In a recent commentary published in Obstetrics & Gynecology, Katie L. Watson, JD, and Louise P. King, MD, JD, describe the issue of “double discrimination” in gynecologic surgery. The authors outlined how lower pay in a specialty where a majority of the surgeons and all of the patients are women may impact quality of care.

The commentary raises a number of concerns in gynecologic surgery that are important to discuss. Ob.gyn. as a whole is underpaid, as are many nonprocedural specialties such as family medicine and internal medicine. When ob.gyns. were predominantly men, the same situation existed – ob.gyns. were paid less than many other procedural specialties. While we’ve come a long way from the relative value unit (RVU) originally determined from the Harvard studies 30 years ago, there is room for additional improvement.

Several rationales were proposed by the authors to explain the disparities in pay between gynecologic surgery and those in urology: patient gender, surgeon gender, and length of training for gynecologic surgeons. The authors cited comparisons between urology and gynecology regarding “anatomically similar, sex-specific procedures” which require closer examination. Many of the code pairs selected were not actually comparable services. For example, management of Peyronie’s disease is a highly complex treatment performed by urologists that is not comparable with vaginectomy, yet this is an example of two codes used in the reference cited by the authors to conclude that surgeries on women are undervalued.

The overall RVUs for a procedure are also dependent upon the global period. The Centers for Medicare & Medicaid Services designated RVUs as the total amount of work before, during, and after a procedure. If a surgery has a 90-day global period, all the work for 90 days thereafter is bundled into the value, whereas if something is a zero-day global, only that day’s work is counted. A gynecologic surgeon who sees a patient back two or three times is coding and billing for those encounters in addition to that initial procedure.

Many of the code comparisons used in the analysis of gender in RVUs compared services with different global periods. Finally, some of the services that were compared had vastly different utilization. Some of the services and codes that were compared are performed extremely rarely and for that reason have not had their values reassessed over the years. There may be inequities in the RVUs for these services, but they will account for extremely little in overall compensation.

As a former chair of the American Medical Association’s RVS Update Committee (RUC), I spent years attempting to revalue ob.gyn. procedures. CMS assigns work RVUs based on physician work, practice expense, and professional liability insurance. The work is calculated using total physician time and intensity based on surveys completed by the specialty. The American College of Obstetrician and Gynecologist’s Committee on Health Economics and Coding, and the AMA RUC have worked diligently over many years to reassess potentially misvalued services. The ultimate RVUs assigned by CMS for gynecologic surgery are determined by the surveys completed by ACOG members. One issue we encountered with reexamining some procedures under RBRVS is that they have become so low volume that it has been difficult to justify the cost and effort to revalue them.

Lack of ob.gyn. training isn’t the full story

On average, ob.gyns. have between 18 and 24 months of surgical training, which is significantly less than other specialties. Lack of training in gynecologic surgery was proposed as another explanation for reduced compensation among female gynecologic surgeons. This is a complex issue not adequately explained by training time for gynecologic surgeons alone. While the number of trained ob.gyns. has increased in recent decades, the surgical volume has diminished and the workload of gynecologic surgery is far lower than it used to be. Surgical volume during and after training was much higher 35 years ago, prior to the advancements of procedures like endometrial ablation or tubal ligation. Women who had finished childbearing often underwent vaginal hysterectomies to manage contraception along with various other conditions.

With the advent of minimally invasive surgery, laparoscopic sterilization became possible, which has reduced the number of hysterectomies performed. Endometrial ablation is an office-based, noninvasive procedure. The development of the levonorgestrel IUD has helped manage abnormal bleeding, further reducing the need for hysterectomy.

This reduction in surgical volume does have an impact on quality of care. The model of tracking surgical outcomes at Kaiser Health System, as mentioned by the authors, could work well in some, but not all centers. A more approachable solution to address surgical volume for the average ob.gyn. would be to implement a mentoring and coaching process whereby recently trained ob.gyns. assist their senior partner(s) in surgery. This was the model years ago: I was trained by an ob.gyn. who was trained as a general surgeon. It was through the experience of assisting on each one of his cases – and him assisting on each one of my cases – that I received incredibly thorough surgical training.

These changes in practice, however, do not impact reimbursement. Rather than discrimination based on the gender of the surgeon, lower salaries in ob.gyn. are more likely to be the result of these and other factors.

The wage and quality gap in ob.gyn.

As a predominantly female surgical specialty, some of the disparity between gynecology and urology could be explained by how each specialty values its work. Here, gender plays a role in that when ob.gyns. are surveyed during the RUC process they may undervalue their work by reporting they can perform a procedure (and the before and after care) faster than what a urologist reports. The survey results may then result in lower RVUs.

Ob.gyn. is an overpopulated specialty for the number of surgeons needed to manage the volume of gynecologic surgery. When a health system wants to hire a general ob.gyn., it doesn’t have trouble finding one, while urologists are more challenging to recruit. This is not because of the structure of resource-based relative value scale (RBRVS) – despite the overall RVUs for gynecologic surgery, gynecologic oncologists are often paid well because health systems need them – but rather to the market economy of hiring physicians in specialty areas where there is demand.

Women are also chronically undervalued for the hours that we spend with patients. Data show that we spend more time with patients, which does not generate as many RVUs, but it generates better outcomes for patients. Evidence shows that women doctors in internal medicine and family medicine have better outcomes than doctors who are men.

On Jan. 1, 2021, Medicare and other payers implemented a new structure to reporting the level of office visit based on either medical decision-making or time spent on the date of encounter. Time spent with patients will now be rewarded – increased RVUs for increased time.

Part of the solution is value-based medicine and moving away from counting RVUs. This is also an opportunity to look at where time is spent in general ob.gyn. training and redistribute it, focusing on what trainees need for their education and not what hospitals need to service labor and delivery. We should step back and look creatively at optimizing the education and the training of ob.gyns., and where possible utilize other health care professionals such as nurse practitioners and midwives to address the uncomplicated obstetric needs of the hospital which could free up ob.gyn. trainees to obtain further surgical education.

To be clear, gender discrimination in compensation is prevalent and a persistent problem in medicine – ob.gyn. is no exception. Many ob.gyns. are employed by large health systems with payment structures and incentives that don’t align with those of the physician or the patient. There is definite misalignment in the way salaries are determined. Transparency on salaries is a critical component of addressing the pay gap that exists between women and men in medicine and in other industries.

The pay gap as it relates to reimbursement for gynecologic surgery, however, is a more complex matter that relates to how the RBRVS system was developed nearly 30 years ago when gynecologic surgery was not predominantly performed by women.

Dr. Levy is a voluntary clinical professor in the department of obstetrics, gynecology, and reproductive sciences at University of California San Diego Health, the former vice president of health policy at ACOG, past chair of the AMA/RUC, and current voting member of the AMA CPT editorial panel. She reported no relevant financial disclosures.

In a recent commentary published in Obstetrics & Gynecology, Katie L. Watson, JD, and Louise P. King, MD, JD, describe the issue of “double discrimination” in gynecologic surgery. The authors outlined how lower pay in a specialty where a majority of the surgeons and all of the patients are women may impact quality of care.

The commentary raises a number of concerns in gynecologic surgery that are important to discuss. Ob.gyn. as a whole is underpaid, as are many nonprocedural specialties such as family medicine and internal medicine. When ob.gyns. were predominantly men, the same situation existed – ob.gyns. were paid less than many other procedural specialties. While we’ve come a long way from the relative value unit (RVU) originally determined from the Harvard studies 30 years ago, there is room for additional improvement.

Several rationales were proposed by the authors to explain the disparities in pay between gynecologic surgery and those in urology: patient gender, surgeon gender, and length of training for gynecologic surgeons. The authors cited comparisons between urology and gynecology regarding “anatomically similar, sex-specific procedures” which require closer examination. Many of the code pairs selected were not actually comparable services. For example, management of Peyronie’s disease is a highly complex treatment performed by urologists that is not comparable with vaginectomy, yet this is an example of two codes used in the reference cited by the authors to conclude that surgeries on women are undervalued.

The overall RVUs for a procedure are also dependent upon the global period. The Centers for Medicare & Medicaid Services designated RVUs as the total amount of work before, during, and after a procedure. If a surgery has a 90-day global period, all the work for 90 days thereafter is bundled into the value, whereas if something is a zero-day global, only that day’s work is counted. A gynecologic surgeon who sees a patient back two or three times is coding and billing for those encounters in addition to that initial procedure.

Many of the code comparisons used in the analysis of gender in RVUs compared services with different global periods. Finally, some of the services that were compared had vastly different utilization. Some of the services and codes that were compared are performed extremely rarely and for that reason have not had their values reassessed over the years. There may be inequities in the RVUs for these services, but they will account for extremely little in overall compensation.

As a former chair of the American Medical Association’s RVS Update Committee (RUC), I spent years attempting to revalue ob.gyn. procedures. CMS assigns work RVUs based on physician work, practice expense, and professional liability insurance. The work is calculated using total physician time and intensity based on surveys completed by the specialty. The American College of Obstetrician and Gynecologist’s Committee on Health Economics and Coding, and the AMA RUC have worked diligently over many years to reassess potentially misvalued services. The ultimate RVUs assigned by CMS for gynecologic surgery are determined by the surveys completed by ACOG members. One issue we encountered with reexamining some procedures under RBRVS is that they have become so low volume that it has been difficult to justify the cost and effort to revalue them.

Lack of ob.gyn. training isn’t the full story

On average, ob.gyns. have between 18 and 24 months of surgical training, which is significantly less than other specialties. Lack of training in gynecologic surgery was proposed as another explanation for reduced compensation among female gynecologic surgeons. This is a complex issue not adequately explained by training time for gynecologic surgeons alone. While the number of trained ob.gyns. has increased in recent decades, the surgical volume has diminished and the workload of gynecologic surgery is far lower than it used to be. Surgical volume during and after training was much higher 35 years ago, prior to the advancements of procedures like endometrial ablation or tubal ligation. Women who had finished childbearing often underwent vaginal hysterectomies to manage contraception along with various other conditions.

With the advent of minimally invasive surgery, laparoscopic sterilization became possible, which has reduced the number of hysterectomies performed. Endometrial ablation is an office-based, noninvasive procedure. The development of the levonorgestrel IUD has helped manage abnormal bleeding, further reducing the need for hysterectomy.

This reduction in surgical volume does have an impact on quality of care. The model of tracking surgical outcomes at Kaiser Health System, as mentioned by the authors, could work well in some, but not all centers. A more approachable solution to address surgical volume for the average ob.gyn. would be to implement a mentoring and coaching process whereby recently trained ob.gyns. assist their senior partner(s) in surgery. This was the model years ago: I was trained by an ob.gyn. who was trained as a general surgeon. It was through the experience of assisting on each one of his cases – and him assisting on each one of my cases – that I received incredibly thorough surgical training.

These changes in practice, however, do not impact reimbursement. Rather than discrimination based on the gender of the surgeon, lower salaries in ob.gyn. are more likely to be the result of these and other factors.

The wage and quality gap in ob.gyn.

As a predominantly female surgical specialty, some of the disparity between gynecology and urology could be explained by how each specialty values its work. Here, gender plays a role in that when ob.gyns. are surveyed during the RUC process they may undervalue their work by reporting they can perform a procedure (and the before and after care) faster than what a urologist reports. The survey results may then result in lower RVUs.

Ob.gyn. is an overpopulated specialty for the number of surgeons needed to manage the volume of gynecologic surgery. When a health system wants to hire a general ob.gyn., it doesn’t have trouble finding one, while urologists are more challenging to recruit. This is not because of the structure of resource-based relative value scale (RBRVS) – despite the overall RVUs for gynecologic surgery, gynecologic oncologists are often paid well because health systems need them – but rather to the market economy of hiring physicians in specialty areas where there is demand.

Women are also chronically undervalued for the hours that we spend with patients. Data show that we spend more time with patients, which does not generate as many RVUs, but it generates better outcomes for patients. Evidence shows that women doctors in internal medicine and family medicine have better outcomes than doctors who are men.

On Jan. 1, 2021, Medicare and other payers implemented a new structure to reporting the level of office visit based on either medical decision-making or time spent on the date of encounter. Time spent with patients will now be rewarded – increased RVUs for increased time.

Part of the solution is value-based medicine and moving away from counting RVUs. This is also an opportunity to look at where time is spent in general ob.gyn. training and redistribute it, focusing on what trainees need for their education and not what hospitals need to service labor and delivery. We should step back and look creatively at optimizing the education and the training of ob.gyns., and where possible utilize other health care professionals such as nurse practitioners and midwives to address the uncomplicated obstetric needs of the hospital which could free up ob.gyn. trainees to obtain further surgical education.

To be clear, gender discrimination in compensation is prevalent and a persistent problem in medicine – ob.gyn. is no exception. Many ob.gyns. are employed by large health systems with payment structures and incentives that don’t align with those of the physician or the patient. There is definite misalignment in the way salaries are determined. Transparency on salaries is a critical component of addressing the pay gap that exists between women and men in medicine and in other industries.

The pay gap as it relates to reimbursement for gynecologic surgery, however, is a more complex matter that relates to how the RBRVS system was developed nearly 30 years ago when gynecologic surgery was not predominantly performed by women.

Dr. Levy is a voluntary clinical professor in the department of obstetrics, gynecology, and reproductive sciences at University of California San Diego Health, the former vice president of health policy at ACOG, past chair of the AMA/RUC, and current voting member of the AMA CPT editorial panel. She reported no relevant financial disclosures.

In a recent commentary published in Obstetrics & Gynecology, Katie L. Watson, JD, and Louise P. King, MD, JD, describe the issue of “double discrimination” in gynecologic surgery. The authors outlined how lower pay in a specialty where a majority of the surgeons and all of the patients are women may impact quality of care.

The commentary raises a number of concerns in gynecologic surgery that are important to discuss. Ob.gyn. as a whole is underpaid, as are many nonprocedural specialties such as family medicine and internal medicine. When ob.gyns. were predominantly men, the same situation existed – ob.gyns. were paid less than many other procedural specialties. While we’ve come a long way from the relative value unit (RVU) originally determined from the Harvard studies 30 years ago, there is room for additional improvement.

Several rationales were proposed by the authors to explain the disparities in pay between gynecologic surgery and those in urology: patient gender, surgeon gender, and length of training for gynecologic surgeons. The authors cited comparisons between urology and gynecology regarding “anatomically similar, sex-specific procedures” which require closer examination. Many of the code pairs selected were not actually comparable services. For example, management of Peyronie’s disease is a highly complex treatment performed by urologists that is not comparable with vaginectomy, yet this is an example of two codes used in the reference cited by the authors to conclude that surgeries on women are undervalued.

The overall RVUs for a procedure are also dependent upon the global period. The Centers for Medicare & Medicaid Services designated RVUs as the total amount of work before, during, and after a procedure. If a surgery has a 90-day global period, all the work for 90 days thereafter is bundled into the value, whereas if something is a zero-day global, only that day’s work is counted. A gynecologic surgeon who sees a patient back two or three times is coding and billing for those encounters in addition to that initial procedure.

Many of the code comparisons used in the analysis of gender in RVUs compared services with different global periods. Finally, some of the services that were compared had vastly different utilization. Some of the services and codes that were compared are performed extremely rarely and for that reason have not had their values reassessed over the years. There may be inequities in the RVUs for these services, but they will account for extremely little in overall compensation.

As a former chair of the American Medical Association’s RVS Update Committee (RUC), I spent years attempting to revalue ob.gyn. procedures. CMS assigns work RVUs based on physician work, practice expense, and professional liability insurance. The work is calculated using total physician time and intensity based on surveys completed by the specialty. The American College of Obstetrician and Gynecologist’s Committee on Health Economics and Coding, and the AMA RUC have worked diligently over many years to reassess potentially misvalued services. The ultimate RVUs assigned by CMS for gynecologic surgery are determined by the surveys completed by ACOG members. One issue we encountered with reexamining some procedures under RBRVS is that they have become so low volume that it has been difficult to justify the cost and effort to revalue them.

Lack of ob.gyn. training isn’t the full story

On average, ob.gyns. have between 18 and 24 months of surgical training, which is significantly less than other specialties. Lack of training in gynecologic surgery was proposed as another explanation for reduced compensation among female gynecologic surgeons. This is a complex issue not adequately explained by training time for gynecologic surgeons alone. While the number of trained ob.gyns. has increased in recent decades, the surgical volume has diminished and the workload of gynecologic surgery is far lower than it used to be. Surgical volume during and after training was much higher 35 years ago, prior to the advancements of procedures like endometrial ablation or tubal ligation. Women who had finished childbearing often underwent vaginal hysterectomies to manage contraception along with various other conditions.

With the advent of minimally invasive surgery, laparoscopic sterilization became possible, which has reduced the number of hysterectomies performed. Endometrial ablation is an office-based, noninvasive procedure. The development of the levonorgestrel IUD has helped manage abnormal bleeding, further reducing the need for hysterectomy.

This reduction in surgical volume does have an impact on quality of care. The model of tracking surgical outcomes at Kaiser Health System, as mentioned by the authors, could work well in some, but not all centers. A more approachable solution to address surgical volume for the average ob.gyn. would be to implement a mentoring and coaching process whereby recently trained ob.gyns. assist their senior partner(s) in surgery. This was the model years ago: I was trained by an ob.gyn. who was trained as a general surgeon. It was through the experience of assisting on each one of his cases – and him assisting on each one of my cases – that I received incredibly thorough surgical training.

These changes in practice, however, do not impact reimbursement. Rather than discrimination based on the gender of the surgeon, lower salaries in ob.gyn. are more likely to be the result of these and other factors.

The wage and quality gap in ob.gyn.

As a predominantly female surgical specialty, some of the disparity between gynecology and urology could be explained by how each specialty values its work. Here, gender plays a role in that when ob.gyns. are surveyed during the RUC process they may undervalue their work by reporting they can perform a procedure (and the before and after care) faster than what a urologist reports. The survey results may then result in lower RVUs.

Ob.gyn. is an overpopulated specialty for the number of surgeons needed to manage the volume of gynecologic surgery. When a health system wants to hire a general ob.gyn., it doesn’t have trouble finding one, while urologists are more challenging to recruit. This is not because of the structure of resource-based relative value scale (RBRVS) – despite the overall RVUs for gynecologic surgery, gynecologic oncologists are often paid well because health systems need them – but rather to the market economy of hiring physicians in specialty areas where there is demand.

Women are also chronically undervalued for the hours that we spend with patients. Data show that we spend more time with patients, which does not generate as many RVUs, but it generates better outcomes for patients. Evidence shows that women doctors in internal medicine and family medicine have better outcomes than doctors who are men.

On Jan. 1, 2021, Medicare and other payers implemented a new structure to reporting the level of office visit based on either medical decision-making or time spent on the date of encounter. Time spent with patients will now be rewarded – increased RVUs for increased time.

Part of the solution is value-based medicine and moving away from counting RVUs. This is also an opportunity to look at where time is spent in general ob.gyn. training and redistribute it, focusing on what trainees need for their education and not what hospitals need to service labor and delivery. We should step back and look creatively at optimizing the education and the training of ob.gyns., and where possible utilize other health care professionals such as nurse practitioners and midwives to address the uncomplicated obstetric needs of the hospital which could free up ob.gyn. trainees to obtain further surgical education.

To be clear, gender discrimination in compensation is prevalent and a persistent problem in medicine – ob.gyn. is no exception. Many ob.gyns. are employed by large health systems with payment structures and incentives that don’t align with those of the physician or the patient. There is definite misalignment in the way salaries are determined. Transparency on salaries is a critical component of addressing the pay gap that exists between women and men in medicine and in other industries.

The pay gap as it relates to reimbursement for gynecologic surgery, however, is a more complex matter that relates to how the RBRVS system was developed nearly 30 years ago when gynecologic surgery was not predominantly performed by women.

Dr. Levy is a voluntary clinical professor in the department of obstetrics, gynecology, and reproductive sciences at University of California San Diego Health, the former vice president of health policy at ACOG, past chair of the AMA/RUC, and current voting member of the AMA CPT editorial panel. She reported no relevant financial disclosures.

Before COVID-19, postural orthostatic tachycardia syndrome (POTS) was one of those diseases that many people, including physicians, dismissed.

“They thought it was just anxious, crazy young women,” said Pam R. Taub, MD, who runs the cardiac rehabilitation program at the University of California, San Diego.

The cryptic autonomic condition was estimated to affect 1-3 million Americans before the pandemic hit. Now case reports confirm that it is a manifestation of postacute sequelae of SARS-CoV-2 infection (PASC), or so-called long-haul COVID-19.

“I’m excited that this condition that has been so often the ugly stepchild of both cardiology and neurology is getting some attention,” said Dr. Taub. She said she is hopeful that the National Institutes of Health’s commitment to PASC research will benefit patients affected by the cardiovascular dysautonomia characterized by orthostatic intolerance in the absence of orthostatic hypotension.

Postinfection POTS is not exclusive to SARS-CoV-2. It has been reported after Lyme disease and Epstein-Barr virus infections, for example. One theory is that some of the antibodies generated against the virus cross react and damage the autonomic nervous system, which regulates heart rate and blood pressure, Dr. Taub explained.

It is not known whether COVID-19 is more likely to trigger POTS than are other infections or whether the rise in cases merely reflects the fact that more than 115 million people worldwide have been infected with the novel coronavirus.

Medscape

Low blood volume, dysregulation of the autonomic nervous system, and autoimmunity may all play a role in POTS, perhaps leading to distinct subtypes, according to a State of the Science document from the NIH; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke.

In Dr. Taub’s experience, “The truth is that patients actually have a mix of the subtypes.”

Kamal Shouman, MD, an autonomic neurologist at Mayo Clinic, Rochester, Minn., said in an interview that he has seen patients present with post–COVID-19 POTS in “all flavors,” including “neuropathic POTS, which is thought of as the classic postinfectious phenomenon.”

Why does it mostly affect athletic women?

The condition, which can be the result of dehydration or prolonged bed rest, leading to deconditioning, affects women disproportionately.

According to Manesh Patel, MD, if a patient with POTS who is not a young woman is presented on medical rounds, the response is, “Tell me again why you think this patient has POTS.”

Mitchel L. Zoler/MDedge News

Poor (wo)man’s tilt test and treatment options

POTS is typically diagnosed with a tilt test and transcranial Doppler. Dr. Taub described her “poor man’s tilt test” of asking the patient to lie down for 5-10 minutes and then having the patient stand up.

She likes the fact that transcranial Doppler helps validate the brain fog that patients report, which can be dismissed as “just your excuse for not wanting to work.” If blood perfusion to the brain is cut by 40%-50%, “how are you going to think clearly?” she said.

Dr. Shouman noted that overall volume expansion with salt water, compression garments, and a graduated exercise program play a major role in the rehabilitation of all POTS patients.

He likes to tailor treatments to the most likely underlying cause. But patients should first undergo a medical assessment by their internists to make sure there isn’t a primary lung or heart problem.

“Once the decision is made for them to be evaluated in the autonomic practice and [a] POTS diagnosis is made, I think it is very useful to determine what type of POTS,” he said.

With hyperadrenergic POTS, “you are looking at a standing norepinephrine level of over 600 pg/mL or so.” For these patients, drugs such as ivabradine or beta-blockers can help, he noted.

Dr. Taub recently conducted a small study that showed a benefit with the selective I_f channel blocker ivabradine for patients with hyperadrenergic POTS unrelated to COVID-19. She tends to favor ivabradine over beta-blockers because it lowers heart rate but not blood pressure. In addition, beta-blockers can exacerbate fatigue and brain fog.

A small crossover study will compare propranolol and ivabradine in POTS. For someone who is very hypovolemic, “you might try a salt tablet or a prescription drug like fludrocortisone,” Dr. Taub explained.

Another problem that patients with POTS experience is an inability to exercise because of orthostatic intolerance. Recumbent exercise targets deconditioning and can tamp down the hyperadrenergic effect. Dr. Shouman’s approach is to start gradually with swimming or the use of a recumbent bike or a rowing machine.

Dr. Taub recommends wearables to patients because POTS is “a very dynamic condition” that is easy to overmedicate or undermedicate. If it’s a good day, the patients are well hydrated, and the standing heart rate is only 80 bpm, she tells them they could titrate down their second dose of ivabradine, for example. The feedback from wearables also helps patients manage their exercise response.

For Dr. Shouman, wearables are not always as accurate as he would like. He tells his patients that it’s okay to use one as long as it doesn’t become a source of anxiety such that they’re constantly checking it.
 

POTS hope: A COVID-19 silver lining?

With increasing attention being paid to long-haul COVID-19, are there any concerns that POTS will get lost among the myriad symptoms connected to PASC?

Dr. Shouman cautioned, “Not all long COVID is POTS,” and said that clinicians at long-haul clinics should be able to recognize the different conditions “when POTS is suspected. I think it is useful for those providers to make the appropriate referral for POTS clinic autonomic assessment.”

He and his colleagues at Mayo have seen quite a few patients who have post–COVID-19 autonomic dysfunction, such as vasodepressor syncope, not just POTS. They plan to write about this soon.

“Of all the things I treat in cardiology, this is the most complex, because there’s so many different systems involved,” said Dr. Taub, who has seen patients recover fully from POTS. “There’s a spectrum, and there’s people that are definitely on one end of the spectrum where they have very severe diseases.”

For her, the important message is, “No matter where you are on the spectrum, there are things we can do to make your symptoms better.” And with grant funding for PASC research, “hopefully we will address the mechanisms of disease, and we’ll be able to cure this,” she said.

Dr. Patel has served as a consultant for Bayer, Janssen, AstraZeneca, and Heartflow and has received research grants from Bayer, Janssen, AstraZeneca, and the National Heart, Lung, and Blood Institute. Dr. Shouman reports no relevant financial relationships. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the National Institutes of Health, the American Heart Association, and the Department of Homeland Security/FEMA.

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

Before COVID-19, postural orthostatic tachycardia syndrome (POTS) was one of those diseases that many people, including physicians, dismissed.

“They thought it was just anxious, crazy young women,” said Pam R. Taub, MD, who runs the cardiac rehabilitation program at the University of California, San Diego.

The cryptic autonomic condition was estimated to affect 1-3 million Americans before the pandemic hit. Now case reports confirm that it is a manifestation of postacute sequelae of SARS-CoV-2 infection (PASC), or so-called long-haul COVID-19.

“I’m excited that this condition that has been so often the ugly stepchild of both cardiology and neurology is getting some attention,” said Dr. Taub. She said she is hopeful that the National Institutes of Health’s commitment to PASC research will benefit patients affected by the cardiovascular dysautonomia characterized by orthostatic intolerance in the absence of orthostatic hypotension.

Postinfection POTS is not exclusive to SARS-CoV-2. It has been reported after Lyme disease and Epstein-Barr virus infections, for example. One theory is that some of the antibodies generated against the virus cross react and damage the autonomic nervous system, which regulates heart rate and blood pressure, Dr. Taub explained.

It is not known whether COVID-19 is more likely to trigger POTS than are other infections or whether the rise in cases merely reflects the fact that more than 115 million people worldwide have been infected with the novel coronavirus.

Medscape

Low blood volume, dysregulation of the autonomic nervous system, and autoimmunity may all play a role in POTS, perhaps leading to distinct subtypes, according to a State of the Science document from the NIH; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke.

In Dr. Taub’s experience, “The truth is that patients actually have a mix of the subtypes.”

Kamal Shouman, MD, an autonomic neurologist at Mayo Clinic, Rochester, Minn., said in an interview that he has seen patients present with post–COVID-19 POTS in “all flavors,” including “neuropathic POTS, which is thought of as the classic postinfectious phenomenon.”

Why does it mostly affect athletic women?

The condition, which can be the result of dehydration or prolonged bed rest, leading to deconditioning, affects women disproportionately.

According to Manesh Patel, MD, if a patient with POTS who is not a young woman is presented on medical rounds, the response is, “Tell me again why you think this patient has POTS.”

Mitchel L. Zoler/MDedge News

Poor (wo)man’s tilt test and treatment options

POTS is typically diagnosed with a tilt test and transcranial Doppler. Dr. Taub described her “poor man’s tilt test” of asking the patient to lie down for 5-10 minutes and then having the patient stand up.

She likes the fact that transcranial Doppler helps validate the brain fog that patients report, which can be dismissed as “just your excuse for not wanting to work.” If blood perfusion to the brain is cut by 40%-50%, “how are you going to think clearly?” she said.

Dr. Shouman noted that overall volume expansion with salt water, compression garments, and a graduated exercise program play a major role in the rehabilitation of all POTS patients.

He likes to tailor treatments to the most likely underlying cause. But patients should first undergo a medical assessment by their internists to make sure there isn’t a primary lung or heart problem.

“Once the decision is made for them to be evaluated in the autonomic practice and [a] POTS diagnosis is made, I think it is very useful to determine what type of POTS,” he said.

With hyperadrenergic POTS, “you are looking at a standing norepinephrine level of over 600 pg/mL or so.” For these patients, drugs such as ivabradine or beta-blockers can help, he noted.

Dr. Taub recently conducted a small study that showed a benefit with the selective I_f channel blocker ivabradine for patients with hyperadrenergic POTS unrelated to COVID-19. She tends to favor ivabradine over beta-blockers because it lowers heart rate but not blood pressure. In addition, beta-blockers can exacerbate fatigue and brain fog.

A small crossover study will compare propranolol and ivabradine in POTS. For someone who is very hypovolemic, “you might try a salt tablet or a prescription drug like fludrocortisone,” Dr. Taub explained.

Another problem that patients with POTS experience is an inability to exercise because of orthostatic intolerance. Recumbent exercise targets deconditioning and can tamp down the hyperadrenergic effect. Dr. Shouman’s approach is to start gradually with swimming or the use of a recumbent bike or a rowing machine.

Dr. Taub recommends wearables to patients because POTS is “a very dynamic condition” that is easy to overmedicate or undermedicate. If it’s a good day, the patients are well hydrated, and the standing heart rate is only 80 bpm, she tells them they could titrate down their second dose of ivabradine, for example. The feedback from wearables also helps patients manage their exercise response.

For Dr. Shouman, wearables are not always as accurate as he would like. He tells his patients that it’s okay to use one as long as it doesn’t become a source of anxiety such that they’re constantly checking it.
 

POTS hope: A COVID-19 silver lining?

With increasing attention being paid to long-haul COVID-19, are there any concerns that POTS will get lost among the myriad symptoms connected to PASC?

Dr. Shouman cautioned, “Not all long COVID is POTS,” and said that clinicians at long-haul clinics should be able to recognize the different conditions “when POTS is suspected. I think it is useful for those providers to make the appropriate referral for POTS clinic autonomic assessment.”

He and his colleagues at Mayo have seen quite a few patients who have post–COVID-19 autonomic dysfunction, such as vasodepressor syncope, not just POTS. They plan to write about this soon.

“Of all the things I treat in cardiology, this is the most complex, because there’s so many different systems involved,” said Dr. Taub, who has seen patients recover fully from POTS. “There’s a spectrum, and there’s people that are definitely on one end of the spectrum where they have very severe diseases.”

For her, the important message is, “No matter where you are on the spectrum, there are things we can do to make your symptoms better.” And with grant funding for PASC research, “hopefully we will address the mechanisms of disease, and we’ll be able to cure this,” she said.

Dr. Patel has served as a consultant for Bayer, Janssen, AstraZeneca, and Heartflow and has received research grants from Bayer, Janssen, AstraZeneca, and the National Heart, Lung, and Blood Institute. Dr. Shouman reports no relevant financial relationships. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the National Institutes of Health, the American Heart Association, and the Department of Homeland Security/FEMA.

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

Before COVID-19, postural orthostatic tachycardia syndrome (POTS) was one of those diseases that many people, including physicians, dismissed.

“They thought it was just anxious, crazy young women,” said Pam R. Taub, MD, who runs the cardiac rehabilitation program at the University of California, San Diego.

The cryptic autonomic condition was estimated to affect 1-3 million Americans before the pandemic hit. Now case reports confirm that it is a manifestation of postacute sequelae of SARS-CoV-2 infection (PASC), or so-called long-haul COVID-19.

“I’m excited that this condition that has been so often the ugly stepchild of both cardiology and neurology is getting some attention,” said Dr. Taub. She said she is hopeful that the National Institutes of Health’s commitment to PASC research will benefit patients affected by the cardiovascular dysautonomia characterized by orthostatic intolerance in the absence of orthostatic hypotension.

Postinfection POTS is not exclusive to SARS-CoV-2. It has been reported after Lyme disease and Epstein-Barr virus infections, for example. One theory is that some of the antibodies generated against the virus cross react and damage the autonomic nervous system, which regulates heart rate and blood pressure, Dr. Taub explained.

It is not known whether COVID-19 is more likely to trigger POTS than are other infections or whether the rise in cases merely reflects the fact that more than 115 million people worldwide have been infected with the novel coronavirus.

Medscape

Low blood volume, dysregulation of the autonomic nervous system, and autoimmunity may all play a role in POTS, perhaps leading to distinct subtypes, according to a State of the Science document from the NIH; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke.

In Dr. Taub’s experience, “The truth is that patients actually have a mix of the subtypes.”

Kamal Shouman, MD, an autonomic neurologist at Mayo Clinic, Rochester, Minn., said in an interview that he has seen patients present with post–COVID-19 POTS in “all flavors,” including “neuropathic POTS, which is thought of as the classic postinfectious phenomenon.”

Why does it mostly affect athletic women?

The condition, which can be the result of dehydration or prolonged bed rest, leading to deconditioning, affects women disproportionately.

According to Manesh Patel, MD, if a patient with POTS who is not a young woman is presented on medical rounds, the response is, “Tell me again why you think this patient has POTS.”

Mitchel L. Zoler/MDedge News

Poor (wo)man’s tilt test and treatment options

POTS is typically diagnosed with a tilt test and transcranial Doppler. Dr. Taub described her “poor man’s tilt test” of asking the patient to lie down for 5-10 minutes and then having the patient stand up.

She likes the fact that transcranial Doppler helps validate the brain fog that patients report, which can be dismissed as “just your excuse for not wanting to work.” If blood perfusion to the brain is cut by 40%-50%, “how are you going to think clearly?” she said.

Dr. Shouman noted that overall volume expansion with salt water, compression garments, and a graduated exercise program play a major role in the rehabilitation of all POTS patients.

He likes to tailor treatments to the most likely underlying cause. But patients should first undergo a medical assessment by their internists to make sure there isn’t a primary lung or heart problem.

“Once the decision is made for them to be evaluated in the autonomic practice and [a] POTS diagnosis is made, I think it is very useful to determine what type of POTS,” he said.

With hyperadrenergic POTS, “you are looking at a standing norepinephrine level of over 600 pg/mL or so.” For these patients, drugs such as ivabradine or beta-blockers can help, he noted.

Dr. Taub recently conducted a small study that showed a benefit with the selective I_f channel blocker ivabradine for patients with hyperadrenergic POTS unrelated to COVID-19. She tends to favor ivabradine over beta-blockers because it lowers heart rate but not blood pressure. In addition, beta-blockers can exacerbate fatigue and brain fog.

A small crossover study will compare propranolol and ivabradine in POTS. For someone who is very hypovolemic, “you might try a salt tablet or a prescription drug like fludrocortisone,” Dr. Taub explained.

Another problem that patients with POTS experience is an inability to exercise because of orthostatic intolerance. Recumbent exercise targets deconditioning and can tamp down the hyperadrenergic effect. Dr. Shouman’s approach is to start gradually with swimming or the use of a recumbent bike or a rowing machine.

Dr. Taub recommends wearables to patients because POTS is “a very dynamic condition” that is easy to overmedicate or undermedicate. If it’s a good day, the patients are well hydrated, and the standing heart rate is only 80 bpm, she tells them they could titrate down their second dose of ivabradine, for example. The feedback from wearables also helps patients manage their exercise response.

For Dr. Shouman, wearables are not always as accurate as he would like. He tells his patients that it’s okay to use one as long as it doesn’t become a source of anxiety such that they’re constantly checking it.
 

POTS hope: A COVID-19 silver lining?

With increasing attention being paid to long-haul COVID-19, are there any concerns that POTS will get lost among the myriad symptoms connected to PASC?

Dr. Shouman cautioned, “Not all long COVID is POTS,” and said that clinicians at long-haul clinics should be able to recognize the different conditions “when POTS is suspected. I think it is useful for those providers to make the appropriate referral for POTS clinic autonomic assessment.”

He and his colleagues at Mayo have seen quite a few patients who have post–COVID-19 autonomic dysfunction, such as vasodepressor syncope, not just POTS. They plan to write about this soon.

“Of all the things I treat in cardiology, this is the most complex, because there’s so many different systems involved,” said Dr. Taub, who has seen patients recover fully from POTS. “There’s a spectrum, and there’s people that are definitely on one end of the spectrum where they have very severe diseases.”

For her, the important message is, “No matter where you are on the spectrum, there are things we can do to make your symptoms better.” And with grant funding for PASC research, “hopefully we will address the mechanisms of disease, and we’ll be able to cure this,” she said.

Dr. Patel has served as a consultant for Bayer, Janssen, AstraZeneca, and Heartflow and has received research grants from Bayer, Janssen, AstraZeneca, and the National Heart, Lung, and Blood Institute. Dr. Shouman reports no relevant financial relationships. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the National Institutes of Health, the American Heart Association, and the Department of Homeland Security/FEMA.

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

To the Editor:

Cutaneous amyloidosis can be secondary to many causes. We describe a case of amyloidosis that was secondary to the deposition of an antiretroviral drug enfuvirtide and clinically presented as bullae over the anterior abdominal wall.

A 65-year-old man with HIV presented with pink vesicles and flaccid bullae on the anterolateral aspect of the lower abdomen (Figure 1) in areas of self-administered subcutaneous injections of enfuvirtide. He reported tissue swelling with a yellow discoloration immediately after injections that would spontaneously subside after a few minutes.

In summary, several types of cutaneous amyloidosis occur, including secondary cutaneous involvement by systemic amyloidosis and drug-induced amyloidosis, and notable histopathologic overlap exists between these types. Given the differing treatment requirements depending on the type of cutaneous amyloidosis, obtaining an appropriate clinical history, including the patient’s medication list, is important to ensure the correct diagnosis is reached. Protein analysis with mass spectrometry can be used if the nature of the amyloid remains indeterminate.

To the Editor:

Cutaneous amyloidosis can be secondary to many causes. We describe a case of amyloidosis that was secondary to the deposition of an antiretroviral drug enfuvirtide and clinically presented as bullae over the anterior abdominal wall.

A 65-year-old man with HIV presented with pink vesicles and flaccid bullae on the anterolateral aspect of the lower abdomen (Figure 1) in areas of self-administered subcutaneous injections of enfuvirtide. He reported tissue swelling with a yellow discoloration immediately after injections that would spontaneously subside after a few minutes.

In summary, several types of cutaneous amyloidosis occur, including secondary cutaneous involvement by systemic amyloidosis and drug-induced amyloidosis, and notable histopathologic overlap exists between these types. Given the differing treatment requirements depending on the type of cutaneous amyloidosis, obtaining an appropriate clinical history, including the patient’s medication list, is important to ensure the correct diagnosis is reached. Protein analysis with mass spectrometry can be used if the nature of the amyloid remains indeterminate.

To the Editor:

Cutaneous amyloidosis can be secondary to many causes. We describe a case of amyloidosis that was secondary to the deposition of an antiretroviral drug enfuvirtide and clinically presented as bullae over the anterior abdominal wall.

A 65-year-old man with HIV presented with pink vesicles and flaccid bullae on the anterolateral aspect of the lower abdomen (Figure 1) in areas of self-administered subcutaneous injections of enfuvirtide. He reported tissue swelling with a yellow discoloration immediately after injections that would spontaneously subside after a few minutes.

In summary, several types of cutaneous amyloidosis occur, including secondary cutaneous involvement by systemic amyloidosis and drug-induced amyloidosis, and notable histopathologic overlap exists between these types. Given the differing treatment requirements depending on the type of cutaneous amyloidosis, obtaining an appropriate clinical history, including the patient’s medication list, is important to ensure the correct diagnosis is reached. Protein analysis with mass spectrometry can be used if the nature of the amyloid remains indeterminate.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

Febuxostat (Uloric) was not associated with increased cardiovascular risk in patients with gout when compared to those who used allopurinol, in an analysis of new users of the drugs in Medicare fee-for-service claims data from the period of 2008-2016.

The findings, published March 25 in the Journal of the American Heart Association, update and echo the results from a similar previous study by the same Brigham and Women’s Hospital research group that covered 2008-2013 Medicare claims data. That original claims data study from 2018 sought to confirm the findings of the postmarketing surveillance CARES (Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities) trial that led to a boxed warning for increased risk of cardiovascular and all-cause mortality vs. allopurinol. The trial, however, did not show a higher rate of major adverse cardiovascular events (MACE) overall with febuxostat.

The recency of the new data with more febuxostat-exposed patients overall provides greater reassurance on the safety of the drug, corresponding author Seoyoung C. Kim, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, said in an interview. “We also were able to get data on cause of death, which we did not have before when we conducted our first paper.”

Dr. Kim said she was not surprised by any of the findings, which were consistent with the results of her earlier work. “Our result on CV death also was consistent and reassuring,” she noted.

The newest Medicare claims study also corroborates results from FAST (Febuxostat Versus Allopurinol Streamlined Trial), a separate postmarketing surveillance study that was ordered by the European Medicines Agency after febuxostat’s approval in 2009. It showed that the two drugs were noninferior to each other for the risk of all-cause mortality or a composite cardiovascular outcome (hospitalization for nonfatal myocardial infarction, biomarker-positive acute coronary syndrome, nonfatal stroke, or cardiovascular death).

“While CARES showed higher CV death and all-cause death rates in febuxostat compared to allopurinol, FAST did not,” Dr. Kim noted. “Our study of more than 111,000 older gout patients treated with either febuxostat or allopurinol in real-world settings also did not find a difference in the risk of MACE, CV mortality, or all-cause mortality,” she added. “Taking these data all together, I think we can be more certain about the CV safety of febuxostat when its use is clinically indicated or needed,” she said.

Study details

Dr. Kim, first author Ajinkya Pawar, PhD, of Brigham and Women’s, and colleagues identified 467,461 people with gout aged 65 years and older who had been enrolled in Medicare for at least a year. They then used propensity-score matching to compare 27,881 first-time users of febuxostat with 83,643 first-time users of allopurinol on the primary outcome of the incidence of major adverse cardiovascular events (MACE), defined as the first occurrence of myocardial infarction, stroke, or cardiovascular mortality.

In the updated study, the mean follow‐up periods for febuxostat and allopurinol were 284 days and 339 days, respectively. Overall, febuxostat was noninferior to allopurinol with regard to MACE (hazard ratio, 0.99; 95% confidence interval, 0.93-1.05), and the results were consistent among patients with baseline CVD (HR, 0.94). In addition, rates of secondary outcomes of MI, stroke, and cardiovascular mortality were not significantly different between febuxostat and allopurinol patients, except for all-cause mortality (HR, 0.92; 95% CI, 0.87-0.98).

The study findings were limited mainly by the potential bias caused by nonadherence to medications, and potential for residual confounding and misclassification bias, the researchers noted.

However, the study was strengthened by its incident new-user design that allowed only patients with no use of either medication for a year before the first dispensing and its active comparator design, and the data are generalizable to the greater population of older gout patients, they said.

Consequently, the data from this large, real-world study support the safety of febuxostat with regard to cardiovascular risk in gout patients, including those with baseline cardiovascular disease, they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed research grants to Brigham and Women’s Hospital from Roche, Pfizer, AbbVie, and Bristol‐Myers Squibb for unrelated studies. Another author reported serving as the principal investigator with research grants from Vertex, Bayer, and Novartis to Brigham and Women’s Hospital for unrelated projects.

Febuxostat (Uloric) was not associated with increased cardiovascular risk in patients with gout when compared to those who used allopurinol, in an analysis of new users of the drugs in Medicare fee-for-service claims data from the period of 2008-2016.

The findings, published March 25 in the Journal of the American Heart Association, update and echo the results from a similar previous study by the same Brigham and Women’s Hospital research group that covered 2008-2013 Medicare claims data. That original claims data study from 2018 sought to confirm the findings of the postmarketing surveillance CARES (Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities) trial that led to a boxed warning for increased risk of cardiovascular and all-cause mortality vs. allopurinol. The trial, however, did not show a higher rate of major adverse cardiovascular events (MACE) overall with febuxostat.

The recency of the new data with more febuxostat-exposed patients overall provides greater reassurance on the safety of the drug, corresponding author Seoyoung C. Kim, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, said in an interview. “We also were able to get data on cause of death, which we did not have before when we conducted our first paper.”

Dr. Kim said she was not surprised by any of the findings, which were consistent with the results of her earlier work. “Our result on CV death also was consistent and reassuring,” she noted.

The newest Medicare claims study also corroborates results from FAST (Febuxostat Versus Allopurinol Streamlined Trial), a separate postmarketing surveillance study that was ordered by the European Medicines Agency after febuxostat’s approval in 2009. It showed that the two drugs were noninferior to each other for the risk of all-cause mortality or a composite cardiovascular outcome (hospitalization for nonfatal myocardial infarction, biomarker-positive acute coronary syndrome, nonfatal stroke, or cardiovascular death).

“While CARES showed higher CV death and all-cause death rates in febuxostat compared to allopurinol, FAST did not,” Dr. Kim noted. “Our study of more than 111,000 older gout patients treated with either febuxostat or allopurinol in real-world settings also did not find a difference in the risk of MACE, CV mortality, or all-cause mortality,” she added. “Taking these data all together, I think we can be more certain about the CV safety of febuxostat when its use is clinically indicated or needed,” she said.

Study details

Dr. Kim, first author Ajinkya Pawar, PhD, of Brigham and Women’s, and colleagues identified 467,461 people with gout aged 65 years and older who had been enrolled in Medicare for at least a year. They then used propensity-score matching to compare 27,881 first-time users of febuxostat with 83,643 first-time users of allopurinol on the primary outcome of the incidence of major adverse cardiovascular events (MACE), defined as the first occurrence of myocardial infarction, stroke, or cardiovascular mortality.

In the updated study, the mean follow‐up periods for febuxostat and allopurinol were 284 days and 339 days, respectively. Overall, febuxostat was noninferior to allopurinol with regard to MACE (hazard ratio, 0.99; 95% confidence interval, 0.93-1.05), and the results were consistent among patients with baseline CVD (HR, 0.94). In addition, rates of secondary outcomes of MI, stroke, and cardiovascular mortality were not significantly different between febuxostat and allopurinol patients, except for all-cause mortality (HR, 0.92; 95% CI, 0.87-0.98).

The study findings were limited mainly by the potential bias caused by nonadherence to medications, and potential for residual confounding and misclassification bias, the researchers noted.

However, the study was strengthened by its incident new-user design that allowed only patients with no use of either medication for a year before the first dispensing and its active comparator design, and the data are generalizable to the greater population of older gout patients, they said.

Consequently, the data from this large, real-world study support the safety of febuxostat with regard to cardiovascular risk in gout patients, including those with baseline cardiovascular disease, they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed research grants to Brigham and Women’s Hospital from Roche, Pfizer, AbbVie, and Bristol‐Myers Squibb for unrelated studies. Another author reported serving as the principal investigator with research grants from Vertex, Bayer, and Novartis to Brigham and Women’s Hospital for unrelated projects.

Febuxostat (Uloric) was not associated with increased cardiovascular risk in patients with gout when compared to those who used allopurinol, in an analysis of new users of the drugs in Medicare fee-for-service claims data from the period of 2008-2016.

The findings, published March 25 in the Journal of the American Heart Association, update and echo the results from a similar previous study by the same Brigham and Women’s Hospital research group that covered 2008-2013 Medicare claims data. That original claims data study from 2018 sought to confirm the findings of the postmarketing surveillance CARES (Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities) trial that led to a boxed warning for increased risk of cardiovascular and all-cause mortality vs. allopurinol. The trial, however, did not show a higher rate of major adverse cardiovascular events (MACE) overall with febuxostat.

The recency of the new data with more febuxostat-exposed patients overall provides greater reassurance on the safety of the drug, corresponding author Seoyoung C. Kim, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, said in an interview. “We also were able to get data on cause of death, which we did not have before when we conducted our first paper.”

Dr. Kim said she was not surprised by any of the findings, which were consistent with the results of her earlier work. “Our result on CV death also was consistent and reassuring,” she noted.

The newest Medicare claims study also corroborates results from FAST (Febuxostat Versus Allopurinol Streamlined Trial), a separate postmarketing surveillance study that was ordered by the European Medicines Agency after febuxostat’s approval in 2009. It showed that the two drugs were noninferior to each other for the risk of all-cause mortality or a composite cardiovascular outcome (hospitalization for nonfatal myocardial infarction, biomarker-positive acute coronary syndrome, nonfatal stroke, or cardiovascular death).

“While CARES showed higher CV death and all-cause death rates in febuxostat compared to allopurinol, FAST did not,” Dr. Kim noted. “Our study of more than 111,000 older gout patients treated with either febuxostat or allopurinol in real-world settings also did not find a difference in the risk of MACE, CV mortality, or all-cause mortality,” she added. “Taking these data all together, I think we can be more certain about the CV safety of febuxostat when its use is clinically indicated or needed,” she said.

Study details

Dr. Kim, first author Ajinkya Pawar, PhD, of Brigham and Women’s, and colleagues identified 467,461 people with gout aged 65 years and older who had been enrolled in Medicare for at least a year. They then used propensity-score matching to compare 27,881 first-time users of febuxostat with 83,643 first-time users of allopurinol on the primary outcome of the incidence of major adverse cardiovascular events (MACE), defined as the first occurrence of myocardial infarction, stroke, or cardiovascular mortality.

In the updated study, the mean follow‐up periods for febuxostat and allopurinol were 284 days and 339 days, respectively. Overall, febuxostat was noninferior to allopurinol with regard to MACE (hazard ratio, 0.99; 95% confidence interval, 0.93-1.05), and the results were consistent among patients with baseline CVD (HR, 0.94). In addition, rates of secondary outcomes of MI, stroke, and cardiovascular mortality were not significantly different between febuxostat and allopurinol patients, except for all-cause mortality (HR, 0.92; 95% CI, 0.87-0.98).

The study findings were limited mainly by the potential bias caused by nonadherence to medications, and potential for residual confounding and misclassification bias, the researchers noted.

However, the study was strengthened by its incident new-user design that allowed only patients with no use of either medication for a year before the first dispensing and its active comparator design, and the data are generalizable to the greater population of older gout patients, they said.

Consequently, the data from this large, real-world study support the safety of febuxostat with regard to cardiovascular risk in gout patients, including those with baseline cardiovascular disease, they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed research grants to Brigham and Women’s Hospital from Roche, Pfizer, AbbVie, and Bristol‐Myers Squibb for unrelated studies. Another author reported serving as the principal investigator with research grants from Vertex, Bayer, and Novartis to Brigham and Women’s Hospital for unrelated projects.

The Food and Drug Administration has expanded the indication for mirabegron (Myrbetriq/Myrbetriq Granules) to treat neurogenic detrusor overactivity (NDO), a bladder dysfunction related to neurologic impairment, in children aged 3 years and older.

This comes 1 year after the FDA approved solifenacin succinate, the first treatment of NDO in pediatric patients aged 2 years and older.

The approval of the drug for these new indications is a “positive step” for the treatment of NDO in young patients, Christine P. Nguyen, MD, director of the FDA’s Division of Urology, Obstetrics, and Gynecology, said in an FDA statement.

“Mirabegron, the active ingredient in Myrbetriq and Myrbetriq Granules, works by a different mechanism of action from the currently approved treatments, providing a new treatment option for these young patients. We remain committed to facilitating the development and approval of safe and effective therapies for pediatric NDO patients,” Dr. Nguyen said.

NDO is a bladder dysfunction that frequently occurs in patients with congenital conditions, such as spina bifida. It also occurs in people who suffer from other diseases or injuries of the nervous system, such as multiple sclerosis and spinal cord injury. Symptoms of the condition include urinary frequency and incontinence.

The condition is characterized by the overactivity of the bladder wall muscle, which is normally relaxed to allow storage of urine. Irregular bladder muscle contraction increases storage pressure and decreases the amount of urine the bladder can hold. This can also put the upper urinary tract at risk for deterioration and cause permanent damage to the kidneys.

The effectiveness of Myrbetriq and Myrbetriq Granules for pediatric NDO was determined in a study of 86 children and adolescents aged 3-17 years. The researchers found that after 24 weeks of treatment, the drug improved the patients’ bladder capacity, reduced the number of bladder wall muscle contractions, and improved the volume of urine that could be held. It also reduced the daily number of episodes of leakage.

Side effects of Myrbetriq and Myrbetriq Granules include urinary tract infection, cold symptoms, angioedema, constipation, and headache. The FDA said the drug may also increase blood pressure and may worsen blood pressure in patients who have a history of hypertension.

The FDA approved mirabegron in 2012 to treat overactive bladder in adults.

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

The Food and Drug Administration has expanded the indication for mirabegron (Myrbetriq/Myrbetriq Granules) to treat neurogenic detrusor overactivity (NDO), a bladder dysfunction related to neurologic impairment, in children aged 3 years and older.

This comes 1 year after the FDA approved solifenacin succinate, the first treatment of NDO in pediatric patients aged 2 years and older.

The approval of the drug for these new indications is a “positive step” for the treatment of NDO in young patients, Christine P. Nguyen, MD, director of the FDA’s Division of Urology, Obstetrics, and Gynecology, said in an FDA statement.

“Mirabegron, the active ingredient in Myrbetriq and Myrbetriq Granules, works by a different mechanism of action from the currently approved treatments, providing a new treatment option for these young patients. We remain committed to facilitating the development and approval of safe and effective therapies for pediatric NDO patients,” Dr. Nguyen said.

NDO is a bladder dysfunction that frequently occurs in patients with congenital conditions, such as spina bifida. It also occurs in people who suffer from other diseases or injuries of the nervous system, such as multiple sclerosis and spinal cord injury. Symptoms of the condition include urinary frequency and incontinence.

The condition is characterized by the overactivity of the bladder wall muscle, which is normally relaxed to allow storage of urine. Irregular bladder muscle contraction increases storage pressure and decreases the amount of urine the bladder can hold. This can also put the upper urinary tract at risk for deterioration and cause permanent damage to the kidneys.

The effectiveness of Myrbetriq and Myrbetriq Granules for pediatric NDO was determined in a study of 86 children and adolescents aged 3-17 years. The researchers found that after 24 weeks of treatment, the drug improved the patients’ bladder capacity, reduced the number of bladder wall muscle contractions, and improved the volume of urine that could be held. It also reduced the daily number of episodes of leakage.

Side effects of Myrbetriq and Myrbetriq Granules include urinary tract infection, cold symptoms, angioedema, constipation, and headache. The FDA said the drug may also increase blood pressure and may worsen blood pressure in patients who have a history of hypertension.

The FDA approved mirabegron in 2012 to treat overactive bladder in adults.

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

The Food and Drug Administration has expanded the indication for mirabegron (Myrbetriq/Myrbetriq Granules) to treat neurogenic detrusor overactivity (NDO), a bladder dysfunction related to neurologic impairment, in children aged 3 years and older.

This comes 1 year after the FDA approved solifenacin succinate, the first treatment of NDO in pediatric patients aged 2 years and older.

The approval of the drug for these new indications is a “positive step” for the treatment of NDO in young patients, Christine P. Nguyen, MD, director of the FDA’s Division of Urology, Obstetrics, and Gynecology, said in an FDA statement.

“Mirabegron, the active ingredient in Myrbetriq and Myrbetriq Granules, works by a different mechanism of action from the currently approved treatments, providing a new treatment option for these young patients. We remain committed to facilitating the development and approval of safe and effective therapies for pediatric NDO patients,” Dr. Nguyen said.

NDO is a bladder dysfunction that frequently occurs in patients with congenital conditions, such as spina bifida. It also occurs in people who suffer from other diseases or injuries of the nervous system, such as multiple sclerosis and spinal cord injury. Symptoms of the condition include urinary frequency and incontinence.

The condition is characterized by the overactivity of the bladder wall muscle, which is normally relaxed to allow storage of urine. Irregular bladder muscle contraction increases storage pressure and decreases the amount of urine the bladder can hold. This can also put the upper urinary tract at risk for deterioration and cause permanent damage to the kidneys.

The effectiveness of Myrbetriq and Myrbetriq Granules for pediatric NDO was determined in a study of 86 children and adolescents aged 3-17 years. The researchers found that after 24 weeks of treatment, the drug improved the patients’ bladder capacity, reduced the number of bladder wall muscle contractions, and improved the volume of urine that could be held. It also reduced the daily number of episodes of leakage.

Side effects of Myrbetriq and Myrbetriq Granules include urinary tract infection, cold symptoms, angioedema, constipation, and headache. The FDA said the drug may also increase blood pressure and may worsen blood pressure in patients who have a history of hypertension.

The FDA approved mirabegron in 2012 to treat overactive bladder in adults.

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

The Diagnosis: Lichen Planus Pigmentosus-Inversus 

Histopathologic examination revealed hyperkeratosis with dense, bandlike, lymphocytic inflammation at the dermoepidermal junction with associated melanin-containing macrophages in the papillary dermis (Figure 1). The physical examination and histopathology were consistent with a diagnosis of lichen planus pigmentosus-inversus (LPPI). Treatment was discussed with the patient, with options including phototherapy, tacrolimus, or a high-dose steroid. Given that the lesions were asymptomatic and not bothersome, the patient denied treatment and agreed to routine follow-up. 

Given the gender, age, and clinical features of our patient, this case represents a classic scenario of LPPI. It currently is unknown if ethnicity plays a role in the disorder. Lichen planus pigmentosus-inversus initially was thought to be more prevalent in White patients; however, studies have been reported in individuals with darker skin.^1,2 

The main differential diagnosis includes erythema dyschromicum perstans, postinflammatory hyperpigmentation, and lichen planus. Although erythema dyschromicum perstans develops in individuals with darker skin, lesions are restricted to the upper torso and limbs.^2-4 In both lichen planus and lichen actinicus, skin findings primarily develop in sun-exposed areas, such as the face, neck, and hands.^4,6 Given the negative history of trauma, postinflammatory hyperpigmentation was unlikely in our patient. Furthermore, a distinguishing characteristic of LPPI is the deposition of melanin deep within the dermal layer.³ 

Lesions developing in nonexposed intertriginous skin makes LPPI unique and distinguishes it from other more common conditions. The lesions commonly are hyperpigmented and are not as pruritic as other lichen-associated conditions. Lichen planus pigmentosus-inversus often persists for months, and the rash generally is resistant to treatment.^2,5 Topical tacrolimus and high-dose steroids may improve symptoms, though results have varied substantially. In addition, some cases have resolved spontaneously.^1,4,6,7 Because LPPI is asymptomatic and benign, spontaneous resolution and routine care is a reasonable treatment strategy. Some cases have supported this strategy as safe and high-value care.² 

The Diagnosis: Lichen Planus Pigmentosus-Inversus 

Histopathologic examination revealed hyperkeratosis with dense, bandlike, lymphocytic inflammation at the dermoepidermal junction with associated melanin-containing macrophages in the papillary dermis (Figure 1). The physical examination and histopathology were consistent with a diagnosis of lichen planus pigmentosus-inversus (LPPI). Treatment was discussed with the patient, with options including phototherapy, tacrolimus, or a high-dose steroid. Given that the lesions were asymptomatic and not bothersome, the patient denied treatment and agreed to routine follow-up. 

Given the gender, age, and clinical features of our patient, this case represents a classic scenario of LPPI. It currently is unknown if ethnicity plays a role in the disorder. Lichen planus pigmentosus-inversus initially was thought to be more prevalent in White patients; however, studies have been reported in individuals with darker skin.^1,2 

The main differential diagnosis includes erythema dyschromicum perstans, postinflammatory hyperpigmentation, and lichen planus. Although erythema dyschromicum perstans develops in individuals with darker skin, lesions are restricted to the upper torso and limbs.^2-4 In both lichen planus and lichen actinicus, skin findings primarily develop in sun-exposed areas, such as the face, neck, and hands.^4,6 Given the negative history of trauma, postinflammatory hyperpigmentation was unlikely in our patient. Furthermore, a distinguishing characteristic of LPPI is the deposition of melanin deep within the dermal layer.³ 

Lesions developing in nonexposed intertriginous skin makes LPPI unique and distinguishes it from other more common conditions. The lesions commonly are hyperpigmented and are not as pruritic as other lichen-associated conditions. Lichen planus pigmentosus-inversus often persists for months, and the rash generally is resistant to treatment.^2,5 Topical tacrolimus and high-dose steroids may improve symptoms, though results have varied substantially. In addition, some cases have resolved spontaneously.^1,4,6,7 Because LPPI is asymptomatic and benign, spontaneous resolution and routine care is a reasonable treatment strategy. Some cases have supported this strategy as safe and high-value care.² 

The Diagnosis: Lichen Planus Pigmentosus-Inversus 

Histopathologic examination revealed hyperkeratosis with dense, bandlike, lymphocytic inflammation at the dermoepidermal junction with associated melanin-containing macrophages in the papillary dermis (Figure 1). The physical examination and histopathology were consistent with a diagnosis of lichen planus pigmentosus-inversus (LPPI). Treatment was discussed with the patient, with options including phototherapy, tacrolimus, or a high-dose steroid. Given that the lesions were asymptomatic and not bothersome, the patient denied treatment and agreed to routine follow-up. 

Given the gender, age, and clinical features of our patient, this case represents a classic scenario of LPPI. It currently is unknown if ethnicity plays a role in the disorder. Lichen planus pigmentosus-inversus initially was thought to be more prevalent in White patients; however, studies have been reported in individuals with darker skin.^1,2 

The main differential diagnosis includes erythema dyschromicum perstans, postinflammatory hyperpigmentation, and lichen planus. Although erythema dyschromicum perstans develops in individuals with darker skin, lesions are restricted to the upper torso and limbs.^2-4 In both lichen planus and lichen actinicus, skin findings primarily develop in sun-exposed areas, such as the face, neck, and hands.^4,6 Given the negative history of trauma, postinflammatory hyperpigmentation was unlikely in our patient. Furthermore, a distinguishing characteristic of LPPI is the deposition of melanin deep within the dermal layer.³ 

Lesions developing in nonexposed intertriginous skin makes LPPI unique and distinguishes it from other more common conditions. The lesions commonly are hyperpigmented and are not as pruritic as other lichen-associated conditions. Lichen planus pigmentosus-inversus often persists for months, and the rash generally is resistant to treatment.^2,5 Topical tacrolimus and high-dose steroids may improve symptoms, though results have varied substantially. In addition, some cases have resolved spontaneously.^1,4,6,7 Because LPPI is asymptomatic and benign, spontaneous resolution and routine care is a reasonable treatment strategy. Some cases have supported this strategy as safe and high-value care.² 

The president question – “Who’s the current president?” – has been a standard one of basic neurology assessments for years, probably since the answer was Ulysses S. Grant. It’s routinely asked by doctors, nurses, EEG techs, medical students, and pretty much anyone else trying to figure out someone’s mental status.

When I first began doing this, the answer was “George Bush” (at that time there’d only been one president by that name, so clarification wasn’t needed). Back then people answered the question (right or wrong) and we moved on. I don’t recall ever getting a dirty look, political lecture, or eye roll as a response.

Unfortunately, it’s not that simple anymore. As people have become increasingly polarized, it’s become seemingly impossible to get a response without a statement of support or anger. At best I get a straight answer. At worst I get a lecture on the “perils of a non-White society” (that was last week). Then they want my opinion, and years of practice have taught me to never discuss politics with patients, regardless of which side they’re on.

I don’t recall this being a problem until the late ‘90s, when the answer was “Clinton.” Occasionally I’d get a sarcastic comment referring to the Lewinsky affair, but that was about it.

Since then it’s gradually escalated, to where the question has become worthless. I don’t have time to hear a political diatribe from either side. This is a doctor appointment, not a debate club. The insistence by some that Trump won leaves me guessing if the person is stubborn or serious, and either way it shouldn’t be my job to figure that out. I take your appointment seriously, so the least you can do is the same.

So I’ve ditched the question for good. The current date, the location of my office, and other less controversial things will have to do. I’m here to take care of you, not have you try to pick a fight or make a political statement.

You’d think such a simple, time-honored, assessment question wouldn’t become such a problem. But in today’s polarized and impolite society, even the seriousness of a medical evaluation is affected by what we’ve allowed ourselves to become.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The president question – “Who’s the current president?” – has been a standard one of basic neurology assessments for years, probably since the answer was Ulysses S. Grant. It’s routinely asked by doctors, nurses, EEG techs, medical students, and pretty much anyone else trying to figure out someone’s mental status.

When I first began doing this, the answer was “George Bush” (at that time there’d only been one president by that name, so clarification wasn’t needed). Back then people answered the question (right or wrong) and we moved on. I don’t recall ever getting a dirty look, political lecture, or eye roll as a response.

Unfortunately, it’s not that simple anymore. As people have become increasingly polarized, it’s become seemingly impossible to get a response without a statement of support or anger. At best I get a straight answer. At worst I get a lecture on the “perils of a non-White society” (that was last week). Then they want my opinion, and years of practice have taught me to never discuss politics with patients, regardless of which side they’re on.

I don’t recall this being a problem until the late ‘90s, when the answer was “Clinton.” Occasionally I’d get a sarcastic comment referring to the Lewinsky affair, but that was about it.

Since then it’s gradually escalated, to where the question has become worthless. I don’t have time to hear a political diatribe from either side. This is a doctor appointment, not a debate club. The insistence by some that Trump won leaves me guessing if the person is stubborn or serious, and either way it shouldn’t be my job to figure that out. I take your appointment seriously, so the least you can do is the same.

So I’ve ditched the question for good. The current date, the location of my office, and other less controversial things will have to do. I’m here to take care of you, not have you try to pick a fight or make a political statement.

You’d think such a simple, time-honored, assessment question wouldn’t become such a problem. But in today’s polarized and impolite society, even the seriousness of a medical evaluation is affected by what we’ve allowed ourselves to become.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The president question – “Who’s the current president?” – has been a standard one of basic neurology assessments for years, probably since the answer was Ulysses S. Grant. It’s routinely asked by doctors, nurses, EEG techs, medical students, and pretty much anyone else trying to figure out someone’s mental status.

When I first began doing this, the answer was “George Bush” (at that time there’d only been one president by that name, so clarification wasn’t needed). Back then people answered the question (right or wrong) and we moved on. I don’t recall ever getting a dirty look, political lecture, or eye roll as a response.

Unfortunately, it’s not that simple anymore. As people have become increasingly polarized, it’s become seemingly impossible to get a response without a statement of support or anger. At best I get a straight answer. At worst I get a lecture on the “perils of a non-White society” (that was last week). Then they want my opinion, and years of practice have taught me to never discuss politics with patients, regardless of which side they’re on.

I don’t recall this being a problem until the late ‘90s, when the answer was “Clinton.” Occasionally I’d get a sarcastic comment referring to the Lewinsky affair, but that was about it.

Since then it’s gradually escalated, to where the question has become worthless. I don’t have time to hear a political diatribe from either side. This is a doctor appointment, not a debate club. The insistence by some that Trump won leaves me guessing if the person is stubborn or serious, and either way it shouldn’t be my job to figure that out. I take your appointment seriously, so the least you can do is the same.

So I’ve ditched the question for good. The current date, the location of my office, and other less controversial things will have to do. I’m here to take care of you, not have you try to pick a fight or make a political statement.

You’d think such a simple, time-honored, assessment question wouldn’t become such a problem. But in today’s polarized and impolite society, even the seriousness of a medical evaluation is affected by what we’ve allowed ourselves to become.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Chimeric antigen receptor (CAR) T-cell therapy, described as a “living drug,” is now available for patients with relapsed/refractory multiple myeloma who have been treated with four or more prior lines of therapy.

The Food and Drug Administration said these patients represent an “unmet medical need” when it granted approval for the new product – idecabtagene vicleucel (ide-cel; Abecma), developed by bluebird bio and Bristol-Myers Squibb.

Ide-cel is the first CAR T-cell therapy to gain approval for use in multiple myeloma. It is also the first CAR T-cell therapy to target B-cell maturation antigen.

Previously approved CAR T-cell products target CD19 and have been approved for use in certain types of leukemia and lymphoma.

All the CAR T-cell therapies are customized treatments that are created specifically for each individual patient from their own blood. The patient’s own T cells are removed from the blood, are genetically modified and expanded, and are then infused back into the patient. These modified T cells then seek out and destroy blood cancer cells, and they continue to do so long term.

In some patients, this has led to eradication of disease that had previously progressed with every other treatment that had been tried – results that have been described as “absolutely remarkable” and “one-shot therapy that looks to be curative.”

However, this cell therapy comes with serious adverse effects, including neurologic toxicity and cytokine release syndrome (CRS), which can be life threatening. For this reason, all these products have a risk evaluation and mitigation strategy, and the use of CAR T-cell therapies is limited to designated centers.

In addition, these CAR T-cells products are phenomenally expensive; hospitals have reported heavy financial losses with their use, and patients have turned to crowdfunding to pay for these therapies.
 

‘Phenomenal’ results in MM

The FDA noted that approval of ide-cel for multiple myeloma is based on data from a multicenter study that involved 127 patients with relapsed/refractory disease who had received at least three prior lines of treatment.

The results from this trial were published Feb. 25 in the New England Journal of Medicine.

An expert not involved in the trial described the results as “phenomenal.”

Krina Patel, MD, an associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that “the response rate of 73% in a patient population with a median of six lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal.

“We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed/refractory patients,” Dr. Patel told this news organization at the time.

The lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Both experts highlighted the poor prognosis for patients with relapsed/refractory disease. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies.

Nevertheless, in some patients, the disease continues to progress. For patients for whom treatments with all three classes of drugs have failed, the median progression-free survival is 3-4 months, and the median overall survival is 9 months.

In contrast, the results reported in the NEJM article showed that overall median progression-free survival was 8.8 months, but it was more than double that (20.2 months) for patients who achieved a complete or stringent complete response.

Estimated median overall survival was 19.4 months, and the overall survival was 78% at 12 months. The authors note that overall survival data are not yet mature.

The patients who were enrolled in the CAR T-cell trial had undergone many previous treatments. They had undergone a median of six prior drug therapies (range, 3-16), and most of the patients (120, 94%) had also undergone autologous hematopoietic stem cell transplant.

In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta-exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta-refractory.

In the NEJM article, the authors report that about a third of patients had a complete response to CAR T-cell therapy.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001); 42 (33%) showed a complete or stringent complete response; and 67 patients (52%) showed a “very good partial response or better,” they write.

In the FDA announcement of the product approval, the figures for complete response were slightly lower. “Of those studied, 28% of patients showed complete response – or disappearance of all signs of multiple myeloma – to Abecma, and 65% of this group remained in complete response to the treatment for at least 12 months,” the agency noted.

The FDA also noted that treatment with Abecma can cause severe side effects. The label carries a boxed warning regarding CRS, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life threatening.

The most common side effects of Abecma are CRS, infections, fatigue, musculoskeletal pain, and a weakened immune system. Side effects from treatment usually appear within the first 1-2 weeks after treatment, but some side effects may occur later.

The agency also noted that, to further evaluate the long-term safety of the drug, it is requiring the manufacturer to conduct a postmarketing observational study.

“The FDA remains committed to advancing novel treatment options for areas of unmet patient need,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“While there is no cure for multiple myeloma, the long-term outlook can vary based on the individual’s age and the stage of the condition at the time of diagnosis. Today’s approval provides a new treatment option for patients who have this uncommon type of cancer.”

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

Chimeric antigen receptor (CAR) T-cell therapy, described as a “living drug,” is now available for patients with relapsed/refractory multiple myeloma who have been treated with four or more prior lines of therapy.

The Food and Drug Administration said these patients represent an “unmet medical need” when it granted approval for the new product – idecabtagene vicleucel (ide-cel; Abecma), developed by bluebird bio and Bristol-Myers Squibb.

Ide-cel is the first CAR T-cell therapy to gain approval for use in multiple myeloma. It is also the first CAR T-cell therapy to target B-cell maturation antigen.

Previously approved CAR T-cell products target CD19 and have been approved for use in certain types of leukemia and lymphoma.

All the CAR T-cell therapies are customized treatments that are created specifically for each individual patient from their own blood. The patient’s own T cells are removed from the blood, are genetically modified and expanded, and are then infused back into the patient. These modified T cells then seek out and destroy blood cancer cells, and they continue to do so long term.

In some patients, this has led to eradication of disease that had previously progressed with every other treatment that had been tried – results that have been described as “absolutely remarkable” and “one-shot therapy that looks to be curative.”

However, this cell therapy comes with serious adverse effects, including neurologic toxicity and cytokine release syndrome (CRS), which can be life threatening. For this reason, all these products have a risk evaluation and mitigation strategy, and the use of CAR T-cell therapies is limited to designated centers.

In addition, these CAR T-cells products are phenomenally expensive; hospitals have reported heavy financial losses with their use, and patients have turned to crowdfunding to pay for these therapies.
 

‘Phenomenal’ results in MM

The FDA noted that approval of ide-cel for multiple myeloma is based on data from a multicenter study that involved 127 patients with relapsed/refractory disease who had received at least three prior lines of treatment.

The results from this trial were published Feb. 25 in the New England Journal of Medicine.

An expert not involved in the trial described the results as “phenomenal.”

Krina Patel, MD, an associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that “the response rate of 73% in a patient population with a median of six lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal.

“We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed/refractory patients,” Dr. Patel told this news organization at the time.

The lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Both experts highlighted the poor prognosis for patients with relapsed/refractory disease. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies.

Nevertheless, in some patients, the disease continues to progress. For patients for whom treatments with all three classes of drugs have failed, the median progression-free survival is 3-4 months, and the median overall survival is 9 months.

In contrast, the results reported in the NEJM article showed that overall median progression-free survival was 8.8 months, but it was more than double that (20.2 months) for patients who achieved a complete or stringent complete response.

Estimated median overall survival was 19.4 months, and the overall survival was 78% at 12 months. The authors note that overall survival data are not yet mature.

The patients who were enrolled in the CAR T-cell trial had undergone many previous treatments. They had undergone a median of six prior drug therapies (range, 3-16), and most of the patients (120, 94%) had also undergone autologous hematopoietic stem cell transplant.

In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta-exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta-refractory.

In the NEJM article, the authors report that about a third of patients had a complete response to CAR T-cell therapy.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001); 42 (33%) showed a complete or stringent complete response; and 67 patients (52%) showed a “very good partial response or better,” they write.

In the FDA announcement of the product approval, the figures for complete response were slightly lower. “Of those studied, 28% of patients showed complete response – or disappearance of all signs of multiple myeloma – to Abecma, and 65% of this group remained in complete response to the treatment for at least 12 months,” the agency noted.

The FDA also noted that treatment with Abecma can cause severe side effects. The label carries a boxed warning regarding CRS, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life threatening.

The most common side effects of Abecma are CRS, infections, fatigue, musculoskeletal pain, and a weakened immune system. Side effects from treatment usually appear within the first 1-2 weeks after treatment, but some side effects may occur later.

The agency also noted that, to further evaluate the long-term safety of the drug, it is requiring the manufacturer to conduct a postmarketing observational study.

“The FDA remains committed to advancing novel treatment options for areas of unmet patient need,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“While there is no cure for multiple myeloma, the long-term outlook can vary based on the individual’s age and the stage of the condition at the time of diagnosis. Today’s approval provides a new treatment option for patients who have this uncommon type of cancer.”

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

Chimeric antigen receptor (CAR) T-cell therapy, described as a “living drug,” is now available for patients with relapsed/refractory multiple myeloma who have been treated with four or more prior lines of therapy.

The Food and Drug Administration said these patients represent an “unmet medical need” when it granted approval for the new product – idecabtagene vicleucel (ide-cel; Abecma), developed by bluebird bio and Bristol-Myers Squibb.

Ide-cel is the first CAR T-cell therapy to gain approval for use in multiple myeloma. It is also the first CAR T-cell therapy to target B-cell maturation antigen.

Previously approved CAR T-cell products target CD19 and have been approved for use in certain types of leukemia and lymphoma.

All the CAR T-cell therapies are customized treatments that are created specifically for each individual patient from their own blood. The patient’s own T cells are removed from the blood, are genetically modified and expanded, and are then infused back into the patient. These modified T cells then seek out and destroy blood cancer cells, and they continue to do so long term.

In some patients, this has led to eradication of disease that had previously progressed with every other treatment that had been tried – results that have been described as “absolutely remarkable” and “one-shot therapy that looks to be curative.”

However, this cell therapy comes with serious adverse effects, including neurologic toxicity and cytokine release syndrome (CRS), which can be life threatening. For this reason, all these products have a risk evaluation and mitigation strategy, and the use of CAR T-cell therapies is limited to designated centers.

In addition, these CAR T-cells products are phenomenally expensive; hospitals have reported heavy financial losses with their use, and patients have turned to crowdfunding to pay for these therapies.
 

‘Phenomenal’ results in MM

The FDA noted that approval of ide-cel for multiple myeloma is based on data from a multicenter study that involved 127 patients with relapsed/refractory disease who had received at least three prior lines of treatment.

The results from this trial were published Feb. 25 in the New England Journal of Medicine.

An expert not involved in the trial described the results as “phenomenal.”

Krina Patel, MD, an associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that “the response rate of 73% in a patient population with a median of six lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal.

“We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed/refractory patients,” Dr. Patel told this news organization at the time.

The lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Both experts highlighted the poor prognosis for patients with relapsed/refractory disease. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies.

Nevertheless, in some patients, the disease continues to progress. For patients for whom treatments with all three classes of drugs have failed, the median progression-free survival is 3-4 months, and the median overall survival is 9 months.

In contrast, the results reported in the NEJM article showed that overall median progression-free survival was 8.8 months, but it was more than double that (20.2 months) for patients who achieved a complete or stringent complete response.

Estimated median overall survival was 19.4 months, and the overall survival was 78% at 12 months. The authors note that overall survival data are not yet mature.

The patients who were enrolled in the CAR T-cell trial had undergone many previous treatments. They had undergone a median of six prior drug therapies (range, 3-16), and most of the patients (120, 94%) had also undergone autologous hematopoietic stem cell transplant.

In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta-exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta-refractory.

In the NEJM article, the authors report that about a third of patients had a complete response to CAR T-cell therapy.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001); 42 (33%) showed a complete or stringent complete response; and 67 patients (52%) showed a “very good partial response or better,” they write.

In the FDA announcement of the product approval, the figures for complete response were slightly lower. “Of those studied, 28% of patients showed complete response – or disappearance of all signs of multiple myeloma – to Abecma, and 65% of this group remained in complete response to the treatment for at least 12 months,” the agency noted.

The FDA also noted that treatment with Abecma can cause severe side effects. The label carries a boxed warning regarding CRS, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life threatening.

The most common side effects of Abecma are CRS, infections, fatigue, musculoskeletal pain, and a weakened immune system. Side effects from treatment usually appear within the first 1-2 weeks after treatment, but some side effects may occur later.

The agency also noted that, to further evaluate the long-term safety of the drug, it is requiring the manufacturer to conduct a postmarketing observational study.

“The FDA remains committed to advancing novel treatment options for areas of unmet patient need,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“While there is no cure for multiple myeloma, the long-term outlook can vary based on the individual’s age and the stage of the condition at the time of diagnosis. Today’s approval provides a new treatment option for patients who have this uncommon type of cancer.”

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

The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.

Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.

One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.

In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.

“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.

“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.

Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.

At present, the WHO advocates only for female vaccination and screening.

Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.

Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.

“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.

“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.

“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.

In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.

Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.

Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
 

Unethical to leave males out?

Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.

Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.

With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.

On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.

“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
 

Eliminating cervical cancer

Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.

Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.

However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.

Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.

In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
 

OPSCC elimination

Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.

HPV-related OPSCCs are mostly associated specifically with HPV 16.

There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.

They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.

The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.

“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”

Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”

The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.

In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.

Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.

The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.

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

The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.

Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.

One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.

In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.

“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.

“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.

Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.

At present, the WHO advocates only for female vaccination and screening.

Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.

Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.

“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.

“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.

“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.

In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.

Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.

Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
 

Unethical to leave males out?

Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.

Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.

With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.

On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.

“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
 

Eliminating cervical cancer

Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.

Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.

However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.

Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.

In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
 

OPSCC elimination

Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.

HPV-related OPSCCs are mostly associated specifically with HPV 16.

There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.

They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.

The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.

“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”

Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”

The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.

In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.

Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.

The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.

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

The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.

Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.

One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.

In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.

“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.

“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.

Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.

At present, the WHO advocates only for female vaccination and screening.

Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.

Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.

“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.

“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.

“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.

In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.

Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.

Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
 

Unethical to leave males out?

Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.

Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.

With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.

On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.

“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
 

Eliminating cervical cancer

Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.

Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.

However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.

Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.

In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
 

OPSCC elimination

Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.

HPV-related OPSCCs are mostly associated specifically with HPV 16.

There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.

They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.

The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.

“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”

Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”

The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.

In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.

Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.

The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.

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