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.

People who suffer abuse as children continue to have higher levels of inflammatory biomarkers as adults, likely placing them at increased risk for chronic health problems, new research shows.

In a study assessing trajectories of inflammation over a 3-year period in healthy adults, those who reported higher rates of physical, sexual, or emotional abuse had higher levels of bioinflammatory blood markers versus those who reported lower rates of abuse. These individuals also had significantly higher rates of loneliness and depression.

“These adverse experiences that people can have in childhood and adolescence really can continue to influence our health at a biological level well into adulthood,” investigator Megan E. Renna, PhD, postdoctoral fellow at Ohio State University, Columbus, said in an interview.

“There may be a somewhat invisible biological effect of that abuse later on in life, in addition to all of the psychological distress that could go along with those experiences,” she added.

The findings were presented at the virtual Anxiety and Depression Association of America Conference 2021.
 

Need for intervention

The investigators assessed the trajectory of inflammatory markers in 85 adults over a period of 3 years. Ages ranged from 47 to 67 years (mean age, 57 years), 81% were women, all were relatively healthy, and there were low rates of medical comorbidities.

Participant data on physical, emotional, and sexual abuse prior to age 18 were ascertained using the Childhood Experiences Questionnaire. Blood samples were assayed for cytokines interleukin-6, IL-8, IL-1 beta and tumor necrosis factor–alpha at each visit.

After controlling for age, sex, body mass index, and medical comorbidities, results showed markers of inflammation increased at a greater rate over time in participants with higher rates of physical (P = .05) and sexual abuse (P = .02), compared with those with no history of childhood abuse.

“So, inflammation was increasing at a faster rate across those three visits for people with versus without an abuse history. And this was abuse experienced before age 18, but the mean age of our participants was about 57,” said Dr. Renna.

“It is likely that emotional abuse plays a role in inflammation but we did not have a big enough sample to show significance,” she added.

Participants who had reported childhood abuse also demonstrated significantly higher rates of loneliness and depression across all visits than those without a history of abuse.

“One of the things this work really highlights is the need for intervention for these children and adolescents who are experiencing abuse. This may have a helpful impact on their psychological health as they age, as well as their physical health,” Dr. Renna said.
 

‘Considerable interest’

In a comment, ADAA President Luana Marques, PhD, Harvard Medical School, Boston, said research is “consistently indicating that childhood adversity puts individuals at risk for a host of problems, including inflammatory concerns, which are precursors for other physical illnesses.”

Such results “demonstrate the importance of early identification and intervention of possible traumatic experiences for youth, and how early intervention at the parent level might also be helpful,” said Dr. Marques, who was not involved with the research.

Also commenting on the study, Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral science at the University of Texas at Austin, and president-elect of the ADAA, said in an interview that the findings are pertinent for the field.

“The investigators demonstrated that a history of childhood physical or sexual abuse was associated with a greater inflammatory response, and this is of considerable interest because this increased inflammatory response very likely contributes to the well-documented increased prevalence of serious medical disorders such as heart disease, diabetes, and cancer in victims of child abuse and neglect,” said Dr. Nemeroff, who was not associated with the research.  

Dr. Renna, Dr. Marques, and Dr. Nemeroff disclosed no relevant financial relationships.

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

People who suffer abuse as children continue to have higher levels of inflammatory biomarkers as adults, likely placing them at increased risk for chronic health problems, new research shows.

In a study assessing trajectories of inflammation over a 3-year period in healthy adults, those who reported higher rates of physical, sexual, or emotional abuse had higher levels of bioinflammatory blood markers versus those who reported lower rates of abuse. These individuals also had significantly higher rates of loneliness and depression.

“These adverse experiences that people can have in childhood and adolescence really can continue to influence our health at a biological level well into adulthood,” investigator Megan E. Renna, PhD, postdoctoral fellow at Ohio State University, Columbus, said in an interview.

“There may be a somewhat invisible biological effect of that abuse later on in life, in addition to all of the psychological distress that could go along with those experiences,” she added.

The findings were presented at the virtual Anxiety and Depression Association of America Conference 2021.
 

Need for intervention

The investigators assessed the trajectory of inflammatory markers in 85 adults over a period of 3 years. Ages ranged from 47 to 67 years (mean age, 57 years), 81% were women, all were relatively healthy, and there were low rates of medical comorbidities.

Participant data on physical, emotional, and sexual abuse prior to age 18 were ascertained using the Childhood Experiences Questionnaire. Blood samples were assayed for cytokines interleukin-6, IL-8, IL-1 beta and tumor necrosis factor–alpha at each visit.

After controlling for age, sex, body mass index, and medical comorbidities, results showed markers of inflammation increased at a greater rate over time in participants with higher rates of physical (P = .05) and sexual abuse (P = .02), compared with those with no history of childhood abuse.

“So, inflammation was increasing at a faster rate across those three visits for people with versus without an abuse history. And this was abuse experienced before age 18, but the mean age of our participants was about 57,” said Dr. Renna.

“It is likely that emotional abuse plays a role in inflammation but we did not have a big enough sample to show significance,” she added.

Participants who had reported childhood abuse also demonstrated significantly higher rates of loneliness and depression across all visits than those without a history of abuse.

“One of the things this work really highlights is the need for intervention for these children and adolescents who are experiencing abuse. This may have a helpful impact on their psychological health as they age, as well as their physical health,” Dr. Renna said.
 

‘Considerable interest’

In a comment, ADAA President Luana Marques, PhD, Harvard Medical School, Boston, said research is “consistently indicating that childhood adversity puts individuals at risk for a host of problems, including inflammatory concerns, which are precursors for other physical illnesses.”

Such results “demonstrate the importance of early identification and intervention of possible traumatic experiences for youth, and how early intervention at the parent level might also be helpful,” said Dr. Marques, who was not involved with the research.

Also commenting on the study, Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral science at the University of Texas at Austin, and president-elect of the ADAA, said in an interview that the findings are pertinent for the field.

“The investigators demonstrated that a history of childhood physical or sexual abuse was associated with a greater inflammatory response, and this is of considerable interest because this increased inflammatory response very likely contributes to the well-documented increased prevalence of serious medical disorders such as heart disease, diabetes, and cancer in victims of child abuse and neglect,” said Dr. Nemeroff, who was not associated with the research.  

Dr. Renna, Dr. Marques, and Dr. Nemeroff disclosed no relevant financial relationships.

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

People who suffer abuse as children continue to have higher levels of inflammatory biomarkers as adults, likely placing them at increased risk for chronic health problems, new research shows.

In a study assessing trajectories of inflammation over a 3-year period in healthy adults, those who reported higher rates of physical, sexual, or emotional abuse had higher levels of bioinflammatory blood markers versus those who reported lower rates of abuse. These individuals also had significantly higher rates of loneliness and depression.

“These adverse experiences that people can have in childhood and adolescence really can continue to influence our health at a biological level well into adulthood,” investigator Megan E. Renna, PhD, postdoctoral fellow at Ohio State University, Columbus, said in an interview.

“There may be a somewhat invisible biological effect of that abuse later on in life, in addition to all of the psychological distress that could go along with those experiences,” she added.

The findings were presented at the virtual Anxiety and Depression Association of America Conference 2021.
 

Need for intervention

The investigators assessed the trajectory of inflammatory markers in 85 adults over a period of 3 years. Ages ranged from 47 to 67 years (mean age, 57 years), 81% were women, all were relatively healthy, and there were low rates of medical comorbidities.

Participant data on physical, emotional, and sexual abuse prior to age 18 were ascertained using the Childhood Experiences Questionnaire. Blood samples were assayed for cytokines interleukin-6, IL-8, IL-1 beta and tumor necrosis factor–alpha at each visit.

After controlling for age, sex, body mass index, and medical comorbidities, results showed markers of inflammation increased at a greater rate over time in participants with higher rates of physical (P = .05) and sexual abuse (P = .02), compared with those with no history of childhood abuse.

“So, inflammation was increasing at a faster rate across those three visits for people with versus without an abuse history. And this was abuse experienced before age 18, but the mean age of our participants was about 57,” said Dr. Renna.

“It is likely that emotional abuse plays a role in inflammation but we did not have a big enough sample to show significance,” she added.

Participants who had reported childhood abuse also demonstrated significantly higher rates of loneliness and depression across all visits than those without a history of abuse.

“One of the things this work really highlights is the need for intervention for these children and adolescents who are experiencing abuse. This may have a helpful impact on their psychological health as they age, as well as their physical health,” Dr. Renna said.
 

‘Considerable interest’

In a comment, ADAA President Luana Marques, PhD, Harvard Medical School, Boston, said research is “consistently indicating that childhood adversity puts individuals at risk for a host of problems, including inflammatory concerns, which are precursors for other physical illnesses.”

Such results “demonstrate the importance of early identification and intervention of possible traumatic experiences for youth, and how early intervention at the parent level might also be helpful,” said Dr. Marques, who was not involved with the research.

Also commenting on the study, Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral science at the University of Texas at Austin, and president-elect of the ADAA, said in an interview that the findings are pertinent for the field.

“The investigators demonstrated that a history of childhood physical or sexual abuse was associated with a greater inflammatory response, and this is of considerable interest because this increased inflammatory response very likely contributes to the well-documented increased prevalence of serious medical disorders such as heart disease, diabetes, and cancer in victims of child abuse and neglect,” said Dr. Nemeroff, who was not associated with the research.  

Dr. Renna, Dr. Marques, and Dr. Nemeroff disclosed no relevant financial relationships.

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

Maintenance therapy with niraparib offers clinical benefit beyond first progression in patients who have platinum-sensitive, recurrent ovarian cancer with germline BRCA mutations, according to final data from the ENGOT-OV16/NOVA trial.

The final analysis showed a significant difference in second progression-free survival (PFS2) with niraparib versus placebo, but only in patients with germline BRCA mutations.

The overall survival analysis was limited because the study was not powered to detect differences in OS. Still, the investigators found a trend toward better OS with niraparib in patients who had germline BRCA mutations.

These results were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11139).

The final analysis of this study was muddied by missing data for many of the 553 patients originally randomized, according to Ursula Matulonis, MD, of the Dana-Farber Cancer Institute in Boston, who presented the study’s results at the meeting.

“Since 2014, approvals of PARP [poly (ADP-ribose) polymerase] inhibitors worldwide in different lines of ovarian cancer therapy have revolutionized the treatment of women with ovarian cancer,” Dr. Matulonis said. “During the time from the initial results of the NOVA study in 2016 to this final analysis, PARP inhibitors have become available commercially globally.”

The wider availability of PARP inhibitors led to premature unblinding and withdrawals from the trial, resulting in missing data for a large proportion of patients.
 

Initial results

In the primary analysis of the trial, the median PFS was 21 months among patients with germline BRCA mutations who received niraparib and 5.5 months for patients with germline BRCA mutations who received placebo (P < .001).

Among patients with no germline BRCA mutations, the median PFS was 9.3 months for those who received niraparib and 3.9 months for placebo-treated controls (P < .001).

At the time of the primary PFS analysis in 2016, 155 of the 553 patients originally enrolled had left the study for reasons other than death.

In both treatment cohorts, a large number of patients were unblinded as to their treatment assignments by investigators, which required them to withdraw consent from the study under the protocol, resulting in the aforementioned loss of some data on subsequent therapy and survival status.

Final results: PFS2 and OS

At the time of the final data lock on Oct. 1, 2020, the mean follow-up was 67 months (5.6 years).

In all, 64 patients originally assigned to niraparib were still on study (28 in the germline BRCA mutation cohort and 36 in the nonmutated cohort), as were 28 patients originally assigned to placebo (9 and 19, respectively).

For the final analysis, the investigators were able to retrieve survival data on 51% of the patients originally enrolled, either through protocol amendments and obtaining consent again or through national databases.

Although crossover to the niraparib arm was not allowed on study, patients could receive a PARP inhibitor following disease progression or study withdrawal. Because of discontinuations, data on postprogression therapy were missing for 138 of the 553 patients (25%).

The hazard ratio for PFS2 with niraparib versus placebo was 0.67 for patients with germline BRCA mutations (95% confidence interval, 0.479-0.948) and 0.81 for patients without the mutations (95% CI, 0.632-1.050).

In an analysis adjusted for subsequent PARP inhibitor therapy, there was no significant difference in median OS between the niraparib and placebo arms, regardless of mutation status. In the cohort without BRCA mutations, the median OS was 31.3 months with niraparib and 35.9 months with placebo (HR, 0.97; 95% CI, 0.74-1.26).

However, there was a trend toward improved OS with niraparib among patients with germline BRCA mutations. The median OS was 43.8 months with niraparib and 34.1 months with placebo (HR, 0.66; 95% CI, 0.44-0.99).
 

Safety: MDS/AML

Hematologic treatment-emergent adverse events occurred primarily in the first year of niraparib treatment. The incidence of grade 3 or greater thrombocytopenia decreased from 33.8% at 1 year to 2.8% in years 2-3. The incidence of anemia decreased from 25.6% to 0.7%, and the neutropenia incidence decreased from 19.3% to 2.1%.

At last follow-up, 13 patients in the niraparib arm (3.5%) and 3 in the placebo arm (1.7%) had developed myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).

The incidence of MDS/AML was 6.6% among patients with germline BRCA mutations who received niraparib, noted invited discussant Deborah K. Armstrong, MD, of the Johns Hopkins Kimmel Cancer Center in Baltimore.

That incidence was nearly as high as the 8% incidence of MDS/AML seen among similar patients in the SOLO-2 trial of olaparib maintenance, she noted.

This observation raises the question “of whether more extensive prior therapy or the longer duration of PARP inhibitor therapy in patients who have recurrent platinum-sensitive disease is the biggest contributor to that,” she said.

Dr. Armstrong commented that it remains to be seen whether the incidence of MDS/AML will increase with longer follow-up, particularly among patients who were more heavily pretreated with chemotherapy prior to PARP inhibitor maintenance, and in patients who remain on a PARP inhibitor until progression in ongoing trials of PARP inhibitors as frontline therapy.

The ENGOT-OV16/NOVA trial was funded by GlaxoSmithKline. Dr. Matulonis reported consulting/advisory fees from Merck, Novartis, and NextCure. Dr. Armstrong disclosed relationships with several companies, not including GlaxoSmithKline.

Maintenance therapy with niraparib offers clinical benefit beyond first progression in patients who have platinum-sensitive, recurrent ovarian cancer with germline BRCA mutations, according to final data from the ENGOT-OV16/NOVA trial.

The final analysis showed a significant difference in second progression-free survival (PFS2) with niraparib versus placebo, but only in patients with germline BRCA mutations.

The overall survival analysis was limited because the study was not powered to detect differences in OS. Still, the investigators found a trend toward better OS with niraparib in patients who had germline BRCA mutations.

These results were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11139).

The final analysis of this study was muddied by missing data for many of the 553 patients originally randomized, according to Ursula Matulonis, MD, of the Dana-Farber Cancer Institute in Boston, who presented the study’s results at the meeting.

“Since 2014, approvals of PARP [poly (ADP-ribose) polymerase] inhibitors worldwide in different lines of ovarian cancer therapy have revolutionized the treatment of women with ovarian cancer,” Dr. Matulonis said. “During the time from the initial results of the NOVA study in 2016 to this final analysis, PARP inhibitors have become available commercially globally.”

The wider availability of PARP inhibitors led to premature unblinding and withdrawals from the trial, resulting in missing data for a large proportion of patients.
 

Initial results

In the primary analysis of the trial, the median PFS was 21 months among patients with germline BRCA mutations who received niraparib and 5.5 months for patients with germline BRCA mutations who received placebo (P < .001).

Among patients with no germline BRCA mutations, the median PFS was 9.3 months for those who received niraparib and 3.9 months for placebo-treated controls (P < .001).

At the time of the primary PFS analysis in 2016, 155 of the 553 patients originally enrolled had left the study for reasons other than death.

In both treatment cohorts, a large number of patients were unblinded as to their treatment assignments by investigators, which required them to withdraw consent from the study under the protocol, resulting in the aforementioned loss of some data on subsequent therapy and survival status.

Final results: PFS2 and OS

At the time of the final data lock on Oct. 1, 2020, the mean follow-up was 67 months (5.6 years).

In all, 64 patients originally assigned to niraparib were still on study (28 in the germline BRCA mutation cohort and 36 in the nonmutated cohort), as were 28 patients originally assigned to placebo (9 and 19, respectively).

For the final analysis, the investigators were able to retrieve survival data on 51% of the patients originally enrolled, either through protocol amendments and obtaining consent again or through national databases.

Although crossover to the niraparib arm was not allowed on study, patients could receive a PARP inhibitor following disease progression or study withdrawal. Because of discontinuations, data on postprogression therapy were missing for 138 of the 553 patients (25%).

The hazard ratio for PFS2 with niraparib versus placebo was 0.67 for patients with germline BRCA mutations (95% confidence interval, 0.479-0.948) and 0.81 for patients without the mutations (95% CI, 0.632-1.050).

In an analysis adjusted for subsequent PARP inhibitor therapy, there was no significant difference in median OS between the niraparib and placebo arms, regardless of mutation status. In the cohort without BRCA mutations, the median OS was 31.3 months with niraparib and 35.9 months with placebo (HR, 0.97; 95% CI, 0.74-1.26).

However, there was a trend toward improved OS with niraparib among patients with germline BRCA mutations. The median OS was 43.8 months with niraparib and 34.1 months with placebo (HR, 0.66; 95% CI, 0.44-0.99).
 

Safety: MDS/AML

Hematologic treatment-emergent adverse events occurred primarily in the first year of niraparib treatment. The incidence of grade 3 or greater thrombocytopenia decreased from 33.8% at 1 year to 2.8% in years 2-3. The incidence of anemia decreased from 25.6% to 0.7%, and the neutropenia incidence decreased from 19.3% to 2.1%.

At last follow-up, 13 patients in the niraparib arm (3.5%) and 3 in the placebo arm (1.7%) had developed myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).

The incidence of MDS/AML was 6.6% among patients with germline BRCA mutations who received niraparib, noted invited discussant Deborah K. Armstrong, MD, of the Johns Hopkins Kimmel Cancer Center in Baltimore.

That incidence was nearly as high as the 8% incidence of MDS/AML seen among similar patients in the SOLO-2 trial of olaparib maintenance, she noted.

This observation raises the question “of whether more extensive prior therapy or the longer duration of PARP inhibitor therapy in patients who have recurrent platinum-sensitive disease is the biggest contributor to that,” she said.

Dr. Armstrong commented that it remains to be seen whether the incidence of MDS/AML will increase with longer follow-up, particularly among patients who were more heavily pretreated with chemotherapy prior to PARP inhibitor maintenance, and in patients who remain on a PARP inhibitor until progression in ongoing trials of PARP inhibitors as frontline therapy.

The ENGOT-OV16/NOVA trial was funded by GlaxoSmithKline. Dr. Matulonis reported consulting/advisory fees from Merck, Novartis, and NextCure. Dr. Armstrong disclosed relationships with several companies, not including GlaxoSmithKline.

Maintenance therapy with niraparib offers clinical benefit beyond first progression in patients who have platinum-sensitive, recurrent ovarian cancer with germline BRCA mutations, according to final data from the ENGOT-OV16/NOVA trial.

The final analysis showed a significant difference in second progression-free survival (PFS2) with niraparib versus placebo, but only in patients with germline BRCA mutations.

The overall survival analysis was limited because the study was not powered to detect differences in OS. Still, the investigators found a trend toward better OS with niraparib in patients who had germline BRCA mutations.

These results were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11139).

The final analysis of this study was muddied by missing data for many of the 553 patients originally randomized, according to Ursula Matulonis, MD, of the Dana-Farber Cancer Institute in Boston, who presented the study’s results at the meeting.

“Since 2014, approvals of PARP [poly (ADP-ribose) polymerase] inhibitors worldwide in different lines of ovarian cancer therapy have revolutionized the treatment of women with ovarian cancer,” Dr. Matulonis said. “During the time from the initial results of the NOVA study in 2016 to this final analysis, PARP inhibitors have become available commercially globally.”

The wider availability of PARP inhibitors led to premature unblinding and withdrawals from the trial, resulting in missing data for a large proportion of patients.
 

Initial results

In the primary analysis of the trial, the median PFS was 21 months among patients with germline BRCA mutations who received niraparib and 5.5 months for patients with germline BRCA mutations who received placebo (P < .001).

Among patients with no germline BRCA mutations, the median PFS was 9.3 months for those who received niraparib and 3.9 months for placebo-treated controls (P < .001).

At the time of the primary PFS analysis in 2016, 155 of the 553 patients originally enrolled had left the study for reasons other than death.

In both treatment cohorts, a large number of patients were unblinded as to their treatment assignments by investigators, which required them to withdraw consent from the study under the protocol, resulting in the aforementioned loss of some data on subsequent therapy and survival status.

Final results: PFS2 and OS

At the time of the final data lock on Oct. 1, 2020, the mean follow-up was 67 months (5.6 years).

In all, 64 patients originally assigned to niraparib were still on study (28 in the germline BRCA mutation cohort and 36 in the nonmutated cohort), as were 28 patients originally assigned to placebo (9 and 19, respectively).

For the final analysis, the investigators were able to retrieve survival data on 51% of the patients originally enrolled, either through protocol amendments and obtaining consent again or through national databases.

Although crossover to the niraparib arm was not allowed on study, patients could receive a PARP inhibitor following disease progression or study withdrawal. Because of discontinuations, data on postprogression therapy were missing for 138 of the 553 patients (25%).

The hazard ratio for PFS2 with niraparib versus placebo was 0.67 for patients with germline BRCA mutations (95% confidence interval, 0.479-0.948) and 0.81 for patients without the mutations (95% CI, 0.632-1.050).

In an analysis adjusted for subsequent PARP inhibitor therapy, there was no significant difference in median OS between the niraparib and placebo arms, regardless of mutation status. In the cohort without BRCA mutations, the median OS was 31.3 months with niraparib and 35.9 months with placebo (HR, 0.97; 95% CI, 0.74-1.26).

However, there was a trend toward improved OS with niraparib among patients with germline BRCA mutations. The median OS was 43.8 months with niraparib and 34.1 months with placebo (HR, 0.66; 95% CI, 0.44-0.99).
 

Safety: MDS/AML

Hematologic treatment-emergent adverse events occurred primarily in the first year of niraparib treatment. The incidence of grade 3 or greater thrombocytopenia decreased from 33.8% at 1 year to 2.8% in years 2-3. The incidence of anemia decreased from 25.6% to 0.7%, and the neutropenia incidence decreased from 19.3% to 2.1%.

At last follow-up, 13 patients in the niraparib arm (3.5%) and 3 in the placebo arm (1.7%) had developed myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).

The incidence of MDS/AML was 6.6% among patients with germline BRCA mutations who received niraparib, noted invited discussant Deborah K. Armstrong, MD, of the Johns Hopkins Kimmel Cancer Center in Baltimore.

That incidence was nearly as high as the 8% incidence of MDS/AML seen among similar patients in the SOLO-2 trial of olaparib maintenance, she noted.

This observation raises the question “of whether more extensive prior therapy or the longer duration of PARP inhibitor therapy in patients who have recurrent platinum-sensitive disease is the biggest contributor to that,” she said.

Dr. Armstrong commented that it remains to be seen whether the incidence of MDS/AML will increase with longer follow-up, particularly among patients who were more heavily pretreated with chemotherapy prior to PARP inhibitor maintenance, and in patients who remain on a PARP inhibitor until progression in ongoing trials of PARP inhibitors as frontline therapy.

The ENGOT-OV16/NOVA trial was funded by GlaxoSmithKline. Dr. Matulonis reported consulting/advisory fees from Merck, Novartis, and NextCure. Dr. Armstrong disclosed relationships with several companies, not including GlaxoSmithKline.

The American Academy of Pediatrics (AAP) released a statement condemning state legislation introduced across the country that would prohibit the medical treatment of children who identify as transgender.

“Politics has no place here. Transgender children, like all children, just want to belong. We will fight state by state, in the courts, and on the national stage to make sure they know they do,” said the American Academy of Pediatrics, an organization that recommends that youth who identify as transgender have access to comprehensive, gender-affirming and “developmentally appropriate” health care.

There has been a lot of controversy among physicians surrounding gender-affirming care for children. In 2019, three separate groups of physicians questioned the hormonal treatment of children and adolescents with gender dysphoria, saying more research is needed to support gender-affirming care recommendations from groups such as the AAP. In addition, California-based endocrinologist Michael K. Laidlaw, MD, called the use of puberty blockers – medication used to delay or prevent the onset of puberty – an “experiment” and “public health problem.”

Some of the bills circulating would prohibit gender-affirming care for children and penalize pediatricians and other physicians for providing such care. Other bills would prevent transgender youth from participating in sports or on athletic teams according to their gender identity, requiring them to join teams aligned with the sex they were assigned at birth.

Jason Rafferty, MD, a pediatrician who authored AAP’s 2018 policy statement encouraging pediatricians to provide gender-affirmative care to children and adolescents, said in an interview that these proposed state bills are targeting a vulnerable population at a vulnerable time.

“You have this marginalized group and right in the midst of a pandemic – and [social isolation] – and you have these policies coming out that are really targeting the most vulnerable,” said Dr. Rafferty, who practices at the Adolescent Healthcare Center at Hasbro Children’s Hospital, Providence, R.I. “Some of the proposed policies would ensure that some of these transgender kids wouldn’t have access to basic medical care [or access to areas] where pediatricians are affirming these kids and creating a safe environment for them.”

M. Brett Cooper, MD, of pediatrics at UT Southwestern Medical Center, Dallas, said in an interview that the proposed state legislations are based on personal beliefs, not evidence-based care.

He said the AAP is speaking out because many of these proposed state legislatures are advancing bills that would affect gender-diverse children.

“Many of these bills are making it close to passing both chambers of a state legislature and thus sent to the governor for approval,” Dr. Cooper said. “In past legislative sessions, bills such as these have never it made out of committee in either a state House or state Senate.”

Early in March, South Dakota Governor Kristi Noem tweeted that she was “excited to sign” a bill that would prevent children who are transgender from participating in sports or on athletic teams according to their gender identity, requiring them to join teams aligned with the sex they were assigned at birth.

Meanwhile, previous studies have shown that teens whose gender identity does not align with their sex assigned at birth were more likely to report a suicide attempt, compared with cisgender youth. A 2015 study has attributed this increased risk of suicide to marginalization, social exclusion, and trauma. The bills being proposed may exacerbate this, according to Dr. Rafferty.

These bills point in the direction of approaches and models that research shows may be harmful to transgender children, he said.

“Beyond that, policies that are out there affecting participation in sports and other activities really just draw attention to these youth in unnecessary ways and really puts their physical and mental health at risk in a school environment,” he added.

“Whether it’s health care, school, community, or home [these policies] just really create a very hostile and dangerous environment toward a population that already is at significant risk,” Dr. Rafferty said.

The AAP’s clinical care guidelines for children who identify as transgender state that pediatricians who provide gender-affirmative care and speak with children and their families about gender issues help foster an environment of nurturance and support.

“Many people think that the care provided to gender diverse young people is rogue,” Dr. Cooper said. “Pediatric gender clinics are often either multidisciplinary or have a readily accessible team, including social work, mental health, and the physician. Medical care for gender diverse youth follows well-established standards of care.”

Dr. Rafferty said it is important for care providers to support children and teenagers who identify as transgender by creating a safe space and helping them identify what they need.

“There’s a lot out there that really tries to unite gender and biological sex together, saying that gender can be reduced to your anatomy,” Dr. Rafferty said. “But I think what we’re coming to appreciate is that our sense of identity is much more complex than simply our genes or biology.”

Dr. Rafferty is a member of the American Academy of Pediatrics, the Society of Adolescent Health and Medicine, and the American Academy of Child and Adolescent Psychiatry. Dr. Cooper is a columnist for Pediatric News and is on the board of trustees for the Texas Medical Association.

The American Academy of Pediatrics (AAP) released a statement condemning state legislation introduced across the country that would prohibit the medical treatment of children who identify as transgender.

“Politics has no place here. Transgender children, like all children, just want to belong. We will fight state by state, in the courts, and on the national stage to make sure they know they do,” said the American Academy of Pediatrics, an organization that recommends that youth who identify as transgender have access to comprehensive, gender-affirming and “developmentally appropriate” health care.

There has been a lot of controversy among physicians surrounding gender-affirming care for children. In 2019, three separate groups of physicians questioned the hormonal treatment of children and adolescents with gender dysphoria, saying more research is needed to support gender-affirming care recommendations from groups such as the AAP. In addition, California-based endocrinologist Michael K. Laidlaw, MD, called the use of puberty blockers – medication used to delay or prevent the onset of puberty – an “experiment” and “public health problem.”

Some of the bills circulating would prohibit gender-affirming care for children and penalize pediatricians and other physicians for providing such care. Other bills would prevent transgender youth from participating in sports or on athletic teams according to their gender identity, requiring them to join teams aligned with the sex they were assigned at birth.

Jason Rafferty, MD, a pediatrician who authored AAP’s 2018 policy statement encouraging pediatricians to provide gender-affirmative care to children and adolescents, said in an interview that these proposed state bills are targeting a vulnerable population at a vulnerable time.

“You have this marginalized group and right in the midst of a pandemic – and [social isolation] – and you have these policies coming out that are really targeting the most vulnerable,” said Dr. Rafferty, who practices at the Adolescent Healthcare Center at Hasbro Children’s Hospital, Providence, R.I. “Some of the proposed policies would ensure that some of these transgender kids wouldn’t have access to basic medical care [or access to areas] where pediatricians are affirming these kids and creating a safe environment for them.”

M. Brett Cooper, MD, of pediatrics at UT Southwestern Medical Center, Dallas, said in an interview that the proposed state legislations are based on personal beliefs, not evidence-based care.

He said the AAP is speaking out because many of these proposed state legislatures are advancing bills that would affect gender-diverse children.

“Many of these bills are making it close to passing both chambers of a state legislature and thus sent to the governor for approval,” Dr. Cooper said. “In past legislative sessions, bills such as these have never it made out of committee in either a state House or state Senate.”

Early in March, South Dakota Governor Kristi Noem tweeted that she was “excited to sign” a bill that would prevent children who are transgender from participating in sports or on athletic teams according to their gender identity, requiring them to join teams aligned with the sex they were assigned at birth.

Meanwhile, previous studies have shown that teens whose gender identity does not align with their sex assigned at birth were more likely to report a suicide attempt, compared with cisgender youth. A 2015 study has attributed this increased risk of suicide to marginalization, social exclusion, and trauma. The bills being proposed may exacerbate this, according to Dr. Rafferty.

These bills point in the direction of approaches and models that research shows may be harmful to transgender children, he said.

“Beyond that, policies that are out there affecting participation in sports and other activities really just draw attention to these youth in unnecessary ways and really puts their physical and mental health at risk in a school environment,” he added.

“Whether it’s health care, school, community, or home [these policies] just really create a very hostile and dangerous environment toward a population that already is at significant risk,” Dr. Rafferty said.

The AAP’s clinical care guidelines for children who identify as transgender state that pediatricians who provide gender-affirmative care and speak with children and their families about gender issues help foster an environment of nurturance and support.

“Many people think that the care provided to gender diverse young people is rogue,” Dr. Cooper said. “Pediatric gender clinics are often either multidisciplinary or have a readily accessible team, including social work, mental health, and the physician. Medical care for gender diverse youth follows well-established standards of care.”

Dr. Rafferty said it is important for care providers to support children and teenagers who identify as transgender by creating a safe space and helping them identify what they need.

“There’s a lot out there that really tries to unite gender and biological sex together, saying that gender can be reduced to your anatomy,” Dr. Rafferty said. “But I think what we’re coming to appreciate is that our sense of identity is much more complex than simply our genes or biology.”

Dr. Rafferty is a member of the American Academy of Pediatrics, the Society of Adolescent Health and Medicine, and the American Academy of Child and Adolescent Psychiatry. Dr. Cooper is a columnist for Pediatric News and is on the board of trustees for the Texas Medical Association.

The American Academy of Pediatrics (AAP) released a statement condemning state legislation introduced across the country that would prohibit the medical treatment of children who identify as transgender.

“Politics has no place here. Transgender children, like all children, just want to belong. We will fight state by state, in the courts, and on the national stage to make sure they know they do,” said the American Academy of Pediatrics, an organization that recommends that youth who identify as transgender have access to comprehensive, gender-affirming and “developmentally appropriate” health care.

There has been a lot of controversy among physicians surrounding gender-affirming care for children. In 2019, three separate groups of physicians questioned the hormonal treatment of children and adolescents with gender dysphoria, saying more research is needed to support gender-affirming care recommendations from groups such as the AAP. In addition, California-based endocrinologist Michael K. Laidlaw, MD, called the use of puberty blockers – medication used to delay or prevent the onset of puberty – an “experiment” and “public health problem.”

Some of the bills circulating would prohibit gender-affirming care for children and penalize pediatricians and other physicians for providing such care. Other bills would prevent transgender youth from participating in sports or on athletic teams according to their gender identity, requiring them to join teams aligned with the sex they were assigned at birth.

Jason Rafferty, MD, a pediatrician who authored AAP’s 2018 policy statement encouraging pediatricians to provide gender-affirmative care to children and adolescents, said in an interview that these proposed state bills are targeting a vulnerable population at a vulnerable time.

“You have this marginalized group and right in the midst of a pandemic – and [social isolation] – and you have these policies coming out that are really targeting the most vulnerable,” said Dr. Rafferty, who practices at the Adolescent Healthcare Center at Hasbro Children’s Hospital, Providence, R.I. “Some of the proposed policies would ensure that some of these transgender kids wouldn’t have access to basic medical care [or access to areas] where pediatricians are affirming these kids and creating a safe environment for them.”

M. Brett Cooper, MD, of pediatrics at UT Southwestern Medical Center, Dallas, said in an interview that the proposed state legislations are based on personal beliefs, not evidence-based care.

He said the AAP is speaking out because many of these proposed state legislatures are advancing bills that would affect gender-diverse children.

“Many of these bills are making it close to passing both chambers of a state legislature and thus sent to the governor for approval,” Dr. Cooper said. “In past legislative sessions, bills such as these have never it made out of committee in either a state House or state Senate.”

Early in March, South Dakota Governor Kristi Noem tweeted that she was “excited to sign” a bill that would prevent children who are transgender from participating in sports or on athletic teams according to their gender identity, requiring them to join teams aligned with the sex they were assigned at birth.

Meanwhile, previous studies have shown that teens whose gender identity does not align with their sex assigned at birth were more likely to report a suicide attempt, compared with cisgender youth. A 2015 study has attributed this increased risk of suicide to marginalization, social exclusion, and trauma. The bills being proposed may exacerbate this, according to Dr. Rafferty.

These bills point in the direction of approaches and models that research shows may be harmful to transgender children, he said.

“Beyond that, policies that are out there affecting participation in sports and other activities really just draw attention to these youth in unnecessary ways and really puts their physical and mental health at risk in a school environment,” he added.

“Whether it’s health care, school, community, or home [these policies] just really create a very hostile and dangerous environment toward a population that already is at significant risk,” Dr. Rafferty said.

The AAP’s clinical care guidelines for children who identify as transgender state that pediatricians who provide gender-affirmative care and speak with children and their families about gender issues help foster an environment of nurturance and support.

“Many people think that the care provided to gender diverse young people is rogue,” Dr. Cooper said. “Pediatric gender clinics are often either multidisciplinary or have a readily accessible team, including social work, mental health, and the physician. Medical care for gender diverse youth follows well-established standards of care.”

Dr. Rafferty said it is important for care providers to support children and teenagers who identify as transgender by creating a safe space and helping them identify what they need.

“There’s a lot out there that really tries to unite gender and biological sex together, saying that gender can be reduced to your anatomy,” Dr. Rafferty said. “But I think what we’re coming to appreciate is that our sense of identity is much more complex than simply our genes or biology.”

Dr. Rafferty is a member of the American Academy of Pediatrics, the Society of Adolescent Health and Medicine, and the American Academy of Child and Adolescent Psychiatry. Dr. Cooper is a columnist for Pediatric News and is on the board of trustees for the Texas Medical Association.

Michigan cardiologist Dinesh M. Shah, MD, has paid the United States $2 million to resolve claims he violated the False Claims Act by knowingly billing federal health care programs for diagnostic tests that were unnecessary or not performed, the Department of Justice announced.

The settlement resolves allegations that, from 2006 to 2017, Dr. Shah and his practice, Michigan Physicians Group (MPG), of which he is sole owner, billed Medicare, Medicaid, and TRICARE for unnecessary diagnostic tests, including ankle brachial index and toe brachial index tests that were routinely performed on patients without first being ordered by a physician and without regard to medical necessity.

The prosecutors also alleged that Dr. Shah was routinely ordering, and MPG was providing, unnecessary nuclear stress tests to some patients.

“Subjecting patients to unnecessary testing in order to fill one’s pockets with taxpayer funds will not be tolerated. Such practices are particularly concerning because overuse of some tests can be harmful to patients,” acting U.S. Attorney Saima Mohsin said in the news release. “With these lawsuits and the accompanying resolution, Dr. Shah and Michigan Physicians Group are being held to account for these exploitative and improper past practices.”

In addition to the settlement, Dr. Shah and MPG entered into an Integrity Agreement with the Office of Inspector General for the Department of Health & Human Services, which will provide oversight of Dr. Shah and MPG’s billing practices for a 3-year period.

There was “no determination of liability” with the settlement, according to the Department of Justice. Dr. Shah’s case was sparked by two whistleblower lawsuits filed by Arlene Klinke and Khrystyna Malva, both former MPG employees.

The settlement comes after a years-long investigation by the HHS acting on behalf of TRICARE, a health care program for active and retired military members. Allegations that William Beaumont Hospital in Royal Oak, Mich., paid eight physicians excessive compensation to increase patient referrals led to an $84.5 million settlement in 2018.

Dr. Shah was one of three private practice cardiologists who denied involvement in the scheme but were named in the settlement, according to Crain’s Detroit Business.

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

Michigan cardiologist Dinesh M. Shah, MD, has paid the United States $2 million to resolve claims he violated the False Claims Act by knowingly billing federal health care programs for diagnostic tests that were unnecessary or not performed, the Department of Justice announced.

The settlement resolves allegations that, from 2006 to 2017, Dr. Shah and his practice, Michigan Physicians Group (MPG), of which he is sole owner, billed Medicare, Medicaid, and TRICARE for unnecessary diagnostic tests, including ankle brachial index and toe brachial index tests that were routinely performed on patients without first being ordered by a physician and without regard to medical necessity.

The prosecutors also alleged that Dr. Shah was routinely ordering, and MPG was providing, unnecessary nuclear stress tests to some patients.

“Subjecting patients to unnecessary testing in order to fill one’s pockets with taxpayer funds will not be tolerated. Such practices are particularly concerning because overuse of some tests can be harmful to patients,” acting U.S. Attorney Saima Mohsin said in the news release. “With these lawsuits and the accompanying resolution, Dr. Shah and Michigan Physicians Group are being held to account for these exploitative and improper past practices.”

In addition to the settlement, Dr. Shah and MPG entered into an Integrity Agreement with the Office of Inspector General for the Department of Health & Human Services, which will provide oversight of Dr. Shah and MPG’s billing practices for a 3-year period.

There was “no determination of liability” with the settlement, according to the Department of Justice. Dr. Shah’s case was sparked by two whistleblower lawsuits filed by Arlene Klinke and Khrystyna Malva, both former MPG employees.

The settlement comes after a years-long investigation by the HHS acting on behalf of TRICARE, a health care program for active and retired military members. Allegations that William Beaumont Hospital in Royal Oak, Mich., paid eight physicians excessive compensation to increase patient referrals led to an $84.5 million settlement in 2018.

Dr. Shah was one of three private practice cardiologists who denied involvement in the scheme but were named in the settlement, according to Crain’s Detroit Business.

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

Michigan cardiologist Dinesh M. Shah, MD, has paid the United States $2 million to resolve claims he violated the False Claims Act by knowingly billing federal health care programs for diagnostic tests that were unnecessary or not performed, the Department of Justice announced.

The settlement resolves allegations that, from 2006 to 2017, Dr. Shah and his practice, Michigan Physicians Group (MPG), of which he is sole owner, billed Medicare, Medicaid, and TRICARE for unnecessary diagnostic tests, including ankle brachial index and toe brachial index tests that were routinely performed on patients without first being ordered by a physician and without regard to medical necessity.

The prosecutors also alleged that Dr. Shah was routinely ordering, and MPG was providing, unnecessary nuclear stress tests to some patients.

“Subjecting patients to unnecessary testing in order to fill one’s pockets with taxpayer funds will not be tolerated. Such practices are particularly concerning because overuse of some tests can be harmful to patients,” acting U.S. Attorney Saima Mohsin said in the news release. “With these lawsuits and the accompanying resolution, Dr. Shah and Michigan Physicians Group are being held to account for these exploitative and improper past practices.”

In addition to the settlement, Dr. Shah and MPG entered into an Integrity Agreement with the Office of Inspector General for the Department of Health & Human Services, which will provide oversight of Dr. Shah and MPG’s billing practices for a 3-year period.

There was “no determination of liability” with the settlement, according to the Department of Justice. Dr. Shah’s case was sparked by two whistleblower lawsuits filed by Arlene Klinke and Khrystyna Malva, both former MPG employees.

The settlement comes after a years-long investigation by the HHS acting on behalf of TRICARE, a health care program for active and retired military members. Allegations that William Beaumont Hospital in Royal Oak, Mich., paid eight physicians excessive compensation to increase patient referrals led to an $84.5 million settlement in 2018.

Dr. Shah was one of three private practice cardiologists who denied involvement in the scheme but were named in the settlement, according to Crain’s Detroit Business.

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

Stereotactic body radiotherapy (SBRT) produced high disease control rates but serious toxicity in a retrospective study of patients with ultra-central lung tumors.

Of the 72 patients studied, 15 (21%) experienced grade 3 or higher toxicity and 10 (14%) died of bronchopulmonary hemorrhage.

This doesn’t completely write off the use of SBRT for ultra-central lung tumors, according to Joyce Lodeweges, MD, of University Medical Center (UMC) Utrecht in the Netherlands.

“We have to inform the patient very well that there are some high risks to this treatment,” she said at the European Lung Cancer Virtual Congress 2021 (Abstract 61M0).

Dr. Lodeweges noted that keeping the biologically effective dose of radiation to the main bronchus below a certain threshold (< 90 Gy) could reduce the risk of toxicity significantly, making SBRT a viable option for some patients. In addition, MRI-guided daily adaptation of the radiation treatment to organs at risk may make the treatment safer.
 

Varying definitions, regimens spur debate

SBRT is standard care in peripherally located, stage I non–small cell lung cancer that is inoperable or if the patient refuses surgery, noted study discussant Yolande Lievens, MD, PhD, of Ghent University Hospital in Belgium.

“[SBRT] has good local control rates with low toxicity even in patients with COPD or being elderly,” Dr. Lievens said.

“In more moderately central tumors, there is quite some evidence that risk-adapted fractionation schemes can be delivered in a safe way and lead to high local control rates,” she added. “For ultra-central legions, there’s still not a recommendation to treat with SBRT because we see a lot of increased toxicity.”

“For ultra-central tumors, SBRT is still under debate,” agreed Dr. Lodeweges. “This is because of the varying definitions in the literature and the varying fractionation schemes used.”

How the location of tumors is defined is important. Central tumors are those that are at least 2 cm away from the main bronchial tree, whereas ultra-central tumors are those that butt onto it or overlap it.

In Dr. Lodeweges’s study, ultra-central tumors were defined as those with a planning target volume (PTV) abutting or overlapping the main bronchi, trachea, and/or esophagus.
 

Study details

Between 2012 and 2020, there were 72 patients with ultra-central lung tumors treated at UMC Utrecht. Most patients (78%) had a PTV covering the main bronchus, with 21% each having PTVs overlapping the trachea or esophagus.

Patients received a protracted SBRT regimen of 60 Gy given in 12 fractions. The median follow-up was 19 months.

The local failure-free survival rate was 98% at 1 year and 85% at 2 years. Overall survival rates were 77% and 52%, respectively.

Receiving a biologically effective dose of more than 90 Gy to the main bronchus increased the risk of grade 3 or higher toxicity. On the other hand, patient age and tumor histology did not affect the risk of adverse events.

The use of antithrombotic therapy didn’t have any bearing on toxicity either, but it’s a possible risk factor to consider, Dr. Lodeweges said. Peri- or endobronchial tumor location is another consideration.
 

Findings in context

How do the results of the current study sit with other studies of SBRT in non–small cell lung cancer? Dr. Lievens pointed out that overall survival at 2 years was lower in the current trial (52%) than in patients with central tumors treated in the RTOG 0813 trial (68%-73%) or those with peripheral tumors in the CHISEL trial (77%).

There were, of course, different fractions and doses of radiotherapy used in these trials, with lower doses and more fractions in the UMC Utrecht study, and there was higher toxicity when ultra-central lesions were treated.

“Optimized radiotherapy dose fractionation regimens are investigated quite intensively to improve the clinical benefit. This is an important area of research,” Dr. Lievens said.

The high local control rates but serious risk of bronchopulmonary hemorrhage seen in the current study “calls for further investigation of dose/volume parameters in the context of the location of the tumor but also in the context of other treatment modalities,” she added. “Advanced technologies in radiotherapy, which allow better imaging and daily adaptation, such as the MR-Linac, can optimize clinical benefits.”

The study was supported by UMC Utrecht and received no commercial funding. Dr. Lodeweges and Dr. Lievens had no relevant conflicts of interest.

Stereotactic body radiotherapy (SBRT) produced high disease control rates but serious toxicity in a retrospective study of patients with ultra-central lung tumors.

Of the 72 patients studied, 15 (21%) experienced grade 3 or higher toxicity and 10 (14%) died of bronchopulmonary hemorrhage.

This doesn’t completely write off the use of SBRT for ultra-central lung tumors, according to Joyce Lodeweges, MD, of University Medical Center (UMC) Utrecht in the Netherlands.

“We have to inform the patient very well that there are some high risks to this treatment,” she said at the European Lung Cancer Virtual Congress 2021 (Abstract 61M0).

Dr. Lodeweges noted that keeping the biologically effective dose of radiation to the main bronchus below a certain threshold (< 90 Gy) could reduce the risk of toxicity significantly, making SBRT a viable option for some patients. In addition, MRI-guided daily adaptation of the radiation treatment to organs at risk may make the treatment safer.
 

Varying definitions, regimens spur debate

SBRT is standard care in peripherally located, stage I non–small cell lung cancer that is inoperable or if the patient refuses surgery, noted study discussant Yolande Lievens, MD, PhD, of Ghent University Hospital in Belgium.

“[SBRT] has good local control rates with low toxicity even in patients with COPD or being elderly,” Dr. Lievens said.

“In more moderately central tumors, there is quite some evidence that risk-adapted fractionation schemes can be delivered in a safe way and lead to high local control rates,” she added. “For ultra-central legions, there’s still not a recommendation to treat with SBRT because we see a lot of increased toxicity.”

“For ultra-central tumors, SBRT is still under debate,” agreed Dr. Lodeweges. “This is because of the varying definitions in the literature and the varying fractionation schemes used.”

How the location of tumors is defined is important. Central tumors are those that are at least 2 cm away from the main bronchial tree, whereas ultra-central tumors are those that butt onto it or overlap it.

In Dr. Lodeweges’s study, ultra-central tumors were defined as those with a planning target volume (PTV) abutting or overlapping the main bronchi, trachea, and/or esophagus.
 

Study details

Between 2012 and 2020, there were 72 patients with ultra-central lung tumors treated at UMC Utrecht. Most patients (78%) had a PTV covering the main bronchus, with 21% each having PTVs overlapping the trachea or esophagus.

Patients received a protracted SBRT regimen of 60 Gy given in 12 fractions. The median follow-up was 19 months.

The local failure-free survival rate was 98% at 1 year and 85% at 2 years. Overall survival rates were 77% and 52%, respectively.

Receiving a biologically effective dose of more than 90 Gy to the main bronchus increased the risk of grade 3 or higher toxicity. On the other hand, patient age and tumor histology did not affect the risk of adverse events.

The use of antithrombotic therapy didn’t have any bearing on toxicity either, but it’s a possible risk factor to consider, Dr. Lodeweges said. Peri- or endobronchial tumor location is another consideration.
 

Findings in context

How do the results of the current study sit with other studies of SBRT in non–small cell lung cancer? Dr. Lievens pointed out that overall survival at 2 years was lower in the current trial (52%) than in patients with central tumors treated in the RTOG 0813 trial (68%-73%) or those with peripheral tumors in the CHISEL trial (77%).

There were, of course, different fractions and doses of radiotherapy used in these trials, with lower doses and more fractions in the UMC Utrecht study, and there was higher toxicity when ultra-central lesions were treated.

“Optimized radiotherapy dose fractionation regimens are investigated quite intensively to improve the clinical benefit. This is an important area of research,” Dr. Lievens said.

The high local control rates but serious risk of bronchopulmonary hemorrhage seen in the current study “calls for further investigation of dose/volume parameters in the context of the location of the tumor but also in the context of other treatment modalities,” she added. “Advanced technologies in radiotherapy, which allow better imaging and daily adaptation, such as the MR-Linac, can optimize clinical benefits.”

The study was supported by UMC Utrecht and received no commercial funding. Dr. Lodeweges and Dr. Lievens had no relevant conflicts of interest.

Stereotactic body radiotherapy (SBRT) produced high disease control rates but serious toxicity in a retrospective study of patients with ultra-central lung tumors.

Of the 72 patients studied, 15 (21%) experienced grade 3 or higher toxicity and 10 (14%) died of bronchopulmonary hemorrhage.

This doesn’t completely write off the use of SBRT for ultra-central lung tumors, according to Joyce Lodeweges, MD, of University Medical Center (UMC) Utrecht in the Netherlands.

“We have to inform the patient very well that there are some high risks to this treatment,” she said at the European Lung Cancer Virtual Congress 2021 (Abstract 61M0).

Dr. Lodeweges noted that keeping the biologically effective dose of radiation to the main bronchus below a certain threshold (< 90 Gy) could reduce the risk of toxicity significantly, making SBRT a viable option for some patients. In addition, MRI-guided daily adaptation of the radiation treatment to organs at risk may make the treatment safer.
 

Varying definitions, regimens spur debate

SBRT is standard care in peripherally located, stage I non–small cell lung cancer that is inoperable or if the patient refuses surgery, noted study discussant Yolande Lievens, MD, PhD, of Ghent University Hospital in Belgium.

“[SBRT] has good local control rates with low toxicity even in patients with COPD or being elderly,” Dr. Lievens said.

“In more moderately central tumors, there is quite some evidence that risk-adapted fractionation schemes can be delivered in a safe way and lead to high local control rates,” she added. “For ultra-central legions, there’s still not a recommendation to treat with SBRT because we see a lot of increased toxicity.”

“For ultra-central tumors, SBRT is still under debate,” agreed Dr. Lodeweges. “This is because of the varying definitions in the literature and the varying fractionation schemes used.”

How the location of tumors is defined is important. Central tumors are those that are at least 2 cm away from the main bronchial tree, whereas ultra-central tumors are those that butt onto it or overlap it.

In Dr. Lodeweges’s study, ultra-central tumors were defined as those with a planning target volume (PTV) abutting or overlapping the main bronchi, trachea, and/or esophagus.
 

Study details

Between 2012 and 2020, there were 72 patients with ultra-central lung tumors treated at UMC Utrecht. Most patients (78%) had a PTV covering the main bronchus, with 21% each having PTVs overlapping the trachea or esophagus.

Patients received a protracted SBRT regimen of 60 Gy given in 12 fractions. The median follow-up was 19 months.

The local failure-free survival rate was 98% at 1 year and 85% at 2 years. Overall survival rates were 77% and 52%, respectively.

Receiving a biologically effective dose of more than 90 Gy to the main bronchus increased the risk of grade 3 or higher toxicity. On the other hand, patient age and tumor histology did not affect the risk of adverse events.

The use of antithrombotic therapy didn’t have any bearing on toxicity either, but it’s a possible risk factor to consider, Dr. Lodeweges said. Peri- or endobronchial tumor location is another consideration.
 

Findings in context

How do the results of the current study sit with other studies of SBRT in non–small cell lung cancer? Dr. Lievens pointed out that overall survival at 2 years was lower in the current trial (52%) than in patients with central tumors treated in the RTOG 0813 trial (68%-73%) or those with peripheral tumors in the CHISEL trial (77%).

There were, of course, different fractions and doses of radiotherapy used in these trials, with lower doses and more fractions in the UMC Utrecht study, and there was higher toxicity when ultra-central lesions were treated.

“Optimized radiotherapy dose fractionation regimens are investigated quite intensively to improve the clinical benefit. This is an important area of research,” Dr. Lievens said.

The high local control rates but serious risk of bronchopulmonary hemorrhage seen in the current study “calls for further investigation of dose/volume parameters in the context of the location of the tumor but also in the context of other treatment modalities,” she added. “Advanced technologies in radiotherapy, which allow better imaging and daily adaptation, such as the MR-Linac, can optimize clinical benefits.”

The study was supported by UMC Utrecht and received no commercial funding. Dr. Lodeweges and Dr. Lievens had no relevant conflicts of interest.

People experiencing long-term symptoms following acute COVID-19 infection are increasingly meeting criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a phenomenon that highlights the need for unified research and clinical approaches, speakers said at a press briefing March 25 held by the advocacy group MEAction.

“Post-COVID lingering illness was predictable. Similar lingering fatigue syndromes have been reported in the scientific literature for nearly 100 years, following a variety of well-documented infections with viruses, bacteria, fungi, and even protozoa,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, Boston.

Core criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for at least 6 months, postexertional malaise (PEM), or a worsening of symptoms following even minor exertion (often described as “crashes”), unrefreshing sleep, and cognitive impairment and/or orthostatic intolerance.

Patients with ME/CFS also commonly experience painful headaches, muscle or joint aches, and allergies/other sensitivities. Although many patients can trace their symptoms to an initiating infection, “the cause is often unclear because the diagnosis is often delayed for months or years after symptom onset,” said Lucinda Bateman, MD, founder of the Bateman Horne Center, Salt Lake City, who leads a clinician coalition that aims to improve ME/CFS management.

In an international survey of 3762 COVID-19 “long-haulers” published in a preprint in December of 2020, the most frequent symptoms reported at least 6 months after illness onset were fatigue in 78%, PEM in 72%, and cognitive dysfunction (“brain fog”) in 55%. At the time of the survey, 45% reported requiring reduced work schedules because of their illness, and 22% reported being unable to work at all.

Dr. Bateman said those findings align with her experience so far with 12 COVID-19 “long haulers” who self-referred to her ME/CFS and fibromyalgia specialty clinic. Nine of the 12 met criteria for postural orthostatic tachycardia syndrome (POTS) based on the 10-minute NASA Lean Test, she said, and half also met the 2016 American College of Rheumatology criteria for fibromyalgia.

“Some were severely impaired. We suspect a small fiber polyneuropathy in about half, and mast cell activation syndrome in more than half. We look forward to doing more testing,” Dr. Bateman said.

To be sure, Dr. Komaroff noted, there are some differences. “Long COVID” patients will often experience breathlessness and ongoing anosmia (loss of taste and smell), which aren’t typical of ME/CFS.

But, he said, “many of the symptoms are quite similar ... My guess is that ME/CFS is an illness with a final common pathway that can be triggered by different things,” said Dr. Komaroff, a senior physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of the Harvard Health Letter.

Based on previous data about CFS suggesting a 10% rate of symptoms persisting at least a year following a variety of infectious agents and the predicted 200 million COVID-19 cases globally by the end of 2021, Dr. Komaroff estimated that about 20 million cases of “long COVID” would be expected in the next year.

‘A huge investment’

On the research side, the National Institutes of Health recently appropriated $1.15 billion dollars over the next 4 years to investigate “the heterogeneity in the recovery process after COVID and to develop treatments for those suffering from [postacute COVID-19 syndrome]” according to a Feb. 5, 2021, blog from the National Institute of Neurological Disorders and Stroke (NINDS).

That same day, another NINDS blog announced “new resources for large-scale ME/CFS research” and emphasized the tie-in with long–COVID-19 syndrome.

“That’s a huge investment. In my opinion, there will be several lingering illnesses following COVID,” Dr. Komaroff said, adding, “It’s my bet that long COVID will prove to be caused by certain kinds of abnormalities in the brain, some of the same abnormalities already identified in ME/CFS. Research will determine whether that’s right or wrong.”

In 2017, NINDS had announced a large increase in funding for ME/CFS research, including the creation of four dedicated research centers. In April 2019, NINDS held a 2-day conference highlighting that ongoing work, as reported by Medscape Medical News.

During the briefing, NINDS clinical director Avindra Nath, MD, described a comprehensive ongoing ME/CFS intramural study he’s been leading since 2016.

He’s now also overseeing two long–COVID-19 studies, one of which has a protocol similar to that of the ME/CFS study and will include individuals who are still experiencing long-term symptoms following confirmed cases of COVID-19. The aim is to screen about 1,300 patients. Several task forces are now examining all of these data together.

“Each aspect is now being analyzed … What we learn from one applies to the other,” Dr. Nath said.  
 

Advice for clinicians

In interviews, Dr. Bateman and Dr. Nath offered clinical advice for managing patients who meet ME/CFS criteria, whether they had confirmed or suspected COVID-19, a different infection, or unknown trigger(s).

Dr. Bateman advised that clinicians assess patients for each of the symptoms individually. “Besides exercise intolerance and PEM, the most commonly missed is orthostatic intolerance. It really doesn’t matter what the cause is, it’s amenable to supportive treatment. It’s one aspect of the illness that contributes to severely impaired function. My plea to all physicians would be for sure to assess for [orthostatic intolerance], and gain an understanding about activity management and avoiding PEM symptoms.”

Dr. Nath noted that an often-challenging situation is when tests for the infectious agent and other blood work come back negative, yet the patient still reports multiple debilitating symptoms. This has been a particular issue with long COVID-19, since many patients became ill early in the pandemic before the polymerase chain reaction (PCR) tests for SARS-CoV-2 were widely available.

“The physician can only order tests that are available at their labs. I think what the physician should do is handle symptoms symptomatically but also refer patients to specialists who are taking care of these patients or to research studies,” he said.

Dr. Bateman added, “Whether they had a documented COVID infection – we just have to let go of that in 2020. Way too many people didn’t have access to a test or the timing wasn’t amenable. If people meet criteria for ME/CFS, it’s irrelevant … It’s mainly a clinical diagnosis. It’s not reliant on identifying the infectious trigger.” 

Dr. Komaroff, who began caring for then-termed “chronic fatigue syndrome” patients and researching the condition more than 30 years ago, said that “every cloud has its silver lining. The increased focus on postinfectious fatigue syndrome is a silver lining in my mind around the terrible dark cloud that is the pandemic of COVID.”

Dr. Komaroff has received personal fees from Serimmune Inc., Ono Pharma, and Deallus, and grants from the NIH. Dr. Bateman is employed by the Bateman Horne Center, which receives grants from the NIH, and fees from Exagen Inc., and Teva Pharmaceutical. Dr. Nath is an NIH employee.

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

People experiencing long-term symptoms following acute COVID-19 infection are increasingly meeting criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a phenomenon that highlights the need for unified research and clinical approaches, speakers said at a press briefing March 25 held by the advocacy group MEAction.

“Post-COVID lingering illness was predictable. Similar lingering fatigue syndromes have been reported in the scientific literature for nearly 100 years, following a variety of well-documented infections with viruses, bacteria, fungi, and even protozoa,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, Boston.

Core criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for at least 6 months, postexertional malaise (PEM), or a worsening of symptoms following even minor exertion (often described as “crashes”), unrefreshing sleep, and cognitive impairment and/or orthostatic intolerance.

Patients with ME/CFS also commonly experience painful headaches, muscle or joint aches, and allergies/other sensitivities. Although many patients can trace their symptoms to an initiating infection, “the cause is often unclear because the diagnosis is often delayed for months or years after symptom onset,” said Lucinda Bateman, MD, founder of the Bateman Horne Center, Salt Lake City, who leads a clinician coalition that aims to improve ME/CFS management.

In an international survey of 3762 COVID-19 “long-haulers” published in a preprint in December of 2020, the most frequent symptoms reported at least 6 months after illness onset were fatigue in 78%, PEM in 72%, and cognitive dysfunction (“brain fog”) in 55%. At the time of the survey, 45% reported requiring reduced work schedules because of their illness, and 22% reported being unable to work at all.

Dr. Bateman said those findings align with her experience so far with 12 COVID-19 “long haulers” who self-referred to her ME/CFS and fibromyalgia specialty clinic. Nine of the 12 met criteria for postural orthostatic tachycardia syndrome (POTS) based on the 10-minute NASA Lean Test, she said, and half also met the 2016 American College of Rheumatology criteria for fibromyalgia.

“Some were severely impaired. We suspect a small fiber polyneuropathy in about half, and mast cell activation syndrome in more than half. We look forward to doing more testing,” Dr. Bateman said.

To be sure, Dr. Komaroff noted, there are some differences. “Long COVID” patients will often experience breathlessness and ongoing anosmia (loss of taste and smell), which aren’t typical of ME/CFS.

But, he said, “many of the symptoms are quite similar ... My guess is that ME/CFS is an illness with a final common pathway that can be triggered by different things,” said Dr. Komaroff, a senior physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of the Harvard Health Letter.

Based on previous data about CFS suggesting a 10% rate of symptoms persisting at least a year following a variety of infectious agents and the predicted 200 million COVID-19 cases globally by the end of 2021, Dr. Komaroff estimated that about 20 million cases of “long COVID” would be expected in the next year.

‘A huge investment’

On the research side, the National Institutes of Health recently appropriated $1.15 billion dollars over the next 4 years to investigate “the heterogeneity in the recovery process after COVID and to develop treatments for those suffering from [postacute COVID-19 syndrome]” according to a Feb. 5, 2021, blog from the National Institute of Neurological Disorders and Stroke (NINDS).

That same day, another NINDS blog announced “new resources for large-scale ME/CFS research” and emphasized the tie-in with long–COVID-19 syndrome.

“That’s a huge investment. In my opinion, there will be several lingering illnesses following COVID,” Dr. Komaroff said, adding, “It’s my bet that long COVID will prove to be caused by certain kinds of abnormalities in the brain, some of the same abnormalities already identified in ME/CFS. Research will determine whether that’s right or wrong.”

In 2017, NINDS had announced a large increase in funding for ME/CFS research, including the creation of four dedicated research centers. In April 2019, NINDS held a 2-day conference highlighting that ongoing work, as reported by Medscape Medical News.

During the briefing, NINDS clinical director Avindra Nath, MD, described a comprehensive ongoing ME/CFS intramural study he’s been leading since 2016.

He’s now also overseeing two long–COVID-19 studies, one of which has a protocol similar to that of the ME/CFS study and will include individuals who are still experiencing long-term symptoms following confirmed cases of COVID-19. The aim is to screen about 1,300 patients. Several task forces are now examining all of these data together.

“Each aspect is now being analyzed … What we learn from one applies to the other,” Dr. Nath said.  
 

Advice for clinicians

In interviews, Dr. Bateman and Dr. Nath offered clinical advice for managing patients who meet ME/CFS criteria, whether they had confirmed or suspected COVID-19, a different infection, or unknown trigger(s).

Dr. Bateman advised that clinicians assess patients for each of the symptoms individually. “Besides exercise intolerance and PEM, the most commonly missed is orthostatic intolerance. It really doesn’t matter what the cause is, it’s amenable to supportive treatment. It’s one aspect of the illness that contributes to severely impaired function. My plea to all physicians would be for sure to assess for [orthostatic intolerance], and gain an understanding about activity management and avoiding PEM symptoms.”

Dr. Nath noted that an often-challenging situation is when tests for the infectious agent and other blood work come back negative, yet the patient still reports multiple debilitating symptoms. This has been a particular issue with long COVID-19, since many patients became ill early in the pandemic before the polymerase chain reaction (PCR) tests for SARS-CoV-2 were widely available.

“The physician can only order tests that are available at their labs. I think what the physician should do is handle symptoms symptomatically but also refer patients to specialists who are taking care of these patients or to research studies,” he said.

Dr. Bateman added, “Whether they had a documented COVID infection – we just have to let go of that in 2020. Way too many people didn’t have access to a test or the timing wasn’t amenable. If people meet criteria for ME/CFS, it’s irrelevant … It’s mainly a clinical diagnosis. It’s not reliant on identifying the infectious trigger.” 

Dr. Komaroff, who began caring for then-termed “chronic fatigue syndrome” patients and researching the condition more than 30 years ago, said that “every cloud has its silver lining. The increased focus on postinfectious fatigue syndrome is a silver lining in my mind around the terrible dark cloud that is the pandemic of COVID.”

Dr. Komaroff has received personal fees from Serimmune Inc., Ono Pharma, and Deallus, and grants from the NIH. Dr. Bateman is employed by the Bateman Horne Center, which receives grants from the NIH, and fees from Exagen Inc., and Teva Pharmaceutical. Dr. Nath is an NIH employee.

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

People experiencing long-term symptoms following acute COVID-19 infection are increasingly meeting criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a phenomenon that highlights the need for unified research and clinical approaches, speakers said at a press briefing March 25 held by the advocacy group MEAction.

“Post-COVID lingering illness was predictable. Similar lingering fatigue syndromes have been reported in the scientific literature for nearly 100 years, following a variety of well-documented infections with viruses, bacteria, fungi, and even protozoa,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, Boston.

Core criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for at least 6 months, postexertional malaise (PEM), or a worsening of symptoms following even minor exertion (often described as “crashes”), unrefreshing sleep, and cognitive impairment and/or orthostatic intolerance.

Patients with ME/CFS also commonly experience painful headaches, muscle or joint aches, and allergies/other sensitivities. Although many patients can trace their symptoms to an initiating infection, “the cause is often unclear because the diagnosis is often delayed for months or years after symptom onset,” said Lucinda Bateman, MD, founder of the Bateman Horne Center, Salt Lake City, who leads a clinician coalition that aims to improve ME/CFS management.

In an international survey of 3762 COVID-19 “long-haulers” published in a preprint in December of 2020, the most frequent symptoms reported at least 6 months after illness onset were fatigue in 78%, PEM in 72%, and cognitive dysfunction (“brain fog”) in 55%. At the time of the survey, 45% reported requiring reduced work schedules because of their illness, and 22% reported being unable to work at all.

Dr. Bateman said those findings align with her experience so far with 12 COVID-19 “long haulers” who self-referred to her ME/CFS and fibromyalgia specialty clinic. Nine of the 12 met criteria for postural orthostatic tachycardia syndrome (POTS) based on the 10-minute NASA Lean Test, she said, and half also met the 2016 American College of Rheumatology criteria for fibromyalgia.

“Some were severely impaired. We suspect a small fiber polyneuropathy in about half, and mast cell activation syndrome in more than half. We look forward to doing more testing,” Dr. Bateman said.

To be sure, Dr. Komaroff noted, there are some differences. “Long COVID” patients will often experience breathlessness and ongoing anosmia (loss of taste and smell), which aren’t typical of ME/CFS.

But, he said, “many of the symptoms are quite similar ... My guess is that ME/CFS is an illness with a final common pathway that can be triggered by different things,” said Dr. Komaroff, a senior physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of the Harvard Health Letter.

Based on previous data about CFS suggesting a 10% rate of symptoms persisting at least a year following a variety of infectious agents and the predicted 200 million COVID-19 cases globally by the end of 2021, Dr. Komaroff estimated that about 20 million cases of “long COVID” would be expected in the next year.

‘A huge investment’

On the research side, the National Institutes of Health recently appropriated $1.15 billion dollars over the next 4 years to investigate “the heterogeneity in the recovery process after COVID and to develop treatments for those suffering from [postacute COVID-19 syndrome]” according to a Feb. 5, 2021, blog from the National Institute of Neurological Disorders and Stroke (NINDS).

That same day, another NINDS blog announced “new resources for large-scale ME/CFS research” and emphasized the tie-in with long–COVID-19 syndrome.

“That’s a huge investment. In my opinion, there will be several lingering illnesses following COVID,” Dr. Komaroff said, adding, “It’s my bet that long COVID will prove to be caused by certain kinds of abnormalities in the brain, some of the same abnormalities already identified in ME/CFS. Research will determine whether that’s right or wrong.”

In 2017, NINDS had announced a large increase in funding for ME/CFS research, including the creation of four dedicated research centers. In April 2019, NINDS held a 2-day conference highlighting that ongoing work, as reported by Medscape Medical News.

During the briefing, NINDS clinical director Avindra Nath, MD, described a comprehensive ongoing ME/CFS intramural study he’s been leading since 2016.

He’s now also overseeing two long–COVID-19 studies, one of which has a protocol similar to that of the ME/CFS study and will include individuals who are still experiencing long-term symptoms following confirmed cases of COVID-19. The aim is to screen about 1,300 patients. Several task forces are now examining all of these data together.

“Each aspect is now being analyzed … What we learn from one applies to the other,” Dr. Nath said.  
 

Advice for clinicians

In interviews, Dr. Bateman and Dr. Nath offered clinical advice for managing patients who meet ME/CFS criteria, whether they had confirmed or suspected COVID-19, a different infection, or unknown trigger(s).

Dr. Bateman advised that clinicians assess patients for each of the symptoms individually. “Besides exercise intolerance and PEM, the most commonly missed is orthostatic intolerance. It really doesn’t matter what the cause is, it’s amenable to supportive treatment. It’s one aspect of the illness that contributes to severely impaired function. My plea to all physicians would be for sure to assess for [orthostatic intolerance], and gain an understanding about activity management and avoiding PEM symptoms.”

Dr. Nath noted that an often-challenging situation is when tests for the infectious agent and other blood work come back negative, yet the patient still reports multiple debilitating symptoms. This has been a particular issue with long COVID-19, since many patients became ill early in the pandemic before the polymerase chain reaction (PCR) tests for SARS-CoV-2 were widely available.

“The physician can only order tests that are available at their labs. I think what the physician should do is handle symptoms symptomatically but also refer patients to specialists who are taking care of these patients or to research studies,” he said.

Dr. Bateman added, “Whether they had a documented COVID infection – we just have to let go of that in 2020. Way too many people didn’t have access to a test or the timing wasn’t amenable. If people meet criteria for ME/CFS, it’s irrelevant … It’s mainly a clinical diagnosis. It’s not reliant on identifying the infectious trigger.” 

Dr. Komaroff, who began caring for then-termed “chronic fatigue syndrome” patients and researching the condition more than 30 years ago, said that “every cloud has its silver lining. The increased focus on postinfectious fatigue syndrome is a silver lining in my mind around the terrible dark cloud that is the pandemic of COVID.”

Dr. Komaroff has received personal fees from Serimmune Inc., Ono Pharma, and Deallus, and grants from the NIH. Dr. Bateman is employed by the Bateman Horne Center, which receives grants from the NIH, and fees from Exagen Inc., and Teva Pharmaceutical. Dr. Nath is an NIH employee.

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

The Food and Drug Administration has approved Medtronic’s Harmony Transcatheter Pulmonary Valve (TPV) System to treat severe pulmonary regurgitation in pediatric and adult patients who have a native or surgically repaired right ventricular outflow tract (RVOT).

The Harmony TPV is the first nonsurgical heart valve to treat severe pulmonary valve regurgitation, which is common in patients with congenital heart disease, the agency said in a news release. Its use can delay the time before a patient needs open-heart surgery and potentially reduce the number of these surgeries required over a lifetime.

“The Harmony TPV provides a new treatment option for adult and pediatric patients with certain types of congenital heart disease,” Bram Zuckerman, MD, director of the Office of Cardiovascular Devices in the FDA’s Center for Devices and Radiological Health, said in the statement.

“It offers a less-invasive treatment alternative to open-heart surgery to patients with a leaky native or surgically repaired RVOT and may help patients improve their quality of life and return to their normal activities more quickly, thus fulfilling an unmet clinical need of many patients with congenital heart disease,” he said.

The Harmony valve, which was granted breakthrough device designation, is a 22-mm or 25-mm porcine pericardium valve, sewn to a nitinol frame. It is implanted with a 25-French delivery system using a coil-loading catheter.

The FDA approval was based on the 70-patient prospective, nonrandomized, multicenter Harmony TPV Clinical study, in which 100% of patients achieved the primary safety endpoint of no procedure or device-related deaths 30 days after implantation.

Among 65 patients with evaluable echocardiographic data, 89.2% met the primary effectiveness endpoint of no additional surgical or interventional device-related procedures and acceptable heart blood flow at 6 months.

Adverse events included irregular or abnormal heart rhythms in 23.9% of patients, including 14.1% ventricular tachycardia; leakage around the valve in 8.5%, including 1.4% major leakage; minor bleeding in 7.0%, narrowing of the pulmonary valve in 4.2%, and movement of the implant in 4.2%.

Follow-up was scheduled annually through 5 years and has been extended to 10 years as part of the postapproval study, the FDA noted.

The Harmony TPV device is contraindicated for patients with an infection in the heart or elsewhere, for patients who cannot tolerate blood-thinning medicines, and for those with a sensitivity to nitinol (titanium or nickel).

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

The Food and Drug Administration has approved Medtronic’s Harmony Transcatheter Pulmonary Valve (TPV) System to treat severe pulmonary regurgitation in pediatric and adult patients who have a native or surgically repaired right ventricular outflow tract (RVOT).

The Harmony TPV is the first nonsurgical heart valve to treat severe pulmonary valve regurgitation, which is common in patients with congenital heart disease, the agency said in a news release. Its use can delay the time before a patient needs open-heart surgery and potentially reduce the number of these surgeries required over a lifetime.

“The Harmony TPV provides a new treatment option for adult and pediatric patients with certain types of congenital heart disease,” Bram Zuckerman, MD, director of the Office of Cardiovascular Devices in the FDA’s Center for Devices and Radiological Health, said in the statement.

“It offers a less-invasive treatment alternative to open-heart surgery to patients with a leaky native or surgically repaired RVOT and may help patients improve their quality of life and return to their normal activities more quickly, thus fulfilling an unmet clinical need of many patients with congenital heart disease,” he said.

The Harmony valve, which was granted breakthrough device designation, is a 22-mm or 25-mm porcine pericardium valve, sewn to a nitinol frame. It is implanted with a 25-French delivery system using a coil-loading catheter.

The FDA approval was based on the 70-patient prospective, nonrandomized, multicenter Harmony TPV Clinical study, in which 100% of patients achieved the primary safety endpoint of no procedure or device-related deaths 30 days after implantation.

Among 65 patients with evaluable echocardiographic data, 89.2% met the primary effectiveness endpoint of no additional surgical or interventional device-related procedures and acceptable heart blood flow at 6 months.

Adverse events included irregular or abnormal heart rhythms in 23.9% of patients, including 14.1% ventricular tachycardia; leakage around the valve in 8.5%, including 1.4% major leakage; minor bleeding in 7.0%, narrowing of the pulmonary valve in 4.2%, and movement of the implant in 4.2%.

Follow-up was scheduled annually through 5 years and has been extended to 10 years as part of the postapproval study, the FDA noted.

The Harmony TPV device is contraindicated for patients with an infection in the heart or elsewhere, for patients who cannot tolerate blood-thinning medicines, and for those with a sensitivity to nitinol (titanium or nickel).

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

The Food and Drug Administration has approved Medtronic’s Harmony Transcatheter Pulmonary Valve (TPV) System to treat severe pulmonary regurgitation in pediatric and adult patients who have a native or surgically repaired right ventricular outflow tract (RVOT).

The Harmony TPV is the first nonsurgical heart valve to treat severe pulmonary valve regurgitation, which is common in patients with congenital heart disease, the agency said in a news release. Its use can delay the time before a patient needs open-heart surgery and potentially reduce the number of these surgeries required over a lifetime.

“The Harmony TPV provides a new treatment option for adult and pediatric patients with certain types of congenital heart disease,” Bram Zuckerman, MD, director of the Office of Cardiovascular Devices in the FDA’s Center for Devices and Radiological Health, said in the statement.

“It offers a less-invasive treatment alternative to open-heart surgery to patients with a leaky native or surgically repaired RVOT and may help patients improve their quality of life and return to their normal activities more quickly, thus fulfilling an unmet clinical need of many patients with congenital heart disease,” he said.

The Harmony valve, which was granted breakthrough device designation, is a 22-mm or 25-mm porcine pericardium valve, sewn to a nitinol frame. It is implanted with a 25-French delivery system using a coil-loading catheter.

The FDA approval was based on the 70-patient prospective, nonrandomized, multicenter Harmony TPV Clinical study, in which 100% of patients achieved the primary safety endpoint of no procedure or device-related deaths 30 days after implantation.

Among 65 patients with evaluable echocardiographic data, 89.2% met the primary effectiveness endpoint of no additional surgical or interventional device-related procedures and acceptable heart blood flow at 6 months.

Adverse events included irregular or abnormal heart rhythms in 23.9% of patients, including 14.1% ventricular tachycardia; leakage around the valve in 8.5%, including 1.4% major leakage; minor bleeding in 7.0%, narrowing of the pulmonary valve in 4.2%, and movement of the implant in 4.2%.

Follow-up was scheduled annually through 5 years and has been extended to 10 years as part of the postapproval study, the FDA noted.

The Harmony TPV device is contraindicated for patients with an infection in the heart or elsewhere, for patients who cannot tolerate blood-thinning medicines, and for those with a sensitivity to nitinol (titanium or nickel).

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