the 2 occipital nerves in the back of the head.
Acute care of cluster headache attacks
In 2011, Ashkenazi and Schwedt published a comprehensive table in Headache outlining the treatment options for acute cluster headache. More recently, a review in CNS Drugs by Brandt and colleagues presented the choices with level 1 evidence for efficacy. They include:
- Sumatriptan, 6 mg subcutaneous injection, or 20 mg nasal spray
- Zolmitriptan, 5 or 10 mg nasal spray
- Oxygen, 100%, 7 to 12 liters per minute via a mask over the nose and mouth
The authors recommend subcutaneous sumatriptan 6 mg and/or high-flow oxygen at 9- to 12- liters per minute for 15 minutes. Subcutaneous sumatriptan, they note, has been shown to achieve pain relief within 15 minutes in 75% of patients who receive it. Moreover, one-third report pain freedom. Oxygen’s efficacy has long been established, and relief comes with no adverse events. As for mask type, though no significant differences have been observed in studies, patients appear to express a preference for the demand valve oxygen type, which allows a high flow rate and is dependent on the user’s breathing rate.
Lidocaine intranasally has been found to be effective when triptans or oxygen do not work, according to a review in The Lancet Neurology by Hoffman and May. The medication is dripped or sprayed into the ipsilateral nostril at a concentration of between 4% and 10%. Pain relief is typically achieved within 10 minutes. This review also reports efficacy with percutaneous vagus nerve stimulation with the gammaCore device and neurostimulation of the sphenopalatine ganglion, though the mechanisms of these approaches are poorly understood.
Evolving therapies for acute cluster headache include the aforementioned CGRP receptor-antagonists. Additionally, intranasal ketamine hydrochloride is under investigation in an open-label, proof-of-concept study; and a zolmitriptan patch is being evaluated in a double-blind, placebo-controlled trial.
Attacks of migraine occur in 12% of the adult population, 3 times more in women than men and are painful and debilitating. Cluster attacks are even more painful and occur in about 0.1% of the population, somewhat more in men. Both types of headache have a variety of effective treatment as detailed above.
Acute migraine headache attacks
A recent review in the Journal of Neuro-Ophthalmology by Konstantinos Spingos and colleagues (including me as the senior author) details typical and new treatments for migraine. We all know about the longstanding options, including the 7 triptans and ergots, as well as over-the-counter analgesics, which can be combined with caffeine, nonsteroidal anti-inflammatory drugs; and many use the 2 categories of medication that I no longer use for migraine, butalbital-containing medications, and opioids.
Now 2 gepants are available—small molecule calcitonin gene-related peptide (CGRP) receptor antagonists. These medications are thought to be a useful alternative for those in whom triptans do not work or are relatively contraindicated due to coronary and cerebrovascular problems and other cardiac risk factors like obesity, smoking, lack of exercise, high cholesterol, and diabetes. Ubrogepant was approved by the FDA in 2019, and rimegepant soon followed in 2020.
- Ubrogepant: In the ACHIEVE trials, approximately 1 in 5 participants who received the 50 mg dose were pain-free at 2 hours. Moreover, nearly 40% of individuals who received it said their worst migraine symptom was resolved at 2 hours. Pain relief at 2 hours was 59%
- Rimegepant: Like ubrogepant, about 20% of trial participants who received the 75 mg melt tablet dose of rimegepant were pain-free at 2 hours. Thirty-seven percent reported that their worst migraine symptom was gone at 2 hours. Patients began to return to normal functioning in 15 minutes.
In addition to gepants, there is 1 ditan approved, which stimulates 5-HT1F receptors. Lasmiditan is the first medication in this class to be FDA-approved. It, too, is considered an alternative in patients in whom triptans are ineffective or when patients should not take a vasoconstrictor. In the most recent phase 3 study, the percentage of individuals who received lasmiditan and were pain-free at 2 hours were 28% (50 mg), 31% (100 mg) and 39% (200 mg). Relief from the migraine sufferers’ most bothersome symptom at 2 hours occurred in 41%, 44%, and 49% of patients, respectively. Lasmiditan is a Class V controlled substance. It has 18% dizziness in clinical trials. After administration, patients should not drive for 8 hours, and it should only be used once in a 24-hour period.
Non-pharmaceutical treatment options for acute migraine include nerve stimulation using electrical and magnetic stimulation devices, and behavioral approaches such as biofeedback training and mindfulness. The Nerivio device for the upper arm is controlled by a smart phone app and seems to work as well as a triptan in some patients with almost no adverse events. Just approved in February is the Relivion device which is worn like a tiara on the head and stimulates the frontal branches of the trigeminal nerve as well as the 2 occipital nerves in the back of the head.
Acute care of cluster headache attacks
In 2011, Ashkenazi and Schwedt published a comprehensive table in Headache outlining the treatment options for acute cluster headache. More recently, a review in CNS Drugs by Brandt and colleagues presented the choices with level 1 evidence for efficacy. They include:
- Sumatriptan, 6 mg subcutaneous injection, or 20 mg nasal spray
- Zolmitriptan, 5 or 10 mg nasal spray
- Oxygen, 100%, 7 to 12 liters per minute via a mask over the nose and mouth
The authors recommend subcutaneous sumatriptan 6 mg and/or high-flow oxygen at 9- to 12- liters per minute for 15 minutes. Subcutaneous sumatriptan, they note, has been shown to achieve pain relief within 15 minutes in 75% of patients who receive it. Moreover, one-third report pain freedom. Oxygen’s efficacy has long been established, and relief comes with no adverse events. As for mask type, though no significant differences have been observed in studies, patients appear to express a preference for the demand valve oxygen type, which allows a high flow rate and is dependent on the user’s breathing rate.
Lidocaine intranasally has been found to be effective when triptans or oxygen do not work, according to a review in The Lancet Neurology by Hoffman and May. The medication is dripped or sprayed into the ipsilateral nostril at a concentration of between 4% and 10%. Pain relief is typically achieved within 10 minutes. This review also reports efficacy with percutaneous vagus nerve stimulation with the gammaCore device and neurostimulation of the sphenopalatine ganglion, though the mechanisms of these approaches are poorly understood.
Evolving therapies for acute cluster headache include the aforementioned CGRP receptor-antagonists. Additionally, intranasal ketamine hydrochloride is under investigation in an open-label, proof-of-concept study; and a zolmitriptan patch is being evaluated in a double-blind, placebo-controlled trial.
Attacks of migraine occur in 12% of the adult population, 3 times more in women than men and are painful and debilitating. Cluster attacks are even more painful and occur in about 0.1% of the population, somewhat more in men. Both types of headache have a variety of effective treatment as detailed above.
The psychiatrist’s role in navigating a toxic news cycle
This transcript has been edited for clarity.
I’m Dr. Gregory Scott Brown, an Austin (Tex.)-based psychiatrist and an affiliate faculty member at the University of Texas Dell Medical School.
Recently, a patient of mine told me that, because of the political environment we find ourselves in, he’s avoiding conversations with some of his longtime friends. Because of this, he’s feeling even more isolated than before.
We’re all coming off the heels of a tough year, and many of us expected that when we entered 2021 we’d quickly turn the page and life would get a whole lot easier. Since the reality is that we’re still dealing with deep divisions, social injustices, and the politicization of evidence-based medicine, emotions are naturally running high.
In listening to my patients over the past few weeks, there’s definitely a sense of optimism about coronavirus vaccines and getting back to life as usual. But there’s also a lingering sense of uncertainty and fear, especially when it comes to the possibility of saying the wrong thing, offending our friends, or just having conversations with people we may disagree with. I’m hearing concerns from my patients that 2020 exposed a dormant hatred that was brewing in the underbelly of our society, in our politics, and in our institutions. Patients are telling me that these concerns are making them anxious and some are avoiding interacting with people they may disagree with altogether because they’re afraid of the difficult conversations that may follow.
Since, like many of my patients as well as many of you, I follow the news, including stories of COVID-related deaths, economic hardships, peaceful protests gone bad, and political vitriol, I’ve had to remind myself about the importance of intentional kindness for effective communication and for supporting mental health.
I was reminded of the paper “Hate in the Counter-Transference” by the well-known pediatrician and psychoanalyst Donald Winnicott. He focuses on how to manage and sort through the strong emotions that may be experienced even during an encounter between a therapist and a patient. Although some of what he has to say doesn’t translate well to modern times, his recommendation that we acknowledge and try to normalize some of our feelings does. And this is how I’ve been starting a conversation with my patients – just by normalizing things a bit.
The past year or so has brought with it a range of intense emotions, including frustration, exhaustion, and some degree of sadness for most of us. When we’re self-aware about our feelings, we can make sense of them early on so that they don’t evolve into maladaptive ones like unhinged anger or hatred. My patients and I actively discuss how our feelings don’t have to get in the way of our ability to live and to interact with each other as we’d like to.
Considering the basic tenets of kindness is a good place to start. I recently spoke with Kelli Harding, MD, a psychiatrist and author of The Rabbit Effect: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. She pointed to research suggesting that kindness can benefit multiple areas of our health, from reducing cardiovascular events to improving mood and anxiety. In her book, she notes that
I tell my patients that we can’t always change our environment, but we can definitely change how we respond to it. This doesn’t mean it’s always an easy process, but there are things we can do. First, we have to acknowledge that some degree of conflict or cordial disagreement is inevitable and it doesn’t have to disrupt our mood.
An interesting study on conflict management pointed out that healthy conflict is actually beneficial in some cases. For instance, in the work environment, conflict can help with team development and better group decision-making. But it’s rigid personality differences, poor communication, emotional stress, and lack of candor that may contribute to so-called high-tension events, and this is where conflict can go awry. These are the areas that we can all focus on improving, not only for performance benefits but for our overall health and well-being as well.
The authors also recommend an active style of engagement as a technique to manage conflict, but in a way that feels both natural and safe. Other authors agree that so-called engaged coping is associated with a higher sense of control and overall improved psychological well-being. What this means is that avoidance may be necessary in the short term, but over time it may lead to more emotional stress and anxiety.
Overcoming the tendency to avoid requires both motivation and self-awareness. We need to know about patterns in our own behavior and how the behavior of others can push our buttons and spiral a healthy disagreement into a heated argument.
I like to recommend the hunger, angry, lonely, tired (HALT) model, which is often used as a self-care gauge in addiction treatment and to reduce medication errors. But I think it’s also a useful way to assess personal readiness for having a difficult conversation. I tell my patients to ask themselves in this moment: “Am I hungry, angry, lonely, or tired?” And if they are, perhaps it’s not the best time for the conversation.
Because 2020 brought with it a new set of challenges, it also forced many of us to focus on things that we just didn’t pay as much attention to before, including checking in on our feelings and the feelings of those around us. It also taught us to pay attention to the way and manner in which we communicate. I think that kindness is much easier to carry into difficult conversations if we approach them with a sense of curiosity before judgment. Ultimately, kindness is one of the best tools for balancing the intense emotions that many of us are feeling right now.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Dr. Gregory Scott Brown, an Austin (Tex.)-based psychiatrist and an affiliate faculty member at the University of Texas Dell Medical School.
Recently, a patient of mine told me that, because of the political environment we find ourselves in, he’s avoiding conversations with some of his longtime friends. Because of this, he’s feeling even more isolated than before.
We’re all coming off the heels of a tough year, and many of us expected that when we entered 2021 we’d quickly turn the page and life would get a whole lot easier. Since the reality is that we’re still dealing with deep divisions, social injustices, and the politicization of evidence-based medicine, emotions are naturally running high.
In listening to my patients over the past few weeks, there’s definitely a sense of optimism about coronavirus vaccines and getting back to life as usual. But there’s also a lingering sense of uncertainty and fear, especially when it comes to the possibility of saying the wrong thing, offending our friends, or just having conversations with people we may disagree with. I’m hearing concerns from my patients that 2020 exposed a dormant hatred that was brewing in the underbelly of our society, in our politics, and in our institutions. Patients are telling me that these concerns are making them anxious and some are avoiding interacting with people they may disagree with altogether because they’re afraid of the difficult conversations that may follow.
Since, like many of my patients as well as many of you, I follow the news, including stories of COVID-related deaths, economic hardships, peaceful protests gone bad, and political vitriol, I’ve had to remind myself about the importance of intentional kindness for effective communication and for supporting mental health.
I was reminded of the paper “Hate in the Counter-Transference” by the well-known pediatrician and psychoanalyst Donald Winnicott. He focuses on how to manage and sort through the strong emotions that may be experienced even during an encounter between a therapist and a patient. Although some of what he has to say doesn’t translate well to modern times, his recommendation that we acknowledge and try to normalize some of our feelings does. And this is how I’ve been starting a conversation with my patients – just by normalizing things a bit.
The past year or so has brought with it a range of intense emotions, including frustration, exhaustion, and some degree of sadness for most of us. When we’re self-aware about our feelings, we can make sense of them early on so that they don’t evolve into maladaptive ones like unhinged anger or hatred. My patients and I actively discuss how our feelings don’t have to get in the way of our ability to live and to interact with each other as we’d like to.
Considering the basic tenets of kindness is a good place to start. I recently spoke with Kelli Harding, MD, a psychiatrist and author of The Rabbit Effect: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. She pointed to research suggesting that kindness can benefit multiple areas of our health, from reducing cardiovascular events to improving mood and anxiety. In her book, she notes that
I tell my patients that we can’t always change our environment, but we can definitely change how we respond to it. This doesn’t mean it’s always an easy process, but there are things we can do. First, we have to acknowledge that some degree of conflict or cordial disagreement is inevitable and it doesn’t have to disrupt our mood.
An interesting study on conflict management pointed out that healthy conflict is actually beneficial in some cases. For instance, in the work environment, conflict can help with team development and better group decision-making. But it’s rigid personality differences, poor communication, emotional stress, and lack of candor that may contribute to so-called high-tension events, and this is where conflict can go awry. These are the areas that we can all focus on improving, not only for performance benefits but for our overall health and well-being as well.
The authors also recommend an active style of engagement as a technique to manage conflict, but in a way that feels both natural and safe. Other authors agree that so-called engaged coping is associated with a higher sense of control and overall improved psychological well-being. What this means is that avoidance may be necessary in the short term, but over time it may lead to more emotional stress and anxiety.
Overcoming the tendency to avoid requires both motivation and self-awareness. We need to know about patterns in our own behavior and how the behavior of others can push our buttons and spiral a healthy disagreement into a heated argument.
I like to recommend the hunger, angry, lonely, tired (HALT) model, which is often used as a self-care gauge in addiction treatment and to reduce medication errors. But I think it’s also a useful way to assess personal readiness for having a difficult conversation. I tell my patients to ask themselves in this moment: “Am I hungry, angry, lonely, or tired?” And if they are, perhaps it’s not the best time for the conversation.
Because 2020 brought with it a new set of challenges, it also forced many of us to focus on things that we just didn’t pay as much attention to before, including checking in on our feelings and the feelings of those around us. It also taught us to pay attention to the way and manner in which we communicate. I think that kindness is much easier to carry into difficult conversations if we approach them with a sense of curiosity before judgment. Ultimately, kindness is one of the best tools for balancing the intense emotions that many of us are feeling right now.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Dr. Gregory Scott Brown, an Austin (Tex.)-based psychiatrist and an affiliate faculty member at the University of Texas Dell Medical School.
Recently, a patient of mine told me that, because of the political environment we find ourselves in, he’s avoiding conversations with some of his longtime friends. Because of this, he’s feeling even more isolated than before.
We’re all coming off the heels of a tough year, and many of us expected that when we entered 2021 we’d quickly turn the page and life would get a whole lot easier. Since the reality is that we’re still dealing with deep divisions, social injustices, and the politicization of evidence-based medicine, emotions are naturally running high.
In listening to my patients over the past few weeks, there’s definitely a sense of optimism about coronavirus vaccines and getting back to life as usual. But there’s also a lingering sense of uncertainty and fear, especially when it comes to the possibility of saying the wrong thing, offending our friends, or just having conversations with people we may disagree with. I’m hearing concerns from my patients that 2020 exposed a dormant hatred that was brewing in the underbelly of our society, in our politics, and in our institutions. Patients are telling me that these concerns are making them anxious and some are avoiding interacting with people they may disagree with altogether because they’re afraid of the difficult conversations that may follow.
Since, like many of my patients as well as many of you, I follow the news, including stories of COVID-related deaths, economic hardships, peaceful protests gone bad, and political vitriol, I’ve had to remind myself about the importance of intentional kindness for effective communication and for supporting mental health.
I was reminded of the paper “Hate in the Counter-Transference” by the well-known pediatrician and psychoanalyst Donald Winnicott. He focuses on how to manage and sort through the strong emotions that may be experienced even during an encounter between a therapist and a patient. Although some of what he has to say doesn’t translate well to modern times, his recommendation that we acknowledge and try to normalize some of our feelings does. And this is how I’ve been starting a conversation with my patients – just by normalizing things a bit.
The past year or so has brought with it a range of intense emotions, including frustration, exhaustion, and some degree of sadness for most of us. When we’re self-aware about our feelings, we can make sense of them early on so that they don’t evolve into maladaptive ones like unhinged anger or hatred. My patients and I actively discuss how our feelings don’t have to get in the way of our ability to live and to interact with each other as we’d like to.
Considering the basic tenets of kindness is a good place to start. I recently spoke with Kelli Harding, MD, a psychiatrist and author of The Rabbit Effect: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. She pointed to research suggesting that kindness can benefit multiple areas of our health, from reducing cardiovascular events to improving mood and anxiety. In her book, she notes that
I tell my patients that we can’t always change our environment, but we can definitely change how we respond to it. This doesn’t mean it’s always an easy process, but there are things we can do. First, we have to acknowledge that some degree of conflict or cordial disagreement is inevitable and it doesn’t have to disrupt our mood.
An interesting study on conflict management pointed out that healthy conflict is actually beneficial in some cases. For instance, in the work environment, conflict can help with team development and better group decision-making. But it’s rigid personality differences, poor communication, emotional stress, and lack of candor that may contribute to so-called high-tension events, and this is where conflict can go awry. These are the areas that we can all focus on improving, not only for performance benefits but for our overall health and well-being as well.
The authors also recommend an active style of engagement as a technique to manage conflict, but in a way that feels both natural and safe. Other authors agree that so-called engaged coping is associated with a higher sense of control and overall improved psychological well-being. What this means is that avoidance may be necessary in the short term, but over time it may lead to more emotional stress and anxiety.
Overcoming the tendency to avoid requires both motivation and self-awareness. We need to know about patterns in our own behavior and how the behavior of others can push our buttons and spiral a healthy disagreement into a heated argument.
I like to recommend the hunger, angry, lonely, tired (HALT) model, which is often used as a self-care gauge in addiction treatment and to reduce medication errors. But I think it’s also a useful way to assess personal readiness for having a difficult conversation. I tell my patients to ask themselves in this moment: “Am I hungry, angry, lonely, or tired?” And if they are, perhaps it’s not the best time for the conversation.
Because 2020 brought with it a new set of challenges, it also forced many of us to focus on things that we just didn’t pay as much attention to before, including checking in on our feelings and the feelings of those around us. It also taught us to pay attention to the way and manner in which we communicate. I think that kindness is much easier to carry into difficult conversations if we approach them with a sense of curiosity before judgment. Ultimately, kindness is one of the best tools for balancing the intense emotions that many of us are feeling right now.
A version of this article first appeared on Medscape.com.
No vascular benefit of testosterone over exercise in aging men
Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.
“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”
To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.
The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.
High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.
Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.
As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.
Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.
In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).
There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.
Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.
“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”
Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.
“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”
Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”
The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.
William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.
“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”
The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.
“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”
To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.
The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.
High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.
Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.
As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.
Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.
In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).
There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.
Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.
“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”
Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.
“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”
Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”
The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.
William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.
“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”
The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.
“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”
To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.
The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.
High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.
Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.
As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.
Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.
In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).
There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.
Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.
“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”
Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.
“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”
Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”
The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.
William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.
“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”
The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.