User login
An Exciting Time to Be a Gastroenterologist
Happy New Year, everyone! As we enter 2025, I’ve been reflecting on just how much has changed in the field of gastroenterology since I completed my fellowship a decade ago.
After developing and disseminating highly effective treatments for hepatitis C, the field of hepatology has shifted rapidly toward identifying and managing other significant causes of liver disease, particularly alcohol-associated liver disease and metabolic dysfunction–associated steatotic liver disease (MASLD). New disease nomenclatures have been developed that have changed the way we describe common diseases – most notably, NALFD is now MASLD and FGID are now DGBI.
There have been marked advances in obesity management, including not only innovations in endobariatric therapies such as intragastric balloons and endoscopic sleeve gastroplasty, but also the introduction of glucagon-like peptide 1 (GLP-1) agonists, which offer new hope in effectively tackling the obesity epidemic. Our growing understanding of the microbiome’s role in health has opened new avenues for treating GI diseases and introduced the potential for more personalized treatment approaches based on individual microbiome profiles. New inflammatory bowel disease (IBD) pharmacotherapeutics have been developed at a dizzying pace – our IBD patients have so many more treatment options today than they did just a decade ago, making treatment decisions much more complex.
Finally, we are just beginning to unleash the potential of artificial intelligence, which is likely to transform the field of medicine and GI clinical practice over the next decade. To be sure, it is an exciting time to be a gastroenterologist, and I can’t wait to see to what the next decade of innovation and discovery will bring.
From the recent AASLD meeting, we bring you exciting new data demonstrating the effectiveness of GLP-1 agonists (specifically, semaglutide) in treating MASH. In January’s Member Spotlight column, we introduce you to Drs. Mindy, Amy, and Kristen Engevik, who share their fascinating career journeys as GI researchers (and sisters!). In our quarterly Perspectives column, Dr. Brijesh Patel and Dr. Gomez Cifuentes share their experiences counseling patients regarding lifestyle modifications for gastroesophageal reflux disease and what strategies have proven to be the most effective adjuncts to pharmacotherapy. We hope you enjoy this and all the exciting content in our January issue.
Megan A. Adams, MD, JD, MSc
Editor in Chief
Happy New Year, everyone! As we enter 2025, I’ve been reflecting on just how much has changed in the field of gastroenterology since I completed my fellowship a decade ago.
After developing and disseminating highly effective treatments for hepatitis C, the field of hepatology has shifted rapidly toward identifying and managing other significant causes of liver disease, particularly alcohol-associated liver disease and metabolic dysfunction–associated steatotic liver disease (MASLD). New disease nomenclatures have been developed that have changed the way we describe common diseases – most notably, NALFD is now MASLD and FGID are now DGBI.
There have been marked advances in obesity management, including not only innovations in endobariatric therapies such as intragastric balloons and endoscopic sleeve gastroplasty, but also the introduction of glucagon-like peptide 1 (GLP-1) agonists, which offer new hope in effectively tackling the obesity epidemic. Our growing understanding of the microbiome’s role in health has opened new avenues for treating GI diseases and introduced the potential for more personalized treatment approaches based on individual microbiome profiles. New inflammatory bowel disease (IBD) pharmacotherapeutics have been developed at a dizzying pace – our IBD patients have so many more treatment options today than they did just a decade ago, making treatment decisions much more complex.
Finally, we are just beginning to unleash the potential of artificial intelligence, which is likely to transform the field of medicine and GI clinical practice over the next decade. To be sure, it is an exciting time to be a gastroenterologist, and I can’t wait to see to what the next decade of innovation and discovery will bring.
From the recent AASLD meeting, we bring you exciting new data demonstrating the effectiveness of GLP-1 agonists (specifically, semaglutide) in treating MASH. In January’s Member Spotlight column, we introduce you to Drs. Mindy, Amy, and Kristen Engevik, who share their fascinating career journeys as GI researchers (and sisters!). In our quarterly Perspectives column, Dr. Brijesh Patel and Dr. Gomez Cifuentes share their experiences counseling patients regarding lifestyle modifications for gastroesophageal reflux disease and what strategies have proven to be the most effective adjuncts to pharmacotherapy. We hope you enjoy this and all the exciting content in our January issue.
Megan A. Adams, MD, JD, MSc
Editor in Chief
Happy New Year, everyone! As we enter 2025, I’ve been reflecting on just how much has changed in the field of gastroenterology since I completed my fellowship a decade ago.
After developing and disseminating highly effective treatments for hepatitis C, the field of hepatology has shifted rapidly toward identifying and managing other significant causes of liver disease, particularly alcohol-associated liver disease and metabolic dysfunction–associated steatotic liver disease (MASLD). New disease nomenclatures have been developed that have changed the way we describe common diseases – most notably, NALFD is now MASLD and FGID are now DGBI.
There have been marked advances in obesity management, including not only innovations in endobariatric therapies such as intragastric balloons and endoscopic sleeve gastroplasty, but also the introduction of glucagon-like peptide 1 (GLP-1) agonists, which offer new hope in effectively tackling the obesity epidemic. Our growing understanding of the microbiome’s role in health has opened new avenues for treating GI diseases and introduced the potential for more personalized treatment approaches based on individual microbiome profiles. New inflammatory bowel disease (IBD) pharmacotherapeutics have been developed at a dizzying pace – our IBD patients have so many more treatment options today than they did just a decade ago, making treatment decisions much more complex.
Finally, we are just beginning to unleash the potential of artificial intelligence, which is likely to transform the field of medicine and GI clinical practice over the next decade. To be sure, it is an exciting time to be a gastroenterologist, and I can’t wait to see to what the next decade of innovation and discovery will bring.
From the recent AASLD meeting, we bring you exciting new data demonstrating the effectiveness of GLP-1 agonists (specifically, semaglutide) in treating MASH. In January’s Member Spotlight column, we introduce you to Drs. Mindy, Amy, and Kristen Engevik, who share their fascinating career journeys as GI researchers (and sisters!). In our quarterly Perspectives column, Dr. Brijesh Patel and Dr. Gomez Cifuentes share their experiences counseling patients regarding lifestyle modifications for gastroesophageal reflux disease and what strategies have proven to be the most effective adjuncts to pharmacotherapy. We hope you enjoy this and all the exciting content in our January issue.
Megan A. Adams, MD, JD, MSc
Editor in Chief
The Slippery Slope of Gender-Affirming Care Bans for Minors
Earlier in December, the Supreme Court heard the first oral arguments in United States v. Skrmetti, a critical case challenging gender-affirming bans for minors in Tennessee. The case has garnered national attention as it is the first case the Supreme Court has undertaken regarding gender-affirming care and the first time an openly transgender attorney presented a case to the high court. The ruling will have nationwide implications as it can single-handedly decide the fate of gender-affirming care for minors, and potentially adults. Even though the final verdict may not come out until June of 2025, the conservative majority of justices seems poised to uphold the Tennessee ban.1 In what is possibly a harbinger of the US ruling, the United Kingdom announced an indefinite ban on gender-affirming care for minors the week after the oral arguments in this case were heard.2
While the legal arguments in the Skrmetti case hinge on sex discrimination and the Equal Protection Clause of the Fourteenth Amendment, the more fundamental argument centers around the question of what is in the best interest of the minor. I’d like to delve deeper into this question as our responsibility as physicians is to the health and well-being of our patients, not partisan politics.
It is essential that we do not allow our personal views to cloud our ability to objectively analyze scientific data and prohibit individuals from accessing the health care from which they’d benefit. Conversely, we should not allow social pressure and ideologic principles interfere with our ability to challenge and regulate emerging treatments.
The answer to the question, “what is in the best interest of a minor?” is somewhat rhetorical. But in the most basic of senses, minors deserve equal protection under the law, a safe environment, good nutrition, healthcare, and an education. Regardless of our beliefs, we would all probably agree that minors should be protected and cared for but disagree about the ways in which we do so. This discrepancy is painfully evident if you dissect legislation as it pertains to these fundamental rights. It should come as no surprise that legislation is often contradictory.
For example, firearm-related injury is now the leading cause of death among minors in the United States.3 It is a public health crisis no different from childhood obesity or substance abuse in adolescents. Despite this fact, politicians are reluctant, and in many cases, downright defiant, about tightening restrictions on firearms. Yet, it is these same politicians who cite that we must “protect our children,” from beneficial gender-affirming medical interventions.
Most major medical organizations, including the American Academy of Pediatrics, the American Medical Association, and the American College of Obstetricians and Gynecologists, support gender-affirming care for minors. Current research into medical care of minors, which includes puberty blockers, hormone treatments, and in rare cases, surgery, demonstrates improvement in mental health outcomes like depression, anxiety, and suicidal ideation.4
Critics of this type of care of minors often cite small sample sizes, selection bias, and lack of long-term data, which raise concerns about the long-term impacts of these treatments. This apprehension is not entirely unfounded as there are fewer clinical trials and studies gender-affirming care than in other fields of medicine. As with all emerging medical fields, research is needed and gender-affirming care for minors is no exception. It is unlikely bans will enhance larger clinical trials but will instead further isolate these already marginalized individuals.
Unlike in the United Kingdom, the legislators in states with bans in effect seem to have little interest in understanding gender-affirming care in this demographic. Instead, they have imposed penalties on parents who seek this type of care from other states and the providers who treat their children. The most insidious consequence of the Tennessee ban, if upheld, is the federally sanctioned interference in the ability of parents to make health care decisions for their child with a medical provider.
Such a move sets a dangerous precedent for politicians to target other forms of healthcare and other marginalized communities. As the ruling pertains to gender-affirming care, politicians and most attorneys are not well-versed in the medical issues in the field. Nor is it in their purview to be. During oral arguments, the Supreme Court Justices were understandably unfamiliar with the medical nuances of this type of treatment. As someone who has met with various politicians to discuss gender-affirming medicine and surgery for adults, I can say that they have very little knowledge. Therefore, isn’t the argument even stronger to leave medical decisions to parents, providers, and patients rather than uninformed policymakers?
References
1. Cole D et al. CNN. Takeaways from the historic transgender care arguments at the Supreme Court. 2024 Dec 4.
CNN.com/2024/12/04/politics/transgender-care-bans-scotus-takeaways/index.html.
2. Triggle N. BBC. Puberty blockers for under-18s banned indefinitely. BBC. 2024 Dec 11. BBC.com/news/articles/cly2z0gx3p5o.
3. Wilson RF et al. MMWR Morb Mortal Wkly Rep. 2023;72(5):1338-1345.
4. Coleman E et al. Int J Transgender Health. 2022;23(suppl 1):S1-S259.
Earlier in December, the Supreme Court heard the first oral arguments in United States v. Skrmetti, a critical case challenging gender-affirming bans for minors in Tennessee. The case has garnered national attention as it is the first case the Supreme Court has undertaken regarding gender-affirming care and the first time an openly transgender attorney presented a case to the high court. The ruling will have nationwide implications as it can single-handedly decide the fate of gender-affirming care for minors, and potentially adults. Even though the final verdict may not come out until June of 2025, the conservative majority of justices seems poised to uphold the Tennessee ban.1 In what is possibly a harbinger of the US ruling, the United Kingdom announced an indefinite ban on gender-affirming care for minors the week after the oral arguments in this case were heard.2
While the legal arguments in the Skrmetti case hinge on sex discrimination and the Equal Protection Clause of the Fourteenth Amendment, the more fundamental argument centers around the question of what is in the best interest of the minor. I’d like to delve deeper into this question as our responsibility as physicians is to the health and well-being of our patients, not partisan politics.
It is essential that we do not allow our personal views to cloud our ability to objectively analyze scientific data and prohibit individuals from accessing the health care from which they’d benefit. Conversely, we should not allow social pressure and ideologic principles interfere with our ability to challenge and regulate emerging treatments.
The answer to the question, “what is in the best interest of a minor?” is somewhat rhetorical. But in the most basic of senses, minors deserve equal protection under the law, a safe environment, good nutrition, healthcare, and an education. Regardless of our beliefs, we would all probably agree that minors should be protected and cared for but disagree about the ways in which we do so. This discrepancy is painfully evident if you dissect legislation as it pertains to these fundamental rights. It should come as no surprise that legislation is often contradictory.
For example, firearm-related injury is now the leading cause of death among minors in the United States.3 It is a public health crisis no different from childhood obesity or substance abuse in adolescents. Despite this fact, politicians are reluctant, and in many cases, downright defiant, about tightening restrictions on firearms. Yet, it is these same politicians who cite that we must “protect our children,” from beneficial gender-affirming medical interventions.
Most major medical organizations, including the American Academy of Pediatrics, the American Medical Association, and the American College of Obstetricians and Gynecologists, support gender-affirming care for minors. Current research into medical care of minors, which includes puberty blockers, hormone treatments, and in rare cases, surgery, demonstrates improvement in mental health outcomes like depression, anxiety, and suicidal ideation.4
Critics of this type of care of minors often cite small sample sizes, selection bias, and lack of long-term data, which raise concerns about the long-term impacts of these treatments. This apprehension is not entirely unfounded as there are fewer clinical trials and studies gender-affirming care than in other fields of medicine. As with all emerging medical fields, research is needed and gender-affirming care for minors is no exception. It is unlikely bans will enhance larger clinical trials but will instead further isolate these already marginalized individuals.
Unlike in the United Kingdom, the legislators in states with bans in effect seem to have little interest in understanding gender-affirming care in this demographic. Instead, they have imposed penalties on parents who seek this type of care from other states and the providers who treat their children. The most insidious consequence of the Tennessee ban, if upheld, is the federally sanctioned interference in the ability of parents to make health care decisions for their child with a medical provider.
Such a move sets a dangerous precedent for politicians to target other forms of healthcare and other marginalized communities. As the ruling pertains to gender-affirming care, politicians and most attorneys are not well-versed in the medical issues in the field. Nor is it in their purview to be. During oral arguments, the Supreme Court Justices were understandably unfamiliar with the medical nuances of this type of treatment. As someone who has met with various politicians to discuss gender-affirming medicine and surgery for adults, I can say that they have very little knowledge. Therefore, isn’t the argument even stronger to leave medical decisions to parents, providers, and patients rather than uninformed policymakers?
References
1. Cole D et al. CNN. Takeaways from the historic transgender care arguments at the Supreme Court. 2024 Dec 4.
CNN.com/2024/12/04/politics/transgender-care-bans-scotus-takeaways/index.html.
2. Triggle N. BBC. Puberty blockers for under-18s banned indefinitely. BBC. 2024 Dec 11. BBC.com/news/articles/cly2z0gx3p5o.
3. Wilson RF et al. MMWR Morb Mortal Wkly Rep. 2023;72(5):1338-1345.
4. Coleman E et al. Int J Transgender Health. 2022;23(suppl 1):S1-S259.
Earlier in December, the Supreme Court heard the first oral arguments in United States v. Skrmetti, a critical case challenging gender-affirming bans for minors in Tennessee. The case has garnered national attention as it is the first case the Supreme Court has undertaken regarding gender-affirming care and the first time an openly transgender attorney presented a case to the high court. The ruling will have nationwide implications as it can single-handedly decide the fate of gender-affirming care for minors, and potentially adults. Even though the final verdict may not come out until June of 2025, the conservative majority of justices seems poised to uphold the Tennessee ban.1 In what is possibly a harbinger of the US ruling, the United Kingdom announced an indefinite ban on gender-affirming care for minors the week after the oral arguments in this case were heard.2
While the legal arguments in the Skrmetti case hinge on sex discrimination and the Equal Protection Clause of the Fourteenth Amendment, the more fundamental argument centers around the question of what is in the best interest of the minor. I’d like to delve deeper into this question as our responsibility as physicians is to the health and well-being of our patients, not partisan politics.
It is essential that we do not allow our personal views to cloud our ability to objectively analyze scientific data and prohibit individuals from accessing the health care from which they’d benefit. Conversely, we should not allow social pressure and ideologic principles interfere with our ability to challenge and regulate emerging treatments.
The answer to the question, “what is in the best interest of a minor?” is somewhat rhetorical. But in the most basic of senses, minors deserve equal protection under the law, a safe environment, good nutrition, healthcare, and an education. Regardless of our beliefs, we would all probably agree that minors should be protected and cared for but disagree about the ways in which we do so. This discrepancy is painfully evident if you dissect legislation as it pertains to these fundamental rights. It should come as no surprise that legislation is often contradictory.
For example, firearm-related injury is now the leading cause of death among minors in the United States.3 It is a public health crisis no different from childhood obesity or substance abuse in adolescents. Despite this fact, politicians are reluctant, and in many cases, downright defiant, about tightening restrictions on firearms. Yet, it is these same politicians who cite that we must “protect our children,” from beneficial gender-affirming medical interventions.
Most major medical organizations, including the American Academy of Pediatrics, the American Medical Association, and the American College of Obstetricians and Gynecologists, support gender-affirming care for minors. Current research into medical care of minors, which includes puberty blockers, hormone treatments, and in rare cases, surgery, demonstrates improvement in mental health outcomes like depression, anxiety, and suicidal ideation.4
Critics of this type of care of minors often cite small sample sizes, selection bias, and lack of long-term data, which raise concerns about the long-term impacts of these treatments. This apprehension is not entirely unfounded as there are fewer clinical trials and studies gender-affirming care than in other fields of medicine. As with all emerging medical fields, research is needed and gender-affirming care for minors is no exception. It is unlikely bans will enhance larger clinical trials but will instead further isolate these already marginalized individuals.
Unlike in the United Kingdom, the legislators in states with bans in effect seem to have little interest in understanding gender-affirming care in this demographic. Instead, they have imposed penalties on parents who seek this type of care from other states and the providers who treat their children. The most insidious consequence of the Tennessee ban, if upheld, is the federally sanctioned interference in the ability of parents to make health care decisions for their child with a medical provider.
Such a move sets a dangerous precedent for politicians to target other forms of healthcare and other marginalized communities. As the ruling pertains to gender-affirming care, politicians and most attorneys are not well-versed in the medical issues in the field. Nor is it in their purview to be. During oral arguments, the Supreme Court Justices were understandably unfamiliar with the medical nuances of this type of treatment. As someone who has met with various politicians to discuss gender-affirming medicine and surgery for adults, I can say that they have very little knowledge. Therefore, isn’t the argument even stronger to leave medical decisions to parents, providers, and patients rather than uninformed policymakers?
References
1. Cole D et al. CNN. Takeaways from the historic transgender care arguments at the Supreme Court. 2024 Dec 4.
CNN.com/2024/12/04/politics/transgender-care-bans-scotus-takeaways/index.html.
2. Triggle N. BBC. Puberty blockers for under-18s banned indefinitely. BBC. 2024 Dec 11. BBC.com/news/articles/cly2z0gx3p5o.
3. Wilson RF et al. MMWR Morb Mortal Wkly Rep. 2023;72(5):1338-1345.
4. Coleman E et al. Int J Transgender Health. 2022;23(suppl 1):S1-S259.
Vulvar and Vaginal Melanoma: A Rare but Important Diagnosis
Cutaneous melanoma is a type of skin cancer typically associated with significant ultraviolet radiation exposure. Melanoma arises from melanocytes, cells found within the lower portion of the epidermis that make the pigment melanin.
While much less common than squamous cell carcinoma or basal cell carcinoma, melanoma is responsible for most deaths from skin cancer. In 2024, there will be more than 100,000 new cases of melanoma and over 8,000 melanoma-related deaths.1 If localized at the time of diagnosis, survival rates are excellent. Cutaneous melanomas are more common in those with fair complexions or who have had long periods of exposure to natural or artificial sunlight.
Melanoma can also occur in mucous membranes. Mucosal melanoma is much less common than cutaneous melanoma and accounts for only a very small percentage of all new melanoma diagnoses. Unlike their cutaneous counterparts, risk factors for mucosal melanomas have yet to be identified. Although there is some disagreement on whether vulvar melanomas represent cutaneous or mucous melanomas, vulvovaginal melanomas have historically been considered to be mucosal melanomas.
Vulvovaginal melanomas are characterized by a high mortality rate, diagnostic challenges, and lack of awareness, making early detection and intervention crucial to improving patient outcomes. The 5-year overall survival rate for vulvar melanoma is 36% and for vaginal melanoma ranges between 5% and 25%.2 Survival rates for vulvovaginal melanomas are lower than for other types of vulvar cancers (72%) or for cutaneous melanomas (72%-81%).2
Racial disparities in survival rates for mucosal and cutaneous melanomas were highlighted in a retrospective study using the Surveillance Epidemiology and End Results (SEER) database. Although the number of Black patients included was small, the median overall survival in that population was less than that in non-Black patients with vulvovaginal melanoma (16 vs. 39 months). Similar findings were noted in Black patients with cutaneous melanoma, compared with non-Black patients (median overall survival, 124 vs 319 months).3
One of the most significant obstacles in the diagnosis of vulvar and vaginal melanoma is its rarity. Both patients and clinicians alike may fail to recognize early warning signs. In a world where skin cancer is heavily publicized, melanoma in the genital area is not as frequently discussed or understood. Postmenopausal patients may have less regular gynecologic care, and unless they present with specific symptoms prompting an exam, melanomas can grow undetected, progressing to more advanced stages before they are discovered.
The median age of patients diagnosed with vulvar and vaginal melanomas is 67-68.4,5 Symptoms can be subtle and nonspecific. Women with vulvar melanoma may experience symptoms that are similar to other vulvar cancers including pruritus, irritation, pain, bleeding, or a new or growing mass. While vaginal melanoma can be asymptomatic, patients frequently present with vaginal bleeding, discharge, and/or pain (including dyspareunia).
Vulvovaginal melanomas may present differently than cutaneous melanomas. Vulvar melanomas are often pigmented and frequently present as ulcerated lesions. In some cases, though, they appear amelanotic (lacking pigment), making them even harder to identify. The ABCDEs of skin cancer (asymmetry, border, color, diameter, evolving) should be applied to these lesions. Change in the size, shape, or pigment of preexisting melanosis (areas of hyperpigmentation caused by increased melanin), should raise concern for possible malignant transformation.
Most vaginal melanomas occur within the distal third of the vagina, frequently along the anterior vaginal wall.6 They can be polypoid or nodular in appearance and may be ulcerated. While biopsy of any suspicious, enlarging/changing, or symptomatic lesion should be performed, it may be prudent to pause prior to biopsy of a vaginal lesion depending on its appearance. Although rare, gestational trophoblastic neoplasia (GTN) can present with vaginal metastases, and these lesions are frequently very vascular and pose a high bleeding risk if biopsied. They may look dark blue or black. If there is any concern for metastatic GTN on vaginal exam, a beta-hCG level should be obtained prior to biopsy.
Treatment of vulvovaginal melanoma may include surgical excision, systemic therapy, radiation therapy, or a combination of treatments. There is growing use of immunotherapy that mirrors cutaneous melanoma therapy.
Vulvar and vaginal melanoma represent a rare yet serious health issue for women and their impact on public health should not be underestimated. Vulvovaginal melanoma often goes unrecognized until it has reached an advanced stage. Increased awareness about these rare forms of melanoma among both patients and healthcare professionals is vital to improve early detection and treatment outcomes. With greater attention to this disease, we can strive for better diagnostic methods, more effective treatments, and ultimately, a reduction in mortality rates associated with vulvar and vaginal melanoma.
Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest.
References
1. National Cancer Institute. Cancer Stat Facts: Melanoma of the skin. 2024 Dec 2. Available from: https://seer.cancer.gov/statfacts/html/melan.html.
2. Piura B. Lancet Oncol. 2008 Oct;9(10):973-81. .
3. Mert I et al. Int J Gynecol Cancer. 2013;23(6):1118-25.
4. Wang D et al. Am J Cancer Res. 2020 Dec 1;10(12):4017-37.
5. Albert A et al. J Gynecol Oncol. 2020 Sep;31(5):e66.
Cutaneous melanoma is a type of skin cancer typically associated with significant ultraviolet radiation exposure. Melanoma arises from melanocytes, cells found within the lower portion of the epidermis that make the pigment melanin.
While much less common than squamous cell carcinoma or basal cell carcinoma, melanoma is responsible for most deaths from skin cancer. In 2024, there will be more than 100,000 new cases of melanoma and over 8,000 melanoma-related deaths.1 If localized at the time of diagnosis, survival rates are excellent. Cutaneous melanomas are more common in those with fair complexions or who have had long periods of exposure to natural or artificial sunlight.
Melanoma can also occur in mucous membranes. Mucosal melanoma is much less common than cutaneous melanoma and accounts for only a very small percentage of all new melanoma diagnoses. Unlike their cutaneous counterparts, risk factors for mucosal melanomas have yet to be identified. Although there is some disagreement on whether vulvar melanomas represent cutaneous or mucous melanomas, vulvovaginal melanomas have historically been considered to be mucosal melanomas.
Vulvovaginal melanomas are characterized by a high mortality rate, diagnostic challenges, and lack of awareness, making early detection and intervention crucial to improving patient outcomes. The 5-year overall survival rate for vulvar melanoma is 36% and for vaginal melanoma ranges between 5% and 25%.2 Survival rates for vulvovaginal melanomas are lower than for other types of vulvar cancers (72%) or for cutaneous melanomas (72%-81%).2
Racial disparities in survival rates for mucosal and cutaneous melanomas were highlighted in a retrospective study using the Surveillance Epidemiology and End Results (SEER) database. Although the number of Black patients included was small, the median overall survival in that population was less than that in non-Black patients with vulvovaginal melanoma (16 vs. 39 months). Similar findings were noted in Black patients with cutaneous melanoma, compared with non-Black patients (median overall survival, 124 vs 319 months).3
One of the most significant obstacles in the diagnosis of vulvar and vaginal melanoma is its rarity. Both patients and clinicians alike may fail to recognize early warning signs. In a world where skin cancer is heavily publicized, melanoma in the genital area is not as frequently discussed or understood. Postmenopausal patients may have less regular gynecologic care, and unless they present with specific symptoms prompting an exam, melanomas can grow undetected, progressing to more advanced stages before they are discovered.
The median age of patients diagnosed with vulvar and vaginal melanomas is 67-68.4,5 Symptoms can be subtle and nonspecific. Women with vulvar melanoma may experience symptoms that are similar to other vulvar cancers including pruritus, irritation, pain, bleeding, or a new or growing mass. While vaginal melanoma can be asymptomatic, patients frequently present with vaginal bleeding, discharge, and/or pain (including dyspareunia).
Vulvovaginal melanomas may present differently than cutaneous melanomas. Vulvar melanomas are often pigmented and frequently present as ulcerated lesions. In some cases, though, they appear amelanotic (lacking pigment), making them even harder to identify. The ABCDEs of skin cancer (asymmetry, border, color, diameter, evolving) should be applied to these lesions. Change in the size, shape, or pigment of preexisting melanosis (areas of hyperpigmentation caused by increased melanin), should raise concern for possible malignant transformation.
Most vaginal melanomas occur within the distal third of the vagina, frequently along the anterior vaginal wall.6 They can be polypoid or nodular in appearance and may be ulcerated. While biopsy of any suspicious, enlarging/changing, or symptomatic lesion should be performed, it may be prudent to pause prior to biopsy of a vaginal lesion depending on its appearance. Although rare, gestational trophoblastic neoplasia (GTN) can present with vaginal metastases, and these lesions are frequently very vascular and pose a high bleeding risk if biopsied. They may look dark blue or black. If there is any concern for metastatic GTN on vaginal exam, a beta-hCG level should be obtained prior to biopsy.
Treatment of vulvovaginal melanoma may include surgical excision, systemic therapy, radiation therapy, or a combination of treatments. There is growing use of immunotherapy that mirrors cutaneous melanoma therapy.
Vulvar and vaginal melanoma represent a rare yet serious health issue for women and their impact on public health should not be underestimated. Vulvovaginal melanoma often goes unrecognized until it has reached an advanced stage. Increased awareness about these rare forms of melanoma among both patients and healthcare professionals is vital to improve early detection and treatment outcomes. With greater attention to this disease, we can strive for better diagnostic methods, more effective treatments, and ultimately, a reduction in mortality rates associated with vulvar and vaginal melanoma.
Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest.
References
1. National Cancer Institute. Cancer Stat Facts: Melanoma of the skin. 2024 Dec 2. Available from: https://seer.cancer.gov/statfacts/html/melan.html.
2. Piura B. Lancet Oncol. 2008 Oct;9(10):973-81. .
3. Mert I et al. Int J Gynecol Cancer. 2013;23(6):1118-25.
4. Wang D et al. Am J Cancer Res. 2020 Dec 1;10(12):4017-37.
5. Albert A et al. J Gynecol Oncol. 2020 Sep;31(5):e66.
Cutaneous melanoma is a type of skin cancer typically associated with significant ultraviolet radiation exposure. Melanoma arises from melanocytes, cells found within the lower portion of the epidermis that make the pigment melanin.
While much less common than squamous cell carcinoma or basal cell carcinoma, melanoma is responsible for most deaths from skin cancer. In 2024, there will be more than 100,000 new cases of melanoma and over 8,000 melanoma-related deaths.1 If localized at the time of diagnosis, survival rates are excellent. Cutaneous melanomas are more common in those with fair complexions or who have had long periods of exposure to natural or artificial sunlight.
Melanoma can also occur in mucous membranes. Mucosal melanoma is much less common than cutaneous melanoma and accounts for only a very small percentage of all new melanoma diagnoses. Unlike their cutaneous counterparts, risk factors for mucosal melanomas have yet to be identified. Although there is some disagreement on whether vulvar melanomas represent cutaneous or mucous melanomas, vulvovaginal melanomas have historically been considered to be mucosal melanomas.
Vulvovaginal melanomas are characterized by a high mortality rate, diagnostic challenges, and lack of awareness, making early detection and intervention crucial to improving patient outcomes. The 5-year overall survival rate for vulvar melanoma is 36% and for vaginal melanoma ranges between 5% and 25%.2 Survival rates for vulvovaginal melanomas are lower than for other types of vulvar cancers (72%) or for cutaneous melanomas (72%-81%).2
Racial disparities in survival rates for mucosal and cutaneous melanomas were highlighted in a retrospective study using the Surveillance Epidemiology and End Results (SEER) database. Although the number of Black patients included was small, the median overall survival in that population was less than that in non-Black patients with vulvovaginal melanoma (16 vs. 39 months). Similar findings were noted in Black patients with cutaneous melanoma, compared with non-Black patients (median overall survival, 124 vs 319 months).3
One of the most significant obstacles in the diagnosis of vulvar and vaginal melanoma is its rarity. Both patients and clinicians alike may fail to recognize early warning signs. In a world where skin cancer is heavily publicized, melanoma in the genital area is not as frequently discussed or understood. Postmenopausal patients may have less regular gynecologic care, and unless they present with specific symptoms prompting an exam, melanomas can grow undetected, progressing to more advanced stages before they are discovered.
The median age of patients diagnosed with vulvar and vaginal melanomas is 67-68.4,5 Symptoms can be subtle and nonspecific. Women with vulvar melanoma may experience symptoms that are similar to other vulvar cancers including pruritus, irritation, pain, bleeding, or a new or growing mass. While vaginal melanoma can be asymptomatic, patients frequently present with vaginal bleeding, discharge, and/or pain (including dyspareunia).
Vulvovaginal melanomas may present differently than cutaneous melanomas. Vulvar melanomas are often pigmented and frequently present as ulcerated lesions. In some cases, though, they appear amelanotic (lacking pigment), making them even harder to identify. The ABCDEs of skin cancer (asymmetry, border, color, diameter, evolving) should be applied to these lesions. Change in the size, shape, or pigment of preexisting melanosis (areas of hyperpigmentation caused by increased melanin), should raise concern for possible malignant transformation.
Most vaginal melanomas occur within the distal third of the vagina, frequently along the anterior vaginal wall.6 They can be polypoid or nodular in appearance and may be ulcerated. While biopsy of any suspicious, enlarging/changing, or symptomatic lesion should be performed, it may be prudent to pause prior to biopsy of a vaginal lesion depending on its appearance. Although rare, gestational trophoblastic neoplasia (GTN) can present with vaginal metastases, and these lesions are frequently very vascular and pose a high bleeding risk if biopsied. They may look dark blue or black. If there is any concern for metastatic GTN on vaginal exam, a beta-hCG level should be obtained prior to biopsy.
Treatment of vulvovaginal melanoma may include surgical excision, systemic therapy, radiation therapy, or a combination of treatments. There is growing use of immunotherapy that mirrors cutaneous melanoma therapy.
Vulvar and vaginal melanoma represent a rare yet serious health issue for women and their impact on public health should not be underestimated. Vulvovaginal melanoma often goes unrecognized until it has reached an advanced stage. Increased awareness about these rare forms of melanoma among both patients and healthcare professionals is vital to improve early detection and treatment outcomes. With greater attention to this disease, we can strive for better diagnostic methods, more effective treatments, and ultimately, a reduction in mortality rates associated with vulvar and vaginal melanoma.
Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest.
References
1. National Cancer Institute. Cancer Stat Facts: Melanoma of the skin. 2024 Dec 2. Available from: https://seer.cancer.gov/statfacts/html/melan.html.
2. Piura B. Lancet Oncol. 2008 Oct;9(10):973-81. .
3. Mert I et al. Int J Gynecol Cancer. 2013;23(6):1118-25.
4. Wang D et al. Am J Cancer Res. 2020 Dec 1;10(12):4017-37.
5. Albert A et al. J Gynecol Oncol. 2020 Sep;31(5):e66.
‘We Don’t Hire Female Doctors With Children’
Hatice became pregnant while working as a medical resident, and her career took a noticeable hit. Her training was downgraded, and her job applications went unanswered. This news organization spoke with her about her experiences and the disadvantages faced by young female doctors with children.
Hatice, can you tell us about your career path?
I initially started my clinical year at a hospital in Cologne, Germany. Then, 8 months in, I got pregnant with my first child during the first COVID-19 wave. After my maternity leave, I returned to the clinic, and that’s when the problems began.
Where did the issues arise?
Suddenly, I wasn’t allowed into the operating rooms (ORs) and was instead sent to the outpatient clinic. I had to fight for every OR slot until, eventually, I said, “This can’t go on. I want to stay in the hospital and gain my surgical experience, but not if I have to keep struggling for it.”
So, initially, it was about wanting to improve the quality of your ongoing training, as they gave you no path forward for further development? And you attribute this to your maternity leave.
It wasn’t just my perception — I was told as much directly. I returned from maternity leave and was told to work in outpatients and cover shifts. I went to my supervisor and explained that I was unhappy with this. We have an OR log, and I wanted to complete my required cases. He replied, “Well, that’s your fault for getting pregnant right away.”
In the Cologne/Düsseldorf/Bonn area, there is no shortage of doctors in training. This means that as soon as I leave, there will be new recruits. So my boss actually said to me at the time, “If you’re gone, you’re gone, then the next candidate will come along.”
Did you return to work part-time after your maternity leave, or full-time?
I returned full-time and took on all my usual duties. Fortunately, my husband takes on a lot at home. He spent a significant time on parental leave and has often been the one to care for our child when they’re sick. So, if you didn’t know, you wouldn’t necessarily realize at work that I have a child.
What happened next?
I discussed the situation with the senior physician responsible for the OR assignments, but she told me not to worry, as I would eventually get the required signature at the end of my training. But that wasn’t my issue — I wanted the professional training. Feeling stuck, I decided to look for other positions.
Did you apply elsewhere to improve your situation?
Yes, but most of my applications went unanswered, which I didn’t understand. When I followed up, I actually received verbal replies from three hospitals, stating, “We don’t hire women with children.”
You’ve shared your experiences publicly on social media. How has the response been? Have other female doctors had similar experiences?
I think the problem of discrimination against women with children is still taboo. You’d think, with the shortage of doctors, that jobs would be available. But I’ve heard from former classmates who now have children that they face similar career obstacles, especially in fields such as internal medicine, where fulfilling rotations is challenging owing to scheduling bias.
This raises the question of adapting working conditions. In your case, it seems that a change in employer attitudes is also needed. What’s your perspective?
It varies depending on the region. I’ve applied across Germany and found that areas outside major cities such as Cologne, Düsseldorf, and Frankfurt tend to be better. In urban centers with a large applicant pool, the atmosphere is different. In smaller areas, finding a job is easier, especially if you’re fluent in German and experienced.
Do you believe that changing the mindset of employers regarding female staff with children could happen with a generational shift?
Honestly, I doubt it. It’s not just an issue at management level — it’s also present among residents. When someone takes leave, colleagues have to cover, which leads to resentment. Yet many female residents will eventually have children themselves. And it’s often overlooked that many men now share childcare responsibilities or take parental leave. Improving staffing levels would help alleviate these pressures.
Returning to structural issues, how is your situation now — can you continue your training?
I’ve since changed positions and am very happy. I didn’t expect such a positive reception with a child in tow.
Lastly, what changes do you think are needed? Is it enough to speak out about such experiences, or are further solutions necessary?
It’s good that topics such as burnout are openly discussed now. With children, there’s a risk for burnout, as you strive to meet all expectations to avoid career setbacks. But there also needs to be an acceptance that women who are hired may become pregnant and may have more than one child. I’m hopeful that over time, this will become normalized, especially as medicine becomes a more female-dominated field.
Is there anything else you’d like to share?
I wish there were more solidarity among women. It’s disheartening to see competition and infighting. More mutual support among women would make a huge difference.
Thank you, Hatice, and best of luck in your career.
Hatice, who prefers not to disclose her last name for privacy, is a fourth-year ENT specialist in training and shares her journey as a young doctor on Instagram under the name dein.hno.arzt.
This article was translated from Coliquio using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Hatice became pregnant while working as a medical resident, and her career took a noticeable hit. Her training was downgraded, and her job applications went unanswered. This news organization spoke with her about her experiences and the disadvantages faced by young female doctors with children.
Hatice, can you tell us about your career path?
I initially started my clinical year at a hospital in Cologne, Germany. Then, 8 months in, I got pregnant with my first child during the first COVID-19 wave. After my maternity leave, I returned to the clinic, and that’s when the problems began.
Where did the issues arise?
Suddenly, I wasn’t allowed into the operating rooms (ORs) and was instead sent to the outpatient clinic. I had to fight for every OR slot until, eventually, I said, “This can’t go on. I want to stay in the hospital and gain my surgical experience, but not if I have to keep struggling for it.”
So, initially, it was about wanting to improve the quality of your ongoing training, as they gave you no path forward for further development? And you attribute this to your maternity leave.
It wasn’t just my perception — I was told as much directly. I returned from maternity leave and was told to work in outpatients and cover shifts. I went to my supervisor and explained that I was unhappy with this. We have an OR log, and I wanted to complete my required cases. He replied, “Well, that’s your fault for getting pregnant right away.”
In the Cologne/Düsseldorf/Bonn area, there is no shortage of doctors in training. This means that as soon as I leave, there will be new recruits. So my boss actually said to me at the time, “If you’re gone, you’re gone, then the next candidate will come along.”
Did you return to work part-time after your maternity leave, or full-time?
I returned full-time and took on all my usual duties. Fortunately, my husband takes on a lot at home. He spent a significant time on parental leave and has often been the one to care for our child when they’re sick. So, if you didn’t know, you wouldn’t necessarily realize at work that I have a child.
What happened next?
I discussed the situation with the senior physician responsible for the OR assignments, but she told me not to worry, as I would eventually get the required signature at the end of my training. But that wasn’t my issue — I wanted the professional training. Feeling stuck, I decided to look for other positions.
Did you apply elsewhere to improve your situation?
Yes, but most of my applications went unanswered, which I didn’t understand. When I followed up, I actually received verbal replies from three hospitals, stating, “We don’t hire women with children.”
You’ve shared your experiences publicly on social media. How has the response been? Have other female doctors had similar experiences?
I think the problem of discrimination against women with children is still taboo. You’d think, with the shortage of doctors, that jobs would be available. But I’ve heard from former classmates who now have children that they face similar career obstacles, especially in fields such as internal medicine, where fulfilling rotations is challenging owing to scheduling bias.
This raises the question of adapting working conditions. In your case, it seems that a change in employer attitudes is also needed. What’s your perspective?
It varies depending on the region. I’ve applied across Germany and found that areas outside major cities such as Cologne, Düsseldorf, and Frankfurt tend to be better. In urban centers with a large applicant pool, the atmosphere is different. In smaller areas, finding a job is easier, especially if you’re fluent in German and experienced.
Do you believe that changing the mindset of employers regarding female staff with children could happen with a generational shift?
Honestly, I doubt it. It’s not just an issue at management level — it’s also present among residents. When someone takes leave, colleagues have to cover, which leads to resentment. Yet many female residents will eventually have children themselves. And it’s often overlooked that many men now share childcare responsibilities or take parental leave. Improving staffing levels would help alleviate these pressures.
Returning to structural issues, how is your situation now — can you continue your training?
I’ve since changed positions and am very happy. I didn’t expect such a positive reception with a child in tow.
Lastly, what changes do you think are needed? Is it enough to speak out about such experiences, or are further solutions necessary?
It’s good that topics such as burnout are openly discussed now. With children, there’s a risk for burnout, as you strive to meet all expectations to avoid career setbacks. But there also needs to be an acceptance that women who are hired may become pregnant and may have more than one child. I’m hopeful that over time, this will become normalized, especially as medicine becomes a more female-dominated field.
Is there anything else you’d like to share?
I wish there were more solidarity among women. It’s disheartening to see competition and infighting. More mutual support among women would make a huge difference.
Thank you, Hatice, and best of luck in your career.
Hatice, who prefers not to disclose her last name for privacy, is a fourth-year ENT specialist in training and shares her journey as a young doctor on Instagram under the name dein.hno.arzt.
This article was translated from Coliquio using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Hatice became pregnant while working as a medical resident, and her career took a noticeable hit. Her training was downgraded, and her job applications went unanswered. This news organization spoke with her about her experiences and the disadvantages faced by young female doctors with children.
Hatice, can you tell us about your career path?
I initially started my clinical year at a hospital in Cologne, Germany. Then, 8 months in, I got pregnant with my first child during the first COVID-19 wave. After my maternity leave, I returned to the clinic, and that’s when the problems began.
Where did the issues arise?
Suddenly, I wasn’t allowed into the operating rooms (ORs) and was instead sent to the outpatient clinic. I had to fight for every OR slot until, eventually, I said, “This can’t go on. I want to stay in the hospital and gain my surgical experience, but not if I have to keep struggling for it.”
So, initially, it was about wanting to improve the quality of your ongoing training, as they gave you no path forward for further development? And you attribute this to your maternity leave.
It wasn’t just my perception — I was told as much directly. I returned from maternity leave and was told to work in outpatients and cover shifts. I went to my supervisor and explained that I was unhappy with this. We have an OR log, and I wanted to complete my required cases. He replied, “Well, that’s your fault for getting pregnant right away.”
In the Cologne/Düsseldorf/Bonn area, there is no shortage of doctors in training. This means that as soon as I leave, there will be new recruits. So my boss actually said to me at the time, “If you’re gone, you’re gone, then the next candidate will come along.”
Did you return to work part-time after your maternity leave, or full-time?
I returned full-time and took on all my usual duties. Fortunately, my husband takes on a lot at home. He spent a significant time on parental leave and has often been the one to care for our child when they’re sick. So, if you didn’t know, you wouldn’t necessarily realize at work that I have a child.
What happened next?
I discussed the situation with the senior physician responsible for the OR assignments, but she told me not to worry, as I would eventually get the required signature at the end of my training. But that wasn’t my issue — I wanted the professional training. Feeling stuck, I decided to look for other positions.
Did you apply elsewhere to improve your situation?
Yes, but most of my applications went unanswered, which I didn’t understand. When I followed up, I actually received verbal replies from three hospitals, stating, “We don’t hire women with children.”
You’ve shared your experiences publicly on social media. How has the response been? Have other female doctors had similar experiences?
I think the problem of discrimination against women with children is still taboo. You’d think, with the shortage of doctors, that jobs would be available. But I’ve heard from former classmates who now have children that they face similar career obstacles, especially in fields such as internal medicine, where fulfilling rotations is challenging owing to scheduling bias.
This raises the question of adapting working conditions. In your case, it seems that a change in employer attitudes is also needed. What’s your perspective?
It varies depending on the region. I’ve applied across Germany and found that areas outside major cities such as Cologne, Düsseldorf, and Frankfurt tend to be better. In urban centers with a large applicant pool, the atmosphere is different. In smaller areas, finding a job is easier, especially if you’re fluent in German and experienced.
Do you believe that changing the mindset of employers regarding female staff with children could happen with a generational shift?
Honestly, I doubt it. It’s not just an issue at management level — it’s also present among residents. When someone takes leave, colleagues have to cover, which leads to resentment. Yet many female residents will eventually have children themselves. And it’s often overlooked that many men now share childcare responsibilities or take parental leave. Improving staffing levels would help alleviate these pressures.
Returning to structural issues, how is your situation now — can you continue your training?
I’ve since changed positions and am very happy. I didn’t expect such a positive reception with a child in tow.
Lastly, what changes do you think are needed? Is it enough to speak out about such experiences, or are further solutions necessary?
It’s good that topics such as burnout are openly discussed now. With children, there’s a risk for burnout, as you strive to meet all expectations to avoid career setbacks. But there also needs to be an acceptance that women who are hired may become pregnant and may have more than one child. I’m hopeful that over time, this will become normalized, especially as medicine becomes a more female-dominated field.
Is there anything else you’d like to share?
I wish there were more solidarity among women. It’s disheartening to see competition and infighting. More mutual support among women would make a huge difference.
Thank you, Hatice, and best of luck in your career.
Hatice, who prefers not to disclose her last name for privacy, is a fourth-year ENT specialist in training and shares her journey as a young doctor on Instagram under the name dein.hno.arzt.
This article was translated from Coliquio using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Why Insurers Keep Denying Claims (And What to Do)
This transcript has been edited for clarity.
Oh, insurance claim denials. When patient care or treatment is warranted by a specific diagnosis, I wish insurers would just reimburse it without any hassle. That’s not reality. Let’s talk about insurance claim denials, how they’re rising and harming patient care, and what we can do about it. That’s kind of complicated.
Rising Trend in Claim Denials and Financial Impact
First, denials are increasing. Experian Health surveyed provider revenue cycle leaders— that’s a fancy term for people who manage billing and insurance claims — and 75% said that denials are increasing. This is up from 42% a few years ago. Those surveyed also said that reimbursement times and errors in claims are also increasing, and changes in policy are happening more frequently. This all adds to the problem.
Aside from being time-consuming and annoying, claim denials take a toll on hospitals and patients. One analysis, which made headlines everywhere, showed that hospitals and health systems spent nearly $20 billion in 2022 trying to repeal overturned claims. This analysis was done by Premier, a health insurance performance company.
Breakdown of Denial Rates and Costs
Let’s do some quick whiteboard math. Health insurance companies get about 3 billion claims per year. According to surveys, about 15% of those claims are denied, so that leaves us with 450 million denied claims. Hospitals spend, on average, $43.84 per denied claim in administrative fees trying to get them overturned.
That’s about $19.7 billion spent on claim denials. Here’s the gut punch: Around 54% of those claims are ultimately paid, so that leaves us with $10.7 billion that we definitely should have saved.
Common Reasons for Denials
Let’s take a look at major causes and what’s going on.
Insurance denial rates are all over the place. It depends on state and plan. According to one analysis, the average for in-network claim denials across some states was 4% to 5%. It was 40% in Mississippi. According to HealthCare.gov, in 2021, around 17% of in-network claims were denied.
The most common reasons were excluded services, a lack of referral or preauthorization, or a medical treatment not being deemed necessary. Then there’s the black box of “other,” just some arbitrary reason to make a claim denial.
Many times, these denials are done by an algorithm, not by individual people.
What’s more, a Kaiser Family Foundation analysis found that private insurers, including Medicare Advantage plans, were more likely to deny claims than public options.
When broken down, the problem was higher among employer-sponsored and marketplace insurance, and less so with Medicare and Medicaid.
Impact on Patient Care
Many consumers don’t truly understand what their health insurance covers and what’s going to be out of pocket, and many people don’t know that they have appeal rights. They don’t know who to call for help either.
The ACA set up Consumer Assistance Programs (CAPs), which are designed to help people navigate health insurance problems. By law, private insurers have to share data with CAPs. Yet, only 3% of people who had trouble with health insurance claims called a CAP for help.
We all know some of the downstream effects of this problem. Patients may skip or delay treatments if they can’t get insurance to cover it or it’s too expensive. When post-acute care, such as transfer to a skilled nursing facility or rehab center, isn’t covered and we’re trying to discharge patients from the hospital, hospital stays become lengthened, which means they’re more expensive, and this comes with its own set of complications.
How Can We Address This?
I’m genuinely curious about what you all have done to efficiently address this problem. I’m looking at this publication from the American Health Information Management Association about major reasons for denial. We’ve already talked about a lack of preauthorization or procedures not being covered, but there are also reasons such as missing or incorrect information, duplicate claims, and not filing within the appropriate time.
Also, if treatments or procedures are bundled, they can’t be filed separately.
Preventing all of this would take a large effort. Healthcare systems would have to have a dedicated team, who would understand all the major reasons for denials, identify common patterns, and then fill everything out with accurate information, with referrals, with preauthorizations, high-specificity codes, and the correct modifiers — and do all of this within the filing deadline every time.
You would need physicians on board, but also people from IT, finance, compliance, case management, registration, and probably a bunch of other people who are already stretched too thin.
Perhaps our government can do more to hold insurers accountable and make sure plans, such as Medicare Advantage, are holding up their end of the public health bargain.
It’s an uphill $20 billion battle, but I’m optimistic. What about you? What’s your unfiltered take on claim denials? What more can we be doing?
Dr. Patel is a clinical instructor, Department of Pediatrics, Columbia University College of Physicians and Surgeons; pediatric hospitalist, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, New York City, and Benioff Children’s Hospital, University of California, San Francisco. He reported a conflict of interest with Medumo.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Oh, insurance claim denials. When patient care or treatment is warranted by a specific diagnosis, I wish insurers would just reimburse it without any hassle. That’s not reality. Let’s talk about insurance claim denials, how they’re rising and harming patient care, and what we can do about it. That’s kind of complicated.
Rising Trend in Claim Denials and Financial Impact
First, denials are increasing. Experian Health surveyed provider revenue cycle leaders— that’s a fancy term for people who manage billing and insurance claims — and 75% said that denials are increasing. This is up from 42% a few years ago. Those surveyed also said that reimbursement times and errors in claims are also increasing, and changes in policy are happening more frequently. This all adds to the problem.
Aside from being time-consuming and annoying, claim denials take a toll on hospitals and patients. One analysis, which made headlines everywhere, showed that hospitals and health systems spent nearly $20 billion in 2022 trying to repeal overturned claims. This analysis was done by Premier, a health insurance performance company.
Breakdown of Denial Rates and Costs
Let’s do some quick whiteboard math. Health insurance companies get about 3 billion claims per year. According to surveys, about 15% of those claims are denied, so that leaves us with 450 million denied claims. Hospitals spend, on average, $43.84 per denied claim in administrative fees trying to get them overturned.
That’s about $19.7 billion spent on claim denials. Here’s the gut punch: Around 54% of those claims are ultimately paid, so that leaves us with $10.7 billion that we definitely should have saved.
Common Reasons for Denials
Let’s take a look at major causes and what’s going on.
Insurance denial rates are all over the place. It depends on state and plan. According to one analysis, the average for in-network claim denials across some states was 4% to 5%. It was 40% in Mississippi. According to HealthCare.gov, in 2021, around 17% of in-network claims were denied.
The most common reasons were excluded services, a lack of referral or preauthorization, or a medical treatment not being deemed necessary. Then there’s the black box of “other,” just some arbitrary reason to make a claim denial.
Many times, these denials are done by an algorithm, not by individual people.
What’s more, a Kaiser Family Foundation analysis found that private insurers, including Medicare Advantage plans, were more likely to deny claims than public options.
When broken down, the problem was higher among employer-sponsored and marketplace insurance, and less so with Medicare and Medicaid.
Impact on Patient Care
Many consumers don’t truly understand what their health insurance covers and what’s going to be out of pocket, and many people don’t know that they have appeal rights. They don’t know who to call for help either.
The ACA set up Consumer Assistance Programs (CAPs), which are designed to help people navigate health insurance problems. By law, private insurers have to share data with CAPs. Yet, only 3% of people who had trouble with health insurance claims called a CAP for help.
We all know some of the downstream effects of this problem. Patients may skip or delay treatments if they can’t get insurance to cover it or it’s too expensive. When post-acute care, such as transfer to a skilled nursing facility or rehab center, isn’t covered and we’re trying to discharge patients from the hospital, hospital stays become lengthened, which means they’re more expensive, and this comes with its own set of complications.
How Can We Address This?
I’m genuinely curious about what you all have done to efficiently address this problem. I’m looking at this publication from the American Health Information Management Association about major reasons for denial. We’ve already talked about a lack of preauthorization or procedures not being covered, but there are also reasons such as missing or incorrect information, duplicate claims, and not filing within the appropriate time.
Also, if treatments or procedures are bundled, they can’t be filed separately.
Preventing all of this would take a large effort. Healthcare systems would have to have a dedicated team, who would understand all the major reasons for denials, identify common patterns, and then fill everything out with accurate information, with referrals, with preauthorizations, high-specificity codes, and the correct modifiers — and do all of this within the filing deadline every time.
You would need physicians on board, but also people from IT, finance, compliance, case management, registration, and probably a bunch of other people who are already stretched too thin.
Perhaps our government can do more to hold insurers accountable and make sure plans, such as Medicare Advantage, are holding up their end of the public health bargain.
It’s an uphill $20 billion battle, but I’m optimistic. What about you? What’s your unfiltered take on claim denials? What more can we be doing?
Dr. Patel is a clinical instructor, Department of Pediatrics, Columbia University College of Physicians and Surgeons; pediatric hospitalist, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, New York City, and Benioff Children’s Hospital, University of California, San Francisco. He reported a conflict of interest with Medumo.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Oh, insurance claim denials. When patient care or treatment is warranted by a specific diagnosis, I wish insurers would just reimburse it without any hassle. That’s not reality. Let’s talk about insurance claim denials, how they’re rising and harming patient care, and what we can do about it. That’s kind of complicated.
Rising Trend in Claim Denials and Financial Impact
First, denials are increasing. Experian Health surveyed provider revenue cycle leaders— that’s a fancy term for people who manage billing and insurance claims — and 75% said that denials are increasing. This is up from 42% a few years ago. Those surveyed also said that reimbursement times and errors in claims are also increasing, and changes in policy are happening more frequently. This all adds to the problem.
Aside from being time-consuming and annoying, claim denials take a toll on hospitals and patients. One analysis, which made headlines everywhere, showed that hospitals and health systems spent nearly $20 billion in 2022 trying to repeal overturned claims. This analysis was done by Premier, a health insurance performance company.
Breakdown of Denial Rates and Costs
Let’s do some quick whiteboard math. Health insurance companies get about 3 billion claims per year. According to surveys, about 15% of those claims are denied, so that leaves us with 450 million denied claims. Hospitals spend, on average, $43.84 per denied claim in administrative fees trying to get them overturned.
That’s about $19.7 billion spent on claim denials. Here’s the gut punch: Around 54% of those claims are ultimately paid, so that leaves us with $10.7 billion that we definitely should have saved.
Common Reasons for Denials
Let’s take a look at major causes and what’s going on.
Insurance denial rates are all over the place. It depends on state and plan. According to one analysis, the average for in-network claim denials across some states was 4% to 5%. It was 40% in Mississippi. According to HealthCare.gov, in 2021, around 17% of in-network claims were denied.
The most common reasons were excluded services, a lack of referral or preauthorization, or a medical treatment not being deemed necessary. Then there’s the black box of “other,” just some arbitrary reason to make a claim denial.
Many times, these denials are done by an algorithm, not by individual people.
What’s more, a Kaiser Family Foundation analysis found that private insurers, including Medicare Advantage plans, were more likely to deny claims than public options.
When broken down, the problem was higher among employer-sponsored and marketplace insurance, and less so with Medicare and Medicaid.
Impact on Patient Care
Many consumers don’t truly understand what their health insurance covers and what’s going to be out of pocket, and many people don’t know that they have appeal rights. They don’t know who to call for help either.
The ACA set up Consumer Assistance Programs (CAPs), which are designed to help people navigate health insurance problems. By law, private insurers have to share data with CAPs. Yet, only 3% of people who had trouble with health insurance claims called a CAP for help.
We all know some of the downstream effects of this problem. Patients may skip or delay treatments if they can’t get insurance to cover it or it’s too expensive. When post-acute care, such as transfer to a skilled nursing facility or rehab center, isn’t covered and we’re trying to discharge patients from the hospital, hospital stays become lengthened, which means they’re more expensive, and this comes with its own set of complications.
How Can We Address This?
I’m genuinely curious about what you all have done to efficiently address this problem. I’m looking at this publication from the American Health Information Management Association about major reasons for denial. We’ve already talked about a lack of preauthorization or procedures not being covered, but there are also reasons such as missing or incorrect information, duplicate claims, and not filing within the appropriate time.
Also, if treatments or procedures are bundled, they can’t be filed separately.
Preventing all of this would take a large effort. Healthcare systems would have to have a dedicated team, who would understand all the major reasons for denials, identify common patterns, and then fill everything out with accurate information, with referrals, with preauthorizations, high-specificity codes, and the correct modifiers — and do all of this within the filing deadline every time.
You would need physicians on board, but also people from IT, finance, compliance, case management, registration, and probably a bunch of other people who are already stretched too thin.
Perhaps our government can do more to hold insurers accountable and make sure plans, such as Medicare Advantage, are holding up their end of the public health bargain.
It’s an uphill $20 billion battle, but I’m optimistic. What about you? What’s your unfiltered take on claim denials? What more can we be doing?
Dr. Patel is a clinical instructor, Department of Pediatrics, Columbia University College of Physicians and Surgeons; pediatric hospitalist, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, New York City, and Benioff Children’s Hospital, University of California, San Francisco. He reported a conflict of interest with Medumo.
A version of this article first appeared on Medscape.com.
Drugs to Target Lp(a): What’s Coming
This transcript has been edited for clarity.
Michelle L. O’Donoghue, MD, MPH: I’m here at the American Heart Association Scientific Sessions. It’s a very exciting meeting, but one of the interesting topics that we’re going to be talking about is lipoprotein(a) [Lp(a)] . It’s definitely one of the hottest sessions of the meeting.
Joining me to discuss this topic is Dr Steve Nicholls, who is arguably one of the leading experts in the world on lipids. He’s a professor of medicine at Monash University in Australia. Welcome. Thanks, Steve.
Stephen J. Nicholls, MBBS, PhD: Thanks for having me.
O’Donoghue: There are two phase 2 studies that we’ll circle back to that are being presented here at the American Heart Association meeting. These are for novel therapeutics that lower Lp(a). Perhaps taking a step back, we know that there’s a large body of evidence to support the concept that Lp(a) plays a causal role in heart disease and atherogenesis, but to date we haven’t had any effective therapies to really lower it.
Thinking about the therapeutics specifically that are on the horizon, perhaps we could start there. Which one is furthest along in development, and how does that look in terms of its ability to lower Lp(a)?
Pelacarsen, an ASO
Nicholls: Most of the therapies are injectable. Most of them are nucleic acid–based therapies, and the one that’s most advanced is an agent called pelacarsen. Pelacarsen is an antisense oligonucleotide (ASO), and it has gone all the way through its early phase 2 studies. It has a fully enrolled cardiovascular outcome trial.
We’re all eagerly awaiting the results of that study sometime in the next year or so. That will be the first large-scale clinical trial that will give us some clinical validation to ask the question of whether substantive lowering of Lp(a) will lower cardiovascular risk, with an agent that in early studies looks like it lowers Lp(a) about 80%.
O’Donoghue: Which is tremendous, because again, we really don’t have any effective therapies right now. I guess one of the big questions is, how much do we need to lower Lp(a) for that to translate into meaningful clinical benefit? What’s your sense there?
Nicholls: Well, we simply don’t know. We’ve tried to look to genetics to try and give us some sort of sense in terms of what that looks like. Lp(a) is a little tricky because the assays and the numbers that get spit out can be tricky in terms of trying to compare apples and apples in different studies.
We think that it’s probably at least a 50- to 75-mg/dL lowering of Lp(a) using the old units. We think that pelacarsen would hit that, and so our hope is that that would translate to a 15%-20% reduction in major cardiovascular events, but again, we’ve never asked this question before.
We have data from PCSK9 inhibitor trials showing that lesser reductions in Lp(a) of 25%-30% with both evolocumab and alirocumab contributed to the clinical benefit that we saw in those studies. Those agents were really good at lowering low-density lipoprotein (LDL) cholesterol, but Lp(a) lowering seemed to matter. One would be very hopeful that if a 25%-30% lowering of Lp(a) is useful, then an 80% or greater lowering of Lp(a) should be really useful.
The siRNAs
O’Donoghue: In addition to the ASO pelacarsen that you mentioned, there are several therapeutics in the pipeline, including three small interfering (si) RNAs that are at least in phase 2 and phase 3 testing at this point in time. There’s olpasiran, which in phase 2 testing led to more than a 95% reduction in Lp(a), and then lepodisiran , which has now moved into phase 3 testing, albeit we haven’t seen yet the phase 2 results.
What is your sense of lepodisiran and its efficacy?
Nicholls: What’s been really quite striking about the siRNAs is the even more profound degree of lowering of Lp(a) that we’re seeing. We’re seeing 90% and greater lowering of Lp(a) in all of those programs. We’re seeing some differences between the programs in terms of the durability of that effect.
I think it would be fair to say that with zerlasiran we’re starting to see perhaps that lowering effect starts to taper off a little bit more quickly than the other two. I think that may have some implications in terms of what dosing regimens may look like in the future.
Even so, we’re talking about therapies that may be dosed 3- to 6-monthly, or even with the potential for being less frequent than that with lepodisiran. Again, I think the phase 2 data will be really important in terms of giving us more information.
O’Donoghue: For the lepodisiran results, I was really quite struck that even though it was small numbers, single dose administered, it really looked like the duration of effect persisted at the higher doses up to about a year.
Nicholls: It looks pretty promising. We’ve launched the ACCLAIM study, the large cardiovascular outcome trial of lepodisiran, with a 6-monthly regimen. We are hopeful that more information may be able to give us the opportunity for even less frequent administration.
That has really important implications for patients where adherence is a particular issue. They may just simply want to come into the clinic. You know, once or twice a year, very much like we’re seeing with inclisiran, and that may be a really effective approach for many patients.
O’Donoghue: You alluded to the zerlasiran results, which were presented here at the American Heart Association meeting, and that even though it led to a robust reduction in Lp(a), it looked like the durability component was maybe a little bit shorter than for some of the other siRNAs that are currently being evaluated.
What’s your sense of that?
Nicholls: It probably is. The implications clinically, at least in an outcome trial when they ultimately get to that point, probably aren’t that important. They’ll probably just have slightly more frequent administration. That may become a bigger issue when it gets out into the clinic.
The nice thing is that if all of these agents appear to be effective, are well tolerated, and get out to the clinic, then clinicians and patients are going to have a lot of choice.
O’Donoghue: I think more competition is always good news for the field, ultimately. I think to your point, especially for a drug that might be self-administered, ultimately, whether it’s once a month or once every 3 months, it doesn’t probably make much difference. I think different choices are needed for different patients.
Perhaps that’s a perfect segue to talk about the oral Lp(a) inhibitor that is also being developed. You presented these results for muvalaplin.
Muvalaplin, an Oral Small Molecule
Nicholls: In terms of frequency of administration, we’re talking about a daily oral therapeutic. For patients who don’t want an injectable and are happy to take a tablet every day, muvalaplin has the potential to be a really good option for them.
Muvalaplin is an oral small-molecule inhibitor. It essentially prevents apolipoprotein(a) [apo(a)] from binding to apolipoprotein B (apo B). We presented phase 1 data at the European Society of Cardiology meeting last year, showing probably Lp(a) lowering on the order of about 65%. Here, we’re going to show that that’s a little bit more. It looks like it’s probably at least 70% lowering using a standard Lp(a) assay. Using an assay that looks specifically at intact Lp(a) particles, it’s probably well in excess of 80%.
Those are really good results. The safety and tolerability with muvalaplin look really good. Again, we’ll need to see that agent move forward into a large outcome trial and we’ve yet to hear about that, at least for now.
O’Donoghue: It’s an interesting challenge that you faced in terms of the assay because, as you say, it really disrupts the apo(a) from binding to the apo B particle, and hence, a traditional assay that just measures apo(a), regardless of whether or not it’s bound to an apo B particle, may be a conservative estimate.
Nicholls: It may, in particular, because we know that apo(a) ultimately then binds to the drug. That assay is measuring what we think is nonfunctional apo(a) in addition to functional apo(a). It’s measuring functional apo(a) that’s still on an actual Lp(a) particle, but if it’s bound to muvalaplin, we think to some degree that’s probably unfair to count that. That’s why trying to develop other assays to try and understand the full effect of the drug is really important in terms of trying to understand how we develop that and move that forward.
O’Donoghue: Is there any evidence yet that the apo(a) particle that is not bound to apo B is in fact nonfunctional as you described it?
Nicholls: We think that’s likely to be the case, but I think there continues to be research in that space to try and settle that question once and for all.
O’Donoghue: Again, I think it’s a really exciting time in this field. Right now, we have three ongoing phase 3 trials. We have the pelacarsen trial that is still in follow-up, and fingers crossed, maybe will report out next year. Olpasiran is also in phase 3 testing, completed enrollment, and also is in the follow-up period. We also have lepodisiran, the ACCLAIM trial, as you mentioned. For people who are perhaps watching and looking to enroll their patients, this trial is still ongoing right now in terms of enrollment.
Nicholls: It is, and what’s nice about the ACCLAIM study is that it includes both primary and secondary prevention patients. For the first time in a big outcome trial, patients with high Lp(a) levels but who have yet to have a clinical event can actually get into a clinical trial.
I’m sure, like you, my clinic is full of patients with high Lp(a) who are really desperate to get into these trials. Many of those primary prevention patients just simply haven’t qualified, so that’s really good news.
The step beyond that, if we’re talking about even less frequent administration, is gene editing. We’re seeing those studies with CRISPR move forward to try to evaluate whether a single gene-editing approach at Lp(a) will be all that you need, which is even a more amazing concept, but that’s a study that needs more work.
O’Donoghue: An exciting space though, for sure. As a final thought, you mentioned the patients in your clinic who you have identified as having high Lp(a). What are you doing right now in your practice for managing those patients? I think there are many practitioners out there who struggle with whether they should really measure their patients’ Lp(a), and whether they want to know that information.
Nicholls: Yeah, it’s really hard. The answer is yes, we do want to know it. We know it’s a great risk enhancer. We know that a patient with a high Lp(a) is somebody whom I want to more intensively treat their other risk factors. I’m aiming for a lower LDL. I’m being much tighter with blood pressure control.
I think there’s some argument from observational data at least that aspirin remains a consideration, particularly in patients where you think there’s a particularly high risk associated with that high Lp(a). I think there are things we absolutely can do today, but we can’t do anything if you don’t know the numbers.
It starts with testing, and then we can move on to what we can do today, and then hopefully in the not-too-distant future, we’ll have specific therapies that really enable for us to address Lp(a) quite definitively.
O’Donoghue: Thanks again for taking the time. This was a very helpful discussion.
Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group. A strong believer in evidence-based medicine, she relishes discussions about the published literature. A native Canadian, Michelle loves spending time outdoors with her family but admits with shame that she’s never strapped on hockey skates. Dr O’Donoghue, Senior Investigator, TIMI Study Group; Associate Professor of Medicine, Harvard Medical School; Associate Physician, Brigham and Women’s Hospital, Boston, Massachusetts, disclosed ties to Janssen; Novartis; CVS Minute Clinic; Merck & Co.; GlaxoSmithKline; Eisai Inc.; AstraZeneca Pharmaceuticals LP; Janssen Pharmaceuticals; Medicines Company; and Amgen. The opinions expressed in this article do not necessarily reflect the views and opinions of Brigham and Women’s Hospital. Stephen J. Nicholls, MBBS, PhD, Director, Victorian Heart Institute, Monash University; Director, Victorian Heart Hospital, Monash Health, Melbourne, Australia, has disclosed ties with Akcea Therapeutics; Amgen; AstraZeneca; Boehringer Ingelheim; CSL Behring; Eli Lilly and Company; Esperion Therapeutics; Kowa Pharmaceuticals; Merck; Novo Nordisk; Pfizer; Sanofi Regeneron; Daichii Sankyo; Vaxxinity; Cyclarity; CSL Sequirus; Takeda; Anthera Pharmaceuticals; Cerenis Therapeutics; Infraredx; New Amsterdam Pharma; Novartis; and Resverlogix.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Michelle L. O’Donoghue, MD, MPH: I’m here at the American Heart Association Scientific Sessions. It’s a very exciting meeting, but one of the interesting topics that we’re going to be talking about is lipoprotein(a) [Lp(a)] . It’s definitely one of the hottest sessions of the meeting.
Joining me to discuss this topic is Dr Steve Nicholls, who is arguably one of the leading experts in the world on lipids. He’s a professor of medicine at Monash University in Australia. Welcome. Thanks, Steve.
Stephen J. Nicholls, MBBS, PhD: Thanks for having me.
O’Donoghue: There are two phase 2 studies that we’ll circle back to that are being presented here at the American Heart Association meeting. These are for novel therapeutics that lower Lp(a). Perhaps taking a step back, we know that there’s a large body of evidence to support the concept that Lp(a) plays a causal role in heart disease and atherogenesis, but to date we haven’t had any effective therapies to really lower it.
Thinking about the therapeutics specifically that are on the horizon, perhaps we could start there. Which one is furthest along in development, and how does that look in terms of its ability to lower Lp(a)?
Pelacarsen, an ASO
Nicholls: Most of the therapies are injectable. Most of them are nucleic acid–based therapies, and the one that’s most advanced is an agent called pelacarsen. Pelacarsen is an antisense oligonucleotide (ASO), and it has gone all the way through its early phase 2 studies. It has a fully enrolled cardiovascular outcome trial.
We’re all eagerly awaiting the results of that study sometime in the next year or so. That will be the first large-scale clinical trial that will give us some clinical validation to ask the question of whether substantive lowering of Lp(a) will lower cardiovascular risk, with an agent that in early studies looks like it lowers Lp(a) about 80%.
O’Donoghue: Which is tremendous, because again, we really don’t have any effective therapies right now. I guess one of the big questions is, how much do we need to lower Lp(a) for that to translate into meaningful clinical benefit? What’s your sense there?
Nicholls: Well, we simply don’t know. We’ve tried to look to genetics to try and give us some sort of sense in terms of what that looks like. Lp(a) is a little tricky because the assays and the numbers that get spit out can be tricky in terms of trying to compare apples and apples in different studies.
We think that it’s probably at least a 50- to 75-mg/dL lowering of Lp(a) using the old units. We think that pelacarsen would hit that, and so our hope is that that would translate to a 15%-20% reduction in major cardiovascular events, but again, we’ve never asked this question before.
We have data from PCSK9 inhibitor trials showing that lesser reductions in Lp(a) of 25%-30% with both evolocumab and alirocumab contributed to the clinical benefit that we saw in those studies. Those agents were really good at lowering low-density lipoprotein (LDL) cholesterol, but Lp(a) lowering seemed to matter. One would be very hopeful that if a 25%-30% lowering of Lp(a) is useful, then an 80% or greater lowering of Lp(a) should be really useful.
The siRNAs
O’Donoghue: In addition to the ASO pelacarsen that you mentioned, there are several therapeutics in the pipeline, including three small interfering (si) RNAs that are at least in phase 2 and phase 3 testing at this point in time. There’s olpasiran, which in phase 2 testing led to more than a 95% reduction in Lp(a), and then lepodisiran , which has now moved into phase 3 testing, albeit we haven’t seen yet the phase 2 results.
What is your sense of lepodisiran and its efficacy?
Nicholls: What’s been really quite striking about the siRNAs is the even more profound degree of lowering of Lp(a) that we’re seeing. We’re seeing 90% and greater lowering of Lp(a) in all of those programs. We’re seeing some differences between the programs in terms of the durability of that effect.
I think it would be fair to say that with zerlasiran we’re starting to see perhaps that lowering effect starts to taper off a little bit more quickly than the other two. I think that may have some implications in terms of what dosing regimens may look like in the future.
Even so, we’re talking about therapies that may be dosed 3- to 6-monthly, or even with the potential for being less frequent than that with lepodisiran. Again, I think the phase 2 data will be really important in terms of giving us more information.
O’Donoghue: For the lepodisiran results, I was really quite struck that even though it was small numbers, single dose administered, it really looked like the duration of effect persisted at the higher doses up to about a year.
Nicholls: It looks pretty promising. We’ve launched the ACCLAIM study, the large cardiovascular outcome trial of lepodisiran, with a 6-monthly regimen. We are hopeful that more information may be able to give us the opportunity for even less frequent administration.
That has really important implications for patients where adherence is a particular issue. They may just simply want to come into the clinic. You know, once or twice a year, very much like we’re seeing with inclisiran, and that may be a really effective approach for many patients.
O’Donoghue: You alluded to the zerlasiran results, which were presented here at the American Heart Association meeting, and that even though it led to a robust reduction in Lp(a), it looked like the durability component was maybe a little bit shorter than for some of the other siRNAs that are currently being evaluated.
What’s your sense of that?
Nicholls: It probably is. The implications clinically, at least in an outcome trial when they ultimately get to that point, probably aren’t that important. They’ll probably just have slightly more frequent administration. That may become a bigger issue when it gets out into the clinic.
The nice thing is that if all of these agents appear to be effective, are well tolerated, and get out to the clinic, then clinicians and patients are going to have a lot of choice.
O’Donoghue: I think more competition is always good news for the field, ultimately. I think to your point, especially for a drug that might be self-administered, ultimately, whether it’s once a month or once every 3 months, it doesn’t probably make much difference. I think different choices are needed for different patients.
Perhaps that’s a perfect segue to talk about the oral Lp(a) inhibitor that is also being developed. You presented these results for muvalaplin.
Muvalaplin, an Oral Small Molecule
Nicholls: In terms of frequency of administration, we’re talking about a daily oral therapeutic. For patients who don’t want an injectable and are happy to take a tablet every day, muvalaplin has the potential to be a really good option for them.
Muvalaplin is an oral small-molecule inhibitor. It essentially prevents apolipoprotein(a) [apo(a)] from binding to apolipoprotein B (apo B). We presented phase 1 data at the European Society of Cardiology meeting last year, showing probably Lp(a) lowering on the order of about 65%. Here, we’re going to show that that’s a little bit more. It looks like it’s probably at least 70% lowering using a standard Lp(a) assay. Using an assay that looks specifically at intact Lp(a) particles, it’s probably well in excess of 80%.
Those are really good results. The safety and tolerability with muvalaplin look really good. Again, we’ll need to see that agent move forward into a large outcome trial and we’ve yet to hear about that, at least for now.
O’Donoghue: It’s an interesting challenge that you faced in terms of the assay because, as you say, it really disrupts the apo(a) from binding to the apo B particle, and hence, a traditional assay that just measures apo(a), regardless of whether or not it’s bound to an apo B particle, may be a conservative estimate.
Nicholls: It may, in particular, because we know that apo(a) ultimately then binds to the drug. That assay is measuring what we think is nonfunctional apo(a) in addition to functional apo(a). It’s measuring functional apo(a) that’s still on an actual Lp(a) particle, but if it’s bound to muvalaplin, we think to some degree that’s probably unfair to count that. That’s why trying to develop other assays to try and understand the full effect of the drug is really important in terms of trying to understand how we develop that and move that forward.
O’Donoghue: Is there any evidence yet that the apo(a) particle that is not bound to apo B is in fact nonfunctional as you described it?
Nicholls: We think that’s likely to be the case, but I think there continues to be research in that space to try and settle that question once and for all.
O’Donoghue: Again, I think it’s a really exciting time in this field. Right now, we have three ongoing phase 3 trials. We have the pelacarsen trial that is still in follow-up, and fingers crossed, maybe will report out next year. Olpasiran is also in phase 3 testing, completed enrollment, and also is in the follow-up period. We also have lepodisiran, the ACCLAIM trial, as you mentioned. For people who are perhaps watching and looking to enroll their patients, this trial is still ongoing right now in terms of enrollment.
Nicholls: It is, and what’s nice about the ACCLAIM study is that it includes both primary and secondary prevention patients. For the first time in a big outcome trial, patients with high Lp(a) levels but who have yet to have a clinical event can actually get into a clinical trial.
I’m sure, like you, my clinic is full of patients with high Lp(a) who are really desperate to get into these trials. Many of those primary prevention patients just simply haven’t qualified, so that’s really good news.
The step beyond that, if we’re talking about even less frequent administration, is gene editing. We’re seeing those studies with CRISPR move forward to try to evaluate whether a single gene-editing approach at Lp(a) will be all that you need, which is even a more amazing concept, but that’s a study that needs more work.
O’Donoghue: An exciting space though, for sure. As a final thought, you mentioned the patients in your clinic who you have identified as having high Lp(a). What are you doing right now in your practice for managing those patients? I think there are many practitioners out there who struggle with whether they should really measure their patients’ Lp(a), and whether they want to know that information.
Nicholls: Yeah, it’s really hard. The answer is yes, we do want to know it. We know it’s a great risk enhancer. We know that a patient with a high Lp(a) is somebody whom I want to more intensively treat their other risk factors. I’m aiming for a lower LDL. I’m being much tighter with blood pressure control.
I think there’s some argument from observational data at least that aspirin remains a consideration, particularly in patients where you think there’s a particularly high risk associated with that high Lp(a). I think there are things we absolutely can do today, but we can’t do anything if you don’t know the numbers.
It starts with testing, and then we can move on to what we can do today, and then hopefully in the not-too-distant future, we’ll have specific therapies that really enable for us to address Lp(a) quite definitively.
O’Donoghue: Thanks again for taking the time. This was a very helpful discussion.
Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group. A strong believer in evidence-based medicine, she relishes discussions about the published literature. A native Canadian, Michelle loves spending time outdoors with her family but admits with shame that she’s never strapped on hockey skates. Dr O’Donoghue, Senior Investigator, TIMI Study Group; Associate Professor of Medicine, Harvard Medical School; Associate Physician, Brigham and Women’s Hospital, Boston, Massachusetts, disclosed ties to Janssen; Novartis; CVS Minute Clinic; Merck & Co.; GlaxoSmithKline; Eisai Inc.; AstraZeneca Pharmaceuticals LP; Janssen Pharmaceuticals; Medicines Company; and Amgen. The opinions expressed in this article do not necessarily reflect the views and opinions of Brigham and Women’s Hospital. Stephen J. Nicholls, MBBS, PhD, Director, Victorian Heart Institute, Monash University; Director, Victorian Heart Hospital, Monash Health, Melbourne, Australia, has disclosed ties with Akcea Therapeutics; Amgen; AstraZeneca; Boehringer Ingelheim; CSL Behring; Eli Lilly and Company; Esperion Therapeutics; Kowa Pharmaceuticals; Merck; Novo Nordisk; Pfizer; Sanofi Regeneron; Daichii Sankyo; Vaxxinity; Cyclarity; CSL Sequirus; Takeda; Anthera Pharmaceuticals; Cerenis Therapeutics; Infraredx; New Amsterdam Pharma; Novartis; and Resverlogix.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Michelle L. O’Donoghue, MD, MPH: I’m here at the American Heart Association Scientific Sessions. It’s a very exciting meeting, but one of the interesting topics that we’re going to be talking about is lipoprotein(a) [Lp(a)] . It’s definitely one of the hottest sessions of the meeting.
Joining me to discuss this topic is Dr Steve Nicholls, who is arguably one of the leading experts in the world on lipids. He’s a professor of medicine at Monash University in Australia. Welcome. Thanks, Steve.
Stephen J. Nicholls, MBBS, PhD: Thanks for having me.
O’Donoghue: There are two phase 2 studies that we’ll circle back to that are being presented here at the American Heart Association meeting. These are for novel therapeutics that lower Lp(a). Perhaps taking a step back, we know that there’s a large body of evidence to support the concept that Lp(a) plays a causal role in heart disease and atherogenesis, but to date we haven’t had any effective therapies to really lower it.
Thinking about the therapeutics specifically that are on the horizon, perhaps we could start there. Which one is furthest along in development, and how does that look in terms of its ability to lower Lp(a)?
Pelacarsen, an ASO
Nicholls: Most of the therapies are injectable. Most of them are nucleic acid–based therapies, and the one that’s most advanced is an agent called pelacarsen. Pelacarsen is an antisense oligonucleotide (ASO), and it has gone all the way through its early phase 2 studies. It has a fully enrolled cardiovascular outcome trial.
We’re all eagerly awaiting the results of that study sometime in the next year or so. That will be the first large-scale clinical trial that will give us some clinical validation to ask the question of whether substantive lowering of Lp(a) will lower cardiovascular risk, with an agent that in early studies looks like it lowers Lp(a) about 80%.
O’Donoghue: Which is tremendous, because again, we really don’t have any effective therapies right now. I guess one of the big questions is, how much do we need to lower Lp(a) for that to translate into meaningful clinical benefit? What’s your sense there?
Nicholls: Well, we simply don’t know. We’ve tried to look to genetics to try and give us some sort of sense in terms of what that looks like. Lp(a) is a little tricky because the assays and the numbers that get spit out can be tricky in terms of trying to compare apples and apples in different studies.
We think that it’s probably at least a 50- to 75-mg/dL lowering of Lp(a) using the old units. We think that pelacarsen would hit that, and so our hope is that that would translate to a 15%-20% reduction in major cardiovascular events, but again, we’ve never asked this question before.
We have data from PCSK9 inhibitor trials showing that lesser reductions in Lp(a) of 25%-30% with both evolocumab and alirocumab contributed to the clinical benefit that we saw in those studies. Those agents were really good at lowering low-density lipoprotein (LDL) cholesterol, but Lp(a) lowering seemed to matter. One would be very hopeful that if a 25%-30% lowering of Lp(a) is useful, then an 80% or greater lowering of Lp(a) should be really useful.
The siRNAs
O’Donoghue: In addition to the ASO pelacarsen that you mentioned, there are several therapeutics in the pipeline, including three small interfering (si) RNAs that are at least in phase 2 and phase 3 testing at this point in time. There’s olpasiran, which in phase 2 testing led to more than a 95% reduction in Lp(a), and then lepodisiran , which has now moved into phase 3 testing, albeit we haven’t seen yet the phase 2 results.
What is your sense of lepodisiran and its efficacy?
Nicholls: What’s been really quite striking about the siRNAs is the even more profound degree of lowering of Lp(a) that we’re seeing. We’re seeing 90% and greater lowering of Lp(a) in all of those programs. We’re seeing some differences between the programs in terms of the durability of that effect.
I think it would be fair to say that with zerlasiran we’re starting to see perhaps that lowering effect starts to taper off a little bit more quickly than the other two. I think that may have some implications in terms of what dosing regimens may look like in the future.
Even so, we’re talking about therapies that may be dosed 3- to 6-monthly, or even with the potential for being less frequent than that with lepodisiran. Again, I think the phase 2 data will be really important in terms of giving us more information.
O’Donoghue: For the lepodisiran results, I was really quite struck that even though it was small numbers, single dose administered, it really looked like the duration of effect persisted at the higher doses up to about a year.
Nicholls: It looks pretty promising. We’ve launched the ACCLAIM study, the large cardiovascular outcome trial of lepodisiran, with a 6-monthly regimen. We are hopeful that more information may be able to give us the opportunity for even less frequent administration.
That has really important implications for patients where adherence is a particular issue. They may just simply want to come into the clinic. You know, once or twice a year, very much like we’re seeing with inclisiran, and that may be a really effective approach for many patients.
O’Donoghue: You alluded to the zerlasiran results, which were presented here at the American Heart Association meeting, and that even though it led to a robust reduction in Lp(a), it looked like the durability component was maybe a little bit shorter than for some of the other siRNAs that are currently being evaluated.
What’s your sense of that?
Nicholls: It probably is. The implications clinically, at least in an outcome trial when they ultimately get to that point, probably aren’t that important. They’ll probably just have slightly more frequent administration. That may become a bigger issue when it gets out into the clinic.
The nice thing is that if all of these agents appear to be effective, are well tolerated, and get out to the clinic, then clinicians and patients are going to have a lot of choice.
O’Donoghue: I think more competition is always good news for the field, ultimately. I think to your point, especially for a drug that might be self-administered, ultimately, whether it’s once a month or once every 3 months, it doesn’t probably make much difference. I think different choices are needed for different patients.
Perhaps that’s a perfect segue to talk about the oral Lp(a) inhibitor that is also being developed. You presented these results for muvalaplin.
Muvalaplin, an Oral Small Molecule
Nicholls: In terms of frequency of administration, we’re talking about a daily oral therapeutic. For patients who don’t want an injectable and are happy to take a tablet every day, muvalaplin has the potential to be a really good option for them.
Muvalaplin is an oral small-molecule inhibitor. It essentially prevents apolipoprotein(a) [apo(a)] from binding to apolipoprotein B (apo B). We presented phase 1 data at the European Society of Cardiology meeting last year, showing probably Lp(a) lowering on the order of about 65%. Here, we’re going to show that that’s a little bit more. It looks like it’s probably at least 70% lowering using a standard Lp(a) assay. Using an assay that looks specifically at intact Lp(a) particles, it’s probably well in excess of 80%.
Those are really good results. The safety and tolerability with muvalaplin look really good. Again, we’ll need to see that agent move forward into a large outcome trial and we’ve yet to hear about that, at least for now.
O’Donoghue: It’s an interesting challenge that you faced in terms of the assay because, as you say, it really disrupts the apo(a) from binding to the apo B particle, and hence, a traditional assay that just measures apo(a), regardless of whether or not it’s bound to an apo B particle, may be a conservative estimate.
Nicholls: It may, in particular, because we know that apo(a) ultimately then binds to the drug. That assay is measuring what we think is nonfunctional apo(a) in addition to functional apo(a). It’s measuring functional apo(a) that’s still on an actual Lp(a) particle, but if it’s bound to muvalaplin, we think to some degree that’s probably unfair to count that. That’s why trying to develop other assays to try and understand the full effect of the drug is really important in terms of trying to understand how we develop that and move that forward.
O’Donoghue: Is there any evidence yet that the apo(a) particle that is not bound to apo B is in fact nonfunctional as you described it?
Nicholls: We think that’s likely to be the case, but I think there continues to be research in that space to try and settle that question once and for all.
O’Donoghue: Again, I think it’s a really exciting time in this field. Right now, we have three ongoing phase 3 trials. We have the pelacarsen trial that is still in follow-up, and fingers crossed, maybe will report out next year. Olpasiran is also in phase 3 testing, completed enrollment, and also is in the follow-up period. We also have lepodisiran, the ACCLAIM trial, as you mentioned. For people who are perhaps watching and looking to enroll their patients, this trial is still ongoing right now in terms of enrollment.
Nicholls: It is, and what’s nice about the ACCLAIM study is that it includes both primary and secondary prevention patients. For the first time in a big outcome trial, patients with high Lp(a) levels but who have yet to have a clinical event can actually get into a clinical trial.
I’m sure, like you, my clinic is full of patients with high Lp(a) who are really desperate to get into these trials. Many of those primary prevention patients just simply haven’t qualified, so that’s really good news.
The step beyond that, if we’re talking about even less frequent administration, is gene editing. We’re seeing those studies with CRISPR move forward to try to evaluate whether a single gene-editing approach at Lp(a) will be all that you need, which is even a more amazing concept, but that’s a study that needs more work.
O’Donoghue: An exciting space though, for sure. As a final thought, you mentioned the patients in your clinic who you have identified as having high Lp(a). What are you doing right now in your practice for managing those patients? I think there are many practitioners out there who struggle with whether they should really measure their patients’ Lp(a), and whether they want to know that information.
Nicholls: Yeah, it’s really hard. The answer is yes, we do want to know it. We know it’s a great risk enhancer. We know that a patient with a high Lp(a) is somebody whom I want to more intensively treat their other risk factors. I’m aiming for a lower LDL. I’m being much tighter with blood pressure control.
I think there’s some argument from observational data at least that aspirin remains a consideration, particularly in patients where you think there’s a particularly high risk associated with that high Lp(a). I think there are things we absolutely can do today, but we can’t do anything if you don’t know the numbers.
It starts with testing, and then we can move on to what we can do today, and then hopefully in the not-too-distant future, we’ll have specific therapies that really enable for us to address Lp(a) quite definitively.
O’Donoghue: Thanks again for taking the time. This was a very helpful discussion.
Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group. A strong believer in evidence-based medicine, she relishes discussions about the published literature. A native Canadian, Michelle loves spending time outdoors with her family but admits with shame that she’s never strapped on hockey skates. Dr O’Donoghue, Senior Investigator, TIMI Study Group; Associate Professor of Medicine, Harvard Medical School; Associate Physician, Brigham and Women’s Hospital, Boston, Massachusetts, disclosed ties to Janssen; Novartis; CVS Minute Clinic; Merck & Co.; GlaxoSmithKline; Eisai Inc.; AstraZeneca Pharmaceuticals LP; Janssen Pharmaceuticals; Medicines Company; and Amgen. The opinions expressed in this article do not necessarily reflect the views and opinions of Brigham and Women’s Hospital. Stephen J. Nicholls, MBBS, PhD, Director, Victorian Heart Institute, Monash University; Director, Victorian Heart Hospital, Monash Health, Melbourne, Australia, has disclosed ties with Akcea Therapeutics; Amgen; AstraZeneca; Boehringer Ingelheim; CSL Behring; Eli Lilly and Company; Esperion Therapeutics; Kowa Pharmaceuticals; Merck; Novo Nordisk; Pfizer; Sanofi Regeneron; Daichii Sankyo; Vaxxinity; Cyclarity; CSL Sequirus; Takeda; Anthera Pharmaceuticals; Cerenis Therapeutics; Infraredx; New Amsterdam Pharma; Novartis; and Resverlogix.
A version of this article appeared on Medscape.com.
Does Virtual Care for UTIs Lead to Increased Antibiotic Use Without Better Outcomes?
TOPLINE:
Virtual visits for urinary tract infections (UTIs) increased by more than 600% from 2015 to 2022, with overall UTI encounters growing by 325.9%. The rate of antibiotic dispensation climbed by 227.3% per 1000 patients, outpacing the 159.8% increase in positive urine cultures.
METHODOLOGY:
- Researchers conducted a retrospective cohort study analyzing 1,220,698 UTI encounters among 428,855 nonpregnant women aged ≥ 18 years at Kaiser Permanente Southern California from 2015 to 2022.
- Analysis included outpatient UTI encounters in ambulatory and urgent care settings, excluding emergency and inpatient visits.
- Data collection encompassed demographic information, urine tests, antibiotic dispensation, and UTI diagnoses using International Classification of Diseases, 9th and 10th Revision codes.
- Encounters conducted by physicians, physician assistants, nurse practitioners, and registered nurses through in-person, phone, video, and health portal platforms were evaluated.
TAKEAWAY:
- Virtual encounters grew by 603.2% compared with a 122.8% increase for in-person visits, with virtual visits accounting for 60% (733,263) of all UTI encounters.
- The rate of UTI encounters per 1000 adult female patients increased by 241.6%, while membership in the health system grew by only 24.4%.
- Antibiotics were prescribed without urine testing in 42.5% (519,135) of encounters, and among encounters with both antibiotic dispensation and urine testing, 57.1% (278,903) had a positive culture.
- According to the authors, the increasing rate of antibiotic dispensation surpassed the growth in positive urine culture rates, suggesting increased use of empiric antibiotics.
IN PRACTICE:
“Our findings underscore the importance of balancing telemedicine’s accessibility with maintaining antibiotic stewardship and highlight the need for updated guidelines,” wrote the authors of the study. An accompanying editorial said, “Unfortunately, our misguided conceptual model has led to several decades of UTI research focusing on bad bugs rather than investigating the natural host defenses, how we might boost these, what perturbs the ecosystem, and how microbial defense occurs within the bladder.”
SOURCE:
The study was led by Ghanshyam Yadav, MD, Kaiser Permanente Southern California in San Diego. It was published online in Obstetrics & Gynecology. The editorial, written by Nazema Y. Siddiqui, MD, MHSc, from the Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, was also published in Obstetrics & Gynecology.
LIMITATIONS:
The retrospective design and analysis at the encounter level did not allow for control of patient and clinician clustering. The study was limited to a single health maintenance organization, which may affect the generalizability of the findings.
DISCLOSURES:
This research received support through a grant from the Regional Research Committee of Kaiser Permanente Southern California (RRC grant number: KP-RRC-20221002). Heidi Brown and Jasmine Tan-Kim disclosed receiving royalties from UpToDate. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Virtual visits for urinary tract infections (UTIs) increased by more than 600% from 2015 to 2022, with overall UTI encounters growing by 325.9%. The rate of antibiotic dispensation climbed by 227.3% per 1000 patients, outpacing the 159.8% increase in positive urine cultures.
METHODOLOGY:
- Researchers conducted a retrospective cohort study analyzing 1,220,698 UTI encounters among 428,855 nonpregnant women aged ≥ 18 years at Kaiser Permanente Southern California from 2015 to 2022.
- Analysis included outpatient UTI encounters in ambulatory and urgent care settings, excluding emergency and inpatient visits.
- Data collection encompassed demographic information, urine tests, antibiotic dispensation, and UTI diagnoses using International Classification of Diseases, 9th and 10th Revision codes.
- Encounters conducted by physicians, physician assistants, nurse practitioners, and registered nurses through in-person, phone, video, and health portal platforms were evaluated.
TAKEAWAY:
- Virtual encounters grew by 603.2% compared with a 122.8% increase for in-person visits, with virtual visits accounting for 60% (733,263) of all UTI encounters.
- The rate of UTI encounters per 1000 adult female patients increased by 241.6%, while membership in the health system grew by only 24.4%.
- Antibiotics were prescribed without urine testing in 42.5% (519,135) of encounters, and among encounters with both antibiotic dispensation and urine testing, 57.1% (278,903) had a positive culture.
- According to the authors, the increasing rate of antibiotic dispensation surpassed the growth in positive urine culture rates, suggesting increased use of empiric antibiotics.
IN PRACTICE:
“Our findings underscore the importance of balancing telemedicine’s accessibility with maintaining antibiotic stewardship and highlight the need for updated guidelines,” wrote the authors of the study. An accompanying editorial said, “Unfortunately, our misguided conceptual model has led to several decades of UTI research focusing on bad bugs rather than investigating the natural host defenses, how we might boost these, what perturbs the ecosystem, and how microbial defense occurs within the bladder.”
SOURCE:
The study was led by Ghanshyam Yadav, MD, Kaiser Permanente Southern California in San Diego. It was published online in Obstetrics & Gynecology. The editorial, written by Nazema Y. Siddiqui, MD, MHSc, from the Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, was also published in Obstetrics & Gynecology.
LIMITATIONS:
The retrospective design and analysis at the encounter level did not allow for control of patient and clinician clustering. The study was limited to a single health maintenance organization, which may affect the generalizability of the findings.
DISCLOSURES:
This research received support through a grant from the Regional Research Committee of Kaiser Permanente Southern California (RRC grant number: KP-RRC-20221002). Heidi Brown and Jasmine Tan-Kim disclosed receiving royalties from UpToDate. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Virtual visits for urinary tract infections (UTIs) increased by more than 600% from 2015 to 2022, with overall UTI encounters growing by 325.9%. The rate of antibiotic dispensation climbed by 227.3% per 1000 patients, outpacing the 159.8% increase in positive urine cultures.
METHODOLOGY:
- Researchers conducted a retrospective cohort study analyzing 1,220,698 UTI encounters among 428,855 nonpregnant women aged ≥ 18 years at Kaiser Permanente Southern California from 2015 to 2022.
- Analysis included outpatient UTI encounters in ambulatory and urgent care settings, excluding emergency and inpatient visits.
- Data collection encompassed demographic information, urine tests, antibiotic dispensation, and UTI diagnoses using International Classification of Diseases, 9th and 10th Revision codes.
- Encounters conducted by physicians, physician assistants, nurse practitioners, and registered nurses through in-person, phone, video, and health portal platforms were evaluated.
TAKEAWAY:
- Virtual encounters grew by 603.2% compared with a 122.8% increase for in-person visits, with virtual visits accounting for 60% (733,263) of all UTI encounters.
- The rate of UTI encounters per 1000 adult female patients increased by 241.6%, while membership in the health system grew by only 24.4%.
- Antibiotics were prescribed without urine testing in 42.5% (519,135) of encounters, and among encounters with both antibiotic dispensation and urine testing, 57.1% (278,903) had a positive culture.
- According to the authors, the increasing rate of antibiotic dispensation surpassed the growth in positive urine culture rates, suggesting increased use of empiric antibiotics.
IN PRACTICE:
“Our findings underscore the importance of balancing telemedicine’s accessibility with maintaining antibiotic stewardship and highlight the need for updated guidelines,” wrote the authors of the study. An accompanying editorial said, “Unfortunately, our misguided conceptual model has led to several decades of UTI research focusing on bad bugs rather than investigating the natural host defenses, how we might boost these, what perturbs the ecosystem, and how microbial defense occurs within the bladder.”
SOURCE:
The study was led by Ghanshyam Yadav, MD, Kaiser Permanente Southern California in San Diego. It was published online in Obstetrics & Gynecology. The editorial, written by Nazema Y. Siddiqui, MD, MHSc, from the Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, was also published in Obstetrics & Gynecology.
LIMITATIONS:
The retrospective design and analysis at the encounter level did not allow for control of patient and clinician clustering. The study was limited to a single health maintenance organization, which may affect the generalizability of the findings.
DISCLOSURES:
This research received support through a grant from the Regional Research Committee of Kaiser Permanente Southern California (RRC grant number: KP-RRC-20221002). Heidi Brown and Jasmine Tan-Kim disclosed receiving royalties from UpToDate. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
UTI in Primary Care: New Guidelines
This transcript has been edited for clarity.
We often see urinary tract infections in primary care, so these guidelines for the prevention, diagnosis and management of urinary tract infection (UTI) are very helpful to reaffirm our knowledge in the areas where know what we’re doing and update our knowledge in areas of uncertainty. These guidelines are from a new group called the WikiGuidelines group. Ordinarily, I wouldn’t have considered reviewing one of these guidelines, but this one was published in JAMA Network Open. It is evidence based and covers the topic really well.
Diagnosis. Order a urinalysis or a urine culture only if the patient is having symptoms of a UTI. This may seem obvious, but particularly among older individuals, in whom asymptomatic bacteriuria is very common and should not be treated, nonspecific symptoms such as just not feeling well for a day do not warrant obtaining a urinalysis and culture. With no clear way to distinguish between asymptomatic bacteriuria and a true UTI, the first step in making the diagnosis of a UTI accurately is ordering urine studies only in people who have a reasonable chance of having an infection.
The guideline suggests that the diagnosis of UTI should be primarily based on clinical symptoms. A urinalysis can provide further information, but the authors caution us against relying solely on the urinalysis. This is an incredibly important evidence-based recommendation. If you think about it, this supports the common practice of treating UTIs over the phone without having to see the patient or check a urinalysis.
The rationale for this recommendation is that urinalysis is neither a sensitive nor specific test for UTI. The sensitivity of leukocyte esterase is only about 80%, and the specificity is even lower. For positive nitrite on urinalysis, the sensitivity is below 50%, meaning the test would be negative more than half the time when someone actually has a UTI. The specificity of urine nitrate is very high (more than 90%), so if the patient is nitrite positive, they clearly have a UTI. This means that a patient’s report of classic UTI symptoms — urinary burning, frequency, and urgency — is about as good if not a better indicator of a UTI than a urinalysis.
The guidelines also say that in simple uncomplicated cystitis in healthy nonpregnant patients, routine urine cultures are not necessary. A fascinating meta-analysis in JAMA showed that, for women presenting to outpatient clinics with at least two symptoms of UTI and absence of vaginal discharge, there was a greater than 90% likelihood of having acute cystitis. A reminder here, however: If a woman is sexually active and at risk for sexually transmitted infections, then consider testing for STIs as well, because the symptoms of an STI can mimic those of a UTI.
Treatment. Treatment for UTI is usually empiric, with treatment initiated before the culture results are known and with cultures being done only for people with complicated infections, such as pyelonephritis, or with recurrent infections. Decisions about what to use for treatment can be influenced by local patterns of resistance and an individual’s risk factors for antimicrobial resistance. As a general rule, for uncomplicated cystitis, nitrofurantoin for 5 days is a reasonable first-line agent. Evidence of efficacy is good, and the risk for antimicrobial resistance is lower vs using antibiotics for other systemic infections.
Other reasonable first-line agents for uncomplicated cystitis include trimethoprim-sulfamethoxazole (TMP-SMX) for 3 days; fosfomycin (oral) single dose; or a beta-lactam (most commonly a first generation cephalosporin), although evidence for duration is unclear. Also mentioned are two unfamiliar antibiotics: pivmecillinam (a beta-lactam agent recently approved by the Food and Drug Administration [FDA], given for 3 days) and gepotidacin (from a new class of antibiotic that is currently under FDA review). Fluoroquinolones should not usually be first-line agents unless other treatment options are not appropriate.
It’s important to distinguish between uncomplicated cystitis and pyelonephritis. For pyelonephritis (infection of the upper urinary tract), the first decision has to do with setting for care, depending on how sick someone is, and the likelihood of gram-negative bacteremia — all of which help whether the patient needs to be hospitalized for intravenous antibiotics, or can be treated as an outpatient. Determine if they need to be admitted for intravenous antibiotics or whether they can be treated as an outpatient. For outpatient treatment of pyelonephritis, the guideline suggests that TMP-SMX or a first-generation cephalosporin are both reasonable first-line agents, with fluoroquinolones being a reasonable choice as well. Ceftriaxone is recommended for first-line therapy for patients who require intravenous treatment.
People often forget that we can do a lot to prevent UTIs, particularly among women with recurrent UTIs. The prevention of UTIs has both nonpharmacologic and pharmacologic approaches.
Nonpharmacologic prevention. One nonpharmacologic strategy is increasing water intake. A randomized controlled trial in women with recurrent cystitis who drank less than 1.5 L of fluid a day showed that the women randomized to consume an additional 1.5 L of water daily had significantly reduced cystitis frequency — approximately 50%. Because this was the only randomized trial to show this effect, this is not a strong recommendation, but there is very little downside in healthy women, so increasing water intake is a reasonable recommendation.
Another commonly discussed intervention is the use of cranberry products. As it turns out, most prospective studies have shown that cranberry products can reduce the risk for symptomatic UTIs in women with recurrent UTI.
Pharmacologic prevention. For postmenopausal women with recurrent UTI, topical vaginal estrogen has a strong base of evidence — more than 30 randomized trials — supporting its effectiveness in UTI: a 50%-90% reduction in the incidence of recurrent UTIs. Topical estrogen has minimal systemic absorption, and there are no concerning safety signals with respect to either thromboembolic disease or cancer (endometrial or breast).
Methenamine hippurate is also recommended and is FDA-approved for prevention of UTIs. It works by releasing formaldehyde in the urine, leading to bacteriostasis, which is how it leads to a decrease in UTIs. Finally, postcoital or daily administration of TMP-SMX, nitrofurantoin, norfloxacin, and ciprofloxacin all have comparable efficacy for prophylaxis, with a meta-analysis showing a decrease in recurrence rate of approximately 85%. The guideline states that there is insufficient evidence to support the use of either probiotics or D-mannose to prevent UTIs.
This is a wonderful update on a common problem. We all have a lot of clinical experience here.
Dr Skolnik, Department of Family Medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia; Associate Director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
We often see urinary tract infections in primary care, so these guidelines for the prevention, diagnosis and management of urinary tract infection (UTI) are very helpful to reaffirm our knowledge in the areas where know what we’re doing and update our knowledge in areas of uncertainty. These guidelines are from a new group called the WikiGuidelines group. Ordinarily, I wouldn’t have considered reviewing one of these guidelines, but this one was published in JAMA Network Open. It is evidence based and covers the topic really well.
Diagnosis. Order a urinalysis or a urine culture only if the patient is having symptoms of a UTI. This may seem obvious, but particularly among older individuals, in whom asymptomatic bacteriuria is very common and should not be treated, nonspecific symptoms such as just not feeling well for a day do not warrant obtaining a urinalysis and culture. With no clear way to distinguish between asymptomatic bacteriuria and a true UTI, the first step in making the diagnosis of a UTI accurately is ordering urine studies only in people who have a reasonable chance of having an infection.
The guideline suggests that the diagnosis of UTI should be primarily based on clinical symptoms. A urinalysis can provide further information, but the authors caution us against relying solely on the urinalysis. This is an incredibly important evidence-based recommendation. If you think about it, this supports the common practice of treating UTIs over the phone without having to see the patient or check a urinalysis.
The rationale for this recommendation is that urinalysis is neither a sensitive nor specific test for UTI. The sensitivity of leukocyte esterase is only about 80%, and the specificity is even lower. For positive nitrite on urinalysis, the sensitivity is below 50%, meaning the test would be negative more than half the time when someone actually has a UTI. The specificity of urine nitrate is very high (more than 90%), so if the patient is nitrite positive, they clearly have a UTI. This means that a patient’s report of classic UTI symptoms — urinary burning, frequency, and urgency — is about as good if not a better indicator of a UTI than a urinalysis.
The guidelines also say that in simple uncomplicated cystitis in healthy nonpregnant patients, routine urine cultures are not necessary. A fascinating meta-analysis in JAMA showed that, for women presenting to outpatient clinics with at least two symptoms of UTI and absence of vaginal discharge, there was a greater than 90% likelihood of having acute cystitis. A reminder here, however: If a woman is sexually active and at risk for sexually transmitted infections, then consider testing for STIs as well, because the symptoms of an STI can mimic those of a UTI.
Treatment. Treatment for UTI is usually empiric, with treatment initiated before the culture results are known and with cultures being done only for people with complicated infections, such as pyelonephritis, or with recurrent infections. Decisions about what to use for treatment can be influenced by local patterns of resistance and an individual’s risk factors for antimicrobial resistance. As a general rule, for uncomplicated cystitis, nitrofurantoin for 5 days is a reasonable first-line agent. Evidence of efficacy is good, and the risk for antimicrobial resistance is lower vs using antibiotics for other systemic infections.
Other reasonable first-line agents for uncomplicated cystitis include trimethoprim-sulfamethoxazole (TMP-SMX) for 3 days; fosfomycin (oral) single dose; or a beta-lactam (most commonly a first generation cephalosporin), although evidence for duration is unclear. Also mentioned are two unfamiliar antibiotics: pivmecillinam (a beta-lactam agent recently approved by the Food and Drug Administration [FDA], given for 3 days) and gepotidacin (from a new class of antibiotic that is currently under FDA review). Fluoroquinolones should not usually be first-line agents unless other treatment options are not appropriate.
It’s important to distinguish between uncomplicated cystitis and pyelonephritis. For pyelonephritis (infection of the upper urinary tract), the first decision has to do with setting for care, depending on how sick someone is, and the likelihood of gram-negative bacteremia — all of which help whether the patient needs to be hospitalized for intravenous antibiotics, or can be treated as an outpatient. Determine if they need to be admitted for intravenous antibiotics or whether they can be treated as an outpatient. For outpatient treatment of pyelonephritis, the guideline suggests that TMP-SMX or a first-generation cephalosporin are both reasonable first-line agents, with fluoroquinolones being a reasonable choice as well. Ceftriaxone is recommended for first-line therapy for patients who require intravenous treatment.
People often forget that we can do a lot to prevent UTIs, particularly among women with recurrent UTIs. The prevention of UTIs has both nonpharmacologic and pharmacologic approaches.
Nonpharmacologic prevention. One nonpharmacologic strategy is increasing water intake. A randomized controlled trial in women with recurrent cystitis who drank less than 1.5 L of fluid a day showed that the women randomized to consume an additional 1.5 L of water daily had significantly reduced cystitis frequency — approximately 50%. Because this was the only randomized trial to show this effect, this is not a strong recommendation, but there is very little downside in healthy women, so increasing water intake is a reasonable recommendation.
Another commonly discussed intervention is the use of cranberry products. As it turns out, most prospective studies have shown that cranberry products can reduce the risk for symptomatic UTIs in women with recurrent UTI.
Pharmacologic prevention. For postmenopausal women with recurrent UTI, topical vaginal estrogen has a strong base of evidence — more than 30 randomized trials — supporting its effectiveness in UTI: a 50%-90% reduction in the incidence of recurrent UTIs. Topical estrogen has minimal systemic absorption, and there are no concerning safety signals with respect to either thromboembolic disease or cancer (endometrial or breast).
Methenamine hippurate is also recommended and is FDA-approved for prevention of UTIs. It works by releasing formaldehyde in the urine, leading to bacteriostasis, which is how it leads to a decrease in UTIs. Finally, postcoital or daily administration of TMP-SMX, nitrofurantoin, norfloxacin, and ciprofloxacin all have comparable efficacy for prophylaxis, with a meta-analysis showing a decrease in recurrence rate of approximately 85%. The guideline states that there is insufficient evidence to support the use of either probiotics or D-mannose to prevent UTIs.
This is a wonderful update on a common problem. We all have a lot of clinical experience here.
Dr Skolnik, Department of Family Medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia; Associate Director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
We often see urinary tract infections in primary care, so these guidelines for the prevention, diagnosis and management of urinary tract infection (UTI) are very helpful to reaffirm our knowledge in the areas where know what we’re doing and update our knowledge in areas of uncertainty. These guidelines are from a new group called the WikiGuidelines group. Ordinarily, I wouldn’t have considered reviewing one of these guidelines, but this one was published in JAMA Network Open. It is evidence based and covers the topic really well.
Diagnosis. Order a urinalysis or a urine culture only if the patient is having symptoms of a UTI. This may seem obvious, but particularly among older individuals, in whom asymptomatic bacteriuria is very common and should not be treated, nonspecific symptoms such as just not feeling well for a day do not warrant obtaining a urinalysis and culture. With no clear way to distinguish between asymptomatic bacteriuria and a true UTI, the first step in making the diagnosis of a UTI accurately is ordering urine studies only in people who have a reasonable chance of having an infection.
The guideline suggests that the diagnosis of UTI should be primarily based on clinical symptoms. A urinalysis can provide further information, but the authors caution us against relying solely on the urinalysis. This is an incredibly important evidence-based recommendation. If you think about it, this supports the common practice of treating UTIs over the phone without having to see the patient or check a urinalysis.
The rationale for this recommendation is that urinalysis is neither a sensitive nor specific test for UTI. The sensitivity of leukocyte esterase is only about 80%, and the specificity is even lower. For positive nitrite on urinalysis, the sensitivity is below 50%, meaning the test would be negative more than half the time when someone actually has a UTI. The specificity of urine nitrate is very high (more than 90%), so if the patient is nitrite positive, they clearly have a UTI. This means that a patient’s report of classic UTI symptoms — urinary burning, frequency, and urgency — is about as good if not a better indicator of a UTI than a urinalysis.
The guidelines also say that in simple uncomplicated cystitis in healthy nonpregnant patients, routine urine cultures are not necessary. A fascinating meta-analysis in JAMA showed that, for women presenting to outpatient clinics with at least two symptoms of UTI and absence of vaginal discharge, there was a greater than 90% likelihood of having acute cystitis. A reminder here, however: If a woman is sexually active and at risk for sexually transmitted infections, then consider testing for STIs as well, because the symptoms of an STI can mimic those of a UTI.
Treatment. Treatment for UTI is usually empiric, with treatment initiated before the culture results are known and with cultures being done only for people with complicated infections, such as pyelonephritis, or with recurrent infections. Decisions about what to use for treatment can be influenced by local patterns of resistance and an individual’s risk factors for antimicrobial resistance. As a general rule, for uncomplicated cystitis, nitrofurantoin for 5 days is a reasonable first-line agent. Evidence of efficacy is good, and the risk for antimicrobial resistance is lower vs using antibiotics for other systemic infections.
Other reasonable first-line agents for uncomplicated cystitis include trimethoprim-sulfamethoxazole (TMP-SMX) for 3 days; fosfomycin (oral) single dose; or a beta-lactam (most commonly a first generation cephalosporin), although evidence for duration is unclear. Also mentioned are two unfamiliar antibiotics: pivmecillinam (a beta-lactam agent recently approved by the Food and Drug Administration [FDA], given for 3 days) and gepotidacin (from a new class of antibiotic that is currently under FDA review). Fluoroquinolones should not usually be first-line agents unless other treatment options are not appropriate.
It’s important to distinguish between uncomplicated cystitis and pyelonephritis. For pyelonephritis (infection of the upper urinary tract), the first decision has to do with setting for care, depending on how sick someone is, and the likelihood of gram-negative bacteremia — all of which help whether the patient needs to be hospitalized for intravenous antibiotics, or can be treated as an outpatient. Determine if they need to be admitted for intravenous antibiotics or whether they can be treated as an outpatient. For outpatient treatment of pyelonephritis, the guideline suggests that TMP-SMX or a first-generation cephalosporin are both reasonable first-line agents, with fluoroquinolones being a reasonable choice as well. Ceftriaxone is recommended for first-line therapy for patients who require intravenous treatment.
People often forget that we can do a lot to prevent UTIs, particularly among women with recurrent UTIs. The prevention of UTIs has both nonpharmacologic and pharmacologic approaches.
Nonpharmacologic prevention. One nonpharmacologic strategy is increasing water intake. A randomized controlled trial in women with recurrent cystitis who drank less than 1.5 L of fluid a day showed that the women randomized to consume an additional 1.5 L of water daily had significantly reduced cystitis frequency — approximately 50%. Because this was the only randomized trial to show this effect, this is not a strong recommendation, but there is very little downside in healthy women, so increasing water intake is a reasonable recommendation.
Another commonly discussed intervention is the use of cranberry products. As it turns out, most prospective studies have shown that cranberry products can reduce the risk for symptomatic UTIs in women with recurrent UTI.
Pharmacologic prevention. For postmenopausal women with recurrent UTI, topical vaginal estrogen has a strong base of evidence — more than 30 randomized trials — supporting its effectiveness in UTI: a 50%-90% reduction in the incidence of recurrent UTIs. Topical estrogen has minimal systemic absorption, and there are no concerning safety signals with respect to either thromboembolic disease or cancer (endometrial or breast).
Methenamine hippurate is also recommended and is FDA-approved for prevention of UTIs. It works by releasing formaldehyde in the urine, leading to bacteriostasis, which is how it leads to a decrease in UTIs. Finally, postcoital or daily administration of TMP-SMX, nitrofurantoin, norfloxacin, and ciprofloxacin all have comparable efficacy for prophylaxis, with a meta-analysis showing a decrease in recurrence rate of approximately 85%. The guideline states that there is insufficient evidence to support the use of either probiotics or D-mannose to prevent UTIs.
This is a wonderful update on a common problem. We all have a lot of clinical experience here.
Dr Skolnik, Department of Family Medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia; Associate Director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
How to Avoid Freaking Out About Kidney Function
This transcript has been edited for clarity.
Matthew F. Watto, MD: I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams.
We had a great discussion with Kidney Boy, Dr Joel Topf, everyone’s favorite nephrologist, and he taught us how to manage blood pressure in chronic kidney disease (CKD).
Paul N. Williams, MD: Dr Topf focuses more on albuminuria than we are used to doing. It’s probably one of the most important prognostic indicators of how a patient is going to do from a renal standpoint.
Historically, I’ve tended to focus on the estimated glomerular filtration rate (eGFR), and the lower that number gets, the more I sweat, but albuminuria is probably equally, if not more, important as a way of prognosticating whether a patient is going to progress to dialysis or transplant. He directed us towards this nifty little calculator, kidneyfailurerisk.com, where you plug in the patient’s age, eGFR, and degree of albuminuria, and it spits out their risk of progressing to hemodialysis or renal transplantation over the next 5 years. It’s a nice way to concretely explain to patients their risk for progression.
Instead of telling the patient, “You are high risk,” Dr Topf will say, “Your risk is 6% of needing dialysis in the next 5 years.” You can even use these thresholds to gauge when to refer a patient. If someone has a 5-year risk between 3% and 5% or higher, that patient should probably be seeing a nephrologist.
If their 2-year risk is greater than 20%, that patient probably should be evaluated for transplantation. This gives us have more concrete numbers to work with rather than just saying, “Your kidneys aren’t working as well as we would like and you should see a kidney doctor.” Patients have a better sense of how serious things might be.
Watto: It’s just easier for them to understand. Dr Topf made the point that we used to have a heat map based on the stage of CKD that would tell you how high a patient’s risk was compared with other people. But patients don’t really understand relative risk, so Dr Topf tells them their absolute risk for ending up on dialysis over the next 2-5 years.
Patients come in and they are worried because they looked at their lab results and see that their creatinine level is red, or their eGFR is low. They think, It says I have stage 3a CKD.
We should probably have the stages of CKD start at stage 3, which should be called stage 1 so it doesn’t sound as bad. Patients think they are halfway to dialysis; they are already at stage 3 and didn’t even know their kidneys were a problem.
Dr Topf said that cystatin C (something I only recently started ordering) can be obtained, and sometimes you can recategorize the patient, especially those with an eGFR between 45 and 60. The cystatin C can predict their renal function better than the creatinine-based equations. If you are using the creatinine equation, he recommends using the 2021 equations.
Another nice thing about cystatin C is that it isn’t tripped up in younger patients with a lot of muscle mass. You just have to watch out for inflammation, which can throw the test off. For example, when a patient is in the intensive care unit, it’s probably not that helpful, but for your outpatients, cystatin C works well.
Williams: I’ve been using it a fair amount in my patients with more muscle mass. And some patients have been taking creatine as a supplement, and that can alter the numbers as well. This is a nice way to get them out of CKD stage 2 or 3 and back where they belong, with normal healthy functioning kidneys.
Watto: Now, Paul, if we find a patient with more advanced CKD — let’s say stage 4, whether by cystatin C or serum creatinine, and their eGFR is less than 30 — should we start peeling off the angiotensin-converting enzyme ACE inhibitor or the angiotensin receptor blocker (ARB)? Those drugs can raise potassium. What should we do here?
Williams: That’s the temptation, Matt, and I feel like that was the old orthodoxy, back in residency. It didn’t take much for us to start taking off ACE inhibitors or ARBs once the kidney function started to drop, but it turns out you may be doing more harm than good.
Some data have shown that if you peel off those medications, you actually increase mortality and cardiovascular risk. So, in general, if you can keep them going, the patient will be better off. Hang onto the ACE inhibitors or ARBs as long as you are able to, because they confer a fair amount of benefit.
Watto: As long as the potassium isn’t in red on your lab’s range. It might go up to 5.2 or 5.4, but as long as it’s stable, that should be OK. You probably wouldn’t initiate an ACE inhibitor or ARB or spironolactone with a potassium level above 5, but if it’s below 5 when you start and it goes up slightly after you start the drug, that could be acceptable.
Another thing we talked about was when a patient progresses to CKD and ends up on dialysis, how helpful are those intradialysis blood pressures in predicting cardiovascular outcomes?
Williams: For someone who’s performing the dialysis, probably really helpful. In the outpatient setting to predict cardiovascular risk, probably less so. Dr Topf makes the point that the readings are done either shortly after or right when the patient is about to have a large-bore catheter inserted into their arm. And then they have liters of fluid drained out of them. So those numbers are going to have huge amounts of variability. You would not base the patient’s blood pressure treatment solely on those numbers. But regardless of what the numbers are, or even regardless of your office numbers, hopefully you’re working with a nephrologist to make sure that you’re actually in concert and not fighting each other with the blood pressure medications.
Watto: Dr Topf said that a lot of the hypertension in dialysis is because of too much volume. If you can get the volume down, you might be able to peel off blood pressure medications instead of adding more. But some patients have issues with cramping; it’s uncomfortable and not everyone tolerates it.
I was really surprised to learn that beta blockers, specifically atenolol, have some evidence of improving cardiovascular outcomes in patients on dialysis. Dr Topf speculated that this was because they are largely dying of cardiovascular disease, so maybe that’s why, but that’s one of the places, the only places I can think of aside from thyroid disease, where atenolol really shines.
If you want to hear this fantastic episode and all the great pearls, then click on this link.
Matthew F. Watto, MD, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, disclosed no relevant financial relationships. Paul N. Williams, MD, has disclosed ties with The Curbsiders.
This transcript has been edited for clarity.
Matthew F. Watto, MD: I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams.
We had a great discussion with Kidney Boy, Dr Joel Topf, everyone’s favorite nephrologist, and he taught us how to manage blood pressure in chronic kidney disease (CKD).
Paul N. Williams, MD: Dr Topf focuses more on albuminuria than we are used to doing. It’s probably one of the most important prognostic indicators of how a patient is going to do from a renal standpoint.
Historically, I’ve tended to focus on the estimated glomerular filtration rate (eGFR), and the lower that number gets, the more I sweat, but albuminuria is probably equally, if not more, important as a way of prognosticating whether a patient is going to progress to dialysis or transplant. He directed us towards this nifty little calculator, kidneyfailurerisk.com, where you plug in the patient’s age, eGFR, and degree of albuminuria, and it spits out their risk of progressing to hemodialysis or renal transplantation over the next 5 years. It’s a nice way to concretely explain to patients their risk for progression.
Instead of telling the patient, “You are high risk,” Dr Topf will say, “Your risk is 6% of needing dialysis in the next 5 years.” You can even use these thresholds to gauge when to refer a patient. If someone has a 5-year risk between 3% and 5% or higher, that patient should probably be seeing a nephrologist.
If their 2-year risk is greater than 20%, that patient probably should be evaluated for transplantation. This gives us have more concrete numbers to work with rather than just saying, “Your kidneys aren’t working as well as we would like and you should see a kidney doctor.” Patients have a better sense of how serious things might be.
Watto: It’s just easier for them to understand. Dr Topf made the point that we used to have a heat map based on the stage of CKD that would tell you how high a patient’s risk was compared with other people. But patients don’t really understand relative risk, so Dr Topf tells them their absolute risk for ending up on dialysis over the next 2-5 years.
Patients come in and they are worried because they looked at their lab results and see that their creatinine level is red, or their eGFR is low. They think, It says I have stage 3a CKD.
We should probably have the stages of CKD start at stage 3, which should be called stage 1 so it doesn’t sound as bad. Patients think they are halfway to dialysis; they are already at stage 3 and didn’t even know their kidneys were a problem.
Dr Topf said that cystatin C (something I only recently started ordering) can be obtained, and sometimes you can recategorize the patient, especially those with an eGFR between 45 and 60. The cystatin C can predict their renal function better than the creatinine-based equations. If you are using the creatinine equation, he recommends using the 2021 equations.
Another nice thing about cystatin C is that it isn’t tripped up in younger patients with a lot of muscle mass. You just have to watch out for inflammation, which can throw the test off. For example, when a patient is in the intensive care unit, it’s probably not that helpful, but for your outpatients, cystatin C works well.
Williams: I’ve been using it a fair amount in my patients with more muscle mass. And some patients have been taking creatine as a supplement, and that can alter the numbers as well. This is a nice way to get them out of CKD stage 2 or 3 and back where they belong, with normal healthy functioning kidneys.
Watto: Now, Paul, if we find a patient with more advanced CKD — let’s say stage 4, whether by cystatin C or serum creatinine, and their eGFR is less than 30 — should we start peeling off the angiotensin-converting enzyme ACE inhibitor or the angiotensin receptor blocker (ARB)? Those drugs can raise potassium. What should we do here?
Williams: That’s the temptation, Matt, and I feel like that was the old orthodoxy, back in residency. It didn’t take much for us to start taking off ACE inhibitors or ARBs once the kidney function started to drop, but it turns out you may be doing more harm than good.
Some data have shown that if you peel off those medications, you actually increase mortality and cardiovascular risk. So, in general, if you can keep them going, the patient will be better off. Hang onto the ACE inhibitors or ARBs as long as you are able to, because they confer a fair amount of benefit.
Watto: As long as the potassium isn’t in red on your lab’s range. It might go up to 5.2 or 5.4, but as long as it’s stable, that should be OK. You probably wouldn’t initiate an ACE inhibitor or ARB or spironolactone with a potassium level above 5, but if it’s below 5 when you start and it goes up slightly after you start the drug, that could be acceptable.
Another thing we talked about was when a patient progresses to CKD and ends up on dialysis, how helpful are those intradialysis blood pressures in predicting cardiovascular outcomes?
Williams: For someone who’s performing the dialysis, probably really helpful. In the outpatient setting to predict cardiovascular risk, probably less so. Dr Topf makes the point that the readings are done either shortly after or right when the patient is about to have a large-bore catheter inserted into their arm. And then they have liters of fluid drained out of them. So those numbers are going to have huge amounts of variability. You would not base the patient’s blood pressure treatment solely on those numbers. But regardless of what the numbers are, or even regardless of your office numbers, hopefully you’re working with a nephrologist to make sure that you’re actually in concert and not fighting each other with the blood pressure medications.
Watto: Dr Topf said that a lot of the hypertension in dialysis is because of too much volume. If you can get the volume down, you might be able to peel off blood pressure medications instead of adding more. But some patients have issues with cramping; it’s uncomfortable and not everyone tolerates it.
I was really surprised to learn that beta blockers, specifically atenolol, have some evidence of improving cardiovascular outcomes in patients on dialysis. Dr Topf speculated that this was because they are largely dying of cardiovascular disease, so maybe that’s why, but that’s one of the places, the only places I can think of aside from thyroid disease, where atenolol really shines.
If you want to hear this fantastic episode and all the great pearls, then click on this link.
Matthew F. Watto, MD, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, disclosed no relevant financial relationships. Paul N. Williams, MD, has disclosed ties with The Curbsiders.
This transcript has been edited for clarity.
Matthew F. Watto, MD: I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams.
We had a great discussion with Kidney Boy, Dr Joel Topf, everyone’s favorite nephrologist, and he taught us how to manage blood pressure in chronic kidney disease (CKD).
Paul N. Williams, MD: Dr Topf focuses more on albuminuria than we are used to doing. It’s probably one of the most important prognostic indicators of how a patient is going to do from a renal standpoint.
Historically, I’ve tended to focus on the estimated glomerular filtration rate (eGFR), and the lower that number gets, the more I sweat, but albuminuria is probably equally, if not more, important as a way of prognosticating whether a patient is going to progress to dialysis or transplant. He directed us towards this nifty little calculator, kidneyfailurerisk.com, where you plug in the patient’s age, eGFR, and degree of albuminuria, and it spits out their risk of progressing to hemodialysis or renal transplantation over the next 5 years. It’s a nice way to concretely explain to patients their risk for progression.
Instead of telling the patient, “You are high risk,” Dr Topf will say, “Your risk is 6% of needing dialysis in the next 5 years.” You can even use these thresholds to gauge when to refer a patient. If someone has a 5-year risk between 3% and 5% or higher, that patient should probably be seeing a nephrologist.
If their 2-year risk is greater than 20%, that patient probably should be evaluated for transplantation. This gives us have more concrete numbers to work with rather than just saying, “Your kidneys aren’t working as well as we would like and you should see a kidney doctor.” Patients have a better sense of how serious things might be.
Watto: It’s just easier for them to understand. Dr Topf made the point that we used to have a heat map based on the stage of CKD that would tell you how high a patient’s risk was compared with other people. But patients don’t really understand relative risk, so Dr Topf tells them their absolute risk for ending up on dialysis over the next 2-5 years.
Patients come in and they are worried because they looked at their lab results and see that their creatinine level is red, or their eGFR is low. They think, It says I have stage 3a CKD.
We should probably have the stages of CKD start at stage 3, which should be called stage 1 so it doesn’t sound as bad. Patients think they are halfway to dialysis; they are already at stage 3 and didn’t even know their kidneys were a problem.
Dr Topf said that cystatin C (something I only recently started ordering) can be obtained, and sometimes you can recategorize the patient, especially those with an eGFR between 45 and 60. The cystatin C can predict their renal function better than the creatinine-based equations. If you are using the creatinine equation, he recommends using the 2021 equations.
Another nice thing about cystatin C is that it isn’t tripped up in younger patients with a lot of muscle mass. You just have to watch out for inflammation, which can throw the test off. For example, when a patient is in the intensive care unit, it’s probably not that helpful, but for your outpatients, cystatin C works well.
Williams: I’ve been using it a fair amount in my patients with more muscle mass. And some patients have been taking creatine as a supplement, and that can alter the numbers as well. This is a nice way to get them out of CKD stage 2 or 3 and back where they belong, with normal healthy functioning kidneys.
Watto: Now, Paul, if we find a patient with more advanced CKD — let’s say stage 4, whether by cystatin C or serum creatinine, and their eGFR is less than 30 — should we start peeling off the angiotensin-converting enzyme ACE inhibitor or the angiotensin receptor blocker (ARB)? Those drugs can raise potassium. What should we do here?
Williams: That’s the temptation, Matt, and I feel like that was the old orthodoxy, back in residency. It didn’t take much for us to start taking off ACE inhibitors or ARBs once the kidney function started to drop, but it turns out you may be doing more harm than good.
Some data have shown that if you peel off those medications, you actually increase mortality and cardiovascular risk. So, in general, if you can keep them going, the patient will be better off. Hang onto the ACE inhibitors or ARBs as long as you are able to, because they confer a fair amount of benefit.
Watto: As long as the potassium isn’t in red on your lab’s range. It might go up to 5.2 or 5.4, but as long as it’s stable, that should be OK. You probably wouldn’t initiate an ACE inhibitor or ARB or spironolactone with a potassium level above 5, but if it’s below 5 when you start and it goes up slightly after you start the drug, that could be acceptable.
Another thing we talked about was when a patient progresses to CKD and ends up on dialysis, how helpful are those intradialysis blood pressures in predicting cardiovascular outcomes?
Williams: For someone who’s performing the dialysis, probably really helpful. In the outpatient setting to predict cardiovascular risk, probably less so. Dr Topf makes the point that the readings are done either shortly after or right when the patient is about to have a large-bore catheter inserted into their arm. And then they have liters of fluid drained out of them. So those numbers are going to have huge amounts of variability. You would not base the patient’s blood pressure treatment solely on those numbers. But regardless of what the numbers are, or even regardless of your office numbers, hopefully you’re working with a nephrologist to make sure that you’re actually in concert and not fighting each other with the blood pressure medications.
Watto: Dr Topf said that a lot of the hypertension in dialysis is because of too much volume. If you can get the volume down, you might be able to peel off blood pressure medications instead of adding more. But some patients have issues with cramping; it’s uncomfortable and not everyone tolerates it.
I was really surprised to learn that beta blockers, specifically atenolol, have some evidence of improving cardiovascular outcomes in patients on dialysis. Dr Topf speculated that this was because they are largely dying of cardiovascular disease, so maybe that’s why, but that’s one of the places, the only places I can think of aside from thyroid disease, where atenolol really shines.
If you want to hear this fantastic episode and all the great pearls, then click on this link.
Matthew F. Watto, MD, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, disclosed no relevant financial relationships. Paul N. Williams, MD, has disclosed ties with The Curbsiders.
Have Your Cake and Eat It, Too: Findings Based on Ingredients in Christmas Desserts From The Great British Bake Off
This transcript has been edited for clarity.
Hello. I’m David Kerr, professor of cancer medicine at University of Oxford. As I become, sadly, older, I’ve become much more interested in the concept of cancer prevention than cancer treatment. Of course, I’m still a practicing cancer physician and researcher. That’s my daily bread and butter. But prevention is important.
There’s a really interesting article in the Christmas edition of The BMJ. This is an opportunity for us to take good science, but lighthearted science, to titillate and amuse our Christmas readers. This is a nice article from the States led by Joshua Wallach. As I say, this brings together good science in a sometimes absurd setting. I’ll read its title: “Association of Health Benefits and Harms of Christmas Dessert Ingredients in Recipes From The Great British Bake Off: Umbrella Review of Umbrella Reviews of Meta-analyses of Observational Studies.”
It’s obviously a very strong statistical underpinning from this group from Yale, predominantly — a half-decent university, as those of us from Oxford would have to admit. They used The Great British Bake Off website, Embase, Medline, and Scopus. They looked at the whole host of umbrella reviews and so on.
They were interested in looking at the relative balance of dangerous and protective ingredients that were recommended in Christmas desserts on this immensely popular television show called The Great British Bake Off. Some of you have watched it and have enjoyed watching the trials and tribulations of the various contestants.
They looked at 48 recipes for Christmas desserts, including cakes, biscuits, pastries, puddings, and conventional desserts. Of all these, there were 178 unique ingredients. Literature research then parsed whether these ingredients were good for you or bad for you.
It was very interesting that, when they put the summary together, the umbrella review of umbrella reviews of meta-analyses compressed together, it was good news for us all. Recipes for Christmas desserts, particularly from The Great British Bake Off — which should be enormously proud of this — tend to use ingredient groups that are associated with reductions rather than increases in the risk for disease. Hurrah!
This means that, clearly, Christmas is a time in which those of us who can, tend to overindulge in food. The granddad falling asleep with a full tummy, sitting with the family in front of a hot fire — all of us can remember and imagine all of that.
Perhaps the most important takeaway point from this observationally, critically important study is that, yes — at Christmas time, enjoy the dessert. You can have your cake and eat it, too. You heard it here. It’s philosophically true and statistically proven: You can have your cake and eat it.
Thanks for listening. I’d be very interested in your own recipes, and whether we think that the American Thanksgiving desserts correlate with British Christmas desserts in some way and are beneficial to your health.
Have a look at this article that is cleverly, wittily written. As always, Medscapers, for the time being, thanks for listening. Over and out.
Dr Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers (Board of Directors); Afrox (charity; Trustee); GlaxoSmithKline and Bayer HealthCare Pharmaceuticals (Consultant); Genomic Health; Merck Serono, Roche.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. I’m David Kerr, professor of cancer medicine at University of Oxford. As I become, sadly, older, I’ve become much more interested in the concept of cancer prevention than cancer treatment. Of course, I’m still a practicing cancer physician and researcher. That’s my daily bread and butter. But prevention is important.
There’s a really interesting article in the Christmas edition of The BMJ. This is an opportunity for us to take good science, but lighthearted science, to titillate and amuse our Christmas readers. This is a nice article from the States led by Joshua Wallach. As I say, this brings together good science in a sometimes absurd setting. I’ll read its title: “Association of Health Benefits and Harms of Christmas Dessert Ingredients in Recipes From The Great British Bake Off: Umbrella Review of Umbrella Reviews of Meta-analyses of Observational Studies.”
It’s obviously a very strong statistical underpinning from this group from Yale, predominantly — a half-decent university, as those of us from Oxford would have to admit. They used The Great British Bake Off website, Embase, Medline, and Scopus. They looked at the whole host of umbrella reviews and so on.
They were interested in looking at the relative balance of dangerous and protective ingredients that were recommended in Christmas desserts on this immensely popular television show called The Great British Bake Off. Some of you have watched it and have enjoyed watching the trials and tribulations of the various contestants.
They looked at 48 recipes for Christmas desserts, including cakes, biscuits, pastries, puddings, and conventional desserts. Of all these, there were 178 unique ingredients. Literature research then parsed whether these ingredients were good for you or bad for you.
It was very interesting that, when they put the summary together, the umbrella review of umbrella reviews of meta-analyses compressed together, it was good news for us all. Recipes for Christmas desserts, particularly from The Great British Bake Off — which should be enormously proud of this — tend to use ingredient groups that are associated with reductions rather than increases in the risk for disease. Hurrah!
This means that, clearly, Christmas is a time in which those of us who can, tend to overindulge in food. The granddad falling asleep with a full tummy, sitting with the family in front of a hot fire — all of us can remember and imagine all of that.
Perhaps the most important takeaway point from this observationally, critically important study is that, yes — at Christmas time, enjoy the dessert. You can have your cake and eat it, too. You heard it here. It’s philosophically true and statistically proven: You can have your cake and eat it.
Thanks for listening. I’d be very interested in your own recipes, and whether we think that the American Thanksgiving desserts correlate with British Christmas desserts in some way and are beneficial to your health.
Have a look at this article that is cleverly, wittily written. As always, Medscapers, for the time being, thanks for listening. Over and out.
Dr Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers (Board of Directors); Afrox (charity; Trustee); GlaxoSmithKline and Bayer HealthCare Pharmaceuticals (Consultant); Genomic Health; Merck Serono, Roche.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. I’m David Kerr, professor of cancer medicine at University of Oxford. As I become, sadly, older, I’ve become much more interested in the concept of cancer prevention than cancer treatment. Of course, I’m still a practicing cancer physician and researcher. That’s my daily bread and butter. But prevention is important.
There’s a really interesting article in the Christmas edition of The BMJ. This is an opportunity for us to take good science, but lighthearted science, to titillate and amuse our Christmas readers. This is a nice article from the States led by Joshua Wallach. As I say, this brings together good science in a sometimes absurd setting. I’ll read its title: “Association of Health Benefits and Harms of Christmas Dessert Ingredients in Recipes From The Great British Bake Off: Umbrella Review of Umbrella Reviews of Meta-analyses of Observational Studies.”
It’s obviously a very strong statistical underpinning from this group from Yale, predominantly — a half-decent university, as those of us from Oxford would have to admit. They used The Great British Bake Off website, Embase, Medline, and Scopus. They looked at the whole host of umbrella reviews and so on.
They were interested in looking at the relative balance of dangerous and protective ingredients that were recommended in Christmas desserts on this immensely popular television show called The Great British Bake Off. Some of you have watched it and have enjoyed watching the trials and tribulations of the various contestants.
They looked at 48 recipes for Christmas desserts, including cakes, biscuits, pastries, puddings, and conventional desserts. Of all these, there were 178 unique ingredients. Literature research then parsed whether these ingredients were good for you or bad for you.
It was very interesting that, when they put the summary together, the umbrella review of umbrella reviews of meta-analyses compressed together, it was good news for us all. Recipes for Christmas desserts, particularly from The Great British Bake Off — which should be enormously proud of this — tend to use ingredient groups that are associated with reductions rather than increases in the risk for disease. Hurrah!
This means that, clearly, Christmas is a time in which those of us who can, tend to overindulge in food. The granddad falling asleep with a full tummy, sitting with the family in front of a hot fire — all of us can remember and imagine all of that.
Perhaps the most important takeaway point from this observationally, critically important study is that, yes — at Christmas time, enjoy the dessert. You can have your cake and eat it, too. You heard it here. It’s philosophically true and statistically proven: You can have your cake and eat it.
Thanks for listening. I’d be very interested in your own recipes, and whether we think that the American Thanksgiving desserts correlate with British Christmas desserts in some way and are beneficial to your health.
Have a look at this article that is cleverly, wittily written. As always, Medscapers, for the time being, thanks for listening. Over and out.
Dr Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers (Board of Directors); Afrox (charity; Trustee); GlaxoSmithKline and Bayer HealthCare Pharmaceuticals (Consultant); Genomic Health; Merck Serono, Roche.
A version of this article appeared on Medscape.com.