The mission of OBG Management is to enhance the quality of reproductive health care and the professional development of obstetrician-gynecologists and all reproductive health care clinicians. As we celebrate the beginning of our 35th anniversary year, we recommit to our mission, providing the highest quality reproductive health information in both print and electronic portals. Guiding all our actions is our deep commitment to being worthy of the trust of our readers.

OBG Management is one of the most widely-read publications dedicated to obstetrician-gynecologists. We recognize that it is difficult for clinicians to keep up with the vast and growing corpus of information that is relevant to clinical practice. A priority goal of OBG Management is to ensure our readers are aware of practice-changing information. The OBG Management Board of Editors guide all aspects of the editorial work at OBG Management, alerting us to upcoming practice-changing discoveries, including new research findings, new medications, and important guidelines. As we begin our 35th anniversary year, we would like to highlight our distinguished Board of Editors. Of note, this year, Dr. Cheryl B. Iglesia was named as Deputy Editor, with an expanded responsibility to curate the gynecology content for OBG Management.

We wish all our readers a wonderful New Year and the best health possible for our patients.

Arnold P. Advincula, MD

I serve on the executive board that oversees the Fellowships in Minimally Invasive Gynecologic Surgery (FMIGS), and in January 2023 will transition into the role of President. I bring to this leadership role nearly 25 years of surgical experience, both as a clinician educator and inventor. My goal during the next 2 years will be to move toward subspecialty recognition of Complex Gynecology. 

Linda D. Bradley, MD

My passion is diagnostic and operative hysteroscopy, simple procedures that can both evaluate and treat intrauterine pathology. Recently, I was thrilled to coauthor an article on office hysteroscopy for Obstetrics & Gynecology (September 2022). I will have a chapter on operative hysteroscopy in the 2023 edition of TeLinde’s Textbook of Gynecology, and I am an author for the topic Office and Operative Hysteroscopy in UpToDate. Locally, I am known as the “foodie gynecologist”—I travel, take cooking classes, and I have more cookbooks than gynecology textbooks. Since Covid, I have embraced biking and just completed a riverboat biking cruise from Salamanca, Spain, to Lisbon, Portugal.

Amy L. Garcia, MD

I am fellowship trained as a minimally invasive gynecologic surgeon (MIGS) and have had a private surgical practice since 2005. I am involved with The American College of Obstetricians and Gynecologists (ACOG), AAGL, and international surgical education for office hysteroscopy and related practice management. I am passionate about working with start-up companies in the gynecologic medical device arena and innovation in gynecologic surgery.

Steven R. Goldstein, MD, NCMP, CCD

I just completed my term as President of the International Menopause Society. This culminated in the society’s 18th World Congress in Lisbon, attended by over 1,700 health care providers from 76 countries. I delivered the Pieter van Keep Memorial Lecture, named for one of the society’s founders who died prematurely of pancreatic cancer. I was further honored by receiving the society’s Distinguished Service Award. I am very proud to have previously received the NAMS Thomas B. Clarkson award for Outstanding Clinical and Basic Science Research in Menopause. I also have one foot in the gynecologic ultrasound world and was given the Joseph H. Holmes Pioneer Award and was the 2023 recipient of the William J. Fry Memorial Lecture Award, both from the American Institute of Ultrasound in Medicine, having written the second book ever on vaginal ultrasonography.

On a personal level, I love to play golf (in spite of my foot drop and 14 orthopedic surgeries). My season tickets show some diversity—the New York City Ballet and St. John’s basketball.

Cheryl B. Iglesia, MD

I am the 49th president of the Society of Gynecologic Surgeons, the 5th woman to hold this position, and the first of Filipino-American descent. I recognize that it is only through extraordinary mentorship and support from other giants in gynecology, like Drs. Andrew Kaunitz (fellow OBG Management Board member), Linda Brubaker, and Dee Fenner and the love, support, and encouragement of my parents, husband, and daughters that I have been able to reach this milestone. A feather in my cap is the recent appointment to Deputy Editor of Gynecology for this journal, under the tutelage of Dr. Robert Barbieri. Over the past 31 years, I have had the privilege of learning from the best experts and gynecologic surgeons and the honor of working with skilled partners as we pass on our collective knowledge to our fellows, residents, and medical students. The passion in this next generation of ObGyns is so invigorating!

PS—In the spirit of continually learning, I want to add the Argentine tango to my dancing repertoire and go on an African safari; both are on my bucket list as the pandemic eases.

Andrew M. Kaunitz, MD, NCMP

Since starting with the University of Florida College of Medicine-Jacksonville in 1984, I have enjoyed caring for patients, training residents and medical students, and being involved with publications and research. My areas of focus are menopause, contraception, gyn ultrasound and evaluation/management of women with abnormal uterine bleeding. In 2020, I received the North American Menopause Society/Leon Speroff Outstanding Educator Award. In 2021, I received the ACOG Distinguished Service Award. I enjoy spending time with my family, neighborhood bicycling, and searching for sharks’ teeth at the beach. 

Barbara Levy, MD

I have been privileged to serve on the OBG Management Editorial Board for several decades. I am passionate about delivering the best possible care for the patients we serve, and helping women’s health care professionals provide that care. Through positions at AAGL, ACOG, and the American Medical Association, I have worked hard to champion best practices and to support fair, equitable, and accessible care for our patients and reimbursement for our services. My true north is to base patient care on reliable, valid, and properly interpreted data.

Continue to: David G. Mutch, MD...

David G. Mutch, MD

I am ending my 6-year term as Chair of the National Cancer Institute’s (NCI) gynecologic cancer steering committee. That is the committee that vets all NCI-sponsored clinical trials in gynecologic oncology. I am on the International Federation of Gynecology and Obstetrics (FIGO) Cancer committee, Co-Chair of the American Joint Committee on Cancer gyn staging committee and on the Reproductive Scientist Development Program selection committee. I also am completing my term as Chair of the Foundation for Women’s Cancer; this is the C3, charitable arm, of the Society of Gynecologic Oncology. We have distributed more than $3.5 million to young investigators to help start their research careers in gynecologic oncology.

Errol R. Norwitz, MD, PhD, MBA

I am a physician-scientist with subspecialty training in high-risk obstetrics (maternal-fetal medicine). I was born and raised in Cape Town, South Africa, and I have trained/practiced in 5 countries on 3 continents. My research interests include the pathophysiology, prediction, prevention, and management of pregnancy complications, primarily preterm birth and preeclampsia. I am a member of the Board of Scientific Counselors of the National Institute of Child Health and Human Development. I am currently President & CEO of Newton-Wellesley Hospital, a comprehensive community-based academic medical center and a member of the Mass General Brigham health care system in Boston, Massachusetts.

Jaimey Pauli, MD

I am the Division Chief and Professor of Maternal-Fetal Medicine (MFM) at the Penn State College of Medicine and Penn State Health Milton S. Hershey Medical Center. I had exceptional mentoring throughout my medical career, particularly by a former member of the Editorial Board, Dr. John T. Repke. One of the biggest perks of my job is that our division provides full-scope MFM care. While I often serve as the more traditional MFM consultant and academic educator, I also provide longitudinal prenatal care and deliver many of my own patients, often through subsequent pregnancies. Serving as a member of the Editorial Board combines my passion for clinical obstetrical care with my talents (as a former English major) of reading, writing, and editing. I believe that the work we do provides accessible, evidence-based, and practical guidance for our colleagues so they can provide excellence in obstetrical care.

JoAnn Pinkerton, MD, NCMP

I am a Professor of Obstetrics and Gynecology and Division Chief of Midlife Health at the University of Virginia (UVA) Health. Passionate about menopause, I am an executive director emeritus of The North American Menopause Society (NAMS) and past-President of NAMS (2008-2009). Within the past few years, I have served as an expert advisor for the recent ACOG Clinical Practice Guidelines on Osteoporosis, the NAMS Position Statements on Hormone Therapy and Osteoporosis, and the Global Consensus on Menopause and Androgen Therapy. I received the 2022 South Atlantic Association of Obstetricians and Gynecologists Lifetime Achievement Award for my expertise and work in menopause and the NAMS 2020 Ann Voda Community Service Award for my biannual community educational symposiums. I remain active in research, currently the lead and UVA principal investigator for the Oasis 2 multicenter clinical trial, which is testing a neurokinin receptor antagonist as a nonhormone therapy for the relief of hot flashes. Serving on the OBG Management Editorial Board is an honor that allows me to use my expertise in menopause management and hormone therapy to provide practical, evidence-based guidance for clinicians.

Joseph S. Sanfilippo, MD, MBA

I feel honored and privileged to have received the Golden Apple Teaching Award from the Universityof Pittsburgh School of Medicine. I am also fortunate to be the recipient of the Faculty Educator of the Month Award for resident teaching. I have been named Top Doctor 20 years in a row. My current academic activities include, since 2007, Program Director for Reproductive Endocrinology & Infertility Fellowship at the University of Pittsburgh and Chair of the Mentor-Mentee Program at University of Pittsburgh Department of Obstetrics, Gynecology & Reproductive Sciences. I am Guest Editor for the medical malpractice section of the journal Clinical Obstetrics and Gynecology. Recently, I completed a patient-focused book, “Experts Guide to Fertility,” which will be published in May 2023 by J Hopkins University Publisher and is designed for patients going through infertility treatment. Regarding outside events, I enjoy climbing steep hills and riding far and wide on my “electric bike.” Highly recommend it!

James Simon, MD, CCD, IF, NCMP

It’s been an honor serving on the OBG Management Board for many years, as a board-certified obstetrician/gynecologist/reproductive endocrinologist, certified menopause practitioner, and sexuality counsellor. Nicknamed “The Menopause Whisperer” by Washingtonian Magazine, my solo, private practice, IntimMedicine Specialists®, one of the few such practices remaining in Washington, DC, is about 6 blocks from the White House. By virtue of my practice’s location, I care for women at the highest levels of government seeking personalized gynecological, menopause, and sexual medicine care. Some high-powered patients believe they have all the answers even before I open my mouth, so I just fall back on my experience as both the President of NAMS, and The International Society for the Study of Women’s Sexual Health, or principal investigator on more than 400 clinical research trials, or Chief Medical Officer of a pharmaceutical company, or author of more than 800 publications. I love what I do every day and cannot imagine slowing down or stopping. ●

The mission of OBG Management is to enhance the quality of reproductive health care and the professional development of obstetrician-gynecologists and all reproductive health care clinicians. As we celebrate the beginning of our 35th anniversary year, we recommit to our mission, providing the highest quality reproductive health information in both print and electronic portals. Guiding all our actions is our deep commitment to being worthy of the trust of our readers.

OBG Management is one of the most widely-read publications dedicated to obstetrician-gynecologists. We recognize that it is difficult for clinicians to keep up with the vast and growing corpus of information that is relevant to clinical practice. A priority goal of OBG Management is to ensure our readers are aware of practice-changing information. The OBG Management Board of Editors guide all aspects of the editorial work at OBG Management, alerting us to upcoming practice-changing discoveries, including new research findings, new medications, and important guidelines. As we begin our 35th anniversary year, we would like to highlight our distinguished Board of Editors. Of note, this year, Dr. Cheryl B. Iglesia was named as Deputy Editor, with an expanded responsibility to curate the gynecology content for OBG Management.

We wish all our readers a wonderful New Year and the best health possible for our patients.

Arnold P. Advincula, MD

I serve on the executive board that oversees the Fellowships in Minimally Invasive Gynecologic Surgery (FMIGS), and in January 2023 will transition into the role of President. I bring to this leadership role nearly 25 years of surgical experience, both as a clinician educator and inventor. My goal during the next 2 years will be to move toward subspecialty recognition of Complex Gynecology. 

Linda D. Bradley, MD

My passion is diagnostic and operative hysteroscopy, simple procedures that can both evaluate and treat intrauterine pathology. Recently, I was thrilled to coauthor an article on office hysteroscopy for Obstetrics & Gynecology (September 2022). I will have a chapter on operative hysteroscopy in the 2023 edition of TeLinde’s Textbook of Gynecology, and I am an author for the topic Office and Operative Hysteroscopy in UpToDate. Locally, I am known as the “foodie gynecologist”—I travel, take cooking classes, and I have more cookbooks than gynecology textbooks. Since Covid, I have embraced biking and just completed a riverboat biking cruise from Salamanca, Spain, to Lisbon, Portugal.

Amy L. Garcia, MD

I am fellowship trained as a minimally invasive gynecologic surgeon (MIGS) and have had a private surgical practice since 2005. I am involved with The American College of Obstetricians and Gynecologists (ACOG), AAGL, and international surgical education for office hysteroscopy and related practice management. I am passionate about working with start-up companies in the gynecologic medical device arena and innovation in gynecologic surgery.

Steven R. Goldstein, MD, NCMP, CCD

I just completed my term as President of the International Menopause Society. This culminated in the society’s 18th World Congress in Lisbon, attended by over 1,700 health care providers from 76 countries. I delivered the Pieter van Keep Memorial Lecture, named for one of the society’s founders who died prematurely of pancreatic cancer. I was further honored by receiving the society’s Distinguished Service Award. I am very proud to have previously received the NAMS Thomas B. Clarkson award for Outstanding Clinical and Basic Science Research in Menopause. I also have one foot in the gynecologic ultrasound world and was given the Joseph H. Holmes Pioneer Award and was the 2023 recipient of the William J. Fry Memorial Lecture Award, both from the American Institute of Ultrasound in Medicine, having written the second book ever on vaginal ultrasonography.

On a personal level, I love to play golf (in spite of my foot drop and 14 orthopedic surgeries). My season tickets show some diversity—the New York City Ballet and St. John’s basketball.

Cheryl B. Iglesia, MD

I am the 49th president of the Society of Gynecologic Surgeons, the 5th woman to hold this position, and the first of Filipino-American descent. I recognize that it is only through extraordinary mentorship and support from other giants in gynecology, like Drs. Andrew Kaunitz (fellow OBG Management Board member), Linda Brubaker, and Dee Fenner and the love, support, and encouragement of my parents, husband, and daughters that I have been able to reach this milestone. A feather in my cap is the recent appointment to Deputy Editor of Gynecology for this journal, under the tutelage of Dr. Robert Barbieri. Over the past 31 years, I have had the privilege of learning from the best experts and gynecologic surgeons and the honor of working with skilled partners as we pass on our collective knowledge to our fellows, residents, and medical students. The passion in this next generation of ObGyns is so invigorating!

PS—In the spirit of continually learning, I want to add the Argentine tango to my dancing repertoire and go on an African safari; both are on my bucket list as the pandemic eases.

Andrew M. Kaunitz, MD, NCMP

Since starting with the University of Florida College of Medicine-Jacksonville in 1984, I have enjoyed caring for patients, training residents and medical students, and being involved with publications and research. My areas of focus are menopause, contraception, gyn ultrasound and evaluation/management of women with abnormal uterine bleeding. In 2020, I received the North American Menopause Society/Leon Speroff Outstanding Educator Award. In 2021, I received the ACOG Distinguished Service Award. I enjoy spending time with my family, neighborhood bicycling, and searching for sharks’ teeth at the beach. 

Barbara Levy, MD

I have been privileged to serve on the OBG Management Editorial Board for several decades. I am passionate about delivering the best possible care for the patients we serve, and helping women’s health care professionals provide that care. Through positions at AAGL, ACOG, and the American Medical Association, I have worked hard to champion best practices and to support fair, equitable, and accessible care for our patients and reimbursement for our services. My true north is to base patient care on reliable, valid, and properly interpreted data.

Continue to: David G. Mutch, MD...

David G. Mutch, MD

I am ending my 6-year term as Chair of the National Cancer Institute’s (NCI) gynecologic cancer steering committee. That is the committee that vets all NCI-sponsored clinical trials in gynecologic oncology. I am on the International Federation of Gynecology and Obstetrics (FIGO) Cancer committee, Co-Chair of the American Joint Committee on Cancer gyn staging committee and on the Reproductive Scientist Development Program selection committee. I also am completing my term as Chair of the Foundation for Women’s Cancer; this is the C3, charitable arm, of the Society of Gynecologic Oncology. We have distributed more than $3.5 million to young investigators to help start their research careers in gynecologic oncology.

Errol R. Norwitz, MD, PhD, MBA

I am a physician-scientist with subspecialty training in high-risk obstetrics (maternal-fetal medicine). I was born and raised in Cape Town, South Africa, and I have trained/practiced in 5 countries on 3 continents. My research interests include the pathophysiology, prediction, prevention, and management of pregnancy complications, primarily preterm birth and preeclampsia. I am a member of the Board of Scientific Counselors of the National Institute of Child Health and Human Development. I am currently President & CEO of Newton-Wellesley Hospital, a comprehensive community-based academic medical center and a member of the Mass General Brigham health care system in Boston, Massachusetts.

Jaimey Pauli, MD

I am the Division Chief and Professor of Maternal-Fetal Medicine (MFM) at the Penn State College of Medicine and Penn State Health Milton S. Hershey Medical Center. I had exceptional mentoring throughout my medical career, particularly by a former member of the Editorial Board, Dr. John T. Repke. One of the biggest perks of my job is that our division provides full-scope MFM care. While I often serve as the more traditional MFM consultant and academic educator, I also provide longitudinal prenatal care and deliver many of my own patients, often through subsequent pregnancies. Serving as a member of the Editorial Board combines my passion for clinical obstetrical care with my talents (as a former English major) of reading, writing, and editing. I believe that the work we do provides accessible, evidence-based, and practical guidance for our colleagues so they can provide excellence in obstetrical care.

JoAnn Pinkerton, MD, NCMP

I am a Professor of Obstetrics and Gynecology and Division Chief of Midlife Health at the University of Virginia (UVA) Health. Passionate about menopause, I am an executive director emeritus of The North American Menopause Society (NAMS) and past-President of NAMS (2008-2009). Within the past few years, I have served as an expert advisor for the recent ACOG Clinical Practice Guidelines on Osteoporosis, the NAMS Position Statements on Hormone Therapy and Osteoporosis, and the Global Consensus on Menopause and Androgen Therapy. I received the 2022 South Atlantic Association of Obstetricians and Gynecologists Lifetime Achievement Award for my expertise and work in menopause and the NAMS 2020 Ann Voda Community Service Award for my biannual community educational symposiums. I remain active in research, currently the lead and UVA principal investigator for the Oasis 2 multicenter clinical trial, which is testing a neurokinin receptor antagonist as a nonhormone therapy for the relief of hot flashes. Serving on the OBG Management Editorial Board is an honor that allows me to use my expertise in menopause management and hormone therapy to provide practical, evidence-based guidance for clinicians.

Joseph S. Sanfilippo, MD, MBA

I feel honored and privileged to have received the Golden Apple Teaching Award from the Universityof Pittsburgh School of Medicine. I am also fortunate to be the recipient of the Faculty Educator of the Month Award for resident teaching. I have been named Top Doctor 20 years in a row. My current academic activities include, since 2007, Program Director for Reproductive Endocrinology & Infertility Fellowship at the University of Pittsburgh and Chair of the Mentor-Mentee Program at University of Pittsburgh Department of Obstetrics, Gynecology & Reproductive Sciences. I am Guest Editor for the medical malpractice section of the journal Clinical Obstetrics and Gynecology. Recently, I completed a patient-focused book, “Experts Guide to Fertility,” which will be published in May 2023 by J Hopkins University Publisher and is designed for patients going through infertility treatment. Regarding outside events, I enjoy climbing steep hills and riding far and wide on my “electric bike.” Highly recommend it!

James Simon, MD, CCD, IF, NCMP

It’s been an honor serving on the OBG Management Board for many years, as a board-certified obstetrician/gynecologist/reproductive endocrinologist, certified menopause practitioner, and sexuality counsellor. Nicknamed “The Menopause Whisperer” by Washingtonian Magazine, my solo, private practice, IntimMedicine Specialists®, one of the few such practices remaining in Washington, DC, is about 6 blocks from the White House. By virtue of my practice’s location, I care for women at the highest levels of government seeking personalized gynecological, menopause, and sexual medicine care. Some high-powered patients believe they have all the answers even before I open my mouth, so I just fall back on my experience as both the President of NAMS, and The International Society for the Study of Women’s Sexual Health, or principal investigator on more than 400 clinical research trials, or Chief Medical Officer of a pharmaceutical company, or author of more than 800 publications. I love what I do every day and cannot imagine slowing down or stopping. ●

The mission of OBG Management is to enhance the quality of reproductive health care and the professional development of obstetrician-gynecologists and all reproductive health care clinicians. As we celebrate the beginning of our 35th anniversary year, we recommit to our mission, providing the highest quality reproductive health information in both print and electronic portals. Guiding all our actions is our deep commitment to being worthy of the trust of our readers.

OBG Management is one of the most widely-read publications dedicated to obstetrician-gynecologists. We recognize that it is difficult for clinicians to keep up with the vast and growing corpus of information that is relevant to clinical practice. A priority goal of OBG Management is to ensure our readers are aware of practice-changing information. The OBG Management Board of Editors guide all aspects of the editorial work at OBG Management, alerting us to upcoming practice-changing discoveries, including new research findings, new medications, and important guidelines. As we begin our 35th anniversary year, we would like to highlight our distinguished Board of Editors. Of note, this year, Dr. Cheryl B. Iglesia was named as Deputy Editor, with an expanded responsibility to curate the gynecology content for OBG Management.

We wish all our readers a wonderful New Year and the best health possible for our patients.

Arnold P. Advincula, MD

I serve on the executive board that oversees the Fellowships in Minimally Invasive Gynecologic Surgery (FMIGS), and in January 2023 will transition into the role of President. I bring to this leadership role nearly 25 years of surgical experience, both as a clinician educator and inventor. My goal during the next 2 years will be to move toward subspecialty recognition of Complex Gynecology. 

Linda D. Bradley, MD

My passion is diagnostic and operative hysteroscopy, simple procedures that can both evaluate and treat intrauterine pathology. Recently, I was thrilled to coauthor an article on office hysteroscopy for Obstetrics & Gynecology (September 2022). I will have a chapter on operative hysteroscopy in the 2023 edition of TeLinde’s Textbook of Gynecology, and I am an author for the topic Office and Operative Hysteroscopy in UpToDate. Locally, I am known as the “foodie gynecologist”—I travel, take cooking classes, and I have more cookbooks than gynecology textbooks. Since Covid, I have embraced biking and just completed a riverboat biking cruise from Salamanca, Spain, to Lisbon, Portugal.

Amy L. Garcia, MD

I am fellowship trained as a minimally invasive gynecologic surgeon (MIGS) and have had a private surgical practice since 2005. I am involved with The American College of Obstetricians and Gynecologists (ACOG), AAGL, and international surgical education for office hysteroscopy and related practice management. I am passionate about working with start-up companies in the gynecologic medical device arena and innovation in gynecologic surgery.

Steven R. Goldstein, MD, NCMP, CCD

I just completed my term as President of the International Menopause Society. This culminated in the society’s 18th World Congress in Lisbon, attended by over 1,700 health care providers from 76 countries. I delivered the Pieter van Keep Memorial Lecture, named for one of the society’s founders who died prematurely of pancreatic cancer. I was further honored by receiving the society’s Distinguished Service Award. I am very proud to have previously received the NAMS Thomas B. Clarkson award for Outstanding Clinical and Basic Science Research in Menopause. I also have one foot in the gynecologic ultrasound world and was given the Joseph H. Holmes Pioneer Award and was the 2023 recipient of the William J. Fry Memorial Lecture Award, both from the American Institute of Ultrasound in Medicine, having written the second book ever on vaginal ultrasonography.

On a personal level, I love to play golf (in spite of my foot drop and 14 orthopedic surgeries). My season tickets show some diversity—the New York City Ballet and St. John’s basketball.

Cheryl B. Iglesia, MD

I am the 49th president of the Society of Gynecologic Surgeons, the 5th woman to hold this position, and the first of Filipino-American descent. I recognize that it is only through extraordinary mentorship and support from other giants in gynecology, like Drs. Andrew Kaunitz (fellow OBG Management Board member), Linda Brubaker, and Dee Fenner and the love, support, and encouragement of my parents, husband, and daughters that I have been able to reach this milestone. A feather in my cap is the recent appointment to Deputy Editor of Gynecology for this journal, under the tutelage of Dr. Robert Barbieri. Over the past 31 years, I have had the privilege of learning from the best experts and gynecologic surgeons and the honor of working with skilled partners as we pass on our collective knowledge to our fellows, residents, and medical students. The passion in this next generation of ObGyns is so invigorating!

PS—In the spirit of continually learning, I want to add the Argentine tango to my dancing repertoire and go on an African safari; both are on my bucket list as the pandemic eases.

Andrew M. Kaunitz, MD, NCMP

Since starting with the University of Florida College of Medicine-Jacksonville in 1984, I have enjoyed caring for patients, training residents and medical students, and being involved with publications and research. My areas of focus are menopause, contraception, gyn ultrasound and evaluation/management of women with abnormal uterine bleeding. In 2020, I received the North American Menopause Society/Leon Speroff Outstanding Educator Award. In 2021, I received the ACOG Distinguished Service Award. I enjoy spending time with my family, neighborhood bicycling, and searching for sharks’ teeth at the beach. 

Barbara Levy, MD

I have been privileged to serve on the OBG Management Editorial Board for several decades. I am passionate about delivering the best possible care for the patients we serve, and helping women’s health care professionals provide that care. Through positions at AAGL, ACOG, and the American Medical Association, I have worked hard to champion best practices and to support fair, equitable, and accessible care for our patients and reimbursement for our services. My true north is to base patient care on reliable, valid, and properly interpreted data.

Continue to: David G. Mutch, MD...

David G. Mutch, MD

I am ending my 6-year term as Chair of the National Cancer Institute’s (NCI) gynecologic cancer steering committee. That is the committee that vets all NCI-sponsored clinical trials in gynecologic oncology. I am on the International Federation of Gynecology and Obstetrics (FIGO) Cancer committee, Co-Chair of the American Joint Committee on Cancer gyn staging committee and on the Reproductive Scientist Development Program selection committee. I also am completing my term as Chair of the Foundation for Women’s Cancer; this is the C3, charitable arm, of the Society of Gynecologic Oncology. We have distributed more than $3.5 million to young investigators to help start their research careers in gynecologic oncology.

Errol R. Norwitz, MD, PhD, MBA

I am a physician-scientist with subspecialty training in high-risk obstetrics (maternal-fetal medicine). I was born and raised in Cape Town, South Africa, and I have trained/practiced in 5 countries on 3 continents. My research interests include the pathophysiology, prediction, prevention, and management of pregnancy complications, primarily preterm birth and preeclampsia. I am a member of the Board of Scientific Counselors of the National Institute of Child Health and Human Development. I am currently President & CEO of Newton-Wellesley Hospital, a comprehensive community-based academic medical center and a member of the Mass General Brigham health care system in Boston, Massachusetts.

Jaimey Pauli, MD

I am the Division Chief and Professor of Maternal-Fetal Medicine (MFM) at the Penn State College of Medicine and Penn State Health Milton S. Hershey Medical Center. I had exceptional mentoring throughout my medical career, particularly by a former member of the Editorial Board, Dr. John T. Repke. One of the biggest perks of my job is that our division provides full-scope MFM care. While I often serve as the more traditional MFM consultant and academic educator, I also provide longitudinal prenatal care and deliver many of my own patients, often through subsequent pregnancies. Serving as a member of the Editorial Board combines my passion for clinical obstetrical care with my talents (as a former English major) of reading, writing, and editing. I believe that the work we do provides accessible, evidence-based, and practical guidance for our colleagues so they can provide excellence in obstetrical care.

JoAnn Pinkerton, MD, NCMP

I am a Professor of Obstetrics and Gynecology and Division Chief of Midlife Health at the University of Virginia (UVA) Health. Passionate about menopause, I am an executive director emeritus of The North American Menopause Society (NAMS) and past-President of NAMS (2008-2009). Within the past few years, I have served as an expert advisor for the recent ACOG Clinical Practice Guidelines on Osteoporosis, the NAMS Position Statements on Hormone Therapy and Osteoporosis, and the Global Consensus on Menopause and Androgen Therapy. I received the 2022 South Atlantic Association of Obstetricians and Gynecologists Lifetime Achievement Award for my expertise and work in menopause and the NAMS 2020 Ann Voda Community Service Award for my biannual community educational symposiums. I remain active in research, currently the lead and UVA principal investigator for the Oasis 2 multicenter clinical trial, which is testing a neurokinin receptor antagonist as a nonhormone therapy for the relief of hot flashes. Serving on the OBG Management Editorial Board is an honor that allows me to use my expertise in menopause management and hormone therapy to provide practical, evidence-based guidance for clinicians.

Joseph S. Sanfilippo, MD, MBA

I feel honored and privileged to have received the Golden Apple Teaching Award from the Universityof Pittsburgh School of Medicine. I am also fortunate to be the recipient of the Faculty Educator of the Month Award for resident teaching. I have been named Top Doctor 20 years in a row. My current academic activities include, since 2007, Program Director for Reproductive Endocrinology & Infertility Fellowship at the University of Pittsburgh and Chair of the Mentor-Mentee Program at University of Pittsburgh Department of Obstetrics, Gynecology & Reproductive Sciences. I am Guest Editor for the medical malpractice section of the journal Clinical Obstetrics and Gynecology. Recently, I completed a patient-focused book, “Experts Guide to Fertility,” which will be published in May 2023 by J Hopkins University Publisher and is designed for patients going through infertility treatment. Regarding outside events, I enjoy climbing steep hills and riding far and wide on my “electric bike.” Highly recommend it!

James Simon, MD, CCD, IF, NCMP

It’s been an honor serving on the OBG Management Board for many years, as a board-certified obstetrician/gynecologist/reproductive endocrinologist, certified menopause practitioner, and sexuality counsellor. Nicknamed “The Menopause Whisperer” by Washingtonian Magazine, my solo, private practice, IntimMedicine Specialists®, one of the few such practices remaining in Washington, DC, is about 6 blocks from the White House. By virtue of my practice’s location, I care for women at the highest levels of government seeking personalized gynecological, menopause, and sexual medicine care. Some high-powered patients believe they have all the answers even before I open my mouth, so I just fall back on my experience as both the President of NAMS, and The International Society for the Study of Women’s Sexual Health, or principal investigator on more than 400 clinical research trials, or Chief Medical Officer of a pharmaceutical company, or author of more than 800 publications. I love what I do every day and cannot imagine slowing down or stopping. ●

The decline in marriage rates in Canada is sharper among adolescent mothers, new data suggest.

An analysis of data from the Canadian Vital Statistics – Birth Database indicates that marriages declined by 80.5% among mothers younger than 18 years between 1989 and 2018.

“This study documents a decrease in marriage prevalence among mothers aged <18, 18-19, 20-24, and 25-49 years and suggests a larger relative decline in prevalence in younger mothers, especially those below age 18,” wrote study author Andrée-Anne Fafard St-Germain, PhD, a postdoctoral trainee at the University of Toronto, and colleagues.

The study was published online in the Canadian Journal of Public Health.


 

A general decline

The researchers estimated marriage rates among mothers in the four age groups mentioned above. They compared marriage rates in each group during the periods 1989-1990 and 2017-2018. The study included records of 10,399,250 mothers. In all, 1,118,630 records were used to identify socioeconomic and geographic patterns.

The researchers found an expected decline in marriage rates between 1989 and 2018, but the decline was steeper among younger women. Marriage rates decreased by 13.6% among women aged 25-49 years (16.0% relative decline), 29.3% among those aged 20-24 years (47.3% relative decline), 14.3% among those aged 18-19 years (60.2% relative decline), and 6.7% among those under 18 (80.5% relative decline).

Compared with Canadian-born mothers, foreign-born mothers were more likely to be married in all age groups (adjusted odds ratios [aORs], 5.18-6.36). Residence in rural locales or small towns was also associated with greater probability of marriage (aOR, 1.27-1.32).

Compared with women in the prairie provinces, those in Ontario were more likely to be married (aOR, 1.23-1.41), while the rate was lower in Quebec (aOR, 0.27-0.70), the Atlantic Provinces (aOR, 0.49-0.65), and the territories (aOR, 0.26-0.49). The researchers found no statistically significant association between neighborhood income quintiles and marriage rates in those younger than 18. They found a greater likelihood of marriage for mothers aged 18-19 years and those aged 20-24 years who resided in neighborhoods in higher income quintiles.
 

Human rights concern

Commenting on the study, Alissa Koski, PhD, assistant professor of epidemiology, biostatistics, and occupational health at McGill University, said, “Nearly all research on child marriage has focused on countries in South Asia and Africa. The authors acknowledge that child marriage remains legal across Canada. This draws attention to a domestic human rights concern that is largely unacknowledged.”

Overall, the study confirms trends that have been noted in Canada and have been studied by sociologists, Dr. Koski added. Traditional marriage rates have been declining for decades, while common-law marriages have been increasing. The mean age at the time of marriage increased from 30.0 years in 2016 to 30.7 years in 2020, according to Statistics Canada.

The study is limited by its failure to account for common-law marriages, which represent 98% of child marriages, said Dr. Koski. “The percentage of mothers in all age groups who were in legal or common-law marriage is almost certainly much higher than reported in this paper. However, because common-law unions are more common among younger people, the percentage of mothers in younger age groups, including those under 18, may be underestimated to a greater extent.”

The authors’ conclusion that the decline in marriages was larger among mothers younger than 18 years is not supported by the data in the article, said Dr. Koski. “That conclusion seems to overlook the fact that the absolute decline was lowest among those below age 18. The percentage decline in marriage was highest among mothers under 18, but this is at least in part because the percentage was so low to begin with. If we look instead at the absolute decline in marriage, it was lowest among mothers under age 18.”

The authors also suggest that the change in socioeconomic conditions associated with marriage may be different among mothers younger than 18 years, compared with mothers aged 18-19 years or 20-24 years. Higher socioeconomic status, as reflected in higher maternal neighborhood income quintiles, was associated with marriage among older adolescent mothers but not among mothers younger than 18 years. The socioeconomic distinction between married mothers younger than 18 years and older mothers could contribute to differences in the health advantages of marriage over time, the authors wrote.

But this conclusion as well is an “inappropriate interpretation ... not supported by the data,” said Dr. Koski. She noted that births to mothers younger than 18 years are rare in Canada, and births to married mothers in that age group are even rarer. That factor could have led the study to be underpowered in this group and yielded odds ratios that are not statistically significant. “The data are consistent with either an increase or a decrease in the odds of marriage. The data were too sparse to measure accurately,” said Dr. Koski.

The study was funded by the Canadian Institutes of Health Research Foundation. Dr. Fafard St-Germain and Dr. Koski reported having no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

The decline in marriage rates in Canada is sharper among adolescent mothers, new data suggest.

An analysis of data from the Canadian Vital Statistics – Birth Database indicates that marriages declined by 80.5% among mothers younger than 18 years between 1989 and 2018.

“This study documents a decrease in marriage prevalence among mothers aged <18, 18-19, 20-24, and 25-49 years and suggests a larger relative decline in prevalence in younger mothers, especially those below age 18,” wrote study author Andrée-Anne Fafard St-Germain, PhD, a postdoctoral trainee at the University of Toronto, and colleagues.

The study was published online in the Canadian Journal of Public Health.


 

A general decline

The researchers estimated marriage rates among mothers in the four age groups mentioned above. They compared marriage rates in each group during the periods 1989-1990 and 2017-2018. The study included records of 10,399,250 mothers. In all, 1,118,630 records were used to identify socioeconomic and geographic patterns.

The researchers found an expected decline in marriage rates between 1989 and 2018, but the decline was steeper among younger women. Marriage rates decreased by 13.6% among women aged 25-49 years (16.0% relative decline), 29.3% among those aged 20-24 years (47.3% relative decline), 14.3% among those aged 18-19 years (60.2% relative decline), and 6.7% among those under 18 (80.5% relative decline).

Compared with Canadian-born mothers, foreign-born mothers were more likely to be married in all age groups (adjusted odds ratios [aORs], 5.18-6.36). Residence in rural locales or small towns was also associated with greater probability of marriage (aOR, 1.27-1.32).

Compared with women in the prairie provinces, those in Ontario were more likely to be married (aOR, 1.23-1.41), while the rate was lower in Quebec (aOR, 0.27-0.70), the Atlantic Provinces (aOR, 0.49-0.65), and the territories (aOR, 0.26-0.49). The researchers found no statistically significant association between neighborhood income quintiles and marriage rates in those younger than 18. They found a greater likelihood of marriage for mothers aged 18-19 years and those aged 20-24 years who resided in neighborhoods in higher income quintiles.
 

Human rights concern

Commenting on the study, Alissa Koski, PhD, assistant professor of epidemiology, biostatistics, and occupational health at McGill University, said, “Nearly all research on child marriage has focused on countries in South Asia and Africa. The authors acknowledge that child marriage remains legal across Canada. This draws attention to a domestic human rights concern that is largely unacknowledged.”

Overall, the study confirms trends that have been noted in Canada and have been studied by sociologists, Dr. Koski added. Traditional marriage rates have been declining for decades, while common-law marriages have been increasing. The mean age at the time of marriage increased from 30.0 years in 2016 to 30.7 years in 2020, according to Statistics Canada.

The study is limited by its failure to account for common-law marriages, which represent 98% of child marriages, said Dr. Koski. “The percentage of mothers in all age groups who were in legal or common-law marriage is almost certainly much higher than reported in this paper. However, because common-law unions are more common among younger people, the percentage of mothers in younger age groups, including those under 18, may be underestimated to a greater extent.”

The authors’ conclusion that the decline in marriages was larger among mothers younger than 18 years is not supported by the data in the article, said Dr. Koski. “That conclusion seems to overlook the fact that the absolute decline was lowest among those below age 18. The percentage decline in marriage was highest among mothers under 18, but this is at least in part because the percentage was so low to begin with. If we look instead at the absolute decline in marriage, it was lowest among mothers under age 18.”

The authors also suggest that the change in socioeconomic conditions associated with marriage may be different among mothers younger than 18 years, compared with mothers aged 18-19 years or 20-24 years. Higher socioeconomic status, as reflected in higher maternal neighborhood income quintiles, was associated with marriage among older adolescent mothers but not among mothers younger than 18 years. The socioeconomic distinction between married mothers younger than 18 years and older mothers could contribute to differences in the health advantages of marriage over time, the authors wrote.

But this conclusion as well is an “inappropriate interpretation ... not supported by the data,” said Dr. Koski. She noted that births to mothers younger than 18 years are rare in Canada, and births to married mothers in that age group are even rarer. That factor could have led the study to be underpowered in this group and yielded odds ratios that are not statistically significant. “The data are consistent with either an increase or a decrease in the odds of marriage. The data were too sparse to measure accurately,” said Dr. Koski.

The study was funded by the Canadian Institutes of Health Research Foundation. Dr. Fafard St-Germain and Dr. Koski reported having no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

The decline in marriage rates in Canada is sharper among adolescent mothers, new data suggest.

An analysis of data from the Canadian Vital Statistics – Birth Database indicates that marriages declined by 80.5% among mothers younger than 18 years between 1989 and 2018.

“This study documents a decrease in marriage prevalence among mothers aged <18, 18-19, 20-24, and 25-49 years and suggests a larger relative decline in prevalence in younger mothers, especially those below age 18,” wrote study author Andrée-Anne Fafard St-Germain, PhD, a postdoctoral trainee at the University of Toronto, and colleagues.

The study was published online in the Canadian Journal of Public Health.


 

A general decline

The researchers estimated marriage rates among mothers in the four age groups mentioned above. They compared marriage rates in each group during the periods 1989-1990 and 2017-2018. The study included records of 10,399,250 mothers. In all, 1,118,630 records were used to identify socioeconomic and geographic patterns.

The researchers found an expected decline in marriage rates between 1989 and 2018, but the decline was steeper among younger women. Marriage rates decreased by 13.6% among women aged 25-49 years (16.0% relative decline), 29.3% among those aged 20-24 years (47.3% relative decline), 14.3% among those aged 18-19 years (60.2% relative decline), and 6.7% among those under 18 (80.5% relative decline).

Compared with Canadian-born mothers, foreign-born mothers were more likely to be married in all age groups (adjusted odds ratios [aORs], 5.18-6.36). Residence in rural locales or small towns was also associated with greater probability of marriage (aOR, 1.27-1.32).

Compared with women in the prairie provinces, those in Ontario were more likely to be married (aOR, 1.23-1.41), while the rate was lower in Quebec (aOR, 0.27-0.70), the Atlantic Provinces (aOR, 0.49-0.65), and the territories (aOR, 0.26-0.49). The researchers found no statistically significant association between neighborhood income quintiles and marriage rates in those younger than 18. They found a greater likelihood of marriage for mothers aged 18-19 years and those aged 20-24 years who resided in neighborhoods in higher income quintiles.
 

Human rights concern

Commenting on the study, Alissa Koski, PhD, assistant professor of epidemiology, biostatistics, and occupational health at McGill University, said, “Nearly all research on child marriage has focused on countries in South Asia and Africa. The authors acknowledge that child marriage remains legal across Canada. This draws attention to a domestic human rights concern that is largely unacknowledged.”

Overall, the study confirms trends that have been noted in Canada and have been studied by sociologists, Dr. Koski added. Traditional marriage rates have been declining for decades, while common-law marriages have been increasing. The mean age at the time of marriage increased from 30.0 years in 2016 to 30.7 years in 2020, according to Statistics Canada.

The study is limited by its failure to account for common-law marriages, which represent 98% of child marriages, said Dr. Koski. “The percentage of mothers in all age groups who were in legal or common-law marriage is almost certainly much higher than reported in this paper. However, because common-law unions are more common among younger people, the percentage of mothers in younger age groups, including those under 18, may be underestimated to a greater extent.”

The authors’ conclusion that the decline in marriages was larger among mothers younger than 18 years is not supported by the data in the article, said Dr. Koski. “That conclusion seems to overlook the fact that the absolute decline was lowest among those below age 18. The percentage decline in marriage was highest among mothers under 18, but this is at least in part because the percentage was so low to begin with. If we look instead at the absolute decline in marriage, it was lowest among mothers under age 18.”

The authors also suggest that the change in socioeconomic conditions associated with marriage may be different among mothers younger than 18 years, compared with mothers aged 18-19 years or 20-24 years. Higher socioeconomic status, as reflected in higher maternal neighborhood income quintiles, was associated with marriage among older adolescent mothers but not among mothers younger than 18 years. The socioeconomic distinction between married mothers younger than 18 years and older mothers could contribute to differences in the health advantages of marriage over time, the authors wrote.

But this conclusion as well is an “inappropriate interpretation ... not supported by the data,” said Dr. Koski. She noted that births to mothers younger than 18 years are rare in Canada, and births to married mothers in that age group are even rarer. That factor could have led the study to be underpowered in this group and yielded odds ratios that are not statistically significant. “The data are consistent with either an increase or a decrease in the odds of marriage. The data were too sparse to measure accurately,” said Dr. Koski.

The study was funded by the Canadian Institutes of Health Research Foundation. Dr. Fafard St-Germain and Dr. Koski reported having no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

The 2022 guideline update released by the KDIGO organization for managing people with diabetes and chronic kidney disease (CKD) highlighted the safety and expanded, evidence-based role for agents from three drug classes: the SGLT2 inhibitors, the GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonists.

But this key take-away from the guideline also underscored the challenges for ensuring fair and affordable access among US patients to these practice-changing medications.

The impact of widespread adoption of these three drug classes into routine US management of people with diabetes and CKD “will be determined by how effective the health care system and its patients and clinicians are at overcoming individual and structural barriers,” write Milda Saunders, MD, and Neda Laiteerapong, MD, in an editorial that accompanied the publication of a synopsis of the 2022 guideline update in Annals of Internal Medicine.

The synopsis is an 11-page distillation of the full 128-page guideline released by the Kidney Disease: Improving Global Outcomes (KDIGO) organization in 2022.

The recommendations in the 2022 guideline update “are exciting for their potential to change the natural history of CKD and diabetes, but their effect could be highly limited by barriers at multiple levels,” write Dr. Saunders and Dr. Laiteerapong, two internal medicine physicians at the University of Chicago.

“Without equitable implementation of the KDIGO 2022 guidelines there is a potential that clinical practice variation will increase and widen health inequities for minoritized people with CKD and diabetes,” they warn.
 

Generics to the rescue

One potentially effective, and likely imminent, way to level the prescribing field for patients with CKD and diabetes is for agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor, glucagonlike peptide-1 (GLP-1) receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes to become available in generic formulations.

That should lower prices and thereby boost wider access and will likely occur fairly soon for at least two of the three drug classes, Dr. Laiteerapong predicts.

Some GLP-1 receptor agonists have already escaped patent exclusivity or will do so in 2023, she notes, including the anticipated ability of one drugmaker to start U.S. marketing of generic liraglutide by the end of 2023.

However, whether that manufacturer, Teva, proceeds with generic liraglutide “is a big question,” Dr. Laiteerapong said in an interview. She cited Teva’s history of failing to introduce a generic formulation of exenatide onto the U.S. market even though it has had a green light to do so since 2017.

The only nonsteroidal mineralocorticoid receptor antagonist now on the market is finerenone (Kerendia), which will not go off patent for several more years, but for some branded SGLT2 inhibitors, U.S. patents will expire in 2025. In addition, remogliflozin is an SGLT2 inhibitor that “may have already lost patent exclusivity,” noted Dr. Laiteerapong, although it has also never received U.S. marketing approval.

Dr. Laiteerapong expressed optimism that the overall trajectory of access is on the rise. “Many people have type 2 diabetes, and these drugs are in demand,” she noted. She also pointed to progress recently made on insulin affordability. “Things will get better as long as people advocate and argue for equity,” she maintained.
 

Incentivize formulary listings

Dr. Laiteerapong cited other approaches that could boost access to these medications, such as “creating incentives for pharmaceutical companies to ensure that [these drugs] are on formularies” of large, government-affiliated U.S. health insurance programs, such as Medicare Advantage plans, Medicare Part D, state Medicaid plans, and coverage through U.S. Veterans Affairs and the Tricare health insurance plans available to active members of the US military.

The editorial she coauthored with Dr. Saunders also calls for future collaborations among various medical societies to create “a more unified and streamlined set of recommendations” that benefits patients with diabetes, CKD, and multiple other chronic conditions.

“Over the last decade, we have seen more societies willing to present cooperative guidelines, as well as a surge in research on patients who live with multiple chronic conditions. There is momentum that will allow these different societies to work together,” Dr. Laiteerapong said.

Dr. Laiteerapong and Dr. Saunders have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The 2022 guideline update released by the KDIGO organization for managing people with diabetes and chronic kidney disease (CKD) highlighted the safety and expanded, evidence-based role for agents from three drug classes: the SGLT2 inhibitors, the GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonists.

But this key take-away from the guideline also underscored the challenges for ensuring fair and affordable access among US patients to these practice-changing medications.

The impact of widespread adoption of these three drug classes into routine US management of people with diabetes and CKD “will be determined by how effective the health care system and its patients and clinicians are at overcoming individual and structural barriers,” write Milda Saunders, MD, and Neda Laiteerapong, MD, in an editorial that accompanied the publication of a synopsis of the 2022 guideline update in Annals of Internal Medicine.

The synopsis is an 11-page distillation of the full 128-page guideline released by the Kidney Disease: Improving Global Outcomes (KDIGO) organization in 2022.

The recommendations in the 2022 guideline update “are exciting for their potential to change the natural history of CKD and diabetes, but their effect could be highly limited by barriers at multiple levels,” write Dr. Saunders and Dr. Laiteerapong, two internal medicine physicians at the University of Chicago.

“Without equitable implementation of the KDIGO 2022 guidelines there is a potential that clinical practice variation will increase and widen health inequities for minoritized people with CKD and diabetes,” they warn.
 

Generics to the rescue

One potentially effective, and likely imminent, way to level the prescribing field for patients with CKD and diabetes is for agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor, glucagonlike peptide-1 (GLP-1) receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes to become available in generic formulations.

That should lower prices and thereby boost wider access and will likely occur fairly soon for at least two of the three drug classes, Dr. Laiteerapong predicts.

Some GLP-1 receptor agonists have already escaped patent exclusivity or will do so in 2023, she notes, including the anticipated ability of one drugmaker to start U.S. marketing of generic liraglutide by the end of 2023.

However, whether that manufacturer, Teva, proceeds with generic liraglutide “is a big question,” Dr. Laiteerapong said in an interview. She cited Teva’s history of failing to introduce a generic formulation of exenatide onto the U.S. market even though it has had a green light to do so since 2017.

The only nonsteroidal mineralocorticoid receptor antagonist now on the market is finerenone (Kerendia), which will not go off patent for several more years, but for some branded SGLT2 inhibitors, U.S. patents will expire in 2025. In addition, remogliflozin is an SGLT2 inhibitor that “may have already lost patent exclusivity,” noted Dr. Laiteerapong, although it has also never received U.S. marketing approval.

Dr. Laiteerapong expressed optimism that the overall trajectory of access is on the rise. “Many people have type 2 diabetes, and these drugs are in demand,” she noted. She also pointed to progress recently made on insulin affordability. “Things will get better as long as people advocate and argue for equity,” she maintained.
 

Incentivize formulary listings

Dr. Laiteerapong cited other approaches that could boost access to these medications, such as “creating incentives for pharmaceutical companies to ensure that [these drugs] are on formularies” of large, government-affiliated U.S. health insurance programs, such as Medicare Advantage plans, Medicare Part D, state Medicaid plans, and coverage through U.S. Veterans Affairs and the Tricare health insurance plans available to active members of the US military.

The editorial she coauthored with Dr. Saunders also calls for future collaborations among various medical societies to create “a more unified and streamlined set of recommendations” that benefits patients with diabetes, CKD, and multiple other chronic conditions.

“Over the last decade, we have seen more societies willing to present cooperative guidelines, as well as a surge in research on patients who live with multiple chronic conditions. There is momentum that will allow these different societies to work together,” Dr. Laiteerapong said.

Dr. Laiteerapong and Dr. Saunders have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The 2022 guideline update released by the KDIGO organization for managing people with diabetes and chronic kidney disease (CKD) highlighted the safety and expanded, evidence-based role for agents from three drug classes: the SGLT2 inhibitors, the GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonists.

But this key take-away from the guideline also underscored the challenges for ensuring fair and affordable access among US patients to these practice-changing medications.

The impact of widespread adoption of these three drug classes into routine US management of people with diabetes and CKD “will be determined by how effective the health care system and its patients and clinicians are at overcoming individual and structural barriers,” write Milda Saunders, MD, and Neda Laiteerapong, MD, in an editorial that accompanied the publication of a synopsis of the 2022 guideline update in Annals of Internal Medicine.

The synopsis is an 11-page distillation of the full 128-page guideline released by the Kidney Disease: Improving Global Outcomes (KDIGO) organization in 2022.

The recommendations in the 2022 guideline update “are exciting for their potential to change the natural history of CKD and diabetes, but their effect could be highly limited by barriers at multiple levels,” write Dr. Saunders and Dr. Laiteerapong, two internal medicine physicians at the University of Chicago.

“Without equitable implementation of the KDIGO 2022 guidelines there is a potential that clinical practice variation will increase and widen health inequities for minoritized people with CKD and diabetes,” they warn.
 

Generics to the rescue

One potentially effective, and likely imminent, way to level the prescribing field for patients with CKD and diabetes is for agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor, glucagonlike peptide-1 (GLP-1) receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes to become available in generic formulations.

That should lower prices and thereby boost wider access and will likely occur fairly soon for at least two of the three drug classes, Dr. Laiteerapong predicts.

Some GLP-1 receptor agonists have already escaped patent exclusivity or will do so in 2023, she notes, including the anticipated ability of one drugmaker to start U.S. marketing of generic liraglutide by the end of 2023.

However, whether that manufacturer, Teva, proceeds with generic liraglutide “is a big question,” Dr. Laiteerapong said in an interview. She cited Teva’s history of failing to introduce a generic formulation of exenatide onto the U.S. market even though it has had a green light to do so since 2017.

The only nonsteroidal mineralocorticoid receptor antagonist now on the market is finerenone (Kerendia), which will not go off patent for several more years, but for some branded SGLT2 inhibitors, U.S. patents will expire in 2025. In addition, remogliflozin is an SGLT2 inhibitor that “may have already lost patent exclusivity,” noted Dr. Laiteerapong, although it has also never received U.S. marketing approval.

Dr. Laiteerapong expressed optimism that the overall trajectory of access is on the rise. “Many people have type 2 diabetes, and these drugs are in demand,” she noted. She also pointed to progress recently made on insulin affordability. “Things will get better as long as people advocate and argue for equity,” she maintained.
 

Incentivize formulary listings

Dr. Laiteerapong cited other approaches that could boost access to these medications, such as “creating incentives for pharmaceutical companies to ensure that [these drugs] are on formularies” of large, government-affiliated U.S. health insurance programs, such as Medicare Advantage plans, Medicare Part D, state Medicaid plans, and coverage through U.S. Veterans Affairs and the Tricare health insurance plans available to active members of the US military.

The editorial she coauthored with Dr. Saunders also calls for future collaborations among various medical societies to create “a more unified and streamlined set of recommendations” that benefits patients with diabetes, CKD, and multiple other chronic conditions.

“Over the last decade, we have seen more societies willing to present cooperative guidelines, as well as a surge in research on patients who live with multiple chronic conditions. There is momentum that will allow these different societies to work together,” Dr. Laiteerapong said.

Dr. Laiteerapong and Dr. Saunders have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among people with type 2 diabetes who self-reported regularly using a proton pump inhibitor (PPI), the incidence of cardiovascular disease (CVD) events as well as all-cause death was significantly increased in a study of more than 19,000 people with type 2 diabetes in a prospective U.K. database.

During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease, compared with nonuse of a PPI, after full adjustment for potential confounding variables.

The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in MI, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.

PPIs are a medication class widely used in both over-the-counter and prescription formulations to reduce acid production in the stomach and to treat gastroesophageal reflux disease and other acid-related disorders. The PPI class includes such widely used agents as esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).

The analyses in this report, which used data collected in the UK Biobank, are “rigorous,” and the findings of “a modest elevation of CVD risk are consistent with a growing number of observational studies in populations with and without diabetes,” commented Mary R. Rooney, PhD, an epidemiologist at Johns Hopkins University, Baltimore, who focuses on diabetes and cardiovascular diseases.
 

Prior observational reports

For example, a report from a prospective, observational study of more than 4300 U.S. residents published in 2021 that Dr. Rooney coauthored documented that cumulative PPI exposure for more than 5 years was significantly linked with a twofold increase in the rate of CVD events, compared with people who did not use a PPI. (This analysis did not examine a possible effect of diabetes status.)

And in a separate prospective, observational study of more than 1,000 Australians with type 2 diabetes, initiation of PPI treatment was significantly linked with a 3.6-fold increased incidence of CVD events, compared with PPI nonuse.

However, Dr. Rooney cautioned that the role of PPI use in raising CVD events “is still an unresolved question. It is too soon to tell if PPI use in people with diabetes should trigger additional caution.” Findings are needed from prospective, randomized trials to determine more definitively whether PPIs play a causal role in the incidence of CVD events, she said in an interview.

U.S. practice often results in unwarranted prolongation of PPI treatment, said the authors of an editorial that accompanied the 2021 report by Dr. Rooney and coauthors.
 

Long-term PPI use threatens harm

“The practice of initiating stress ulcer prophylaxis [by administering a PPI] in critical care is common,” wrote the authors of the 2021 editorial, Nitin Malik, MD, and William S. Weintraub, MD. “Although it is data driven and well intentioned, the possibility of causing harm – if it is continued on a long-term basis after resolution of the acute illness – is palpable.”

The new analyses using UK Biobank data included 19,229 adults with type 2 diabetes and no preexisting coronary artery disease, MI, heart failure, or stroke. The cohort included 15,954 people (83%) who did not report using a PPI and 3,275 who currently used PPIs regularly. Study limitations include self-report as the only verification of PPI use and lack of information on type of PPI, dose size, or use duration.

The findings remained consistent in several sensitivity analyses, including a propensity score–matched analysis and after further adjustment for use of histamine₂ receptor antagonists, a drug class with indications similar to those for PPIs.

The authors of the report speculated that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.

The study received no commercial funding. The authors and Dr. Rooney disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among people with type 2 diabetes who self-reported regularly using a proton pump inhibitor (PPI), the incidence of cardiovascular disease (CVD) events as well as all-cause death was significantly increased in a study of more than 19,000 people with type 2 diabetes in a prospective U.K. database.

During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease, compared with nonuse of a PPI, after full adjustment for potential confounding variables.

The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in MI, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.

PPIs are a medication class widely used in both over-the-counter and prescription formulations to reduce acid production in the stomach and to treat gastroesophageal reflux disease and other acid-related disorders. The PPI class includes such widely used agents as esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).

The analyses in this report, which used data collected in the UK Biobank, are “rigorous,” and the findings of “a modest elevation of CVD risk are consistent with a growing number of observational studies in populations with and without diabetes,” commented Mary R. Rooney, PhD, an epidemiologist at Johns Hopkins University, Baltimore, who focuses on diabetes and cardiovascular diseases.
 

Prior observational reports

For example, a report from a prospective, observational study of more than 4300 U.S. residents published in 2021 that Dr. Rooney coauthored documented that cumulative PPI exposure for more than 5 years was significantly linked with a twofold increase in the rate of CVD events, compared with people who did not use a PPI. (This analysis did not examine a possible effect of diabetes status.)

And in a separate prospective, observational study of more than 1,000 Australians with type 2 diabetes, initiation of PPI treatment was significantly linked with a 3.6-fold increased incidence of CVD events, compared with PPI nonuse.

However, Dr. Rooney cautioned that the role of PPI use in raising CVD events “is still an unresolved question. It is too soon to tell if PPI use in people with diabetes should trigger additional caution.” Findings are needed from prospective, randomized trials to determine more definitively whether PPIs play a causal role in the incidence of CVD events, she said in an interview.

U.S. practice often results in unwarranted prolongation of PPI treatment, said the authors of an editorial that accompanied the 2021 report by Dr. Rooney and coauthors.
 

Long-term PPI use threatens harm

“The practice of initiating stress ulcer prophylaxis [by administering a PPI] in critical care is common,” wrote the authors of the 2021 editorial, Nitin Malik, MD, and William S. Weintraub, MD. “Although it is data driven and well intentioned, the possibility of causing harm – if it is continued on a long-term basis after resolution of the acute illness – is palpable.”

The new analyses using UK Biobank data included 19,229 adults with type 2 diabetes and no preexisting coronary artery disease, MI, heart failure, or stroke. The cohort included 15,954 people (83%) who did not report using a PPI and 3,275 who currently used PPIs regularly. Study limitations include self-report as the only verification of PPI use and lack of information on type of PPI, dose size, or use duration.

The findings remained consistent in several sensitivity analyses, including a propensity score–matched analysis and after further adjustment for use of histamine₂ receptor antagonists, a drug class with indications similar to those for PPIs.

The authors of the report speculated that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.

The study received no commercial funding. The authors and Dr. Rooney disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among people with type 2 diabetes who self-reported regularly using a proton pump inhibitor (PPI), the incidence of cardiovascular disease (CVD) events as well as all-cause death was significantly increased in a study of more than 19,000 people with type 2 diabetes in a prospective U.K. database.

During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease, compared with nonuse of a PPI, after full adjustment for potential confounding variables.

The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in MI, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.

PPIs are a medication class widely used in both over-the-counter and prescription formulations to reduce acid production in the stomach and to treat gastroesophageal reflux disease and other acid-related disorders. The PPI class includes such widely used agents as esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).

The analyses in this report, which used data collected in the UK Biobank, are “rigorous,” and the findings of “a modest elevation of CVD risk are consistent with a growing number of observational studies in populations with and without diabetes,” commented Mary R. Rooney, PhD, an epidemiologist at Johns Hopkins University, Baltimore, who focuses on diabetes and cardiovascular diseases.
 

Prior observational reports

For example, a report from a prospective, observational study of more than 4300 U.S. residents published in 2021 that Dr. Rooney coauthored documented that cumulative PPI exposure for more than 5 years was significantly linked with a twofold increase in the rate of CVD events, compared with people who did not use a PPI. (This analysis did not examine a possible effect of diabetes status.)

And in a separate prospective, observational study of more than 1,000 Australians with type 2 diabetes, initiation of PPI treatment was significantly linked with a 3.6-fold increased incidence of CVD events, compared with PPI nonuse.

However, Dr. Rooney cautioned that the role of PPI use in raising CVD events “is still an unresolved question. It is too soon to tell if PPI use in people with diabetes should trigger additional caution.” Findings are needed from prospective, randomized trials to determine more definitively whether PPIs play a causal role in the incidence of CVD events, she said in an interview.

U.S. practice often results in unwarranted prolongation of PPI treatment, said the authors of an editorial that accompanied the 2021 report by Dr. Rooney and coauthors.
 

Long-term PPI use threatens harm

“The practice of initiating stress ulcer prophylaxis [by administering a PPI] in critical care is common,” wrote the authors of the 2021 editorial, Nitin Malik, MD, and William S. Weintraub, MD. “Although it is data driven and well intentioned, the possibility of causing harm – if it is continued on a long-term basis after resolution of the acute illness – is palpable.”

The new analyses using UK Biobank data included 19,229 adults with type 2 diabetes and no preexisting coronary artery disease, MI, heart failure, or stroke. The cohort included 15,954 people (83%) who did not report using a PPI and 3,275 who currently used PPIs regularly. Study limitations include self-report as the only verification of PPI use and lack of information on type of PPI, dose size, or use duration.

The findings remained consistent in several sensitivity analyses, including a propensity score–matched analysis and after further adjustment for use of histamine₂ receptor antagonists, a drug class with indications similar to those for PPIs.

The authors of the report speculated that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.

The study received no commercial funding. The authors and Dr. Rooney disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with acute decompensated heart failure who were frail at baseline improved more with targeted, early physical rehabilitation than those who were prefrail, a new analysis of the REHAB-HF study suggests.

“The robust response to the intervention by frail patients exceeded our expectations,” Gordon R. Reeves, MD, PT, of Novant Health Heart and Vascular Institute, Charlotte, N.C., told this news organization. “The effect size from improvement in physical function among frail patients was very large, with at least four times the minimal meaningful improvement, based on the Short Physical Performance Battery (SPPB).”

Furthermore, the interaction between baseline frailty status and treatment in REHAB-HF was such that a 2.6-fold larger improvement in SPPB was seen among frail versus prefrail patients.

However, Dr. Reeves noted, “We need to further evaluate safety and efficacy as it relates to adverse clinical events. Specifically, we observed a numerically higher number of deaths with the REHAB-HF intervention, which warrants further investigation before the intervention is implemented in clinical practice.”

The study was published online  in JAMA Cardiology.
 

Interpret with caution

Dr. Reeves and colleagues conducted a prespecified secondary analysis of the previously published Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial, a multicenter, randomized controlled trial that showed that a 3-month early, transitional, tailored, multidomain physical rehabilitation intervention improved physical function and quality of life (QoL), compared with usual care. The secondary analysis aimed to evaluate whether baseline frailty altered the benefits of the intervention or was associated with risk of adverse outcomes.

According to Dr. Reeves, REHAB-HF differs from more traditional cardiac rehab programs in several ways.

• The intervention targets patients with acute HF, including HF with preserved ejection fraction (HFpEF). Medicare policy limits standard cardiac rehabilitation in HF to long-term patients with HF with reduced ejection fraction (HFrEF) only who have been stabilized for 6 weeks or longer after a recent hospitalization.
• It addresses multiple physical function domains, including balance, mobility, functional strength, and endurance. Standard cardiac rehab is primarily focused on endurance training, which can result in injuries and falls if deficits in balance, mobility, and strength are not addressed first.
• It is delivered one to one rather than in a group setting and primarily by physical therapists who are experts in the rehabilitation of medically complex patients.
• It is transitional, beginning in the hospital, then moving to the outpatient setting, then to home and includes a home assessment.

For the analysis, the Fried phenotype model was used to assess baseline frailty across five domains: unintentional weight loss during the past year; self-reported exhaustion; grip strength; slowness, as assessed by gait speed; and low physical activity, as assessed by the Short Form-12 Physical Composite Score.

At the baseline visit, patients were categorized as frail if they met three or more of these criteria. They were categorized as prefrail if they met one or two criteria and as nonfrail if they met none of the criteria. Because of the small number of nonfrail participants, the analysis included only frail and prefrail participants.

The analysis included 337 participants (mean age, 72; 54%, women; 50%, Black). At baseline, 57% were frail, and 43% were prefrail.

A significant interaction was seen between baseline frailty and the intervention for the primary trial endpoint of overall SPPB score, with a 2.6-fold larger improvement in SPPB among frail (2.1) versus prefrail (0.8) patients.

Trends favored a larger intervention effect size, with significant improvement among frail versus prefrail participants for 6-minute walk distance, QoL, and the geriatric depression score.

“However, we must interpret these findings with caution,” the authors write. “The REHAB-HF trial was not adequately powered to determine the effect of the intervention on clinical events.” This plus the number of deaths “underscore the need for additional research, including prospective clinical trials, investigating the effect of physical function interventions on clinical events among frail patients with HF.”

To address this need, the researchers recently launched a larger clinical trial, called REHAB-HFpEF, which is powered to assess the impact of the intervention on clinical events, according to Dr. Reeves. “As the name implies,” he said, “this trial is focused on older patients recently hospitalized with HFpEF, who, [compared with HFrEF] also showed a more robust response to the intervention, with worse physical function and very high prevalence of frailty near the time of hospital discharge.”
 

‘Never too old or sick to benefit’

Jonathan H. Whiteson, MD, vice chair of clinical operations and medical director of cardiac and pulmonary rehabilitation at NYU Langone Health’s Rusk Rehabilitation, said, “We have seen in clinical practice and in other (non–heart failure) clinical areas that frail older patients do improve proportionally more than younger and less frail patients with rehabilitation programs. Encouragingly, this very much supports the practice that patients are never too old or too sick to benefit from an individualized multidisciplinary rehabilitation program.”

However, he noted, “patients had to be independent with basic activities of daily living to be included in the study,” so many frail, elderly patients with heart failure who are not independent were not included in the study. It also wasn’t clear whether patients who received postacute care at a rehab facility before going home were included in the trial.

Furthermore, he said, outcomes over 1 to 5 years are needed to understand the long-term impact of the intervention.

On the other hand, he added, the fact that about half of participants were Black and were women is a “tremendous strength.”

“Repeating this study in population groups at high risk for frailty with different diagnoses, such as chronic lung diseases, interstitial lung diseases, chronic kidney disease, and rheumatologic disorders will further support the value of rehabilitation in improving patient health, function, quality of life, and reducing rehospitalizations and health care costs,” Dr. Whiteson concluded.

The study was supported by grants from the National Key R&D program. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with acute decompensated heart failure who were frail at baseline improved more with targeted, early physical rehabilitation than those who were prefrail, a new analysis of the REHAB-HF study suggests.

“The robust response to the intervention by frail patients exceeded our expectations,” Gordon R. Reeves, MD, PT, of Novant Health Heart and Vascular Institute, Charlotte, N.C., told this news organization. “The effect size from improvement in physical function among frail patients was very large, with at least four times the minimal meaningful improvement, based on the Short Physical Performance Battery (SPPB).”

Furthermore, the interaction between baseline frailty status and treatment in REHAB-HF was such that a 2.6-fold larger improvement in SPPB was seen among frail versus prefrail patients.

However, Dr. Reeves noted, “We need to further evaluate safety and efficacy as it relates to adverse clinical events. Specifically, we observed a numerically higher number of deaths with the REHAB-HF intervention, which warrants further investigation before the intervention is implemented in clinical practice.”

The study was published online  in JAMA Cardiology.
 

Interpret with caution

Dr. Reeves and colleagues conducted a prespecified secondary analysis of the previously published Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial, a multicenter, randomized controlled trial that showed that a 3-month early, transitional, tailored, multidomain physical rehabilitation intervention improved physical function and quality of life (QoL), compared with usual care. The secondary analysis aimed to evaluate whether baseline frailty altered the benefits of the intervention or was associated with risk of adverse outcomes.

According to Dr. Reeves, REHAB-HF differs from more traditional cardiac rehab programs in several ways.

• The intervention targets patients with acute HF, including HF with preserved ejection fraction (HFpEF). Medicare policy limits standard cardiac rehabilitation in HF to long-term patients with HF with reduced ejection fraction (HFrEF) only who have been stabilized for 6 weeks or longer after a recent hospitalization.
• It addresses multiple physical function domains, including balance, mobility, functional strength, and endurance. Standard cardiac rehab is primarily focused on endurance training, which can result in injuries and falls if deficits in balance, mobility, and strength are not addressed first.
• It is delivered one to one rather than in a group setting and primarily by physical therapists who are experts in the rehabilitation of medically complex patients.
• It is transitional, beginning in the hospital, then moving to the outpatient setting, then to home and includes a home assessment.

For the analysis, the Fried phenotype model was used to assess baseline frailty across five domains: unintentional weight loss during the past year; self-reported exhaustion; grip strength; slowness, as assessed by gait speed; and low physical activity, as assessed by the Short Form-12 Physical Composite Score.

At the baseline visit, patients were categorized as frail if they met three or more of these criteria. They were categorized as prefrail if they met one or two criteria and as nonfrail if they met none of the criteria. Because of the small number of nonfrail participants, the analysis included only frail and prefrail participants.

The analysis included 337 participants (mean age, 72; 54%, women; 50%, Black). At baseline, 57% were frail, and 43% were prefrail.

A significant interaction was seen between baseline frailty and the intervention for the primary trial endpoint of overall SPPB score, with a 2.6-fold larger improvement in SPPB among frail (2.1) versus prefrail (0.8) patients.

Trends favored a larger intervention effect size, with significant improvement among frail versus prefrail participants for 6-minute walk distance, QoL, and the geriatric depression score.

“However, we must interpret these findings with caution,” the authors write. “The REHAB-HF trial was not adequately powered to determine the effect of the intervention on clinical events.” This plus the number of deaths “underscore the need for additional research, including prospective clinical trials, investigating the effect of physical function interventions on clinical events among frail patients with HF.”

To address this need, the researchers recently launched a larger clinical trial, called REHAB-HFpEF, which is powered to assess the impact of the intervention on clinical events, according to Dr. Reeves. “As the name implies,” he said, “this trial is focused on older patients recently hospitalized with HFpEF, who, [compared with HFrEF] also showed a more robust response to the intervention, with worse physical function and very high prevalence of frailty near the time of hospital discharge.”
 

‘Never too old or sick to benefit’

Jonathan H. Whiteson, MD, vice chair of clinical operations and medical director of cardiac and pulmonary rehabilitation at NYU Langone Health’s Rusk Rehabilitation, said, “We have seen in clinical practice and in other (non–heart failure) clinical areas that frail older patients do improve proportionally more than younger and less frail patients with rehabilitation programs. Encouragingly, this very much supports the practice that patients are never too old or too sick to benefit from an individualized multidisciplinary rehabilitation program.”

However, he noted, “patients had to be independent with basic activities of daily living to be included in the study,” so many frail, elderly patients with heart failure who are not independent were not included in the study. It also wasn’t clear whether patients who received postacute care at a rehab facility before going home were included in the trial.

Furthermore, he said, outcomes over 1 to 5 years are needed to understand the long-term impact of the intervention.

On the other hand, he added, the fact that about half of participants were Black and were women is a “tremendous strength.”

“Repeating this study in population groups at high risk for frailty with different diagnoses, such as chronic lung diseases, interstitial lung diseases, chronic kidney disease, and rheumatologic disorders will further support the value of rehabilitation in improving patient health, function, quality of life, and reducing rehospitalizations and health care costs,” Dr. Whiteson concluded.

The study was supported by grants from the National Key R&D program. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with acute decompensated heart failure who were frail at baseline improved more with targeted, early physical rehabilitation than those who were prefrail, a new analysis of the REHAB-HF study suggests.

“The robust response to the intervention by frail patients exceeded our expectations,” Gordon R. Reeves, MD, PT, of Novant Health Heart and Vascular Institute, Charlotte, N.C., told this news organization. “The effect size from improvement in physical function among frail patients was very large, with at least four times the minimal meaningful improvement, based on the Short Physical Performance Battery (SPPB).”

Furthermore, the interaction between baseline frailty status and treatment in REHAB-HF was such that a 2.6-fold larger improvement in SPPB was seen among frail versus prefrail patients.

However, Dr. Reeves noted, “We need to further evaluate safety and efficacy as it relates to adverse clinical events. Specifically, we observed a numerically higher number of deaths with the REHAB-HF intervention, which warrants further investigation before the intervention is implemented in clinical practice.”

The study was published online  in JAMA Cardiology.
 

Interpret with caution

Dr. Reeves and colleagues conducted a prespecified secondary analysis of the previously published Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial, a multicenter, randomized controlled trial that showed that a 3-month early, transitional, tailored, multidomain physical rehabilitation intervention improved physical function and quality of life (QoL), compared with usual care. The secondary analysis aimed to evaluate whether baseline frailty altered the benefits of the intervention or was associated with risk of adverse outcomes.

According to Dr. Reeves, REHAB-HF differs from more traditional cardiac rehab programs in several ways.

• The intervention targets patients with acute HF, including HF with preserved ejection fraction (HFpEF). Medicare policy limits standard cardiac rehabilitation in HF to long-term patients with HF with reduced ejection fraction (HFrEF) only who have been stabilized for 6 weeks or longer after a recent hospitalization.
• It addresses multiple physical function domains, including balance, mobility, functional strength, and endurance. Standard cardiac rehab is primarily focused on endurance training, which can result in injuries and falls if deficits in balance, mobility, and strength are not addressed first.
• It is delivered one to one rather than in a group setting and primarily by physical therapists who are experts in the rehabilitation of medically complex patients.
• It is transitional, beginning in the hospital, then moving to the outpatient setting, then to home and includes a home assessment.

For the analysis, the Fried phenotype model was used to assess baseline frailty across five domains: unintentional weight loss during the past year; self-reported exhaustion; grip strength; slowness, as assessed by gait speed; and low physical activity, as assessed by the Short Form-12 Physical Composite Score.

At the baseline visit, patients were categorized as frail if they met three or more of these criteria. They were categorized as prefrail if they met one or two criteria and as nonfrail if they met none of the criteria. Because of the small number of nonfrail participants, the analysis included only frail and prefrail participants.

The analysis included 337 participants (mean age, 72; 54%, women; 50%, Black). At baseline, 57% were frail, and 43% were prefrail.

A significant interaction was seen between baseline frailty and the intervention for the primary trial endpoint of overall SPPB score, with a 2.6-fold larger improvement in SPPB among frail (2.1) versus prefrail (0.8) patients.

Trends favored a larger intervention effect size, with significant improvement among frail versus prefrail participants for 6-minute walk distance, QoL, and the geriatric depression score.

“However, we must interpret these findings with caution,” the authors write. “The REHAB-HF trial was not adequately powered to determine the effect of the intervention on clinical events.” This plus the number of deaths “underscore the need for additional research, including prospective clinical trials, investigating the effect of physical function interventions on clinical events among frail patients with HF.”

To address this need, the researchers recently launched a larger clinical trial, called REHAB-HFpEF, which is powered to assess the impact of the intervention on clinical events, according to Dr. Reeves. “As the name implies,” he said, “this trial is focused on older patients recently hospitalized with HFpEF, who, [compared with HFrEF] also showed a more robust response to the intervention, with worse physical function and very high prevalence of frailty near the time of hospital discharge.”
 

‘Never too old or sick to benefit’

Jonathan H. Whiteson, MD, vice chair of clinical operations and medical director of cardiac and pulmonary rehabilitation at NYU Langone Health’s Rusk Rehabilitation, said, “We have seen in clinical practice and in other (non–heart failure) clinical areas that frail older patients do improve proportionally more than younger and less frail patients with rehabilitation programs. Encouragingly, this very much supports the practice that patients are never too old or too sick to benefit from an individualized multidisciplinary rehabilitation program.”

However, he noted, “patients had to be independent with basic activities of daily living to be included in the study,” so many frail, elderly patients with heart failure who are not independent were not included in the study. It also wasn’t clear whether patients who received postacute care at a rehab facility before going home were included in the trial.

Furthermore, he said, outcomes over 1 to 5 years are needed to understand the long-term impact of the intervention.

On the other hand, he added, the fact that about half of participants were Black and were women is a “tremendous strength.”

“Repeating this study in population groups at high risk for frailty with different diagnoses, such as chronic lung diseases, interstitial lung diseases, chronic kidney disease, and rheumatologic disorders will further support the value of rehabilitation in improving patient health, function, quality of life, and reducing rehospitalizations and health care costs,” Dr. Whiteson concluded.

The study was supported by grants from the National Key R&D program. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Due to advances in medicine, people are living longer with the aid of increased options for life-prolonging treatments. These treatment options may improve the quantity but not necessarily the quality of life.¹

Kidney failure can be treated with renal replacement therapy (dialysis or renal transplantation) or supportive care.² In 2017, the global prevalence of kidney failure was about 5.3 to 9.7 million.³ In the United States, about 500,000 patients are receiving maintenance dialysis for end-stage renal disease (ESRD), and about 1 in 4 will stop dialysis before death, coupled with hospice enrollment.⁴ ESRD is 2 times more prevalent among veterans than in nonveterans, which can be due in part to high rates of comorbid predisposing conditions, such as diabetes mellitus, hypertension, and advanced age, among others.⁵ The decision to discontinue dialysis and receive hospice care tends to be more difficult than choosing to withhold or forego dialysis.⁶

A study conducted among patients who were taken off hemodialysis before death reported that the 2 most common reasons for the withdrawal were acute medical complications and frailty.⁷ A retrospective study among patients with ESRD receiving hemodialysis highlighted the underutilization of hospice care in this patient population.⁸ The study also found that those patients who were aged > 75 years, had poor functional status, and had dialysis-related complications, such as sepsis and anemia, were more likely to elect withdrawal of hemodialysis. There was no difference in overall survival or quality of life among patients who were aged ≥ 75 years with multiple comorbidities and functional impairment who elected conservative management vs those who started dialysis.⁸ Long-term continuous dialysis has been associated with a lower quality of life, increased dependence on others, and a variety of symptoms, such as pain, nausea, insomnia, anxiety, or depression.⁹

Conservative Care vs Medical Paternalism

In the United States, it is unusual for patients with ESRD to choose conservative care, and supportive services are less available for those who do compared with patients with ESRD in Europe, Asia, Australia, and Canada.¹⁰ A study looking at a small number of US nephrologists has shown they may have limited experience in caring for patients who forego dialysis and they are not comfortable offering conservative management over dialysis.¹⁰ Another small study from Sweden also showed that many nephrologists do not feel prepared for end-of-life care and conversations.¹¹

Patients often rely on knowledgeable recommendations from medical experts. However, medical paternalism occurs when a physician makes decisions deemed to be in the patient’s best interest but are against the patient’s wishes or when the patient is unable to give their consent.¹² Hard paternalism occurs when the patient is competent to make their own medical decisions, while soft paternalism occurs when a patient is not competent to make their own medical decisions.¹³

Patient autonomy is widely recognized as an ethical principle in medicine. It recognizes patients as well-informed decision makers who may act without excessive influence to make intentional determinations on their own behalf.¹⁴ Autonomy can be exercised at any point during the health care process.¹² Although ethical and legal guidelines encourage physicians to recommend appropriate treatment, medical opinion cannot overrule the wishes of a competent patient who refuses treatment.¹²

Case Presentation

Mr. S presented to the emergency department at a US Department of Veterans Affairs (VA) medical center with abdominal pain from recurrent pancreatitis. The patient aged > 65 years had a history of depression, ESRD, and was receiving hemodialysis. A computed tomography scan revealed a new pancreatic mass, and he was referred to the palliative care (PC) department nurse practitioner (NP) for a goals-of-care discussion. PC was informed to assist with hospice care initiation: The patient elected a do-not-resuscitate (DNR) code status and hospice care.

At the consultation, Mr. S stated that he had decided to forego life-prolonging treatments, including hemodialysis, and declined further evaluation for his pancreatic mass. He shared a good understanding of concerns for malignancy with his mass but did not wish to pursue further diagnostics as he knew his life expectancy was very limited without dialysis. He had been dependent on hemodialysis for the past 10 years. He had briefly received hospice care 5 years before but changed his mind and decided to pursue standard care, including life-prolonging dialysis treatments. He reported no depression, suicidal ideation, or intentions of hastening his death. He stated that he was just physically tired from his ongoing dialysis, recurrent hospitalizations, and being repeatedly subjected to diagnostic tests. Mr. S added that he had discussed his plan with his family, including his son and sister-in-law who is married to his brother. Mr. S previously identified his brother as his surrogate decision maker.

Mr. S shared that his brother had sustained a traumatic brain injury and was now unable to engage in a meaningful conversation. He shared that his family supported his decision. He also recognized that with his debility, he would need inpatient hospice care. On finding out that Mr. S’s brother was no longer able to act as the surrogate decision maker, the PC NP asked whether he wanted her to contact his son to share the outcome of their visit. The patient declined, adding that he had discussed his care plans with his family and did not feel that his health care team needed to have additional discussions with them.

Mr. S also reported chronic, recurrent right upper quadrant pain. He was prescribed oxycodone 10 mg every 4 hours as needed; however, it did little to control his pain. He also reported generalized pruritus, a complication of his renal failure.

After 1 week, Mr. S was transferred to the inpatient hospice unit. At that time, he allowed the hospice team to contact his son for medical updates and identified him as the primary point of contact for the hospice team if the need arose to reach his family. Due to the restrictions imposed by the pandemic, Mr. S had virtual video visits with his family. Mr. S developed intermittent confusion and worsening fatigue over time. His son was informed of his deteriorating condition and visited his father. Mr. S died peacefully 2 days later with his family present.

Multidisciplinary Inputs on the Case

Medicine. In discussing the case with medicine, the PC NP was informed that the goals the patient had for his care, which included stopping dialysis, having a DNR code status and pursuing hospice care, along with the patient’s pain symptoms prompted the PC consultation. The resident also shared concerns about the patient’s refusal to have his surrogate decision maker and family contacted regarding his decisions for his care.

Palliative care. After meeting with the patient and assisting in identifying goals for care, the PC NP recommended initiation of hospice care in the hospital while the patient awaited transfer to the inpatient hospice unit. The PC NP also recommended a psychiatric evaluation to rule out untreated depression that might influence the patient’s decision making. A follow-up visit with nephrology was also recommended. Optimal management of his distressing physical symptoms was recommended, including prescribing hydromorphone instead of oxycodone for his pain and starting a topical emollient for pruritus.

Nephrology. The patient’s electronic health records (EHR) showed that he informed nephrology of his desire to pursue hospice care and that he decided against further dialysis, including as-needed dialysis for comfort. The records also indicated that the patient understood the consequences of discontinuing dialysis.

Psychiatry. The patient’s EHR also showed that during his psychiatric visits, Mr. S reported he had no thoughts of suicide, and it was against his spiritual beliefs. He said he made his own medical decisions and expressed that his health care team should not attempt to change his mind. He also said he understood that stopping dialysis could lead to early death. He stated he had a close relationship with his family and discussed his medical decisions with them. He was tearful at times when he talked about his family. Mr. S shared his frustration about repeatedly being asked the same questions on succeeding visits.

After evaluation, psychiatry diagnosed Mr. S with mood disorder with depressive features and he was prescribed methylphenidate 5 mg daily and sertraline 25 mg daily. They also recommended continuing to offer dialysis in a supportive manner since the patient had changed his mind about hospice in the past. However, psychiatry followed the patient daily for 5 days and concluded that his medical decisions were not clouded by mood symptoms.

Discussion

Patients who are aged > 65 years and on dialysis are more likely to experience higher rates of hospitalization, intensive care unit admission, procedures, and death in the hospital compared with patients who have cancer or heart failure. They also use hospice services less.¹⁵ Often this is not consistent with a patient’s wishes but may occur due to limited discussion of goals, values, and preferences between physician and patient.¹⁵ Many nephrologists do not engage in these conversations for fear of upsetting patients, their perceived lack of skill in prognostication and discussing the topic, or the lack of time to have the conversation.¹⁵ It is important to have an honest and open communication with patients that allows them to be fully informed as they make their medical decisions and exercise their autonomy.

Medicare hospice guidelines also are used to help determine hospice appropriateness among veterans in the VA. Medicare requires enrollees to discontinue disease-modifying treatment for the medical condition leading to their hospice diagnosis, which can result in late hospice referrals and shorter hospice stays.¹⁶ Even though hospice referrals for patients with ESRD have increased over time, they are still happening close to the time of death, and patients’ health care utilization near the end of life remains unchanged.¹⁶ According to Medicare, patients qualify for hospice care if they are terminally ill (defined as having a life expectancy of ≤ 6 months), choose comfort care over curative care for their terminal illness, and sign a statement electing hospice care over treatments for their terminal illness.¹⁷ A DNR order is not a condition for hospice admission.¹⁸

The VA defines hospice care as comfort care provided to patients with a terminal condition, a life expectancy of ≤ 6 months, and who are no longer seeking treatment other than those that are palliative.¹⁹ Based on his ESRD, Mr. S was qualified for hospice care, and his goals for care were consistent with the hospice philosophy. Most families of patients who elected to withdraw dialysis reported a good death, using the criteria of the duration of dying, discomfort, and psychosocial circumstances.²⁰

Role of HCPs

Health care practitioners (HCPs) are expected to help patients understand the risks and benefits of their choices and its alternative, align patients’ goals with those risks and benefits, and assist patients in making choices that promote their goals and autonomy.²¹ Family members are often not involved in medical decision making when patients have the capacity to make their own decisions.²² Patients will also have to give permission for protected health information to be shared with their family members.²² On the other hand, families have been shown to provide valuable emotional support to patients and are considered second patients themselves in the sense that they can be impacted by patients’ clinical situation.²² Families may also need care, time, and attention from HCPs.²²

Mr. S was found capable of making his own decisions, and part of that decision was that his family not to be present for the goals-of-care discussion. He added that he would discuss the care decisions with his family. At the time of registering for VA health care services, Mr. S had provided his health care team with his brother and sister-in-law’s emergency contact information as well as named his brother surrogate decision maker. As Mr. S’s condition was expected to rapidly decline wthout dialysis, the HCPs would be able to notify family members once his condition changed, including death.

Neuroplasticity changes can contribute to chronic pain that may also lead to depression.²³ Chronic pain and depression may involve the same brain structures, neurotransmitters, and signaling pathway.²³ Factors leading to chronic pain and depression include decreased availability of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine in the central nervous system, decreased brain-derived neurotrophic factor, inflammatory response, and increased glutamate activity.²³ Depression and hopelessness have been associated with the desire to hasten death among patients with a terminal illness.²⁴ Worse mental health has been associated with the desire to hasten death among patients who are older and functionally impaired.²⁵ It was important to optimize Mr. S’s treatment for pain and depression to ensure that these factors were not influencing his medical decisions.

With increasing recognition of the need to improve quality of life, health care utilization, and provide care consistent with patients’ goals in nephrology, the concept of renal PC is emerging but remains limited.²⁶ The need to improve supportive care or PC for patients starting on dialysis for ESRD is high as these patients tend to be older (aged > 75 years), have high rates of cardiovascular comorbidities, can have coexisting cognitive impairment and functional debility, and have an adjusted mortality rate of up to 32.5% within 1 year of starting dialysis.²⁶ Some ways to enhance renal PC programs include incorporating PC skill development and training within nephrology fellowships, educating patients with chronic and ESRD about PC and options for medical management without dialysis, and increasing the collaboration between nephrology and PC.²⁶

Outcomes and Implications

Respect for the ethical principle of autonomy is paramount in health care. Patients should be able to give informed consent for treatment decisions without undue influence from their HCPs and should be able to withdraw that consent at any point during treatment. Factors that may influence patients’ ability to make medical decisions should be considered, including untreated or poorly treated symptoms. The involvement of PC helps optimize symptom management, provide support, and assist in goals-of-care discussions. Advanced practice PC nurses can offer other members of the health care team additional information and support in end-of-life care. Family involvement should be encouraged even for patients who can make their own medical decisions for emotional support and to assist families in what could be a traumatic event, such as the loss of a loved one.

The desire to pursue a comfort-focused approach to terminal illness and stop disease-modifying treatments are criteria for hospice care. An interdisciplinary approach to end-of-life care is beneficial, and every specialty should be equipped to engage in honest communication and skillful prognostication. These conversations should start early in the course of a terminal illness. Multiple factors contribute to poor clinical outcomes among patients with ESRD even with renal replacement therapy, such as dialysis. There is a need to improve PC training in the field of nephrology.

Conclusions

Mr. S was able to choose to withdraw potentially life-prolonging treatments with the support of his family and HCPs. He was able to continue receiving high-quality care and treatment in accordance with his wishes and goals for his care. The provision of interdisciplinary care that focused on supporting him allowed for his peaceful and comfortable death.

Due to advances in medicine, people are living longer with the aid of increased options for life-prolonging treatments. These treatment options may improve the quantity but not necessarily the quality of life.¹

Kidney failure can be treated with renal replacement therapy (dialysis or renal transplantation) or supportive care.² In 2017, the global prevalence of kidney failure was about 5.3 to 9.7 million.³ In the United States, about 500,000 patients are receiving maintenance dialysis for end-stage renal disease (ESRD), and about 1 in 4 will stop dialysis before death, coupled with hospice enrollment.⁴ ESRD is 2 times more prevalent among veterans than in nonveterans, which can be due in part to high rates of comorbid predisposing conditions, such as diabetes mellitus, hypertension, and advanced age, among others.⁵ The decision to discontinue dialysis and receive hospice care tends to be more difficult than choosing to withhold or forego dialysis.⁶

A study conducted among patients who were taken off hemodialysis before death reported that the 2 most common reasons for the withdrawal were acute medical complications and frailty.⁷ A retrospective study among patients with ESRD receiving hemodialysis highlighted the underutilization of hospice care in this patient population.⁸ The study also found that those patients who were aged > 75 years, had poor functional status, and had dialysis-related complications, such as sepsis and anemia, were more likely to elect withdrawal of hemodialysis. There was no difference in overall survival or quality of life among patients who were aged ≥ 75 years with multiple comorbidities and functional impairment who elected conservative management vs those who started dialysis.⁸ Long-term continuous dialysis has been associated with a lower quality of life, increased dependence on others, and a variety of symptoms, such as pain, nausea, insomnia, anxiety, or depression.⁹

Conservative Care vs Medical Paternalism

In the United States, it is unusual for patients with ESRD to choose conservative care, and supportive services are less available for those who do compared with patients with ESRD in Europe, Asia, Australia, and Canada.¹⁰ A study looking at a small number of US nephrologists has shown they may have limited experience in caring for patients who forego dialysis and they are not comfortable offering conservative management over dialysis.¹⁰ Another small study from Sweden also showed that many nephrologists do not feel prepared for end-of-life care and conversations.¹¹

Patients often rely on knowledgeable recommendations from medical experts. However, medical paternalism occurs when a physician makes decisions deemed to be in the patient’s best interest but are against the patient’s wishes or when the patient is unable to give their consent.¹² Hard paternalism occurs when the patient is competent to make their own medical decisions, while soft paternalism occurs when a patient is not competent to make their own medical decisions.¹³

Patient autonomy is widely recognized as an ethical principle in medicine. It recognizes patients as well-informed decision makers who may act without excessive influence to make intentional determinations on their own behalf.¹⁴ Autonomy can be exercised at any point during the health care process.¹² Although ethical and legal guidelines encourage physicians to recommend appropriate treatment, medical opinion cannot overrule the wishes of a competent patient who refuses treatment.¹²

Case Presentation

Mr. S presented to the emergency department at a US Department of Veterans Affairs (VA) medical center with abdominal pain from recurrent pancreatitis. The patient aged > 65 years had a history of depression, ESRD, and was receiving hemodialysis. A computed tomography scan revealed a new pancreatic mass, and he was referred to the palliative care (PC) department nurse practitioner (NP) for a goals-of-care discussion. PC was informed to assist with hospice care initiation: The patient elected a do-not-resuscitate (DNR) code status and hospice care.

At the consultation, Mr. S stated that he had decided to forego life-prolonging treatments, including hemodialysis, and declined further evaluation for his pancreatic mass. He shared a good understanding of concerns for malignancy with his mass but did not wish to pursue further diagnostics as he knew his life expectancy was very limited without dialysis. He had been dependent on hemodialysis for the past 10 years. He had briefly received hospice care 5 years before but changed his mind and decided to pursue standard care, including life-prolonging dialysis treatments. He reported no depression, suicidal ideation, or intentions of hastening his death. He stated that he was just physically tired from his ongoing dialysis, recurrent hospitalizations, and being repeatedly subjected to diagnostic tests. Mr. S added that he had discussed his plan with his family, including his son and sister-in-law who is married to his brother. Mr. S previously identified his brother as his surrogate decision maker.

Mr. S shared that his brother had sustained a traumatic brain injury and was now unable to engage in a meaningful conversation. He shared that his family supported his decision. He also recognized that with his debility, he would need inpatient hospice care. On finding out that Mr. S’s brother was no longer able to act as the surrogate decision maker, the PC NP asked whether he wanted her to contact his son to share the outcome of their visit. The patient declined, adding that he had discussed his care plans with his family and did not feel that his health care team needed to have additional discussions with them.

Mr. S also reported chronic, recurrent right upper quadrant pain. He was prescribed oxycodone 10 mg every 4 hours as needed; however, it did little to control his pain. He also reported generalized pruritus, a complication of his renal failure.

After 1 week, Mr. S was transferred to the inpatient hospice unit. At that time, he allowed the hospice team to contact his son for medical updates and identified him as the primary point of contact for the hospice team if the need arose to reach his family. Due to the restrictions imposed by the pandemic, Mr. S had virtual video visits with his family. Mr. S developed intermittent confusion and worsening fatigue over time. His son was informed of his deteriorating condition and visited his father. Mr. S died peacefully 2 days later with his family present.

Multidisciplinary Inputs on the Case

Medicine. In discussing the case with medicine, the PC NP was informed that the goals the patient had for his care, which included stopping dialysis, having a DNR code status and pursuing hospice care, along with the patient’s pain symptoms prompted the PC consultation. The resident also shared concerns about the patient’s refusal to have his surrogate decision maker and family contacted regarding his decisions for his care.

Palliative care. After meeting with the patient and assisting in identifying goals for care, the PC NP recommended initiation of hospice care in the hospital while the patient awaited transfer to the inpatient hospice unit. The PC NP also recommended a psychiatric evaluation to rule out untreated depression that might influence the patient’s decision making. A follow-up visit with nephrology was also recommended. Optimal management of his distressing physical symptoms was recommended, including prescribing hydromorphone instead of oxycodone for his pain and starting a topical emollient for pruritus.

Nephrology. The patient’s electronic health records (EHR) showed that he informed nephrology of his desire to pursue hospice care and that he decided against further dialysis, including as-needed dialysis for comfort. The records also indicated that the patient understood the consequences of discontinuing dialysis.

Psychiatry. The patient’s EHR also showed that during his psychiatric visits, Mr. S reported he had no thoughts of suicide, and it was against his spiritual beliefs. He said he made his own medical decisions and expressed that his health care team should not attempt to change his mind. He also said he understood that stopping dialysis could lead to early death. He stated he had a close relationship with his family and discussed his medical decisions with them. He was tearful at times when he talked about his family. Mr. S shared his frustration about repeatedly being asked the same questions on succeeding visits.

After evaluation, psychiatry diagnosed Mr. S with mood disorder with depressive features and he was prescribed methylphenidate 5 mg daily and sertraline 25 mg daily. They also recommended continuing to offer dialysis in a supportive manner since the patient had changed his mind about hospice in the past. However, psychiatry followed the patient daily for 5 days and concluded that his medical decisions were not clouded by mood symptoms.

Discussion

Patients who are aged > 65 years and on dialysis are more likely to experience higher rates of hospitalization, intensive care unit admission, procedures, and death in the hospital compared with patients who have cancer or heart failure. They also use hospice services less.¹⁵ Often this is not consistent with a patient’s wishes but may occur due to limited discussion of goals, values, and preferences between physician and patient.¹⁵ Many nephrologists do not engage in these conversations for fear of upsetting patients, their perceived lack of skill in prognostication and discussing the topic, or the lack of time to have the conversation.¹⁵ It is important to have an honest and open communication with patients that allows them to be fully informed as they make their medical decisions and exercise their autonomy.

Medicare hospice guidelines also are used to help determine hospice appropriateness among veterans in the VA. Medicare requires enrollees to discontinue disease-modifying treatment for the medical condition leading to their hospice diagnosis, which can result in late hospice referrals and shorter hospice stays.¹⁶ Even though hospice referrals for patients with ESRD have increased over time, they are still happening close to the time of death, and patients’ health care utilization near the end of life remains unchanged.¹⁶ According to Medicare, patients qualify for hospice care if they are terminally ill (defined as having a life expectancy of ≤ 6 months), choose comfort care over curative care for their terminal illness, and sign a statement electing hospice care over treatments for their terminal illness.¹⁷ A DNR order is not a condition for hospice admission.¹⁸

The VA defines hospice care as comfort care provided to patients with a terminal condition, a life expectancy of ≤ 6 months, and who are no longer seeking treatment other than those that are palliative.¹⁹ Based on his ESRD, Mr. S was qualified for hospice care, and his goals for care were consistent with the hospice philosophy. Most families of patients who elected to withdraw dialysis reported a good death, using the criteria of the duration of dying, discomfort, and psychosocial circumstances.²⁰

Role of HCPs

Health care practitioners (HCPs) are expected to help patients understand the risks and benefits of their choices and its alternative, align patients’ goals with those risks and benefits, and assist patients in making choices that promote their goals and autonomy.²¹ Family members are often not involved in medical decision making when patients have the capacity to make their own decisions.²² Patients will also have to give permission for protected health information to be shared with their family members.²² On the other hand, families have been shown to provide valuable emotional support to patients and are considered second patients themselves in the sense that they can be impacted by patients’ clinical situation.²² Families may also need care, time, and attention from HCPs.²²

Mr. S was found capable of making his own decisions, and part of that decision was that his family not to be present for the goals-of-care discussion. He added that he would discuss the care decisions with his family. At the time of registering for VA health care services, Mr. S had provided his health care team with his brother and sister-in-law’s emergency contact information as well as named his brother surrogate decision maker. As Mr. S’s condition was expected to rapidly decline wthout dialysis, the HCPs would be able to notify family members once his condition changed, including death.

Neuroplasticity changes can contribute to chronic pain that may also lead to depression.²³ Chronic pain and depression may involve the same brain structures, neurotransmitters, and signaling pathway.²³ Factors leading to chronic pain and depression include decreased availability of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine in the central nervous system, decreased brain-derived neurotrophic factor, inflammatory response, and increased glutamate activity.²³ Depression and hopelessness have been associated with the desire to hasten death among patients with a terminal illness.²⁴ Worse mental health has been associated with the desire to hasten death among patients who are older and functionally impaired.²⁵ It was important to optimize Mr. S’s treatment for pain and depression to ensure that these factors were not influencing his medical decisions.

With increasing recognition of the need to improve quality of life, health care utilization, and provide care consistent with patients’ goals in nephrology, the concept of renal PC is emerging but remains limited.²⁶ The need to improve supportive care or PC for patients starting on dialysis for ESRD is high as these patients tend to be older (aged > 75 years), have high rates of cardiovascular comorbidities, can have coexisting cognitive impairment and functional debility, and have an adjusted mortality rate of up to 32.5% within 1 year of starting dialysis.²⁶ Some ways to enhance renal PC programs include incorporating PC skill development and training within nephrology fellowships, educating patients with chronic and ESRD about PC and options for medical management without dialysis, and increasing the collaboration between nephrology and PC.²⁶

Outcomes and Implications

Respect for the ethical principle of autonomy is paramount in health care. Patients should be able to give informed consent for treatment decisions without undue influence from their HCPs and should be able to withdraw that consent at any point during treatment. Factors that may influence patients’ ability to make medical decisions should be considered, including untreated or poorly treated symptoms. The involvement of PC helps optimize symptom management, provide support, and assist in goals-of-care discussions. Advanced practice PC nurses can offer other members of the health care team additional information and support in end-of-life care. Family involvement should be encouraged even for patients who can make their own medical decisions for emotional support and to assist families in what could be a traumatic event, such as the loss of a loved one.

The desire to pursue a comfort-focused approach to terminal illness and stop disease-modifying treatments are criteria for hospice care. An interdisciplinary approach to end-of-life care is beneficial, and every specialty should be equipped to engage in honest communication and skillful prognostication. These conversations should start early in the course of a terminal illness. Multiple factors contribute to poor clinical outcomes among patients with ESRD even with renal replacement therapy, such as dialysis. There is a need to improve PC training in the field of nephrology.

Conclusions

Mr. S was able to choose to withdraw potentially life-prolonging treatments with the support of his family and HCPs. He was able to continue receiving high-quality care and treatment in accordance with his wishes and goals for his care. The provision of interdisciplinary care that focused on supporting him allowed for his peaceful and comfortable death.

Due to advances in medicine, people are living longer with the aid of increased options for life-prolonging treatments. These treatment options may improve the quantity but not necessarily the quality of life.¹

Kidney failure can be treated with renal replacement therapy (dialysis or renal transplantation) or supportive care.² In 2017, the global prevalence of kidney failure was about 5.3 to 9.7 million.³ In the United States, about 500,000 patients are receiving maintenance dialysis for end-stage renal disease (ESRD), and about 1 in 4 will stop dialysis before death, coupled with hospice enrollment.⁴ ESRD is 2 times more prevalent among veterans than in nonveterans, which can be due in part to high rates of comorbid predisposing conditions, such as diabetes mellitus, hypertension, and advanced age, among others.⁵ The decision to discontinue dialysis and receive hospice care tends to be more difficult than choosing to withhold or forego dialysis.⁶

A study conducted among patients who were taken off hemodialysis before death reported that the 2 most common reasons for the withdrawal were acute medical complications and frailty.⁷ A retrospective study among patients with ESRD receiving hemodialysis highlighted the underutilization of hospice care in this patient population.⁸ The study also found that those patients who were aged > 75 years, had poor functional status, and had dialysis-related complications, such as sepsis and anemia, were more likely to elect withdrawal of hemodialysis. There was no difference in overall survival or quality of life among patients who were aged ≥ 75 years with multiple comorbidities and functional impairment who elected conservative management vs those who started dialysis.⁸ Long-term continuous dialysis has been associated with a lower quality of life, increased dependence on others, and a variety of symptoms, such as pain, nausea, insomnia, anxiety, or depression.⁹

Conservative Care vs Medical Paternalism

In the United States, it is unusual for patients with ESRD to choose conservative care, and supportive services are less available for those who do compared with patients with ESRD in Europe, Asia, Australia, and Canada.¹⁰ A study looking at a small number of US nephrologists has shown they may have limited experience in caring for patients who forego dialysis and they are not comfortable offering conservative management over dialysis.¹⁰ Another small study from Sweden also showed that many nephrologists do not feel prepared for end-of-life care and conversations.¹¹

Patients often rely on knowledgeable recommendations from medical experts. However, medical paternalism occurs when a physician makes decisions deemed to be in the patient’s best interest but are against the patient’s wishes or when the patient is unable to give their consent.¹² Hard paternalism occurs when the patient is competent to make their own medical decisions, while soft paternalism occurs when a patient is not competent to make their own medical decisions.¹³

Patient autonomy is widely recognized as an ethical principle in medicine. It recognizes patients as well-informed decision makers who may act without excessive influence to make intentional determinations on their own behalf.¹⁴ Autonomy can be exercised at any point during the health care process.¹² Although ethical and legal guidelines encourage physicians to recommend appropriate treatment, medical opinion cannot overrule the wishes of a competent patient who refuses treatment.¹²

Case Presentation

Mr. S presented to the emergency department at a US Department of Veterans Affairs (VA) medical center with abdominal pain from recurrent pancreatitis. The patient aged > 65 years had a history of depression, ESRD, and was receiving hemodialysis. A computed tomography scan revealed a new pancreatic mass, and he was referred to the palliative care (PC) department nurse practitioner (NP) for a goals-of-care discussion. PC was informed to assist with hospice care initiation: The patient elected a do-not-resuscitate (DNR) code status and hospice care.

At the consultation, Mr. S stated that he had decided to forego life-prolonging treatments, including hemodialysis, and declined further evaluation for his pancreatic mass. He shared a good understanding of concerns for malignancy with his mass but did not wish to pursue further diagnostics as he knew his life expectancy was very limited without dialysis. He had been dependent on hemodialysis for the past 10 years. He had briefly received hospice care 5 years before but changed his mind and decided to pursue standard care, including life-prolonging dialysis treatments. He reported no depression, suicidal ideation, or intentions of hastening his death. He stated that he was just physically tired from his ongoing dialysis, recurrent hospitalizations, and being repeatedly subjected to diagnostic tests. Mr. S added that he had discussed his plan with his family, including his son and sister-in-law who is married to his brother. Mr. S previously identified his brother as his surrogate decision maker.

Mr. S shared that his brother had sustained a traumatic brain injury and was now unable to engage in a meaningful conversation. He shared that his family supported his decision. He also recognized that with his debility, he would need inpatient hospice care. On finding out that Mr. S’s brother was no longer able to act as the surrogate decision maker, the PC NP asked whether he wanted her to contact his son to share the outcome of their visit. The patient declined, adding that he had discussed his care plans with his family and did not feel that his health care team needed to have additional discussions with them.

Mr. S also reported chronic, recurrent right upper quadrant pain. He was prescribed oxycodone 10 mg every 4 hours as needed; however, it did little to control his pain. He also reported generalized pruritus, a complication of his renal failure.

After 1 week, Mr. S was transferred to the inpatient hospice unit. At that time, he allowed the hospice team to contact his son for medical updates and identified him as the primary point of contact for the hospice team if the need arose to reach his family. Due to the restrictions imposed by the pandemic, Mr. S had virtual video visits with his family. Mr. S developed intermittent confusion and worsening fatigue over time. His son was informed of his deteriorating condition and visited his father. Mr. S died peacefully 2 days later with his family present.

Multidisciplinary Inputs on the Case

Medicine. In discussing the case with medicine, the PC NP was informed that the goals the patient had for his care, which included stopping dialysis, having a DNR code status and pursuing hospice care, along with the patient’s pain symptoms prompted the PC consultation. The resident also shared concerns about the patient’s refusal to have his surrogate decision maker and family contacted regarding his decisions for his care.

Palliative care. After meeting with the patient and assisting in identifying goals for care, the PC NP recommended initiation of hospice care in the hospital while the patient awaited transfer to the inpatient hospice unit. The PC NP also recommended a psychiatric evaluation to rule out untreated depression that might influence the patient’s decision making. A follow-up visit with nephrology was also recommended. Optimal management of his distressing physical symptoms was recommended, including prescribing hydromorphone instead of oxycodone for his pain and starting a topical emollient for pruritus.

Nephrology. The patient’s electronic health records (EHR) showed that he informed nephrology of his desire to pursue hospice care and that he decided against further dialysis, including as-needed dialysis for comfort. The records also indicated that the patient understood the consequences of discontinuing dialysis.

Psychiatry. The patient’s EHR also showed that during his psychiatric visits, Mr. S reported he had no thoughts of suicide, and it was against his spiritual beliefs. He said he made his own medical decisions and expressed that his health care team should not attempt to change his mind. He also said he understood that stopping dialysis could lead to early death. He stated he had a close relationship with his family and discussed his medical decisions with them. He was tearful at times when he talked about his family. Mr. S shared his frustration about repeatedly being asked the same questions on succeeding visits.

After evaluation, psychiatry diagnosed Mr. S with mood disorder with depressive features and he was prescribed methylphenidate 5 mg daily and sertraline 25 mg daily. They also recommended continuing to offer dialysis in a supportive manner since the patient had changed his mind about hospice in the past. However, psychiatry followed the patient daily for 5 days and concluded that his medical decisions were not clouded by mood symptoms.

Discussion

Patients who are aged > 65 years and on dialysis are more likely to experience higher rates of hospitalization, intensive care unit admission, procedures, and death in the hospital compared with patients who have cancer or heart failure. They also use hospice services less.¹⁵ Often this is not consistent with a patient’s wishes but may occur due to limited discussion of goals, values, and preferences between physician and patient.¹⁵ Many nephrologists do not engage in these conversations for fear of upsetting patients, their perceived lack of skill in prognostication and discussing the topic, or the lack of time to have the conversation.¹⁵ It is important to have an honest and open communication with patients that allows them to be fully informed as they make their medical decisions and exercise their autonomy.

Medicare hospice guidelines also are used to help determine hospice appropriateness among veterans in the VA. Medicare requires enrollees to discontinue disease-modifying treatment for the medical condition leading to their hospice diagnosis, which can result in late hospice referrals and shorter hospice stays.¹⁶ Even though hospice referrals for patients with ESRD have increased over time, they are still happening close to the time of death, and patients’ health care utilization near the end of life remains unchanged.¹⁶ According to Medicare, patients qualify for hospice care if they are terminally ill (defined as having a life expectancy of ≤ 6 months), choose comfort care over curative care for their terminal illness, and sign a statement electing hospice care over treatments for their terminal illness.¹⁷ A DNR order is not a condition for hospice admission.¹⁸

The VA defines hospice care as comfort care provided to patients with a terminal condition, a life expectancy of ≤ 6 months, and who are no longer seeking treatment other than those that are palliative.¹⁹ Based on his ESRD, Mr. S was qualified for hospice care, and his goals for care were consistent with the hospice philosophy. Most families of patients who elected to withdraw dialysis reported a good death, using the criteria of the duration of dying, discomfort, and psychosocial circumstances.²⁰

Role of HCPs

Health care practitioners (HCPs) are expected to help patients understand the risks and benefits of their choices and its alternative, align patients’ goals with those risks and benefits, and assist patients in making choices that promote their goals and autonomy.²¹ Family members are often not involved in medical decision making when patients have the capacity to make their own decisions.²² Patients will also have to give permission for protected health information to be shared with their family members.²² On the other hand, families have been shown to provide valuable emotional support to patients and are considered second patients themselves in the sense that they can be impacted by patients’ clinical situation.²² Families may also need care, time, and attention from HCPs.²²

Mr. S was found capable of making his own decisions, and part of that decision was that his family not to be present for the goals-of-care discussion. He added that he would discuss the care decisions with his family. At the time of registering for VA health care services, Mr. S had provided his health care team with his brother and sister-in-law’s emergency contact information as well as named his brother surrogate decision maker. As Mr. S’s condition was expected to rapidly decline wthout dialysis, the HCPs would be able to notify family members once his condition changed, including death.

Neuroplasticity changes can contribute to chronic pain that may also lead to depression.²³ Chronic pain and depression may involve the same brain structures, neurotransmitters, and signaling pathway.²³ Factors leading to chronic pain and depression include decreased availability of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine in the central nervous system, decreased brain-derived neurotrophic factor, inflammatory response, and increased glutamate activity.²³ Depression and hopelessness have been associated with the desire to hasten death among patients with a terminal illness.²⁴ Worse mental health has been associated with the desire to hasten death among patients who are older and functionally impaired.²⁵ It was important to optimize Mr. S’s treatment for pain and depression to ensure that these factors were not influencing his medical decisions.

With increasing recognition of the need to improve quality of life, health care utilization, and provide care consistent with patients’ goals in nephrology, the concept of renal PC is emerging but remains limited.²⁶ The need to improve supportive care or PC for patients starting on dialysis for ESRD is high as these patients tend to be older (aged > 75 years), have high rates of cardiovascular comorbidities, can have coexisting cognitive impairment and functional debility, and have an adjusted mortality rate of up to 32.5% within 1 year of starting dialysis.²⁶ Some ways to enhance renal PC programs include incorporating PC skill development and training within nephrology fellowships, educating patients with chronic and ESRD about PC and options for medical management without dialysis, and increasing the collaboration between nephrology and PC.²⁶

Outcomes and Implications

Respect for the ethical principle of autonomy is paramount in health care. Patients should be able to give informed consent for treatment decisions without undue influence from their HCPs and should be able to withdraw that consent at any point during treatment. Factors that may influence patients’ ability to make medical decisions should be considered, including untreated or poorly treated symptoms. The involvement of PC helps optimize symptom management, provide support, and assist in goals-of-care discussions. Advanced practice PC nurses can offer other members of the health care team additional information and support in end-of-life care. Family involvement should be encouraged even for patients who can make their own medical decisions for emotional support and to assist families in what could be a traumatic event, such as the loss of a loved one.

The desire to pursue a comfort-focused approach to terminal illness and stop disease-modifying treatments are criteria for hospice care. An interdisciplinary approach to end-of-life care is beneficial, and every specialty should be equipped to engage in honest communication and skillful prognostication. These conversations should start early in the course of a terminal illness. Multiple factors contribute to poor clinical outcomes among patients with ESRD even with renal replacement therapy, such as dialysis. There is a need to improve PC training in the field of nephrology.

Conclusions

Mr. S was able to choose to withdraw potentially life-prolonging treatments with the support of his family and HCPs. He was able to continue receiving high-quality care and treatment in accordance with his wishes and goals for his care. The provision of interdisciplinary care that focused on supporting him allowed for his peaceful and comfortable death.

Antihypertensive medications that stimulate rather than inhibit type 2 and 4 angiotensin II receptors can lower the rate of dementia among new users of these medications, new research suggests.

Results from a cohort study of more than 57,000 older Medicare beneficiaries showed that the initiation of antihypertensives that stimulate the receptors was linked to a 16% lower risk for incident Alzheimer’s disease and related dementia (ADRD) and an 18% lower risk for vascular dementia compared with those that inhibit the receptors.

“Achieving appropriate blood pressure control is essential for maximizing brain health, and this promising research suggests certain antihypertensives could yield brain benefit compared to others,” lead study author Zachary A. Marcum, PharmD, PhD, associate professor, University of Washington School of Pharmacy, Seattle, told this news organization.

The findings were published online in JAMA Network Open.
 

Medicare beneficiaries

Previous observational studies showed that antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, in comparison with those that don’t, were associated with lower rates of dementia. However, those studies included individuals with prevalent hypertension and were relatively small.

The new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries aged at least 65 years with new-onset hypertension. The mean age of participants was 73.8 years, 62.9% were women, and 86.9% were White.

Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.

Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers.

“All these medications lower blood pressure, but they do it in different ways,” said Dr. Marcum.

The researchers were interested in the varying activity of these drugs at the type 2 and 4 angiotensin II receptors.

For each 30-day interval, they categorized beneficiaries into four groups: a stimulating medication group (n = 4,879) consisting of individuals mostly taking stimulating antihypertensives; an inhibiting medication group (n = 10,303) that mostly included individuals prescribed this type of antihypertensive; a mixed group (n = 2,179) that included a combination of the first two classifications; and a nonuser group (n = 40,413) of individuals who were not using either type of drug.

The primary outcome was time to first occurrence of ADRD. The secondary outcome was time to first occurrence of vascular dementia.

Researchers controlled for cardiovascular risk factors and sociodemographic characteristics, such as age, sex, race/ethnicity, and receipt of low-income subsidy.
 

Unanswered questions

After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio, 0.84; 95% confidence interval, 0.79-0.90; P < .001).

The mixed regimen was also associated with statistically significant (P = .001) reduced odds of ADRD compared with the inhibiting medications.

As for vascular dementia, use of stimulating vs. inhibiting medications was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Again, use of the mixed regimen was associated with reduced risk of vascular dementia compared with the inhibiting medications (P = .03).

A variety of potential mechanisms might explain the superiority of stimulating agents when it comes to dementia risk, said Dr. Marcum. These could include, for example, increased blood flow to the brain and reduced amyloid.

“But more mechanistic work is needed as well as evaluation of dose responses, because that’s not something we looked at in this study,” Dr. Marcum said. “There are still a lot of unanswered questions.”
 

Stimulators instead of inhibitors?

The results of the current analysis come on the heels of some previous work showing the benefits of lowering blood pressure. For example, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure below 120 mm Hg significantly reduces risk for heart disease, stroke, and death from these diseases.

But in contrast to previous research, the current study included only beneficiaries with incident hypertension and new use of antihypertensive medications, and it adjusted for time-varying confounding.

Prescribing stimulating instead of inhibiting treatments could make a difference at the population level, Dr. Marcum noted.

“If we could shift the prescribing a little bit from inhibiting to stimulating, that could possibly reduce dementia risk,” he said.

However, “we’re not suggesting [that all patients] have their regimen switched,” he added.

That’s because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Dr. Marcum noted. As an example, beta-blockers are used post heart attack.

As well, factors such as cost and side effects should be taken into consideration when prescribing an antihypertensive drug.

The new results could be used to set up a comparison in a future randomized controlled trial that would provide the strongest evidence for estimating causal effects of treatments, said Dr. Marcum.
 

‘More convincing’

Carlos G. Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai, New York, said the study is “more convincing” than previous related research, as it has a larger sample size and a longer follow-up.

“And the exquisite statistical analysis gives more robustness, more solidity, to the hypothesis that drugs that stimulate type 2 and 4 angiotensin II receptors might be protective for dementia,” said Dr. Santos-Gallego, who was not involved with the research.

However, he noted that the retrospective study had some limitations, including the underdiagnosis of dementia. “The diagnosis of dementia is, honestly, very poorly done in the clinical setting,” he said.

As well, the study could be subject to “confounding by indication,” Dr. Santos-Gallego said. “There could be a third variable, another confounding factor, that’s responsible both for the dementia and for the prescription of these drugs,” he added.

For example, he noted that comorbidities such as atrial fibrillation, myocardial infarction, and heart failure might increase the risk of dementia.

He agreed with the investigators that a randomized clinical trial would address these limitations. “All comorbidities would be equally shared” in the randomized groups, and all participants would be given “a specific test for dementia at the same time,” Dr. Santos-Gallego said.

Still, he noted that the new results are in keeping with hypertension guidelines that recommend stimulating drugs.

“This trial definitely shows that the current hypertension guidelines are good treatment for our patients, not only to control blood pressure and not only to prevent infarction to prevent stroke but also to prevent dementia,” said Dr. Santos-Gallego.

Also commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the new data provide “clarity” on why previous research had differing results on the effect of antihypertensives on cognition.

Among the caveats of this new analysis is that “it’s unclear if the demographics in this study are fully representative of Medicare beneficiaries,” said Dr. Snyder.

She, too, said a clinical trial is important “to understand if there is a preventative and/or treatment potential in the medications that stimulate type 2 and 4 angiotensin II receptors.”

The study received funding from the National Institute on Aging. Dr. Marcum and Dr. Santos-Gallego have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Antihypertensive medications that stimulate rather than inhibit type 2 and 4 angiotensin II receptors can lower the rate of dementia among new users of these medications, new research suggests.

Results from a cohort study of more than 57,000 older Medicare beneficiaries showed that the initiation of antihypertensives that stimulate the receptors was linked to a 16% lower risk for incident Alzheimer’s disease and related dementia (ADRD) and an 18% lower risk for vascular dementia compared with those that inhibit the receptors.

“Achieving appropriate blood pressure control is essential for maximizing brain health, and this promising research suggests certain antihypertensives could yield brain benefit compared to others,” lead study author Zachary A. Marcum, PharmD, PhD, associate professor, University of Washington School of Pharmacy, Seattle, told this news organization.

The findings were published online in JAMA Network Open.
 

Medicare beneficiaries

Previous observational studies showed that antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, in comparison with those that don’t, were associated with lower rates of dementia. However, those studies included individuals with prevalent hypertension and were relatively small.

The new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries aged at least 65 years with new-onset hypertension. The mean age of participants was 73.8 years, 62.9% were women, and 86.9% were White.

Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.

Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers.

“All these medications lower blood pressure, but they do it in different ways,” said Dr. Marcum.

The researchers were interested in the varying activity of these drugs at the type 2 and 4 angiotensin II receptors.

For each 30-day interval, they categorized beneficiaries into four groups: a stimulating medication group (n = 4,879) consisting of individuals mostly taking stimulating antihypertensives; an inhibiting medication group (n = 10,303) that mostly included individuals prescribed this type of antihypertensive; a mixed group (n = 2,179) that included a combination of the first two classifications; and a nonuser group (n = 40,413) of individuals who were not using either type of drug.

The primary outcome was time to first occurrence of ADRD. The secondary outcome was time to first occurrence of vascular dementia.

Researchers controlled for cardiovascular risk factors and sociodemographic characteristics, such as age, sex, race/ethnicity, and receipt of low-income subsidy.
 

Unanswered questions

After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio, 0.84; 95% confidence interval, 0.79-0.90; P < .001).

The mixed regimen was also associated with statistically significant (P = .001) reduced odds of ADRD compared with the inhibiting medications.

As for vascular dementia, use of stimulating vs. inhibiting medications was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Again, use of the mixed regimen was associated with reduced risk of vascular dementia compared with the inhibiting medications (P = .03).

A variety of potential mechanisms might explain the superiority of stimulating agents when it comes to dementia risk, said Dr. Marcum. These could include, for example, increased blood flow to the brain and reduced amyloid.

“But more mechanistic work is needed as well as evaluation of dose responses, because that’s not something we looked at in this study,” Dr. Marcum said. “There are still a lot of unanswered questions.”
 

Stimulators instead of inhibitors?

The results of the current analysis come on the heels of some previous work showing the benefits of lowering blood pressure. For example, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure below 120 mm Hg significantly reduces risk for heart disease, stroke, and death from these diseases.

But in contrast to previous research, the current study included only beneficiaries with incident hypertension and new use of antihypertensive medications, and it adjusted for time-varying confounding.

Prescribing stimulating instead of inhibiting treatments could make a difference at the population level, Dr. Marcum noted.

“If we could shift the prescribing a little bit from inhibiting to stimulating, that could possibly reduce dementia risk,” he said.

However, “we’re not suggesting [that all patients] have their regimen switched,” he added.

That’s because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Dr. Marcum noted. As an example, beta-blockers are used post heart attack.

As well, factors such as cost and side effects should be taken into consideration when prescribing an antihypertensive drug.

The new results could be used to set up a comparison in a future randomized controlled trial that would provide the strongest evidence for estimating causal effects of treatments, said Dr. Marcum.
 

‘More convincing’

Carlos G. Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai, New York, said the study is “more convincing” than previous related research, as it has a larger sample size and a longer follow-up.

“And the exquisite statistical analysis gives more robustness, more solidity, to the hypothesis that drugs that stimulate type 2 and 4 angiotensin II receptors might be protective for dementia,” said Dr. Santos-Gallego, who was not involved with the research.

However, he noted that the retrospective study had some limitations, including the underdiagnosis of dementia. “The diagnosis of dementia is, honestly, very poorly done in the clinical setting,” he said.

As well, the study could be subject to “confounding by indication,” Dr. Santos-Gallego said. “There could be a third variable, another confounding factor, that’s responsible both for the dementia and for the prescription of these drugs,” he added.

For example, he noted that comorbidities such as atrial fibrillation, myocardial infarction, and heart failure might increase the risk of dementia.

He agreed with the investigators that a randomized clinical trial would address these limitations. “All comorbidities would be equally shared” in the randomized groups, and all participants would be given “a specific test for dementia at the same time,” Dr. Santos-Gallego said.

Still, he noted that the new results are in keeping with hypertension guidelines that recommend stimulating drugs.

“This trial definitely shows that the current hypertension guidelines are good treatment for our patients, not only to control blood pressure and not only to prevent infarction to prevent stroke but also to prevent dementia,” said Dr. Santos-Gallego.

Also commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the new data provide “clarity” on why previous research had differing results on the effect of antihypertensives on cognition.

Among the caveats of this new analysis is that “it’s unclear if the demographics in this study are fully representative of Medicare beneficiaries,” said Dr. Snyder.

She, too, said a clinical trial is important “to understand if there is a preventative and/or treatment potential in the medications that stimulate type 2 and 4 angiotensin II receptors.”

The study received funding from the National Institute on Aging. Dr. Marcum and Dr. Santos-Gallego have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Antihypertensive medications that stimulate rather than inhibit type 2 and 4 angiotensin II receptors can lower the rate of dementia among new users of these medications, new research suggests.

Results from a cohort study of more than 57,000 older Medicare beneficiaries showed that the initiation of antihypertensives that stimulate the receptors was linked to a 16% lower risk for incident Alzheimer’s disease and related dementia (ADRD) and an 18% lower risk for vascular dementia compared with those that inhibit the receptors.

“Achieving appropriate blood pressure control is essential for maximizing brain health, and this promising research suggests certain antihypertensives could yield brain benefit compared to others,” lead study author Zachary A. Marcum, PharmD, PhD, associate professor, University of Washington School of Pharmacy, Seattle, told this news organization.

The findings were published online in JAMA Network Open.
 

Medicare beneficiaries

Previous observational studies showed that antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, in comparison with those that don’t, were associated with lower rates of dementia. However, those studies included individuals with prevalent hypertension and were relatively small.

The new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries aged at least 65 years with new-onset hypertension. The mean age of participants was 73.8 years, 62.9% were women, and 86.9% were White.

Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.

Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers.

“All these medications lower blood pressure, but they do it in different ways,” said Dr. Marcum.

The researchers were interested in the varying activity of these drugs at the type 2 and 4 angiotensin II receptors.

For each 30-day interval, they categorized beneficiaries into four groups: a stimulating medication group (n = 4,879) consisting of individuals mostly taking stimulating antihypertensives; an inhibiting medication group (n = 10,303) that mostly included individuals prescribed this type of antihypertensive; a mixed group (n = 2,179) that included a combination of the first two classifications; and a nonuser group (n = 40,413) of individuals who were not using either type of drug.

The primary outcome was time to first occurrence of ADRD. The secondary outcome was time to first occurrence of vascular dementia.

Researchers controlled for cardiovascular risk factors and sociodemographic characteristics, such as age, sex, race/ethnicity, and receipt of low-income subsidy.
 

Unanswered questions

After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio, 0.84; 95% confidence interval, 0.79-0.90; P < .001).

The mixed regimen was also associated with statistically significant (P = .001) reduced odds of ADRD compared with the inhibiting medications.

As for vascular dementia, use of stimulating vs. inhibiting medications was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Again, use of the mixed regimen was associated with reduced risk of vascular dementia compared with the inhibiting medications (P = .03).

A variety of potential mechanisms might explain the superiority of stimulating agents when it comes to dementia risk, said Dr. Marcum. These could include, for example, increased blood flow to the brain and reduced amyloid.

“But more mechanistic work is needed as well as evaluation of dose responses, because that’s not something we looked at in this study,” Dr. Marcum said. “There are still a lot of unanswered questions.”
 

Stimulators instead of inhibitors?

The results of the current analysis come on the heels of some previous work showing the benefits of lowering blood pressure. For example, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure below 120 mm Hg significantly reduces risk for heart disease, stroke, and death from these diseases.

But in contrast to previous research, the current study included only beneficiaries with incident hypertension and new use of antihypertensive medications, and it adjusted for time-varying confounding.

Prescribing stimulating instead of inhibiting treatments could make a difference at the population level, Dr. Marcum noted.

“If we could shift the prescribing a little bit from inhibiting to stimulating, that could possibly reduce dementia risk,” he said.

However, “we’re not suggesting [that all patients] have their regimen switched,” he added.

That’s because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Dr. Marcum noted. As an example, beta-blockers are used post heart attack.

As well, factors such as cost and side effects should be taken into consideration when prescribing an antihypertensive drug.

The new results could be used to set up a comparison in a future randomized controlled trial that would provide the strongest evidence for estimating causal effects of treatments, said Dr. Marcum.
 

‘More convincing’

Carlos G. Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai, New York, said the study is “more convincing” than previous related research, as it has a larger sample size and a longer follow-up.

“And the exquisite statistical analysis gives more robustness, more solidity, to the hypothesis that drugs that stimulate type 2 and 4 angiotensin II receptors might be protective for dementia,” said Dr. Santos-Gallego, who was not involved with the research.

However, he noted that the retrospective study had some limitations, including the underdiagnosis of dementia. “The diagnosis of dementia is, honestly, very poorly done in the clinical setting,” he said.

As well, the study could be subject to “confounding by indication,” Dr. Santos-Gallego said. “There could be a third variable, another confounding factor, that’s responsible both for the dementia and for the prescription of these drugs,” he added.

For example, he noted that comorbidities such as atrial fibrillation, myocardial infarction, and heart failure might increase the risk of dementia.

He agreed with the investigators that a randomized clinical trial would address these limitations. “All comorbidities would be equally shared” in the randomized groups, and all participants would be given “a specific test for dementia at the same time,” Dr. Santos-Gallego said.

Still, he noted that the new results are in keeping with hypertension guidelines that recommend stimulating drugs.

“This trial definitely shows that the current hypertension guidelines are good treatment for our patients, not only to control blood pressure and not only to prevent infarction to prevent stroke but also to prevent dementia,” said Dr. Santos-Gallego.

Also commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the new data provide “clarity” on why previous research had differing results on the effect of antihypertensives on cognition.

Among the caveats of this new analysis is that “it’s unclear if the demographics in this study are fully representative of Medicare beneficiaries,” said Dr. Snyder.

She, too, said a clinical trial is important “to understand if there is a preventative and/or treatment potential in the medications that stimulate type 2 and 4 angiotensin II receptors.”

The study received funding from the National Institute on Aging. Dr. Marcum and Dr. Santos-Gallego have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A small cohort study of pediatric rheumatology patients with generalized joint hypermobility (GJH) who presented to a specialized rheumatology* clinic suggests that many such patients have abnormal bleeding symptoms, in comparison with health control patients.

The study of 81 patients with GJH found that about three quarters had significantly elevated median bleeding scores, but only 12% had been assessed by hematology for bleeding.

“We propose that screening for bleeding symptoms should be integrated into the routine care for all patients with GJH, with hematology referrals for patients with increased bleeding concerns,” wrote a research team led by Nicole E. Kendel, MD, a pediatric hematologist-oncologist at Akron Children’s Hospital in Ohio, in a study published online in Arthritis Care and Research.

“Further studies are needed to understand the mechanism of bleeding, evaluate comorbidities associated with these bleeding symptoms, and potentially allow for tailored pharmacologic therapy,” the authors stated.
 

Background

Dr. Kendel’s team had reported moderate menstruation-associated limitations in school, social, and physical activities among female adolescents with GJH. “This cohort also experienced nonreproductive bleeding symptoms and demonstrated minimal hemostatic laboratory abnormalities, indicating that this population may be underdiagnosed and subsequently poorly managed,” she said in an interview. “As excessive bleeding symptoms could have a significant impact on overall health and quality of life, we thought it was important to define the incidence and natural course of bleeding symptoms in a more generalized subset of this population.”

Although the investigators hypothesized that there would be a statistically significant increase in bleeding scores, “we were still impressed by the frequency of abnormal scores, particularly when looking at the low percentage of patients [12%] who had previously been referred to hematology,” she said.
 

Study results

The median age of the study cohort was 13 years (interquartile range, 10-16 years), and 72.8% were female. The mean Beighton score, which measures joint flexibility, was 6.2 (range, 4-9). All participants were seen by rheumatologists and were diagnosed for conditions on the hypermobility spectrum. Those conditions ranged from GJH to hypermobile Ehlers-Danlos syndrome (hEDS).

Abnormal bleeding, as measured by the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool, was found in 75% (95% confidence interval [CI], 64%-84%). Overall mean and median bleeding scores were 5.2 and 4, respectively; scores ranged from 0 to 16. Abnormal scores of ≥ 3 were observed for patients < 8 years of age, ≥ 4 for men ≥ 18 years of age, and ≥ 6 for women ≥ 18 years of age. These measures were significantly elevated compared with those reported for historical healthy pediatric control persons (P < .001).

The most common hemorrhagic symptom was oral bleeding (74.1%) that occurred with tooth brushing, flossing, tooth loss, or eruption. Others reported easy bruising (59.3%) and bleeding from minor wounds (42%). In terms of procedures, tooth extraction requiring additional packing was reported by 25.9%, and 22.2% reported significant bleeding after otolaryngologic procedures, such as tonsillectomy/adenoidectomy, septoplasty, and nasal turbinate reduction.

Prolonged or heavy menstrual periods were reported by 37.3% of female patients.

Bleeding scores did not differ by biological sex or NSAID use, nor did any correlation emerge between patients’ bleeding and Beighton scores. However, there was a positive correlation with increasing age, a phenomenon observed with other bleeding disorders and in the healthy population, the authors noted.

Of the 10 study participants who had previously undergone hematologic assessment, one had been diagnosed with acquired, heart disease–related von Willebrand disease, and another with mild bleeding disorder.

Severe connective tissue disorders are associated with increased bleeding symptoms in the adult population, Dr. Kendel said, but few studies have assessed bleeding across the GJH spectrum, particularly in children.

Bleeding is thought to be due to modifications of collagen in the blood vessels. “These modifications create mechanical weakness of the vessel wall, as well as defective subendothelial connective tissue supporting those blood vessels,” Dr. Kendel explained. She noted that altered collagen creates defective interactions between collagen and other coagulation factors.

“Even in the presence of a normal laboratory evaluation, GJH can lead to symptoms consistent with a mild bleeding disorder,” she continued. “These symptoms are both preventable and treatable. I’m hopeful more centers will start routinely evaluating for increased bleeding symptoms, with referral to hematology for those with increased bleeding concerns.”

Commenting on the study’s recommendation, Beth S. Gottlieb, MD, chief of the division of pediatric rheumatology at Northwell Health in New Hyde Park, N.Y., who was not involved in the investigation, said a brief questionnaire on bleeding risk is a reasonable addition to a rheumatology office visit.

“Joint hypermobility is very common, but not all affected children meet the criteria for the hypermobile form of hEDS,” she told this news organization. “Screening for bleeding tendency is often done as routine medical history questions. Once a child is identified as hypermobile, these screening questions are usually asked, but utilizing one of the formal bleeding risk questionnaires is not currently routine.”

According to Dr. Gottlieb, it remains unclear whether screening would have a significant impact on children who have been diagnosed with hypermobility. “Most of these children are young and may not yet have a significant history for bleeding tendency,” she said. “Education of families is always important, and it will be essential to educate without adding unnecessary stress. Screening guidelines may be an important tool that is easy to incorporate into routine clinical practice.”
 

Limitation

The study was limited by selection bias, as patients had all been referred to a specialized rheumatology clinic.

The study was supported by the Clinical and Translational Intramural Funding Program of the Abigail Wexner Research Institute. The authors and Dr. Gottlieb have disclosed no relevant financial relationships.

*Correction, 1/11/2023: An earlier version of this story misstated the type of specialty clinic where patients were first seen. 

A version of this article first appeared on Medscape.com.

A small cohort study of pediatric rheumatology patients with generalized joint hypermobility (GJH) who presented to a specialized rheumatology* clinic suggests that many such patients have abnormal bleeding symptoms, in comparison with health control patients.

The study of 81 patients with GJH found that about three quarters had significantly elevated median bleeding scores, but only 12% had been assessed by hematology for bleeding.

“We propose that screening for bleeding symptoms should be integrated into the routine care for all patients with GJH, with hematology referrals for patients with increased bleeding concerns,” wrote a research team led by Nicole E. Kendel, MD, a pediatric hematologist-oncologist at Akron Children’s Hospital in Ohio, in a study published online in Arthritis Care and Research.

“Further studies are needed to understand the mechanism of bleeding, evaluate comorbidities associated with these bleeding symptoms, and potentially allow for tailored pharmacologic therapy,” the authors stated.
 

Background

Dr. Kendel’s team had reported moderate menstruation-associated limitations in school, social, and physical activities among female adolescents with GJH. “This cohort also experienced nonreproductive bleeding symptoms and demonstrated minimal hemostatic laboratory abnormalities, indicating that this population may be underdiagnosed and subsequently poorly managed,” she said in an interview. “As excessive bleeding symptoms could have a significant impact on overall health and quality of life, we thought it was important to define the incidence and natural course of bleeding symptoms in a more generalized subset of this population.”

Although the investigators hypothesized that there would be a statistically significant increase in bleeding scores, “we were still impressed by the frequency of abnormal scores, particularly when looking at the low percentage of patients [12%] who had previously been referred to hematology,” she said.
 

Study results

The median age of the study cohort was 13 years (interquartile range, 10-16 years), and 72.8% were female. The mean Beighton score, which measures joint flexibility, was 6.2 (range, 4-9). All participants were seen by rheumatologists and were diagnosed for conditions on the hypermobility spectrum. Those conditions ranged from GJH to hypermobile Ehlers-Danlos syndrome (hEDS).

Abnormal bleeding, as measured by the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool, was found in 75% (95% confidence interval [CI], 64%-84%). Overall mean and median bleeding scores were 5.2 and 4, respectively; scores ranged from 0 to 16. Abnormal scores of ≥ 3 were observed for patients < 8 years of age, ≥ 4 for men ≥ 18 years of age, and ≥ 6 for women ≥ 18 years of age. These measures were significantly elevated compared with those reported for historical healthy pediatric control persons (P < .001).

The most common hemorrhagic symptom was oral bleeding (74.1%) that occurred with tooth brushing, flossing, tooth loss, or eruption. Others reported easy bruising (59.3%) and bleeding from minor wounds (42%). In terms of procedures, tooth extraction requiring additional packing was reported by 25.9%, and 22.2% reported significant bleeding after otolaryngologic procedures, such as tonsillectomy/adenoidectomy, septoplasty, and nasal turbinate reduction.

Prolonged or heavy menstrual periods were reported by 37.3% of female patients.

Bleeding scores did not differ by biological sex or NSAID use, nor did any correlation emerge between patients’ bleeding and Beighton scores. However, there was a positive correlation with increasing age, a phenomenon observed with other bleeding disorders and in the healthy population, the authors noted.

Of the 10 study participants who had previously undergone hematologic assessment, one had been diagnosed with acquired, heart disease–related von Willebrand disease, and another with mild bleeding disorder.

Severe connective tissue disorders are associated with increased bleeding symptoms in the adult population, Dr. Kendel said, but few studies have assessed bleeding across the GJH spectrum, particularly in children.

Bleeding is thought to be due to modifications of collagen in the blood vessels. “These modifications create mechanical weakness of the vessel wall, as well as defective subendothelial connective tissue supporting those blood vessels,” Dr. Kendel explained. She noted that altered collagen creates defective interactions between collagen and other coagulation factors.

“Even in the presence of a normal laboratory evaluation, GJH can lead to symptoms consistent with a mild bleeding disorder,” she continued. “These symptoms are both preventable and treatable. I’m hopeful more centers will start routinely evaluating for increased bleeding symptoms, with referral to hematology for those with increased bleeding concerns.”

Commenting on the study’s recommendation, Beth S. Gottlieb, MD, chief of the division of pediatric rheumatology at Northwell Health in New Hyde Park, N.Y., who was not involved in the investigation, said a brief questionnaire on bleeding risk is a reasonable addition to a rheumatology office visit.

“Joint hypermobility is very common, but not all affected children meet the criteria for the hypermobile form of hEDS,” she told this news organization. “Screening for bleeding tendency is often done as routine medical history questions. Once a child is identified as hypermobile, these screening questions are usually asked, but utilizing one of the formal bleeding risk questionnaires is not currently routine.”

According to Dr. Gottlieb, it remains unclear whether screening would have a significant impact on children who have been diagnosed with hypermobility. “Most of these children are young and may not yet have a significant history for bleeding tendency,” she said. “Education of families is always important, and it will be essential to educate without adding unnecessary stress. Screening guidelines may be an important tool that is easy to incorporate into routine clinical practice.”
 

Limitation

The study was limited by selection bias, as patients had all been referred to a specialized rheumatology clinic.

The study was supported by the Clinical and Translational Intramural Funding Program of the Abigail Wexner Research Institute. The authors and Dr. Gottlieb have disclosed no relevant financial relationships.

*Correction, 1/11/2023: An earlier version of this story misstated the type of specialty clinic where patients were first seen. 

A version of this article first appeared on Medscape.com.

A small cohort study of pediatric rheumatology patients with generalized joint hypermobility (GJH) who presented to a specialized rheumatology* clinic suggests that many such patients have abnormal bleeding symptoms, in comparison with health control patients.

The study of 81 patients with GJH found that about three quarters had significantly elevated median bleeding scores, but only 12% had been assessed by hematology for bleeding.

“We propose that screening for bleeding symptoms should be integrated into the routine care for all patients with GJH, with hematology referrals for patients with increased bleeding concerns,” wrote a research team led by Nicole E. Kendel, MD, a pediatric hematologist-oncologist at Akron Children’s Hospital in Ohio, in a study published online in Arthritis Care and Research.

“Further studies are needed to understand the mechanism of bleeding, evaluate comorbidities associated with these bleeding symptoms, and potentially allow for tailored pharmacologic therapy,” the authors stated.
 

Background

Dr. Kendel’s team had reported moderate menstruation-associated limitations in school, social, and physical activities among female adolescents with GJH. “This cohort also experienced nonreproductive bleeding symptoms and demonstrated minimal hemostatic laboratory abnormalities, indicating that this population may be underdiagnosed and subsequently poorly managed,” she said in an interview. “As excessive bleeding symptoms could have a significant impact on overall health and quality of life, we thought it was important to define the incidence and natural course of bleeding symptoms in a more generalized subset of this population.”

Although the investigators hypothesized that there would be a statistically significant increase in bleeding scores, “we were still impressed by the frequency of abnormal scores, particularly when looking at the low percentage of patients [12%] who had previously been referred to hematology,” she said.
 

Study results

The median age of the study cohort was 13 years (interquartile range, 10-16 years), and 72.8% were female. The mean Beighton score, which measures joint flexibility, was 6.2 (range, 4-9). All participants were seen by rheumatologists and were diagnosed for conditions on the hypermobility spectrum. Those conditions ranged from GJH to hypermobile Ehlers-Danlos syndrome (hEDS).

Abnormal bleeding, as measured by the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool, was found in 75% (95% confidence interval [CI], 64%-84%). Overall mean and median bleeding scores were 5.2 and 4, respectively; scores ranged from 0 to 16. Abnormal scores of ≥ 3 were observed for patients < 8 years of age, ≥ 4 for men ≥ 18 years of age, and ≥ 6 for women ≥ 18 years of age. These measures were significantly elevated compared with those reported for historical healthy pediatric control persons (P < .001).

The most common hemorrhagic symptom was oral bleeding (74.1%) that occurred with tooth brushing, flossing, tooth loss, or eruption. Others reported easy bruising (59.3%) and bleeding from minor wounds (42%). In terms of procedures, tooth extraction requiring additional packing was reported by 25.9%, and 22.2% reported significant bleeding after otolaryngologic procedures, such as tonsillectomy/adenoidectomy, septoplasty, and nasal turbinate reduction.

Prolonged or heavy menstrual periods were reported by 37.3% of female patients.

Bleeding scores did not differ by biological sex or NSAID use, nor did any correlation emerge between patients’ bleeding and Beighton scores. However, there was a positive correlation with increasing age, a phenomenon observed with other bleeding disorders and in the healthy population, the authors noted.

Of the 10 study participants who had previously undergone hematologic assessment, one had been diagnosed with acquired, heart disease–related von Willebrand disease, and another with mild bleeding disorder.

Severe connective tissue disorders are associated with increased bleeding symptoms in the adult population, Dr. Kendel said, but few studies have assessed bleeding across the GJH spectrum, particularly in children.

Bleeding is thought to be due to modifications of collagen in the blood vessels. “These modifications create mechanical weakness of the vessel wall, as well as defective subendothelial connective tissue supporting those blood vessels,” Dr. Kendel explained. She noted that altered collagen creates defective interactions between collagen and other coagulation factors.

“Even in the presence of a normal laboratory evaluation, GJH can lead to symptoms consistent with a mild bleeding disorder,” she continued. “These symptoms are both preventable and treatable. I’m hopeful more centers will start routinely evaluating for increased bleeding symptoms, with referral to hematology for those with increased bleeding concerns.”

Commenting on the study’s recommendation, Beth S. Gottlieb, MD, chief of the division of pediatric rheumatology at Northwell Health in New Hyde Park, N.Y., who was not involved in the investigation, said a brief questionnaire on bleeding risk is a reasonable addition to a rheumatology office visit.

“Joint hypermobility is very common, but not all affected children meet the criteria for the hypermobile form of hEDS,” she told this news organization. “Screening for bleeding tendency is often done as routine medical history questions. Once a child is identified as hypermobile, these screening questions are usually asked, but utilizing one of the formal bleeding risk questionnaires is not currently routine.”

According to Dr. Gottlieb, it remains unclear whether screening would have a significant impact on children who have been diagnosed with hypermobility. “Most of these children are young and may not yet have a significant history for bleeding tendency,” she said. “Education of families is always important, and it will be essential to educate without adding unnecessary stress. Screening guidelines may be an important tool that is easy to incorporate into routine clinical practice.”
 

Limitation

The study was limited by selection bias, as patients had all been referred to a specialized rheumatology clinic.

The study was supported by the Clinical and Translational Intramural Funding Program of the Abigail Wexner Research Institute. The authors and Dr. Gottlieb have disclosed no relevant financial relationships.

*Correction, 1/11/2023: An earlier version of this story misstated the type of specialty clinic where patients were first seen. 

A version of this article first appeared on Medscape.com.

Reporting on chronic lymphocytic leukemia (CLL) highlights from the American Society of Hematology meetings, Dr Nicholas Burwick of the Puget Sound Veterans Administration Health Care System discusses studies ranging from first-line treatment to options for relapsed/refractory disease. 

Dr Burwick cites a Veterans Health Administration study documenting the increasing movement toward novel agents as frontline treatment in CLL since 2018, and the emerging trend toward use of second-generation Bruton tyrosine kinase (BTK) inhibitors. 

Next, he discusses a study examining the frontline combination of ibrutinib and venetoclax, which may help overcome poor prognosis associated with unmutated IGHV CLL. 

In another study, the combination of venetoclax and ibrutinib was examined in high-risk patients treated with ibrutinib for 1 year. The results showed the combination deepens responses and even offers the potential for discontinuation of therapy. 

Turning to relapsed/refractory disease, Dr Burwick highlights the latest results of pirtobrutinib, which continues to show efficacy among heavily pretreated patients regardless of prior therapy, reason for discontinuation, or mutation status. 

Finally, he points to zanubrutinib, which demonstrated superiority to ibrutinib in a long-range study of progression-free survival.  

--

Nicholas R. Burwick, MD, Associate Professor, Division of Hematology, Department of Medicine, University of Washington; Attending Physician, Division of Hematology, Department of Medicine, Puget Sound VA Health Care System, Seattle, Washington 

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships. 

Reporting on chronic lymphocytic leukemia (CLL) highlights from the American Society of Hematology meetings, Dr Nicholas Burwick of the Puget Sound Veterans Administration Health Care System discusses studies ranging from first-line treatment to options for relapsed/refractory disease. 

Dr Burwick cites a Veterans Health Administration study documenting the increasing movement toward novel agents as frontline treatment in CLL since 2018, and the emerging trend toward use of second-generation Bruton tyrosine kinase (BTK) inhibitors. 

Next, he discusses a study examining the frontline combination of ibrutinib and venetoclax, which may help overcome poor prognosis associated with unmutated IGHV CLL. 

In another study, the combination of venetoclax and ibrutinib was examined in high-risk patients treated with ibrutinib for 1 year. The results showed the combination deepens responses and even offers the potential for discontinuation of therapy. 

Turning to relapsed/refractory disease, Dr Burwick highlights the latest results of pirtobrutinib, which continues to show efficacy among heavily pretreated patients regardless of prior therapy, reason for discontinuation, or mutation status. 

Finally, he points to zanubrutinib, which demonstrated superiority to ibrutinib in a long-range study of progression-free survival.  

--

Nicholas R. Burwick, MD, Associate Professor, Division of Hematology, Department of Medicine, University of Washington; Attending Physician, Division of Hematology, Department of Medicine, Puget Sound VA Health Care System, Seattle, Washington 

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships. 

Reporting on chronic lymphocytic leukemia (CLL) highlights from the American Society of Hematology meetings, Dr Nicholas Burwick of the Puget Sound Veterans Administration Health Care System discusses studies ranging from first-line treatment to options for relapsed/refractory disease. 

Dr Burwick cites a Veterans Health Administration study documenting the increasing movement toward novel agents as frontline treatment in CLL since 2018, and the emerging trend toward use of second-generation Bruton tyrosine kinase (BTK) inhibitors. 

Next, he discusses a study examining the frontline combination of ibrutinib and venetoclax, which may help overcome poor prognosis associated with unmutated IGHV CLL. 

In another study, the combination of venetoclax and ibrutinib was examined in high-risk patients treated with ibrutinib for 1 year. The results showed the combination deepens responses and even offers the potential for discontinuation of therapy. 

Turning to relapsed/refractory disease, Dr Burwick highlights the latest results of pirtobrutinib, which continues to show efficacy among heavily pretreated patients regardless of prior therapy, reason for discontinuation, or mutation status. 

Finally, he points to zanubrutinib, which demonstrated superiority to ibrutinib in a long-range study of progression-free survival.  

--

Nicholas R. Burwick, MD, Associate Professor, Division of Hematology, Department of Medicine, University of Washington; Attending Physician, Division of Hematology, Department of Medicine, Puget Sound VA Health Care System, Seattle, Washington 

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships. 

You discuss and decide on the best course of treatment for your patients, write prescriptions, and recommend lifestyle modifications to enhance treatment outcomes and overall wellness. But once they leave your office, following through is up to the patient. What happens when they don’t listen?

The term “nonadherent” has gradually replaced “noncompliant” in the physician lexicon as a nod to the evolving doctor-patient relationship. Noncompliance implies that a patient isn’t following their doctor’s orders. Adherence, on the other hand, is a measure of how closely your patient’s behavior matches the recommendations you’ve made. It’s a subtle difference but an important distinction in approaching care.

“Noncompliance is inherently negative feedback to the patient, whereas there’s a reason for nonadherence, and it’s usually external,” said Sharon Rabinovitz, MD, president of the Georgia Academy of Family Physicians.
 

Why won’t patients listen?

The reasons behind a patient’s nonadherence are multifaceted, but they are often driven by social determinants of health, such as transportation, poor health literacy, finances, and lack of access to pharmacies.

Other times, patients don’t want to take medicine, don’t prioritize their health, or they find the dietary and lifestyle modifications doctors suggest too hard to make or they struggle at losing weight, eating more healthfully, or cutting back on alcohol, for instance.

“When you come down to it, the big hindrance of it all is cost and the ability for the patient to be able to afford some of the things that we think they should be able to do,” said Teresa Lovins, MD, a physician in private practice Columbus, Ind., and a member of the board of directors of the American Academy of Family Physicians.

Another common deterrent to treatment is undesired side effects that a patient may not want to mention.

“For example, a lot of patients who are taking antidepressants have sexual dysfunction associated with those medications,” said Dr. Rabinovitz. “If you don’t ask the right questions, you’re not going to be able to fully assess the experience the patient is having and a reason why they might not take it [the medication].”

Much nonadherence is intentional and is based on experience, belief systems, and knowledge. For example, the American Medical Association finds that patients may not understand why they need a certain treatment (and therefore dismiss it), or they may be overloaded with multiple medications, fear dependency on a drug, have a mistrust of pharmaceutical companies or the medical system as a whole, or have symptoms of depression that make taking healthy actions more difficult. In addition, patients may be unable to afford their medication, or their lack of symptoms may lead them to believe they don’t really need the prescription, as occurs with disorders such as hypertension or high cholesterol.

“In my training, we did something called Balint training, where we would get together as a group with attendings and discuss cases that were difficult from a biopsychosocial perspective and consider all the factors in the patient perspective, including family dynamics, social systems, and economic realities,” said Russell Blackwelder, MD, director of geriatric education and associate professor of family medicine at the Medical University of South Carolina, Charleston.

“That training was, for me, very helpful for opening up and being more empathetic and really examining the patient’s point of view and everything that impacts them.”

Dr. Lovins agreed that it’s crucial to establish a good rapport and build mutual trust.

“If you don’t know the patient, you have a harder time asking the right questions to get to the meat of why they’re not taking their medicine or what they’re not doing to help their health,” she said. “It takes a little bit of trust on both parts to get to that question that really gets to the heart of why they’re not doing what you’re asking them to do.”
 

How to encourage adherence

Although there may not be a one-size-fits-all approach for achieving general adherence or adherence to a medication regimen, some methods may increase success.

Kenneth Zweig, MD, an internist at Northern Virginia Family Practice Associates, Alexandria, said that convincing patients to make one small change that they can sustain can get the ball rolling.

“I had one patient who was very overweight and had high blood pressure, high cholesterol, back pain, insomnia, and depression, who was also drinking three to four beers a night,” Dr. Zweig said. “After a long discussion, I challenged him to stop all alcohol for 1 week. At the end of the week, he noticed that he slept better, lost some weight, had lower blood pressure, and had more energy. Once he saw the benefits of this one change, he was motivated to improve other aspects of his health as well. He improved his diet, started exercising, and lost over 50 pounds. He has persisted with these lifestyle changes ever since.”

A team-based approach may also increase treatment understanding and adherence. In one older study, patients who were assigned to team-based care, including care by pharmacists, were significantly more adherent to medication regimens. Patients were more comfortable asking questions and raising concerns when they felt their treatment plan was a collaboration between several providers and themselves.

Dr. Lovins said to always approach the patient with a positive. “Say, what can we do together to make this work? What are your questions about this medication? And try and focus on the positive things that you can change instead of leaving the patient with a negative feeling or that you’re angry with them or that you’re unhappy with their choices. Patients respond better when they are treated as part of the team.”

Fear of judgment can also be a barrier to honesty between patients and their doctors. Shame creates a reluctance to admit nonadherence. Dr. Lovins said in an interview that it’s the physician’s responsibility to create a blame-free space for patients to speak openly about their struggles with treatment and reasons for nonadherence.
 

When should you redirect care?

Ultimately, the goal is good care and treatment of disease. However, if you and your patient are at an impasse and progress is stalling or failing, it may be appropriate to encourage the patient to seek care elsewhere.

“Just like any relationship, some physician-patient relationships are just not a good fit,” said Dr. Blackwelder. And this may be the reason why the patient is nonadherent — something between the two of you doesn’t click.

While there are ethical considerations for this decision, most medical boards have guidelines on how to go about it, Dr. Blackwelder said in an interview. “In the state of South Carolina, we have to be available to provide urgent coverage for at least 30 days and notify the patient in writing that they need to find somebody else and to help them find somebody else if we can.”

Just as with care, a clear conversation is the best practice if you’re proposing a potential shift away from a physician-patient relationship. You might say: We’re not making the kind of progress I’d like to see, and I’m wondering if you think working with another doctor may help you.

“The most important thing is being very honest and transparent with the patient that you’re concerned you’re not making the appropriate strides forward,” said Dr. Rabinovitz. Then you can ask, ‘Am I the right doctor to help you reach your goals? And if not, how can I help you get to where you need to be?’ ”

A version of this article first appeared on Medscape.com.

You discuss and decide on the best course of treatment for your patients, write prescriptions, and recommend lifestyle modifications to enhance treatment outcomes and overall wellness. But once they leave your office, following through is up to the patient. What happens when they don’t listen?

The term “nonadherent” has gradually replaced “noncompliant” in the physician lexicon as a nod to the evolving doctor-patient relationship. Noncompliance implies that a patient isn’t following their doctor’s orders. Adherence, on the other hand, is a measure of how closely your patient’s behavior matches the recommendations you’ve made. It’s a subtle difference but an important distinction in approaching care.

“Noncompliance is inherently negative feedback to the patient, whereas there’s a reason for nonadherence, and it’s usually external,” said Sharon Rabinovitz, MD, president of the Georgia Academy of Family Physicians.
 

Why won’t patients listen?

The reasons behind a patient’s nonadherence are multifaceted, but they are often driven by social determinants of health, such as transportation, poor health literacy, finances, and lack of access to pharmacies.

Other times, patients don’t want to take medicine, don’t prioritize their health, or they find the dietary and lifestyle modifications doctors suggest too hard to make or they struggle at losing weight, eating more healthfully, or cutting back on alcohol, for instance.

“When you come down to it, the big hindrance of it all is cost and the ability for the patient to be able to afford some of the things that we think they should be able to do,” said Teresa Lovins, MD, a physician in private practice Columbus, Ind., and a member of the board of directors of the American Academy of Family Physicians.

Another common deterrent to treatment is undesired side effects that a patient may not want to mention.

“For example, a lot of patients who are taking antidepressants have sexual dysfunction associated with those medications,” said Dr. Rabinovitz. “If you don’t ask the right questions, you’re not going to be able to fully assess the experience the patient is having and a reason why they might not take it [the medication].”

Much nonadherence is intentional and is based on experience, belief systems, and knowledge. For example, the American Medical Association finds that patients may not understand why they need a certain treatment (and therefore dismiss it), or they may be overloaded with multiple medications, fear dependency on a drug, have a mistrust of pharmaceutical companies or the medical system as a whole, or have symptoms of depression that make taking healthy actions more difficult. In addition, patients may be unable to afford their medication, or their lack of symptoms may lead them to believe they don’t really need the prescription, as occurs with disorders such as hypertension or high cholesterol.

“In my training, we did something called Balint training, where we would get together as a group with attendings and discuss cases that were difficult from a biopsychosocial perspective and consider all the factors in the patient perspective, including family dynamics, social systems, and economic realities,” said Russell Blackwelder, MD, director of geriatric education and associate professor of family medicine at the Medical University of South Carolina, Charleston.

“That training was, for me, very helpful for opening up and being more empathetic and really examining the patient’s point of view and everything that impacts them.”

Dr. Lovins agreed that it’s crucial to establish a good rapport and build mutual trust.

“If you don’t know the patient, you have a harder time asking the right questions to get to the meat of why they’re not taking their medicine or what they’re not doing to help their health,” she said. “It takes a little bit of trust on both parts to get to that question that really gets to the heart of why they’re not doing what you’re asking them to do.”
 

How to encourage adherence

Although there may not be a one-size-fits-all approach for achieving general adherence or adherence to a medication regimen, some methods may increase success.

Kenneth Zweig, MD, an internist at Northern Virginia Family Practice Associates, Alexandria, said that convincing patients to make one small change that they can sustain can get the ball rolling.

“I had one patient who was very overweight and had high blood pressure, high cholesterol, back pain, insomnia, and depression, who was also drinking three to four beers a night,” Dr. Zweig said. “After a long discussion, I challenged him to stop all alcohol for 1 week. At the end of the week, he noticed that he slept better, lost some weight, had lower blood pressure, and had more energy. Once he saw the benefits of this one change, he was motivated to improve other aspects of his health as well. He improved his diet, started exercising, and lost over 50 pounds. He has persisted with these lifestyle changes ever since.”

A team-based approach may also increase treatment understanding and adherence. In one older study, patients who were assigned to team-based care, including care by pharmacists, were significantly more adherent to medication regimens. Patients were more comfortable asking questions and raising concerns when they felt their treatment plan was a collaboration between several providers and themselves.

Dr. Lovins said to always approach the patient with a positive. “Say, what can we do together to make this work? What are your questions about this medication? And try and focus on the positive things that you can change instead of leaving the patient with a negative feeling or that you’re angry with them or that you’re unhappy with their choices. Patients respond better when they are treated as part of the team.”

Fear of judgment can also be a barrier to honesty between patients and their doctors. Shame creates a reluctance to admit nonadherence. Dr. Lovins said in an interview that it’s the physician’s responsibility to create a blame-free space for patients to speak openly about their struggles with treatment and reasons for nonadherence.
 

When should you redirect care?

Ultimately, the goal is good care and treatment of disease. However, if you and your patient are at an impasse and progress is stalling or failing, it may be appropriate to encourage the patient to seek care elsewhere.

“Just like any relationship, some physician-patient relationships are just not a good fit,” said Dr. Blackwelder. And this may be the reason why the patient is nonadherent — something between the two of you doesn’t click.

While there are ethical considerations for this decision, most medical boards have guidelines on how to go about it, Dr. Blackwelder said in an interview. “In the state of South Carolina, we have to be available to provide urgent coverage for at least 30 days and notify the patient in writing that they need to find somebody else and to help them find somebody else if we can.”

Just as with care, a clear conversation is the best practice if you’re proposing a potential shift away from a physician-patient relationship. You might say: We’re not making the kind of progress I’d like to see, and I’m wondering if you think working with another doctor may help you.

“The most important thing is being very honest and transparent with the patient that you’re concerned you’re not making the appropriate strides forward,” said Dr. Rabinovitz. Then you can ask, ‘Am I the right doctor to help you reach your goals? And if not, how can I help you get to where you need to be?’ ”

A version of this article first appeared on Medscape.com.

You discuss and decide on the best course of treatment for your patients, write prescriptions, and recommend lifestyle modifications to enhance treatment outcomes and overall wellness. But once they leave your office, following through is up to the patient. What happens when they don’t listen?

The term “nonadherent” has gradually replaced “noncompliant” in the physician lexicon as a nod to the evolving doctor-patient relationship. Noncompliance implies that a patient isn’t following their doctor’s orders. Adherence, on the other hand, is a measure of how closely your patient’s behavior matches the recommendations you’ve made. It’s a subtle difference but an important distinction in approaching care.

“Noncompliance is inherently negative feedback to the patient, whereas there’s a reason for nonadherence, and it’s usually external,” said Sharon Rabinovitz, MD, president of the Georgia Academy of Family Physicians.
 

Why won’t patients listen?

The reasons behind a patient’s nonadherence are multifaceted, but they are often driven by social determinants of health, such as transportation, poor health literacy, finances, and lack of access to pharmacies.

Other times, patients don’t want to take medicine, don’t prioritize their health, or they find the dietary and lifestyle modifications doctors suggest too hard to make or they struggle at losing weight, eating more healthfully, or cutting back on alcohol, for instance.

“When you come down to it, the big hindrance of it all is cost and the ability for the patient to be able to afford some of the things that we think they should be able to do,” said Teresa Lovins, MD, a physician in private practice Columbus, Ind., and a member of the board of directors of the American Academy of Family Physicians.

Another common deterrent to treatment is undesired side effects that a patient may not want to mention.

“For example, a lot of patients who are taking antidepressants have sexual dysfunction associated with those medications,” said Dr. Rabinovitz. “If you don’t ask the right questions, you’re not going to be able to fully assess the experience the patient is having and a reason why they might not take it [the medication].”

Much nonadherence is intentional and is based on experience, belief systems, and knowledge. For example, the American Medical Association finds that patients may not understand why they need a certain treatment (and therefore dismiss it), or they may be overloaded with multiple medications, fear dependency on a drug, have a mistrust of pharmaceutical companies or the medical system as a whole, or have symptoms of depression that make taking healthy actions more difficult. In addition, patients may be unable to afford their medication, or their lack of symptoms may lead them to believe they don’t really need the prescription, as occurs with disorders such as hypertension or high cholesterol.

“In my training, we did something called Balint training, where we would get together as a group with attendings and discuss cases that were difficult from a biopsychosocial perspective and consider all the factors in the patient perspective, including family dynamics, social systems, and economic realities,” said Russell Blackwelder, MD, director of geriatric education and associate professor of family medicine at the Medical University of South Carolina, Charleston.

“That training was, for me, very helpful for opening up and being more empathetic and really examining the patient’s point of view and everything that impacts them.”

Dr. Lovins agreed that it’s crucial to establish a good rapport and build mutual trust.

“If you don’t know the patient, you have a harder time asking the right questions to get to the meat of why they’re not taking their medicine or what they’re not doing to help their health,” she said. “It takes a little bit of trust on both parts to get to that question that really gets to the heart of why they’re not doing what you’re asking them to do.”
 

How to encourage adherence

Although there may not be a one-size-fits-all approach for achieving general adherence or adherence to a medication regimen, some methods may increase success.

Kenneth Zweig, MD, an internist at Northern Virginia Family Practice Associates, Alexandria, said that convincing patients to make one small change that they can sustain can get the ball rolling.

“I had one patient who was very overweight and had high blood pressure, high cholesterol, back pain, insomnia, and depression, who was also drinking three to four beers a night,” Dr. Zweig said. “After a long discussion, I challenged him to stop all alcohol for 1 week. At the end of the week, he noticed that he slept better, lost some weight, had lower blood pressure, and had more energy. Once he saw the benefits of this one change, he was motivated to improve other aspects of his health as well. He improved his diet, started exercising, and lost over 50 pounds. He has persisted with these lifestyle changes ever since.”

A team-based approach may also increase treatment understanding and adherence. In one older study, patients who were assigned to team-based care, including care by pharmacists, were significantly more adherent to medication regimens. Patients were more comfortable asking questions and raising concerns when they felt their treatment plan was a collaboration between several providers and themselves.

Dr. Lovins said to always approach the patient with a positive. “Say, what can we do together to make this work? What are your questions about this medication? And try and focus on the positive things that you can change instead of leaving the patient with a negative feeling or that you’re angry with them or that you’re unhappy with their choices. Patients respond better when they are treated as part of the team.”

Fear of judgment can also be a barrier to honesty between patients and their doctors. Shame creates a reluctance to admit nonadherence. Dr. Lovins said in an interview that it’s the physician’s responsibility to create a blame-free space for patients to speak openly about their struggles with treatment and reasons for nonadherence.
 

When should you redirect care?

Ultimately, the goal is good care and treatment of disease. However, if you and your patient are at an impasse and progress is stalling or failing, it may be appropriate to encourage the patient to seek care elsewhere.

“Just like any relationship, some physician-patient relationships are just not a good fit,” said Dr. Blackwelder. And this may be the reason why the patient is nonadherent — something between the two of you doesn’t click.

While there are ethical considerations for this decision, most medical boards have guidelines on how to go about it, Dr. Blackwelder said in an interview. “In the state of South Carolina, we have to be available to provide urgent coverage for at least 30 days and notify the patient in writing that they need to find somebody else and to help them find somebody else if we can.”

Just as with care, a clear conversation is the best practice if you’re proposing a potential shift away from a physician-patient relationship. You might say: We’re not making the kind of progress I’d like to see, and I’m wondering if you think working with another doctor may help you.

“The most important thing is being very honest and transparent with the patient that you’re concerned you’re not making the appropriate strides forward,” said Dr. Rabinovitz. Then you can ask, ‘Am I the right doctor to help you reach your goals? And if not, how can I help you get to where you need to be?’ ”

A version of this article first appeared on Medscape.com.