Ob.Gyn. News

The U.S. Food and Drug Administration has approved pafolacianine (Cytalux), an imaging drug indicated for use in adult patients with ovarian cancer undergoing surgery.

The new drug “is designed to improve the ability to locate additional ovarian cancerous tissue that is normally difficult to detect during surgery,” according to the agency.

Pafolacianine, administered via intravenous injection prior to surgery, is the first FDA-approved tumor-targeted fluorescent agent for ovarian cancer.

In a press statement, drug inventor Philip Low, PhD, of Purdue University in West Lafayette, Ind., said the agent causes ovarian cancer lesions to “light up like stars against a night sky.”

Improving detection of ovarian cancer lesions is critical given that ovarian cancer is one of the “deadliest of all female reproductive system cancers,” according to the American Cancer Society. The organization estimates that there will be more than 21,000 new cases and more than 13,000 deaths in 2021.

Currently, surgeons use preoperative imaging as well as visual inspection of tumors under normal light and examination by touch to identify ovarian cancer lesions.

Pafolacianine offers a new tool to enhance surgeons’ ability “to identify deadly ovarian tumors that may otherwise go undetected,” Alex Gorovets, MD, deputy director of the office of specialty medicine in the FDA’s Center for Drug Evaluation and Research, said in a press statement.

Ovarian cancer often causes the body to overproduce the folate receptor protein in cell membranes. Pafolacianine, employed with a near-infrared fluorescence imaging system cleared by the FDA for use alongside the drug, binds to and illuminates these proteins under fluorescent light, “boosting surgeons’ ability to identify the cancerous tissue,” the agency in a statement.

The safety and effectiveness of pafolacianine was evaluated in a randomized, multi-center, open-label study of women diagnosed with ovarian cancer or with high clinical suspicion of ovarian cancer. Of the 134 women undergoing surgery who received a dose of pafolacianine and were evaluated under both normal and fluorescent light, 26.9% had at least one cancerous lesion detected that was not observed by standard visual or tactile inspection.

The most common side effects of pafolacianine were infusion-related reactions, including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, itching, and hypersensitivity.

Pafolacianine may cause fetal harm when administered to a pregnant woman. The use of folate, folic acid, or folate-containing supplements should be avoided within 48 hours before administration of pafolacianine. 

The FDA also cautioned about the possible risk of image interpretation errors, including false negatives and false positives, with the use of the new drug and near-infrared fluorescence imaging system.

The FDA previously granted pafolacianine orphan-drug, priority, and fast track designations.

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

The U.S. Food and Drug Administration has approved pafolacianine (Cytalux), an imaging drug indicated for use in adult patients with ovarian cancer undergoing surgery.

The new drug “is designed to improve the ability to locate additional ovarian cancerous tissue that is normally difficult to detect during surgery,” according to the agency.

Pafolacianine, administered via intravenous injection prior to surgery, is the first FDA-approved tumor-targeted fluorescent agent for ovarian cancer.

In a press statement, drug inventor Philip Low, PhD, of Purdue University in West Lafayette, Ind., said the agent causes ovarian cancer lesions to “light up like stars against a night sky.”

Improving detection of ovarian cancer lesions is critical given that ovarian cancer is one of the “deadliest of all female reproductive system cancers,” according to the American Cancer Society. The organization estimates that there will be more than 21,000 new cases and more than 13,000 deaths in 2021.

Currently, surgeons use preoperative imaging as well as visual inspection of tumors under normal light and examination by touch to identify ovarian cancer lesions.

Pafolacianine offers a new tool to enhance surgeons’ ability “to identify deadly ovarian tumors that may otherwise go undetected,” Alex Gorovets, MD, deputy director of the office of specialty medicine in the FDA’s Center for Drug Evaluation and Research, said in a press statement.

Ovarian cancer often causes the body to overproduce the folate receptor protein in cell membranes. Pafolacianine, employed with a near-infrared fluorescence imaging system cleared by the FDA for use alongside the drug, binds to and illuminates these proteins under fluorescent light, “boosting surgeons’ ability to identify the cancerous tissue,” the agency in a statement.

The safety and effectiveness of pafolacianine was evaluated in a randomized, multi-center, open-label study of women diagnosed with ovarian cancer or with high clinical suspicion of ovarian cancer. Of the 134 women undergoing surgery who received a dose of pafolacianine and were evaluated under both normal and fluorescent light, 26.9% had at least one cancerous lesion detected that was not observed by standard visual or tactile inspection.

The most common side effects of pafolacianine were infusion-related reactions, including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, itching, and hypersensitivity.

Pafolacianine may cause fetal harm when administered to a pregnant woman. The use of folate, folic acid, or folate-containing supplements should be avoided within 48 hours before administration of pafolacianine. 

The FDA also cautioned about the possible risk of image interpretation errors, including false negatives and false positives, with the use of the new drug and near-infrared fluorescence imaging system.

The FDA previously granted pafolacianine orphan-drug, priority, and fast track designations.

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

The U.S. Food and Drug Administration has approved pafolacianine (Cytalux), an imaging drug indicated for use in adult patients with ovarian cancer undergoing surgery.

The new drug “is designed to improve the ability to locate additional ovarian cancerous tissue that is normally difficult to detect during surgery,” according to the agency.

Pafolacianine, administered via intravenous injection prior to surgery, is the first FDA-approved tumor-targeted fluorescent agent for ovarian cancer.

In a press statement, drug inventor Philip Low, PhD, of Purdue University in West Lafayette, Ind., said the agent causes ovarian cancer lesions to “light up like stars against a night sky.”

Improving detection of ovarian cancer lesions is critical given that ovarian cancer is one of the “deadliest of all female reproductive system cancers,” according to the American Cancer Society. The organization estimates that there will be more than 21,000 new cases and more than 13,000 deaths in 2021.

Currently, surgeons use preoperative imaging as well as visual inspection of tumors under normal light and examination by touch to identify ovarian cancer lesions.

Pafolacianine offers a new tool to enhance surgeons’ ability “to identify deadly ovarian tumors that may otherwise go undetected,” Alex Gorovets, MD, deputy director of the office of specialty medicine in the FDA’s Center for Drug Evaluation and Research, said in a press statement.

Ovarian cancer often causes the body to overproduce the folate receptor protein in cell membranes. Pafolacianine, employed with a near-infrared fluorescence imaging system cleared by the FDA for use alongside the drug, binds to and illuminates these proteins under fluorescent light, “boosting surgeons’ ability to identify the cancerous tissue,” the agency in a statement.

The safety and effectiveness of pafolacianine was evaluated in a randomized, multi-center, open-label study of women diagnosed with ovarian cancer or with high clinical suspicion of ovarian cancer. Of the 134 women undergoing surgery who received a dose of pafolacianine and were evaluated under both normal and fluorescent light, 26.9% had at least one cancerous lesion detected that was not observed by standard visual or tactile inspection.

The most common side effects of pafolacianine were infusion-related reactions, including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, itching, and hypersensitivity.

Pafolacianine may cause fetal harm when administered to a pregnant woman. The use of folate, folic acid, or folate-containing supplements should be avoided within 48 hours before administration of pafolacianine. 

The FDA also cautioned about the possible risk of image interpretation errors, including false negatives and false positives, with the use of the new drug and near-infrared fluorescence imaging system.

The FDA previously granted pafolacianine orphan-drug, priority, and fast track designations.

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

Merck’s antiviral pill for COVID-19, molnupiravir, appears to be far less effective than early results from the clinical trial first suggested.

According to an analysis by scientists at the Food and Drug Administration, the experimental pill cut the risk of hospitalization or death from COVID-19 by about 30%, compared to a placebo, and the pill showed no benefit for people with antibodies against COVID-19 from prior infection.

The updated analysis showed 48 hospitalizations or deaths among study participants who were randomly assigned to take the antiviral drug, compared to 68 among those who took a placebo.

Those results come from the full set of 1,433 patients who were randomized in the clinical trial, which just became available last week.

Initial results from the first 775 patients enrolled in the clinical trial, which were issued in a company news release in October, had said the drug cut the risk of hospitalization or death for patients at high risk of severe disease by about 50%.

Merck has been producing millions of doses of molnupiravir, which is the first antiviral pill to treat COVID-19 infections. The United Kingdom’s drug regulator authorized use of the medication in early November. The company said it expected to distribute the medication globally by the end of 2021.

In October, two Indian drug companies halted late-stage clinical trials of a generic version of molnupiravir after the studies failed to find any benefit to patients with moderate COVID-19. Trials in patients with milder symptoms are still ongoing.

On Nov. 27, the New England Journal of Medicine postponed its planned early release of the molnupiravir study results, citing “new information.”

The medication is designed to be given as four pills taken every 12 hours for 5 days. It’s most effective when taken within the first few days of new symptoms, something that requires convenient and affordable testing.

The new results seem to put molnupiravir far below the effectiveness of existing treatments.

The infused monoclonal antibody cocktail REGEN-COV, which the FDA has already authorized for emergency use, is about 85% effective at preventing hospitalization or death in patients who are at risk for severe COVID-19 outcomes, and it appears to be just as effective in people who already have antibodies against COVID-19, which is why it is being given to both vaccinated and unvaccinated patients, the FDA said.

In early November, Pfizer said its experimental antiviral pill Paxlovid cut the risk of hospitalization or death by 89%.

In briefing documents posted ahead of an advisory committee meeting Nov. 30, the FDA highlights other potential safety issues with the Merck drug, which works by causing the virus to make mistakes as it copies itself, eventually causing the virus to mutate itself to death.

The agency has asked the advisory committee to weigh in on the right patient population for the drug: Should pregnant women get it? Could the drug harm a developing fetus?

Should vaccinated people with breakthrough infections get it? Would it work for them? People with reduced immune function are more likely to get a breakthrough infection. They’re also more likely to shed virus for a longer period of time, making them perfect incubators for variants. What could happen if we give this type of patient a drug that increases mutations?

And what about mutations caused by the medication? Could they increase the potential for more variants? The agency concluded the risk of this happening was low.

In animal studies, the drug impacted bone formation. For this reason, the agency has agreed with the drug company that molnupiravir should not be given to anyone under the age of 18.

Aside from these concerns, the FDA says there were no major safety issues among people who took part in the clinical trial, though they acknowledge that number is small.

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

Merck’s antiviral pill for COVID-19, molnupiravir, appears to be far less effective than early results from the clinical trial first suggested.

According to an analysis by scientists at the Food and Drug Administration, the experimental pill cut the risk of hospitalization or death from COVID-19 by about 30%, compared to a placebo, and the pill showed no benefit for people with antibodies against COVID-19 from prior infection.

The updated analysis showed 48 hospitalizations or deaths among study participants who were randomly assigned to take the antiviral drug, compared to 68 among those who took a placebo.

Those results come from the full set of 1,433 patients who were randomized in the clinical trial, which just became available last week.

Initial results from the first 775 patients enrolled in the clinical trial, which were issued in a company news release in October, had said the drug cut the risk of hospitalization or death for patients at high risk of severe disease by about 50%.

Merck has been producing millions of doses of molnupiravir, which is the first antiviral pill to treat COVID-19 infections. The United Kingdom’s drug regulator authorized use of the medication in early November. The company said it expected to distribute the medication globally by the end of 2021.

In October, two Indian drug companies halted late-stage clinical trials of a generic version of molnupiravir after the studies failed to find any benefit to patients with moderate COVID-19. Trials in patients with milder symptoms are still ongoing.

On Nov. 27, the New England Journal of Medicine postponed its planned early release of the molnupiravir study results, citing “new information.”

The medication is designed to be given as four pills taken every 12 hours for 5 days. It’s most effective when taken within the first few days of new symptoms, something that requires convenient and affordable testing.

The new results seem to put molnupiravir far below the effectiveness of existing treatments.

The infused monoclonal antibody cocktail REGEN-COV, which the FDA has already authorized for emergency use, is about 85% effective at preventing hospitalization or death in patients who are at risk for severe COVID-19 outcomes, and it appears to be just as effective in people who already have antibodies against COVID-19, which is why it is being given to both vaccinated and unvaccinated patients, the FDA said.

In early November, Pfizer said its experimental antiviral pill Paxlovid cut the risk of hospitalization or death by 89%.

In briefing documents posted ahead of an advisory committee meeting Nov. 30, the FDA highlights other potential safety issues with the Merck drug, which works by causing the virus to make mistakes as it copies itself, eventually causing the virus to mutate itself to death.

The agency has asked the advisory committee to weigh in on the right patient population for the drug: Should pregnant women get it? Could the drug harm a developing fetus?

Should vaccinated people with breakthrough infections get it? Would it work for them? People with reduced immune function are more likely to get a breakthrough infection. They’re also more likely to shed virus for a longer period of time, making them perfect incubators for variants. What could happen if we give this type of patient a drug that increases mutations?

And what about mutations caused by the medication? Could they increase the potential for more variants? The agency concluded the risk of this happening was low.

In animal studies, the drug impacted bone formation. For this reason, the agency has agreed with the drug company that molnupiravir should not be given to anyone under the age of 18.

Aside from these concerns, the FDA says there were no major safety issues among people who took part in the clinical trial, though they acknowledge that number is small.

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

Merck’s antiviral pill for COVID-19, molnupiravir, appears to be far less effective than early results from the clinical trial first suggested.

According to an analysis by scientists at the Food and Drug Administration, the experimental pill cut the risk of hospitalization or death from COVID-19 by about 30%, compared to a placebo, and the pill showed no benefit for people with antibodies against COVID-19 from prior infection.

The updated analysis showed 48 hospitalizations or deaths among study participants who were randomly assigned to take the antiviral drug, compared to 68 among those who took a placebo.

Those results come from the full set of 1,433 patients who were randomized in the clinical trial, which just became available last week.

Initial results from the first 775 patients enrolled in the clinical trial, which were issued in a company news release in October, had said the drug cut the risk of hospitalization or death for patients at high risk of severe disease by about 50%.

Merck has been producing millions of doses of molnupiravir, which is the first antiviral pill to treat COVID-19 infections. The United Kingdom’s drug regulator authorized use of the medication in early November. The company said it expected to distribute the medication globally by the end of 2021.

In October, two Indian drug companies halted late-stage clinical trials of a generic version of molnupiravir after the studies failed to find any benefit to patients with moderate COVID-19. Trials in patients with milder symptoms are still ongoing.

On Nov. 27, the New England Journal of Medicine postponed its planned early release of the molnupiravir study results, citing “new information.”

The medication is designed to be given as four pills taken every 12 hours for 5 days. It’s most effective when taken within the first few days of new symptoms, something that requires convenient and affordable testing.

The new results seem to put molnupiravir far below the effectiveness of existing treatments.

The infused monoclonal antibody cocktail REGEN-COV, which the FDA has already authorized for emergency use, is about 85% effective at preventing hospitalization or death in patients who are at risk for severe COVID-19 outcomes, and it appears to be just as effective in people who already have antibodies against COVID-19, which is why it is being given to both vaccinated and unvaccinated patients, the FDA said.

In early November, Pfizer said its experimental antiviral pill Paxlovid cut the risk of hospitalization or death by 89%.

In briefing documents posted ahead of an advisory committee meeting Nov. 30, the FDA highlights other potential safety issues with the Merck drug, which works by causing the virus to make mistakes as it copies itself, eventually causing the virus to mutate itself to death.

The agency has asked the advisory committee to weigh in on the right patient population for the drug: Should pregnant women get it? Could the drug harm a developing fetus?

Should vaccinated people with breakthrough infections get it? Would it work for them? People with reduced immune function are more likely to get a breakthrough infection. They’re also more likely to shed virus for a longer period of time, making them perfect incubators for variants. What could happen if we give this type of patient a drug that increases mutations?

And what about mutations caused by the medication? Could they increase the potential for more variants? The agency concluded the risk of this happening was low.

In animal studies, the drug impacted bone formation. For this reason, the agency has agreed with the drug company that molnupiravir should not be given to anyone under the age of 18.

Aside from these concerns, the FDA says there were no major safety issues among people who took part in the clinical trial, though they acknowledge that number is small.

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

Ramy Sedhom, MD, a medical oncologist and a palliative care physician at Penn Medicine Princeton Health in Plainsboro, N.J., will always wonder if prior authorization refusals led to his patient’s death.

The patient had advanced gastric cancer and the insurer initially denied a PET scan to rule out metastatic disease. When the scan was eventually allowed, it revealed that the cancer had spread.

Standard treatment would have been difficult for the patient, an older individual with comorbidities. But Dr. Sedhom knew that a European study had reported equal efficacy and fewer side effects with a reduced chemotherapy regimen, and he thought that was the best approach in this situation.

The insurer disagreed with Dr. Sedhom’s decision and, while the two argued, the patient’s symptoms worsened. He was admitted to the hospital, where he experienced a decline in function, common for older patients. “Long story short, he was never able to seek treatment and then transitioned to hospice,” Dr. Sedhom said. “It was one of those situations where there was a 3- to 4-week delay in what should have been standard care.”

That course of events is not an outlier but everyday life for physicians trying to navigate insurers’ prior authorization rules before they can treat their patients. Nearly 4 years after major organizations — American Hospital Association, America’s Health Insurance Plans, American Medical Association, Blue Cross Blue Shield Association, and others — signed a consensus statement agreeing to improve the prior authorization process, physicians say little progress has been made.

Indeed, 83% of physicians say that the number of prior authorizations required for prescription medications and medical services has increased over the last 5 years, according to survey results released earlier this year.

“It’s decidedly worse — there’s no question about it,” said Andrew R. Spector, MD, a neurologist and sleep medicine specialist at Duke Health in Durham, N.C. “Drugs that I used to get without prior authorizations now require them.”

When Vignesh I. Doraiswamy, MD, an internal medicine hospitalist at the Ohio State University Wexner Medical Center in Columbus, discharged a patient with Clostridioides difficile infection, he followed clinical guidelines to prescribe vancomycin for 10 to 14 days. “And the insurance company said, ‘Well, yeah, we only authorize about 5 days,’ which just makes no sense,” Dr. Doraiswamy said. “There’s nowhere in any literature that says 5 days is sufficient. What worries me is that is the standard of care we are supposed to give and yet we are unable to.”

Yash B. Jobanputra, MD, a cardiology fellow at Saint Vincent Hospital in Worcester, Mass., laments that prior authorization is used in situations that simply do not make common sense. During his residency, a woman who had tested positive for the BRCA gene mutation with a strong family history of breast cancer needed a breast ultrasound and an MRI scan every 6 months to 1 year. Despite the documentation that she was at extremely high risk for developing breast cancer, he had to go through prior authorization every time she was due for new images.

“I had to call the insurance company, they would put me on hold, I would wait to speak to a physician — and the end response would be, ‘Yeah, this is what needs to be done,’” he said. “But having established her positive status once should be enough really. I shouldn’t have to go through the circus all over again.”

Prior authorization is also being used for routine diagnostics, such as a Holter monitor for patients complaining of heart palpitations. “Depending on the insurance, for some patients we can give it to them in the clinic right away,” Dr. Jobanputra said. “Whereas some others we have to wait until we get prior authorization from the insurance company and the patient has to come back again to the hospital to get the monitor. That is a delay in patient care.”

The delays also extend to emergency care, Dr. Doraiswamy said. He cites the example of a heart attack patient who needed an emergency heart catheterization but ran into a prior authorization delay. “I just said, ‘Try your best not to get stressed’ which is not easy for a patient finding out their stay wasn’t covered when they had just been through a heart attack,” he said. “Then I spent 20 to 30 minutes — most of it on hold — to answer the question ‘Why did this patient need to get admitted?’ “

Physicians feel disrespected because that type of prior authorization hassle is just busywork. “Rarely is a valid stay that was initially denied, not eventually accepted,” Dr. Doraiswamy said. “But why couldn’t they have just seen that the guy had a heart attack and he obviously needed to be in the hospital?”

For Dr. Spector, the Duke Health sleep medicine specialist, prior authorization is not just a speed bump, it’s a full stop. Insurers have started mandating a multiple sleep latency test (MSLT) to confirm narcolepsy before covering medication to treat the condition. “We know that the MSLT is very often wrong,” he said. “There are a lot of times we’re dealing with patients with narcolepsy who simply don’t meet the testing criteria that the insurance requires, and payers will not accept our clinical judgment.”

In his view, the prior authorization landscape is worsening — and not only because a “faulty test” is being used to deny treatment. “The appeal process is worse,” Dr. Spector said. “I used to be able to get on the phone and do a peer-to-peer review with a physician who I could reason with… but that doesn’t happen anymore. There is virtually no way to bypass these blanket rules.”

Other survey findings also stand in direct contradiction of the 2018 consensus agreement:

A large majority (87%) of physicians report that prior authorization interferes with continuity of care, even though the industry groups agreed that patients should be protected from treatment disruption when there is a formulary or treatment-coverage change.

Despite a consensus to encourage transparency and easy accessibility of prior authorization requirements, 68% of physicians reported that it is difficult to determine whether a prescription medication requires prior authorization, and 58% report that it’s difficult for medical services.

Phone and fax are the most commonly used methods for completing prior authorizations, despite agreement that electronic prior authorization, using existing national standard transactions, should be accelerated. Fewer than one quarter of physicians said that their electronic health record system supports electronic prior authorization for prescription medications.

Dr. Spector wants to see legislation that forces insurers to live up to some of the tenets of the 2018 consensus statement. In September, a new Texas law went into effect, exempting physicians from prior authorization if, during the previous six months, 90% of their treatments met an insurer›s medical necessity criteria. In January, the recently approved Prior Authorization Reform Act in Illinois will reduce the number of services subject to prior authorization, mandate a prior authorization decision within 5 days, and set disciplinary measures for health plans that do not comply, among other things.

“What gives me hope is that at least somewhere in the country, somebody is doing something,” Dr. Spector said. “And if it goes well, maybe other insurers will adopt it. I’m really hoping they demonstrate that the money they can save on the administration of all the appeals and prior authorization paperwork can actually go into caring for patients.”

In addition to state-level action, reform may also be advancing at the federal level. In October, a bill was introduced in the U.S. Senate that mirrors a prior authorization reform bill introduced in the House of Representatives last May. Both bills have broad bipartisan support; the House bill has more than 235 co-sponsors.

In an interview with this news organization, Rep. Ami Bera, MD, (D-CA) said it is “very realistic” that the bill will become law during this session of Congress. “We do think this bill will get marked up in committee and hopefully we can get it to the floor either as a stand-alone bill where we know we have the votes to pass it or as part of a larger legislative package,” he said.

If approved, the Improving Seniors’ Timely Access to Care Act of 2021 would require that Medicare Advantage plans minimize the use of prior authorization for routinely approved services; require real-time decisions for certain requests; report the extent of their use of prior authorization and their rate of approvals or denials, among other things; and establish an electronic prior authorization system.

Medicare Advantage plans are private insurers that are regulated by the Centers for Medicare & Medicaid Services (CMS), which will create the specific rules and penalties associated with the reforms, if they become law. “One would presume that a condition of being a Medicare Advantage plan is that you’re going to have to comply with these new regulations,” said Katie Orrico, senior vice president of health policy and advocacy for the American Association of Neurological Surgeons and Congress of Neurological Surgeons (AANS/CNS). “So they will have some amount of teeth in the form of a mandate.”

The AANS and CNS are part of the Regulatory Relief Coalition, a group of 14 national physician specialty organizations. Winning prior authorization reform in the Medicare Advantage plans is part of its bigger strategy. “If those commercial plans have to follow a set of rules and processes for Medicare, then why not just expand those same processes to all other parts of their business?” Ms. Orrico said. 

Despite his frustration with their prior authorization processes, Dr. Doraiswamy, the Ohio State hospitalist, agrees that working to improve insurers’ practices is the best way forward. “It’s so easy to make them look like these evil, giant conglomerations that exist solely to suck money and not care about anyone’s health, but I don’t know if that’s necessarily the case,” he said. “We really have to figure out how best to work with insurance companies to make sure that, while they are profit-generating institutions, that [profit] shouldn’t come at the cost of patient care.”

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

Ramy Sedhom, MD, a medical oncologist and a palliative care physician at Penn Medicine Princeton Health in Plainsboro, N.J., will always wonder if prior authorization refusals led to his patient’s death.

The patient had advanced gastric cancer and the insurer initially denied a PET scan to rule out metastatic disease. When the scan was eventually allowed, it revealed that the cancer had spread.

Standard treatment would have been difficult for the patient, an older individual with comorbidities. But Dr. Sedhom knew that a European study had reported equal efficacy and fewer side effects with a reduced chemotherapy regimen, and he thought that was the best approach in this situation.

The insurer disagreed with Dr. Sedhom’s decision and, while the two argued, the patient’s symptoms worsened. He was admitted to the hospital, where he experienced a decline in function, common for older patients. “Long story short, he was never able to seek treatment and then transitioned to hospice,” Dr. Sedhom said. “It was one of those situations where there was a 3- to 4-week delay in what should have been standard care.”

That course of events is not an outlier but everyday life for physicians trying to navigate insurers’ prior authorization rules before they can treat their patients. Nearly 4 years after major organizations — American Hospital Association, America’s Health Insurance Plans, American Medical Association, Blue Cross Blue Shield Association, and others — signed a consensus statement agreeing to improve the prior authorization process, physicians say little progress has been made.

Indeed, 83% of physicians say that the number of prior authorizations required for prescription medications and medical services has increased over the last 5 years, according to survey results released earlier this year.

“It’s decidedly worse — there’s no question about it,” said Andrew R. Spector, MD, a neurologist and sleep medicine specialist at Duke Health in Durham, N.C. “Drugs that I used to get without prior authorizations now require them.”

When Vignesh I. Doraiswamy, MD, an internal medicine hospitalist at the Ohio State University Wexner Medical Center in Columbus, discharged a patient with Clostridioides difficile infection, he followed clinical guidelines to prescribe vancomycin for 10 to 14 days. “And the insurance company said, ‘Well, yeah, we only authorize about 5 days,’ which just makes no sense,” Dr. Doraiswamy said. “There’s nowhere in any literature that says 5 days is sufficient. What worries me is that is the standard of care we are supposed to give and yet we are unable to.”

Yash B. Jobanputra, MD, a cardiology fellow at Saint Vincent Hospital in Worcester, Mass., laments that prior authorization is used in situations that simply do not make common sense. During his residency, a woman who had tested positive for the BRCA gene mutation with a strong family history of breast cancer needed a breast ultrasound and an MRI scan every 6 months to 1 year. Despite the documentation that she was at extremely high risk for developing breast cancer, he had to go through prior authorization every time she was due for new images.

“I had to call the insurance company, they would put me on hold, I would wait to speak to a physician — and the end response would be, ‘Yeah, this is what needs to be done,’” he said. “But having established her positive status once should be enough really. I shouldn’t have to go through the circus all over again.”

Prior authorization is also being used for routine diagnostics, such as a Holter monitor for patients complaining of heart palpitations. “Depending on the insurance, for some patients we can give it to them in the clinic right away,” Dr. Jobanputra said. “Whereas some others we have to wait until we get prior authorization from the insurance company and the patient has to come back again to the hospital to get the monitor. That is a delay in patient care.”

The delays also extend to emergency care, Dr. Doraiswamy said. He cites the example of a heart attack patient who needed an emergency heart catheterization but ran into a prior authorization delay. “I just said, ‘Try your best not to get stressed’ which is not easy for a patient finding out their stay wasn’t covered when they had just been through a heart attack,” he said. “Then I spent 20 to 30 minutes — most of it on hold — to answer the question ‘Why did this patient need to get admitted?’ “

Physicians feel disrespected because that type of prior authorization hassle is just busywork. “Rarely is a valid stay that was initially denied, not eventually accepted,” Dr. Doraiswamy said. “But why couldn’t they have just seen that the guy had a heart attack and he obviously needed to be in the hospital?”

For Dr. Spector, the Duke Health sleep medicine specialist, prior authorization is not just a speed bump, it’s a full stop. Insurers have started mandating a multiple sleep latency test (MSLT) to confirm narcolepsy before covering medication to treat the condition. “We know that the MSLT is very often wrong,” he said. “There are a lot of times we’re dealing with patients with narcolepsy who simply don’t meet the testing criteria that the insurance requires, and payers will not accept our clinical judgment.”

In his view, the prior authorization landscape is worsening — and not only because a “faulty test” is being used to deny treatment. “The appeal process is worse,” Dr. Spector said. “I used to be able to get on the phone and do a peer-to-peer review with a physician who I could reason with… but that doesn’t happen anymore. There is virtually no way to bypass these blanket rules.”

Other survey findings also stand in direct contradiction of the 2018 consensus agreement:

A large majority (87%) of physicians report that prior authorization interferes with continuity of care, even though the industry groups agreed that patients should be protected from treatment disruption when there is a formulary or treatment-coverage change.

Despite a consensus to encourage transparency and easy accessibility of prior authorization requirements, 68% of physicians reported that it is difficult to determine whether a prescription medication requires prior authorization, and 58% report that it’s difficult for medical services.

Phone and fax are the most commonly used methods for completing prior authorizations, despite agreement that electronic prior authorization, using existing national standard transactions, should be accelerated. Fewer than one quarter of physicians said that their electronic health record system supports electronic prior authorization for prescription medications.

Dr. Spector wants to see legislation that forces insurers to live up to some of the tenets of the 2018 consensus statement. In September, a new Texas law went into effect, exempting physicians from prior authorization if, during the previous six months, 90% of their treatments met an insurer›s medical necessity criteria. In January, the recently approved Prior Authorization Reform Act in Illinois will reduce the number of services subject to prior authorization, mandate a prior authorization decision within 5 days, and set disciplinary measures for health plans that do not comply, among other things.

“What gives me hope is that at least somewhere in the country, somebody is doing something,” Dr. Spector said. “And if it goes well, maybe other insurers will adopt it. I’m really hoping they demonstrate that the money they can save on the administration of all the appeals and prior authorization paperwork can actually go into caring for patients.”

In addition to state-level action, reform may also be advancing at the federal level. In October, a bill was introduced in the U.S. Senate that mirrors a prior authorization reform bill introduced in the House of Representatives last May. Both bills have broad bipartisan support; the House bill has more than 235 co-sponsors.

In an interview with this news organization, Rep. Ami Bera, MD, (D-CA) said it is “very realistic” that the bill will become law during this session of Congress. “We do think this bill will get marked up in committee and hopefully we can get it to the floor either as a stand-alone bill where we know we have the votes to pass it or as part of a larger legislative package,” he said.

If approved, the Improving Seniors’ Timely Access to Care Act of 2021 would require that Medicare Advantage plans minimize the use of prior authorization for routinely approved services; require real-time decisions for certain requests; report the extent of their use of prior authorization and their rate of approvals or denials, among other things; and establish an electronic prior authorization system.

Medicare Advantage plans are private insurers that are regulated by the Centers for Medicare & Medicaid Services (CMS), which will create the specific rules and penalties associated with the reforms, if they become law. “One would presume that a condition of being a Medicare Advantage plan is that you’re going to have to comply with these new regulations,” said Katie Orrico, senior vice president of health policy and advocacy for the American Association of Neurological Surgeons and Congress of Neurological Surgeons (AANS/CNS). “So they will have some amount of teeth in the form of a mandate.”

The AANS and CNS are part of the Regulatory Relief Coalition, a group of 14 national physician specialty organizations. Winning prior authorization reform in the Medicare Advantage plans is part of its bigger strategy. “If those commercial plans have to follow a set of rules and processes for Medicare, then why not just expand those same processes to all other parts of their business?” Ms. Orrico said. 

Despite his frustration with their prior authorization processes, Dr. Doraiswamy, the Ohio State hospitalist, agrees that working to improve insurers’ practices is the best way forward. “It’s so easy to make them look like these evil, giant conglomerations that exist solely to suck money and not care about anyone’s health, but I don’t know if that’s necessarily the case,” he said. “We really have to figure out how best to work with insurance companies to make sure that, while they are profit-generating institutions, that [profit] shouldn’t come at the cost of patient care.”

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

Ramy Sedhom, MD, a medical oncologist and a palliative care physician at Penn Medicine Princeton Health in Plainsboro, N.J., will always wonder if prior authorization refusals led to his patient’s death.

The patient had advanced gastric cancer and the insurer initially denied a PET scan to rule out metastatic disease. When the scan was eventually allowed, it revealed that the cancer had spread.

Standard treatment would have been difficult for the patient, an older individual with comorbidities. But Dr. Sedhom knew that a European study had reported equal efficacy and fewer side effects with a reduced chemotherapy regimen, and he thought that was the best approach in this situation.

The insurer disagreed with Dr. Sedhom’s decision and, while the two argued, the patient’s symptoms worsened. He was admitted to the hospital, where he experienced a decline in function, common for older patients. “Long story short, he was never able to seek treatment and then transitioned to hospice,” Dr. Sedhom said. “It was one of those situations where there was a 3- to 4-week delay in what should have been standard care.”

That course of events is not an outlier but everyday life for physicians trying to navigate insurers’ prior authorization rules before they can treat their patients. Nearly 4 years after major organizations — American Hospital Association, America’s Health Insurance Plans, American Medical Association, Blue Cross Blue Shield Association, and others — signed a consensus statement agreeing to improve the prior authorization process, physicians say little progress has been made.

Indeed, 83% of physicians say that the number of prior authorizations required for prescription medications and medical services has increased over the last 5 years, according to survey results released earlier this year.

“It’s decidedly worse — there’s no question about it,” said Andrew R. Spector, MD, a neurologist and sleep medicine specialist at Duke Health in Durham, N.C. “Drugs that I used to get without prior authorizations now require them.”

When Vignesh I. Doraiswamy, MD, an internal medicine hospitalist at the Ohio State University Wexner Medical Center in Columbus, discharged a patient with Clostridioides difficile infection, he followed clinical guidelines to prescribe vancomycin for 10 to 14 days. “And the insurance company said, ‘Well, yeah, we only authorize about 5 days,’ which just makes no sense,” Dr. Doraiswamy said. “There’s nowhere in any literature that says 5 days is sufficient. What worries me is that is the standard of care we are supposed to give and yet we are unable to.”

Yash B. Jobanputra, MD, a cardiology fellow at Saint Vincent Hospital in Worcester, Mass., laments that prior authorization is used in situations that simply do not make common sense. During his residency, a woman who had tested positive for the BRCA gene mutation with a strong family history of breast cancer needed a breast ultrasound and an MRI scan every 6 months to 1 year. Despite the documentation that she was at extremely high risk for developing breast cancer, he had to go through prior authorization every time she was due for new images.

“I had to call the insurance company, they would put me on hold, I would wait to speak to a physician — and the end response would be, ‘Yeah, this is what needs to be done,’” he said. “But having established her positive status once should be enough really. I shouldn’t have to go through the circus all over again.”

Prior authorization is also being used for routine diagnostics, such as a Holter monitor for patients complaining of heart palpitations. “Depending on the insurance, for some patients we can give it to them in the clinic right away,” Dr. Jobanputra said. “Whereas some others we have to wait until we get prior authorization from the insurance company and the patient has to come back again to the hospital to get the monitor. That is a delay in patient care.”

The delays also extend to emergency care, Dr. Doraiswamy said. He cites the example of a heart attack patient who needed an emergency heart catheterization but ran into a prior authorization delay. “I just said, ‘Try your best not to get stressed’ which is not easy for a patient finding out their stay wasn’t covered when they had just been through a heart attack,” he said. “Then I spent 20 to 30 minutes — most of it on hold — to answer the question ‘Why did this patient need to get admitted?’ “

Physicians feel disrespected because that type of prior authorization hassle is just busywork. “Rarely is a valid stay that was initially denied, not eventually accepted,” Dr. Doraiswamy said. “But why couldn’t they have just seen that the guy had a heart attack and he obviously needed to be in the hospital?”

For Dr. Spector, the Duke Health sleep medicine specialist, prior authorization is not just a speed bump, it’s a full stop. Insurers have started mandating a multiple sleep latency test (MSLT) to confirm narcolepsy before covering medication to treat the condition. “We know that the MSLT is very often wrong,” he said. “There are a lot of times we’re dealing with patients with narcolepsy who simply don’t meet the testing criteria that the insurance requires, and payers will not accept our clinical judgment.”

In his view, the prior authorization landscape is worsening — and not only because a “faulty test” is being used to deny treatment. “The appeal process is worse,” Dr. Spector said. “I used to be able to get on the phone and do a peer-to-peer review with a physician who I could reason with… but that doesn’t happen anymore. There is virtually no way to bypass these blanket rules.”

Other survey findings also stand in direct contradiction of the 2018 consensus agreement:

A large majority (87%) of physicians report that prior authorization interferes with continuity of care, even though the industry groups agreed that patients should be protected from treatment disruption when there is a formulary or treatment-coverage change.

Despite a consensus to encourage transparency and easy accessibility of prior authorization requirements, 68% of physicians reported that it is difficult to determine whether a prescription medication requires prior authorization, and 58% report that it’s difficult for medical services.

Phone and fax are the most commonly used methods for completing prior authorizations, despite agreement that electronic prior authorization, using existing national standard transactions, should be accelerated. Fewer than one quarter of physicians said that their electronic health record system supports electronic prior authorization for prescription medications.

Dr. Spector wants to see legislation that forces insurers to live up to some of the tenets of the 2018 consensus statement. In September, a new Texas law went into effect, exempting physicians from prior authorization if, during the previous six months, 90% of their treatments met an insurer›s medical necessity criteria. In January, the recently approved Prior Authorization Reform Act in Illinois will reduce the number of services subject to prior authorization, mandate a prior authorization decision within 5 days, and set disciplinary measures for health plans that do not comply, among other things.

“What gives me hope is that at least somewhere in the country, somebody is doing something,” Dr. Spector said. “And if it goes well, maybe other insurers will adopt it. I’m really hoping they demonstrate that the money they can save on the administration of all the appeals and prior authorization paperwork can actually go into caring for patients.”

In addition to state-level action, reform may also be advancing at the federal level. In October, a bill was introduced in the U.S. Senate that mirrors a prior authorization reform bill introduced in the House of Representatives last May. Both bills have broad bipartisan support; the House bill has more than 235 co-sponsors.

In an interview with this news organization, Rep. Ami Bera, MD, (D-CA) said it is “very realistic” that the bill will become law during this session of Congress. “We do think this bill will get marked up in committee and hopefully we can get it to the floor either as a stand-alone bill where we know we have the votes to pass it or as part of a larger legislative package,” he said.

If approved, the Improving Seniors’ Timely Access to Care Act of 2021 would require that Medicare Advantage plans minimize the use of prior authorization for routinely approved services; require real-time decisions for certain requests; report the extent of their use of prior authorization and their rate of approvals or denials, among other things; and establish an electronic prior authorization system.

Medicare Advantage plans are private insurers that are regulated by the Centers for Medicare & Medicaid Services (CMS), which will create the specific rules and penalties associated with the reforms, if they become law. “One would presume that a condition of being a Medicare Advantage plan is that you’re going to have to comply with these new regulations,” said Katie Orrico, senior vice president of health policy and advocacy for the American Association of Neurological Surgeons and Congress of Neurological Surgeons (AANS/CNS). “So they will have some amount of teeth in the form of a mandate.”

The AANS and CNS are part of the Regulatory Relief Coalition, a group of 14 national physician specialty organizations. Winning prior authorization reform in the Medicare Advantage plans is part of its bigger strategy. “If those commercial plans have to follow a set of rules and processes for Medicare, then why not just expand those same processes to all other parts of their business?” Ms. Orrico said. 

Despite his frustration with their prior authorization processes, Dr. Doraiswamy, the Ohio State hospitalist, agrees that working to improve insurers’ practices is the best way forward. “It’s so easy to make them look like these evil, giant conglomerations that exist solely to suck money and not care about anyone’s health, but I don’t know if that’s necessarily the case,” he said. “We really have to figure out how best to work with insurance companies to make sure that, while they are profit-generating institutions, that [profit] shouldn’t come at the cost of patient care.”

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

Human papillomavirus (HPV) vaccination helps prevent cervical cancer and saves lives, new nationwide data suggest.

The analysis adds to a growing body of evidence demonstrating vaccine-associated changes in cervical cancer incidence and mortality.

Previous data from the United Kingdom, published earlier in November, showed that cervical cancer rates were 87% lower among girls who received the HPV vaccine compared to previously unvaccinated generations. Based on the analysis, the authors concluded that the UK’s HPV immunization program “almost eliminated cervical cancer” in women born since September 1995.

The latest study, published Nov. 29 in JAMA Pediatrics , reports a 38% drop in cervical cancer incidence and a 43% decline in mortality among young women and girls after HPV vaccination was introduced in the United States.

“These results are encouraging,” Peter Sasieni, MD, of King’s College London, and senior author on the U.K. study, told this news organization in an email.

The difference in incidence rates between the U.K. and U.S. studies, Dr. Sasieni explained, is likely due to HPV vaccine coverage not expanding as significantly in the United States as it has in the United Kingdom, and “thus one would anticipate a lower impact on the population in the U.S.”

In the U.S. analysis, Justin Barnes, MD, a radiation oncology resident at Washington University, St. Louis, and colleagues examined cervical cancer incidence between January 2001 and December 2017 using Surveillance, Epidemiology, and End Results and National Program of Cancer Registries data as well as mortality data from the National Center for Health Statistics.

Dr. Barnes and colleagues then compared changes in cervical cancer incidence and mortality between prevaccination years (January 2001 to December 2005) and postvaccination years (January 2010 to December 2017) among three age cohorts – 15-24 years, 25-29 years, and 30-39 years.

“The older 2 groups were included as comparison, given their low vaccination rates,” Dr. Barnes and colleagues explained.

Results show that between the prevaccination and postvaccination periods, the incidence of cervical cancer dropped by 38% in the youngest cohort and by only 16% in the middle-aged group and 8% in the oldest cohort.

Women and girls in the youngest group saw a striking drop in mortality: a 43% decline, which translated to a mortality rate of 0.6 per 100,000.

On the other hand, the authors report a 4.7% decline in mortality in the oldest group and a 4.3% increase in mortality in the middle-aged group – translating to a mortality rate of 1.89 per 100,000 and 0.57 per 100,000, respectively.

Overall, “these nationwide data showed decreased cervical cancer incidence and mortality among women and girls aged 15-24 years after HPV vaccine introduction,” Dr. Barnes and colleagues wrote. The changes in cervical cancer incidence and mortality observed in the youngest age group “were greater than changes in those aged 25 to 29 years and 30 to 39 years, suggesting possible associations with HPV vaccination.”

This analysis lines up with previous evidence from U.S. epidemiologic data, which “have shown decreased cervical cancer incidence after vaccine implementation in women and girls aged 15 to 24 years but not older women.”

Although “the number of deaths and hence the number of potentially averted deaths in young women and girls was small,” the study adds to the current literature by “providing suggestive evidence for vaccine-associated decreases in cervical cancer mortality,” investigators concluded.

The authors have disclosed no relevant financial relationships.

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

Human papillomavirus (HPV) vaccination helps prevent cervical cancer and saves lives, new nationwide data suggest.

The analysis adds to a growing body of evidence demonstrating vaccine-associated changes in cervical cancer incidence and mortality.

Previous data from the United Kingdom, published earlier in November, showed that cervical cancer rates were 87% lower among girls who received the HPV vaccine compared to previously unvaccinated generations. Based on the analysis, the authors concluded that the UK’s HPV immunization program “almost eliminated cervical cancer” in women born since September 1995.

The latest study, published Nov. 29 in JAMA Pediatrics , reports a 38% drop in cervical cancer incidence and a 43% decline in mortality among young women and girls after HPV vaccination was introduced in the United States.

“These results are encouraging,” Peter Sasieni, MD, of King’s College London, and senior author on the U.K. study, told this news organization in an email.

The difference in incidence rates between the U.K. and U.S. studies, Dr. Sasieni explained, is likely due to HPV vaccine coverage not expanding as significantly in the United States as it has in the United Kingdom, and “thus one would anticipate a lower impact on the population in the U.S.”

In the U.S. analysis, Justin Barnes, MD, a radiation oncology resident at Washington University, St. Louis, and colleagues examined cervical cancer incidence between January 2001 and December 2017 using Surveillance, Epidemiology, and End Results and National Program of Cancer Registries data as well as mortality data from the National Center for Health Statistics.

Dr. Barnes and colleagues then compared changes in cervical cancer incidence and mortality between prevaccination years (January 2001 to December 2005) and postvaccination years (January 2010 to December 2017) among three age cohorts – 15-24 years, 25-29 years, and 30-39 years.

“The older 2 groups were included as comparison, given their low vaccination rates,” Dr. Barnes and colleagues explained.

Results show that between the prevaccination and postvaccination periods, the incidence of cervical cancer dropped by 38% in the youngest cohort and by only 16% in the middle-aged group and 8% in the oldest cohort.

Women and girls in the youngest group saw a striking drop in mortality: a 43% decline, which translated to a mortality rate of 0.6 per 100,000.

On the other hand, the authors report a 4.7% decline in mortality in the oldest group and a 4.3% increase in mortality in the middle-aged group – translating to a mortality rate of 1.89 per 100,000 and 0.57 per 100,000, respectively.

Overall, “these nationwide data showed decreased cervical cancer incidence and mortality among women and girls aged 15-24 years after HPV vaccine introduction,” Dr. Barnes and colleagues wrote. The changes in cervical cancer incidence and mortality observed in the youngest age group “were greater than changes in those aged 25 to 29 years and 30 to 39 years, suggesting possible associations with HPV vaccination.”

This analysis lines up with previous evidence from U.S. epidemiologic data, which “have shown decreased cervical cancer incidence after vaccine implementation in women and girls aged 15 to 24 years but not older women.”

Although “the number of deaths and hence the number of potentially averted deaths in young women and girls was small,” the study adds to the current literature by “providing suggestive evidence for vaccine-associated decreases in cervical cancer mortality,” investigators concluded.

The authors have disclosed no relevant financial relationships.

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

Human papillomavirus (HPV) vaccination helps prevent cervical cancer and saves lives, new nationwide data suggest.

The analysis adds to a growing body of evidence demonstrating vaccine-associated changes in cervical cancer incidence and mortality.

Previous data from the United Kingdom, published earlier in November, showed that cervical cancer rates were 87% lower among girls who received the HPV vaccine compared to previously unvaccinated generations. Based on the analysis, the authors concluded that the UK’s HPV immunization program “almost eliminated cervical cancer” in women born since September 1995.

The latest study, published Nov. 29 in JAMA Pediatrics , reports a 38% drop in cervical cancer incidence and a 43% decline in mortality among young women and girls after HPV vaccination was introduced in the United States.

“These results are encouraging,” Peter Sasieni, MD, of King’s College London, and senior author on the U.K. study, told this news organization in an email.

The difference in incidence rates between the U.K. and U.S. studies, Dr. Sasieni explained, is likely due to HPV vaccine coverage not expanding as significantly in the United States as it has in the United Kingdom, and “thus one would anticipate a lower impact on the population in the U.S.”

In the U.S. analysis, Justin Barnes, MD, a radiation oncology resident at Washington University, St. Louis, and colleagues examined cervical cancer incidence between January 2001 and December 2017 using Surveillance, Epidemiology, and End Results and National Program of Cancer Registries data as well as mortality data from the National Center for Health Statistics.

Dr. Barnes and colleagues then compared changes in cervical cancer incidence and mortality between prevaccination years (January 2001 to December 2005) and postvaccination years (January 2010 to December 2017) among three age cohorts – 15-24 years, 25-29 years, and 30-39 years.

“The older 2 groups were included as comparison, given their low vaccination rates,” Dr. Barnes and colleagues explained.

Results show that between the prevaccination and postvaccination periods, the incidence of cervical cancer dropped by 38% in the youngest cohort and by only 16% in the middle-aged group and 8% in the oldest cohort.

Women and girls in the youngest group saw a striking drop in mortality: a 43% decline, which translated to a mortality rate of 0.6 per 100,000.

On the other hand, the authors report a 4.7% decline in mortality in the oldest group and a 4.3% increase in mortality in the middle-aged group – translating to a mortality rate of 1.89 per 100,000 and 0.57 per 100,000, respectively.

Overall, “these nationwide data showed decreased cervical cancer incidence and mortality among women and girls aged 15-24 years after HPV vaccine introduction,” Dr. Barnes and colleagues wrote. The changes in cervical cancer incidence and mortality observed in the youngest age group “were greater than changes in those aged 25 to 29 years and 30 to 39 years, suggesting possible associations with HPV vaccination.”

This analysis lines up with previous evidence from U.S. epidemiologic data, which “have shown decreased cervical cancer incidence after vaccine implementation in women and girls aged 15 to 24 years but not older women.”

Although “the number of deaths and hence the number of potentially averted deaths in young women and girls was small,” the study adds to the current literature by “providing suggestive evidence for vaccine-associated decreases in cervical cancer mortality,” investigators concluded.

The authors have disclosed no relevant financial relationships.

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

Municipal budget allocations can affect severe maternal morbidity (SMM) rates, a cross-sectional study published in JAMA Network Open reported.

Led by Felix M. Muchomba, PhD, an assistant professor at Rutgers University School of Social Work in New Brunswick, N.J., the study found that local expenditures on fire and ambulance, transportation, health, housing, and libraries were negatively associated with SMM. Specifically, annual per-capita expenditures of $1,000 and higher in these categories were associated with a 35.4%-67.3% lower risk of SMM: odds ratios, 0.33 (95% confidence interval, 0.15-0.72) to 0.65 (95% CI, 0.46-0.91).

In contrast, expenditures on police were positively associated with SMM: OR, 1.15 (95% CI, 1.04-1.28).

In the first study of environmental services spending and SMM done at the municipal level – others have focused on state and county funding – Dr. Muchomba’s group analyzed 2008-2018 birth files linked to maternal hospital discharge records and U.S. Census municipal expenditures data.

The study’s cohort comprised 1,001,410 mothers giving birth in New Jersey hospitals with a mean age of 29.8 years. Of these,10.9 % were Asian, 14.8% were Black, 28.0% were Hispanic, and 44.7% were White.

Per-capita municipal expenditures were reviewed for a broad range of city services: education, public health, fire and ambulance, parks, recreation, natural resources, housing, community development, public welfare; police; transportation, and libraries. “Each year municipalities spend about $600 billion nationwide on local services, investing far more than counties do,” Dr. Muchomba said.

Among developed nations, the United States has a rate of high maternal morbidity, a determinant of maternal mortality, and New Jersey has one of the highest rates in the country, although, paradoxically, it has one of the lowest state poverty rates and one of the highest state income levels, he added, said explaining the impetus for the study.

Previous research has found that state and local investment in non–health specific services can reduce infant mortality rates (IMR). Last year, for example, a national study of 2000-2016 data led by Neal D. Goldstein, PhD, MRI, an assistant professor of epidemiology and biostatistics at Drexel University in Philadelphia, reported that a $0.30 per-person increase in environmental spending was associated with a decrease of 0.03 deaths per 1,000 live births, and a $0.73 per-person increase in social services spending was associated with a decrease of 0.02 deaths per 1,000 live births. “IMR is reflective of, and amenable to broad social, economic, and health care delivery contexts within a society. State and local governments, via increased social and environmental expenditures, have the potential to reduce, albeit not eliminate, IMR disparities,” Dr. Goldstein’s group wrote in Pediatrics.

According to Aimee J. Palumbo, PhD, MPH, an assistant professor in the department of epidemiology & biostatistics in the College of Public Health at Temple University in Philadelphia, who was not involved in the study, the current study’s results are broadly consistent with those of the Goldstein study, of which she is a coauthor, in that it shows spending on public welfare is associated with better outcomes following birth.

“This analysis, however, is done at the municipality level, which allows it to evaluate variations in spending that occur at more local levels, rather than the state level like ours,” she said in an interview. “The researchers are also able to control for individual-level factors,” which is good as it is really suggestive of the impact that spending has on outcomes after controlling for some individual characteristics.”

Both studies speak to the importance of exploring funding for social services and specific programs that affect health, Dr. Palumbo added.

Services that affect nonmedical determinants of health broadly affect how people live their daily lives, Dr. Muchomba said – where they live, how they get to work and to medical appointments, where they shop, how they engage in recreation.

“Housing is very important for mothers since it provides a safe space to shelter during pregnancy and during recovery from childbirth. It’s a safe place to store medications and to prepare healthy food,” he continued. “But much of the housing in New Jersey is very expensive, and some mothers may have to decide between paying the rent and buying healthy food.”

In other benefits, local services spending provides transportation to jobs and health care, bus shelters, effective waste management, viable sidewalks, safe crosswalks, and public exercise venues that help to reduce obesity.

The category that Dr. Muchomba is most often asked about is libraries. “Why libraries? Our hypothesis is that libraries provide some low-income people with their only access to computers and the Internet. They’re a major resource for information and a proxy for the delivery of other services,” he said. In addition, many libraries offer English as a second language classes, which may increase health literacy among immigrants.

A major objective of the 2020 Maternal Health Action Plan of the U.S. Department of Health & Human Services is to better target resources by identifying problem spots for maternal morbidity and mortality. “Our findings strongly suggest that surveillance at the municipal level, a level rarely considered in studies of health outcomes, would be important for success in such efforts,” the authors wrote.

Dr. Muchomba believes doctors can have a role to play in targeting of spending for local services that can reduce maternal morbidity and mortality. “Many physicians are engaged in community health outreach efforts. As respected people in the community, they need to be aware of these other determinants of health that may be driving maternal morbidity rates in their communities.”

This research was supported by the Robert Wood Johnson Foundation, the National Center for Advancing Translational Sciences, the U.S. Department of Health & Human Services Health Resources and Service Administration and the Child Health Institute of New Jersey. Dr. Muchomba reported a grant from Eunice Kennedy Shriver National Institute of Child Health and Human Development outside of the submitted work. Dr. Palumbo had no potential competing interests to disclose.

Municipal budget allocations can affect severe maternal morbidity (SMM) rates, a cross-sectional study published in JAMA Network Open reported.

Led by Felix M. Muchomba, PhD, an assistant professor at Rutgers University School of Social Work in New Brunswick, N.J., the study found that local expenditures on fire and ambulance, transportation, health, housing, and libraries were negatively associated with SMM. Specifically, annual per-capita expenditures of $1,000 and higher in these categories were associated with a 35.4%-67.3% lower risk of SMM: odds ratios, 0.33 (95% confidence interval, 0.15-0.72) to 0.65 (95% CI, 0.46-0.91).

In contrast, expenditures on police were positively associated with SMM: OR, 1.15 (95% CI, 1.04-1.28).

In the first study of environmental services spending and SMM done at the municipal level – others have focused on state and county funding – Dr. Muchomba’s group analyzed 2008-2018 birth files linked to maternal hospital discharge records and U.S. Census municipal expenditures data.

The study’s cohort comprised 1,001,410 mothers giving birth in New Jersey hospitals with a mean age of 29.8 years. Of these,10.9 % were Asian, 14.8% were Black, 28.0% were Hispanic, and 44.7% were White.

Per-capita municipal expenditures were reviewed for a broad range of city services: education, public health, fire and ambulance, parks, recreation, natural resources, housing, community development, public welfare; police; transportation, and libraries. “Each year municipalities spend about $600 billion nationwide on local services, investing far more than counties do,” Dr. Muchomba said.

Among developed nations, the United States has a rate of high maternal morbidity, a determinant of maternal mortality, and New Jersey has one of the highest rates in the country, although, paradoxically, it has one of the lowest state poverty rates and one of the highest state income levels, he added, said explaining the impetus for the study.

Previous research has found that state and local investment in non–health specific services can reduce infant mortality rates (IMR). Last year, for example, a national study of 2000-2016 data led by Neal D. Goldstein, PhD, MRI, an assistant professor of epidemiology and biostatistics at Drexel University in Philadelphia, reported that a $0.30 per-person increase in environmental spending was associated with a decrease of 0.03 deaths per 1,000 live births, and a $0.73 per-person increase in social services spending was associated with a decrease of 0.02 deaths per 1,000 live births. “IMR is reflective of, and amenable to broad social, economic, and health care delivery contexts within a society. State and local governments, via increased social and environmental expenditures, have the potential to reduce, albeit not eliminate, IMR disparities,” Dr. Goldstein’s group wrote in Pediatrics.

According to Aimee J. Palumbo, PhD, MPH, an assistant professor in the department of epidemiology & biostatistics in the College of Public Health at Temple University in Philadelphia, who was not involved in the study, the current study’s results are broadly consistent with those of the Goldstein study, of which she is a coauthor, in that it shows spending on public welfare is associated with better outcomes following birth.

“This analysis, however, is done at the municipality level, which allows it to evaluate variations in spending that occur at more local levels, rather than the state level like ours,” she said in an interview. “The researchers are also able to control for individual-level factors,” which is good as it is really suggestive of the impact that spending has on outcomes after controlling for some individual characteristics.”

Both studies speak to the importance of exploring funding for social services and specific programs that affect health, Dr. Palumbo added.

Services that affect nonmedical determinants of health broadly affect how people live their daily lives, Dr. Muchomba said – where they live, how they get to work and to medical appointments, where they shop, how they engage in recreation.

“Housing is very important for mothers since it provides a safe space to shelter during pregnancy and during recovery from childbirth. It’s a safe place to store medications and to prepare healthy food,” he continued. “But much of the housing in New Jersey is very expensive, and some mothers may have to decide between paying the rent and buying healthy food.”

In other benefits, local services spending provides transportation to jobs and health care, bus shelters, effective waste management, viable sidewalks, safe crosswalks, and public exercise venues that help to reduce obesity.

The category that Dr. Muchomba is most often asked about is libraries. “Why libraries? Our hypothesis is that libraries provide some low-income people with their only access to computers and the Internet. They’re a major resource for information and a proxy for the delivery of other services,” he said. In addition, many libraries offer English as a second language classes, which may increase health literacy among immigrants.

A major objective of the 2020 Maternal Health Action Plan of the U.S. Department of Health & Human Services is to better target resources by identifying problem spots for maternal morbidity and mortality. “Our findings strongly suggest that surveillance at the municipal level, a level rarely considered in studies of health outcomes, would be important for success in such efforts,” the authors wrote.

Dr. Muchomba believes doctors can have a role to play in targeting of spending for local services that can reduce maternal morbidity and mortality. “Many physicians are engaged in community health outreach efforts. As respected people in the community, they need to be aware of these other determinants of health that may be driving maternal morbidity rates in their communities.”

This research was supported by the Robert Wood Johnson Foundation, the National Center for Advancing Translational Sciences, the U.S. Department of Health & Human Services Health Resources and Service Administration and the Child Health Institute of New Jersey. Dr. Muchomba reported a grant from Eunice Kennedy Shriver National Institute of Child Health and Human Development outside of the submitted work. Dr. Palumbo had no potential competing interests to disclose.

Municipal budget allocations can affect severe maternal morbidity (SMM) rates, a cross-sectional study published in JAMA Network Open reported.

Led by Felix M. Muchomba, PhD, an assistant professor at Rutgers University School of Social Work in New Brunswick, N.J., the study found that local expenditures on fire and ambulance, transportation, health, housing, and libraries were negatively associated with SMM. Specifically, annual per-capita expenditures of $1,000 and higher in these categories were associated with a 35.4%-67.3% lower risk of SMM: odds ratios, 0.33 (95% confidence interval, 0.15-0.72) to 0.65 (95% CI, 0.46-0.91).

In contrast, expenditures on police were positively associated with SMM: OR, 1.15 (95% CI, 1.04-1.28).

In the first study of environmental services spending and SMM done at the municipal level – others have focused on state and county funding – Dr. Muchomba’s group analyzed 2008-2018 birth files linked to maternal hospital discharge records and U.S. Census municipal expenditures data.

The study’s cohort comprised 1,001,410 mothers giving birth in New Jersey hospitals with a mean age of 29.8 years. Of these,10.9 % were Asian, 14.8% were Black, 28.0% were Hispanic, and 44.7% were White.

Per-capita municipal expenditures were reviewed for a broad range of city services: education, public health, fire and ambulance, parks, recreation, natural resources, housing, community development, public welfare; police; transportation, and libraries. “Each year municipalities spend about $600 billion nationwide on local services, investing far more than counties do,” Dr. Muchomba said.

Among developed nations, the United States has a rate of high maternal morbidity, a determinant of maternal mortality, and New Jersey has one of the highest rates in the country, although, paradoxically, it has one of the lowest state poverty rates and one of the highest state income levels, he added, said explaining the impetus for the study.

Previous research has found that state and local investment in non–health specific services can reduce infant mortality rates (IMR). Last year, for example, a national study of 2000-2016 data led by Neal D. Goldstein, PhD, MRI, an assistant professor of epidemiology and biostatistics at Drexel University in Philadelphia, reported that a $0.30 per-person increase in environmental spending was associated with a decrease of 0.03 deaths per 1,000 live births, and a $0.73 per-person increase in social services spending was associated with a decrease of 0.02 deaths per 1,000 live births. “IMR is reflective of, and amenable to broad social, economic, and health care delivery contexts within a society. State and local governments, via increased social and environmental expenditures, have the potential to reduce, albeit not eliminate, IMR disparities,” Dr. Goldstein’s group wrote in Pediatrics.

According to Aimee J. Palumbo, PhD, MPH, an assistant professor in the department of epidemiology & biostatistics in the College of Public Health at Temple University in Philadelphia, who was not involved in the study, the current study’s results are broadly consistent with those of the Goldstein study, of which she is a coauthor, in that it shows spending on public welfare is associated with better outcomes following birth.

“This analysis, however, is done at the municipality level, which allows it to evaluate variations in spending that occur at more local levels, rather than the state level like ours,” she said in an interview. “The researchers are also able to control for individual-level factors,” which is good as it is really suggestive of the impact that spending has on outcomes after controlling for some individual characteristics.”

Both studies speak to the importance of exploring funding for social services and specific programs that affect health, Dr. Palumbo added.

Services that affect nonmedical determinants of health broadly affect how people live their daily lives, Dr. Muchomba said – where they live, how they get to work and to medical appointments, where they shop, how they engage in recreation.

“Housing is very important for mothers since it provides a safe space to shelter during pregnancy and during recovery from childbirth. It’s a safe place to store medications and to prepare healthy food,” he continued. “But much of the housing in New Jersey is very expensive, and some mothers may have to decide between paying the rent and buying healthy food.”

In other benefits, local services spending provides transportation to jobs and health care, bus shelters, effective waste management, viable sidewalks, safe crosswalks, and public exercise venues that help to reduce obesity.

The category that Dr. Muchomba is most often asked about is libraries. “Why libraries? Our hypothesis is that libraries provide some low-income people with their only access to computers and the Internet. They’re a major resource for information and a proxy for the delivery of other services,” he said. In addition, many libraries offer English as a second language classes, which may increase health literacy among immigrants.

A major objective of the 2020 Maternal Health Action Plan of the U.S. Department of Health & Human Services is to better target resources by identifying problem spots for maternal morbidity and mortality. “Our findings strongly suggest that surveillance at the municipal level, a level rarely considered in studies of health outcomes, would be important for success in such efforts,” the authors wrote.

Dr. Muchomba believes doctors can have a role to play in targeting of spending for local services that can reduce maternal morbidity and mortality. “Many physicians are engaged in community health outreach efforts. As respected people in the community, they need to be aware of these other determinants of health that may be driving maternal morbidity rates in their communities.”

This research was supported by the Robert Wood Johnson Foundation, the National Center for Advancing Translational Sciences, the U.S. Department of Health & Human Services Health Resources and Service Administration and the Child Health Institute of New Jersey. Dr. Muchomba reported a grant from Eunice Kennedy Shriver National Institute of Child Health and Human Development outside of the submitted work. Dr. Palumbo had no potential competing interests to disclose.

Gynecologists have experience managing human papillomavirus–associated diseases of the lower genital tract. However, HPV also causes warty disease, dysplasia, and carcinoma of the head and neck. Risk factors for head and neck cancer include smoking and smokeless tobacco use, alcohol consumption, periodontal disease, radiation exposure, and HPV. The incidence of HPV-associated head and neck cancer is rising, particularly among men, at a rate of 2.7% per year.¹ The incidence of HPV-associated squamous cell carcinoma of the oropharynx now surpasses that of cervical cancer. Concerns exist regarding occupational exposure to HPV by health care providers (HCP) who perform smoke-generating procedures on HPV-infected tissues, and the potential for them to develop head and neck pathology.

In March of 2020, the American Society for Colposcopy and Cervical Pathology made the recommendation that clinicians who are routinely exposed to HPV should protect themselves against the sequela of occupationally acquired HPV by receiving the HPV vaccine.² They advocate for the “complete provider team” including physicians, advanced practice providers, nurses, operative technicians, and residents and fellows to be considered for protective vaccination.

Similar to disease patterns in the genital tract, different strains of HPV have differing propensity to cause benign, premalignant, and malignant disease states. HPV 6 and 11 are more commonly associated with warty disease in the nares, pharynx, and tonsillar tissues. HPV 16, 18, 31, and 33 (most commonly 16) are considered high risk for carcinoma formation, particularly of the tonsils and base of the tongue.

The procedures most implicated in occupational HPV exposure include ablative procedures for anogenital warts, laser ablation of vaginal and vulvar dysplasia, and electrosurgical excisional procedures for cervical dysplasia. Smoke plumes from HPV-associated procedures are known to contain HPV for both laser and electrocautery sources.³ A study of 134 patients undergoing surgical procedures for laser ablation of HPV-infected tissues detected concordant strains of HPV in approximately 30% of smoke plumes and approximately 1.5% of surgeons’ nares.⁴ Not all procedures appear to carry the same risk. Electrocoagulation procedures appear to yield fewer postprocedural positive mucosal swabs for HPV, compared with those taken after CO₂ laser.⁵

Animal studies have shown that papilloma virus procured from smoke plume has the capacity to generate disease. When 10 calves were inoculated with bovine papillary virus obtained from smoke plumes from laser ablation of bovine papillomavirus lesions, all calves manifested BPV fibropapilloma lesions at the sites of inoculation.⁶

There appears to be an increased incidence of HPV-associated head and neck disease among surgeons who perform procedures on HPV tissues, and there have been multiple case reports that have cited examples of HPV-associated benign and malignant disease among HCPs with frequent occupational exposure to HPV anogenital ablative and excisional procedures.⁷ While these observations are not proof of causation, they are cause for concern.

While the ASCCP guidelines advocate for HPV vaccination as a strategy for prevention of occupationally related HPV-associated disease, there are other strategies in place to minimize risk. The CDC guidelines for environmental infection control in health care facilities include the following recommendations:

• In settings where surgical lasers are used, wear appropriate personnel protective equipment (PPE), including N95 or N100 respirators to minimize exposure to laser plumes.
• Use central wall suction units with in-line filters to evacuate minimal laser plumes.
• Use a mechanical smoke evaluation system with a high efficiency filter to manage the generation of large amounts of laser plume, when ablating tissue infected with HPV.
• Use local exhaust ventilation (LEV).⁸

When closely adhered to, these methods appear to provide high-level protection. Data suggest that, when HCPs can access appropriate protective equipment, risks for HPV exposure are low. However, this is more feasible for larger hospital facilities, and may be more limited in outpatient settings. This has led to the consideration of background protection in the form of HPV vaccination for at-risk HCPs. This is analogous to mandates for HCPs to receive hepatitis B vaccination despite the concomitant practice of universal precautions in health care settings. Preventative strategies are typically most efficacious when performed in concert.

After nearly 2 decades of widespread use, we have confidence in the safety of the HPV vaccination. Its benefit through age 45 has been established, leading to the 2018 FDA approval for the 9-valent HPV vaccine, Guardisil-9, for this expanded age group. It would seem logical that systematic administration of the HPV vaccine for at-risk HCPs would be both feasible and safe. There are well-established systems for administering vaccines for HCPs in all health care systems. Perhaps health system administrators should consider routinely offering HPV vaccination for at-risk employees as part of their occupational health care responsibilities. One important caveat being the cost and efficacy of HPV vaccination in this group has not been not established.

In the meantime, it is critical that gynecology providers be aware of their risk for occupational exposure to HPV when using laser and electrocautery techniques on HPV-infected tissues and the potential for them developing head and neck pathology. They should strictly adhere to preventative measures such as use of fit-tested N-95 respirators, mechanical smoke evacuators with high-efficiency filters and work in environments with adequate room ventilation. We all should individually evaluate what role HPV vaccination may play for us in augmenting our own safety.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Van Dyne EA et al. MMWR Morb Mortal Wkly Rep. 2018 Aug 24;67(33):918-24.

2. ASCCP. ASCCP recommends HPV vaccination for providers.

3. Fox-Lewis A et al. Occup Environ Med. 2020 Dec;77(12):809-17.

4. Zhou Q et al. Cancer Manag Res. 2019;11:3643-54

5. Bergbrant I et al. Acta Derm Venereol. 1994 Sep;74(5):393-5.

6. Garden J et al. Arch Dermatol. 2002 Oct;138(10):1303-7.

7. Harrison R, Huh W. Obstet Gynecol. 2020;136:663-5.

8. CDC. 1996. DHHS (NIOSH) Publication Number 96-128.

Gynecologists have experience managing human papillomavirus–associated diseases of the lower genital tract. However, HPV also causes warty disease, dysplasia, and carcinoma of the head and neck. Risk factors for head and neck cancer include smoking and smokeless tobacco use, alcohol consumption, periodontal disease, radiation exposure, and HPV. The incidence of HPV-associated head and neck cancer is rising, particularly among men, at a rate of 2.7% per year.¹ The incidence of HPV-associated squamous cell carcinoma of the oropharynx now surpasses that of cervical cancer. Concerns exist regarding occupational exposure to HPV by health care providers (HCP) who perform smoke-generating procedures on HPV-infected tissues, and the potential for them to develop head and neck pathology.

In March of 2020, the American Society for Colposcopy and Cervical Pathology made the recommendation that clinicians who are routinely exposed to HPV should protect themselves against the sequela of occupationally acquired HPV by receiving the HPV vaccine.² They advocate for the “complete provider team” including physicians, advanced practice providers, nurses, operative technicians, and residents and fellows to be considered for protective vaccination.

Similar to disease patterns in the genital tract, different strains of HPV have differing propensity to cause benign, premalignant, and malignant disease states. HPV 6 and 11 are more commonly associated with warty disease in the nares, pharynx, and tonsillar tissues. HPV 16, 18, 31, and 33 (most commonly 16) are considered high risk for carcinoma formation, particularly of the tonsils and base of the tongue.

The procedures most implicated in occupational HPV exposure include ablative procedures for anogenital warts, laser ablation of vaginal and vulvar dysplasia, and electrosurgical excisional procedures for cervical dysplasia. Smoke plumes from HPV-associated procedures are known to contain HPV for both laser and electrocautery sources.³ A study of 134 patients undergoing surgical procedures for laser ablation of HPV-infected tissues detected concordant strains of HPV in approximately 30% of smoke plumes and approximately 1.5% of surgeons’ nares.⁴ Not all procedures appear to carry the same risk. Electrocoagulation procedures appear to yield fewer postprocedural positive mucosal swabs for HPV, compared with those taken after CO₂ laser.⁵

Animal studies have shown that papilloma virus procured from smoke plume has the capacity to generate disease. When 10 calves were inoculated with bovine papillary virus obtained from smoke plumes from laser ablation of bovine papillomavirus lesions, all calves manifested BPV fibropapilloma lesions at the sites of inoculation.⁶

There appears to be an increased incidence of HPV-associated head and neck disease among surgeons who perform procedures on HPV tissues, and there have been multiple case reports that have cited examples of HPV-associated benign and malignant disease among HCPs with frequent occupational exposure to HPV anogenital ablative and excisional procedures.⁷ While these observations are not proof of causation, they are cause for concern.

While the ASCCP guidelines advocate for HPV vaccination as a strategy for prevention of occupationally related HPV-associated disease, there are other strategies in place to minimize risk. The CDC guidelines for environmental infection control in health care facilities include the following recommendations:

• In settings where surgical lasers are used, wear appropriate personnel protective equipment (PPE), including N95 or N100 respirators to minimize exposure to laser plumes.
• Use central wall suction units with in-line filters to evacuate minimal laser plumes.
• Use a mechanical smoke evaluation system with a high efficiency filter to manage the generation of large amounts of laser plume, when ablating tissue infected with HPV.
• Use local exhaust ventilation (LEV).⁸

When closely adhered to, these methods appear to provide high-level protection. Data suggest that, when HCPs can access appropriate protective equipment, risks for HPV exposure are low. However, this is more feasible for larger hospital facilities, and may be more limited in outpatient settings. This has led to the consideration of background protection in the form of HPV vaccination for at-risk HCPs. This is analogous to mandates for HCPs to receive hepatitis B vaccination despite the concomitant practice of universal precautions in health care settings. Preventative strategies are typically most efficacious when performed in concert.

After nearly 2 decades of widespread use, we have confidence in the safety of the HPV vaccination. Its benefit through age 45 has been established, leading to the 2018 FDA approval for the 9-valent HPV vaccine, Guardisil-9, for this expanded age group. It would seem logical that systematic administration of the HPV vaccine for at-risk HCPs would be both feasible and safe. There are well-established systems for administering vaccines for HCPs in all health care systems. Perhaps health system administrators should consider routinely offering HPV vaccination for at-risk employees as part of their occupational health care responsibilities. One important caveat being the cost and efficacy of HPV vaccination in this group has not been not established.

In the meantime, it is critical that gynecology providers be aware of their risk for occupational exposure to HPV when using laser and electrocautery techniques on HPV-infected tissues and the potential for them developing head and neck pathology. They should strictly adhere to preventative measures such as use of fit-tested N-95 respirators, mechanical smoke evacuators with high-efficiency filters and work in environments with adequate room ventilation. We all should individually evaluate what role HPV vaccination may play for us in augmenting our own safety.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Van Dyne EA et al. MMWR Morb Mortal Wkly Rep. 2018 Aug 24;67(33):918-24.

2. ASCCP. ASCCP recommends HPV vaccination for providers.

3. Fox-Lewis A et al. Occup Environ Med. 2020 Dec;77(12):809-17.

4. Zhou Q et al. Cancer Manag Res. 2019;11:3643-54

5. Bergbrant I et al. Acta Derm Venereol. 1994 Sep;74(5):393-5.

6. Garden J et al. Arch Dermatol. 2002 Oct;138(10):1303-7.

7. Harrison R, Huh W. Obstet Gynecol. 2020;136:663-5.

8. CDC. 1996. DHHS (NIOSH) Publication Number 96-128.

Gynecologists have experience managing human papillomavirus–associated diseases of the lower genital tract. However, HPV also causes warty disease, dysplasia, and carcinoma of the head and neck. Risk factors for head and neck cancer include smoking and smokeless tobacco use, alcohol consumption, periodontal disease, radiation exposure, and HPV. The incidence of HPV-associated head and neck cancer is rising, particularly among men, at a rate of 2.7% per year.¹ The incidence of HPV-associated squamous cell carcinoma of the oropharynx now surpasses that of cervical cancer. Concerns exist regarding occupational exposure to HPV by health care providers (HCP) who perform smoke-generating procedures on HPV-infected tissues, and the potential for them to develop head and neck pathology.

In March of 2020, the American Society for Colposcopy and Cervical Pathology made the recommendation that clinicians who are routinely exposed to HPV should protect themselves against the sequela of occupationally acquired HPV by receiving the HPV vaccine.² They advocate for the “complete provider team” including physicians, advanced practice providers, nurses, operative technicians, and residents and fellows to be considered for protective vaccination.

Similar to disease patterns in the genital tract, different strains of HPV have differing propensity to cause benign, premalignant, and malignant disease states. HPV 6 and 11 are more commonly associated with warty disease in the nares, pharynx, and tonsillar tissues. HPV 16, 18, 31, and 33 (most commonly 16) are considered high risk for carcinoma formation, particularly of the tonsils and base of the tongue.

The procedures most implicated in occupational HPV exposure include ablative procedures for anogenital warts, laser ablation of vaginal and vulvar dysplasia, and electrosurgical excisional procedures for cervical dysplasia. Smoke plumes from HPV-associated procedures are known to contain HPV for both laser and electrocautery sources.³ A study of 134 patients undergoing surgical procedures for laser ablation of HPV-infected tissues detected concordant strains of HPV in approximately 30% of smoke plumes and approximately 1.5% of surgeons’ nares.⁴ Not all procedures appear to carry the same risk. Electrocoagulation procedures appear to yield fewer postprocedural positive mucosal swabs for HPV, compared with those taken after CO₂ laser.⁵

Animal studies have shown that papilloma virus procured from smoke plume has the capacity to generate disease. When 10 calves were inoculated with bovine papillary virus obtained from smoke plumes from laser ablation of bovine papillomavirus lesions, all calves manifested BPV fibropapilloma lesions at the sites of inoculation.⁶

There appears to be an increased incidence of HPV-associated head and neck disease among surgeons who perform procedures on HPV tissues, and there have been multiple case reports that have cited examples of HPV-associated benign and malignant disease among HCPs with frequent occupational exposure to HPV anogenital ablative and excisional procedures.⁷ While these observations are not proof of causation, they are cause for concern.

While the ASCCP guidelines advocate for HPV vaccination as a strategy for prevention of occupationally related HPV-associated disease, there are other strategies in place to minimize risk. The CDC guidelines for environmental infection control in health care facilities include the following recommendations:

• In settings where surgical lasers are used, wear appropriate personnel protective equipment (PPE), including N95 or N100 respirators to minimize exposure to laser plumes.
• Use central wall suction units with in-line filters to evacuate minimal laser plumes.
• Use a mechanical smoke evaluation system with a high efficiency filter to manage the generation of large amounts of laser plume, when ablating tissue infected with HPV.
• Use local exhaust ventilation (LEV).⁸

When closely adhered to, these methods appear to provide high-level protection. Data suggest that, when HCPs can access appropriate protective equipment, risks for HPV exposure are low. However, this is more feasible for larger hospital facilities, and may be more limited in outpatient settings. This has led to the consideration of background protection in the form of HPV vaccination for at-risk HCPs. This is analogous to mandates for HCPs to receive hepatitis B vaccination despite the concomitant practice of universal precautions in health care settings. Preventative strategies are typically most efficacious when performed in concert.

After nearly 2 decades of widespread use, we have confidence in the safety of the HPV vaccination. Its benefit through age 45 has been established, leading to the 2018 FDA approval for the 9-valent HPV vaccine, Guardisil-9, for this expanded age group. It would seem logical that systematic administration of the HPV vaccine for at-risk HCPs would be both feasible and safe. There are well-established systems for administering vaccines for HCPs in all health care systems. Perhaps health system administrators should consider routinely offering HPV vaccination for at-risk employees as part of their occupational health care responsibilities. One important caveat being the cost and efficacy of HPV vaccination in this group has not been not established.

In the meantime, it is critical that gynecology providers be aware of their risk for occupational exposure to HPV when using laser and electrocautery techniques on HPV-infected tissues and the potential for them developing head and neck pathology. They should strictly adhere to preventative measures such as use of fit-tested N-95 respirators, mechanical smoke evacuators with high-efficiency filters and work in environments with adequate room ventilation. We all should individually evaluate what role HPV vaccination may play for us in augmenting our own safety.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Van Dyne EA et al. MMWR Morb Mortal Wkly Rep. 2018 Aug 24;67(33):918-24.

2. ASCCP. ASCCP recommends HPV vaccination for providers.

3. Fox-Lewis A et al. Occup Environ Med. 2020 Dec;77(12):809-17.

4. Zhou Q et al. Cancer Manag Res. 2019;11:3643-54

5. Bergbrant I et al. Acta Derm Venereol. 1994 Sep;74(5):393-5.

6. Garden J et al. Arch Dermatol. 2002 Oct;138(10):1303-7.

7. Harrison R, Huh W. Obstet Gynecol. 2020;136:663-5.

8. CDC. 1996. DHHS (NIOSH) Publication Number 96-128.

A number of clinical trials in gynecologic cancers have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Uterine precancer (endometrial intraepithelial neoplasia). A phase 2 study sponsored by the National Cancer Institute is seeking adults with endometrial intraepithelial neoplasia (also called complex atypical hyperplasia or atypical hyperplasia) who are scheduled for hysterectomy within 3 months. Researchers are using the window of opportunity before an already-scheduled hysterectomy to see whether adding metformin to megestrol acetate, a treatment standard for nonsurgical patients, increases the effectiveness of megestrol in slowing this type of neoplasia. Participants will receive twice-daily oral medication for 4 weeks then undergo hysterectomy. The trial aims to enroll 50 participants. It began recruiting on Sept. 21 at its Northwestern University site in Evanston, Ill.; sites in California, Colorado, and North Carolina are also planned. The primary outcome is the change in endometrial cell proliferation. Overall survival (OS) and quality of life (QoL) will not be measured. .

Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, who is not involved in this trial, was approached for comment. “This is an interesting study concept, and patients with endometrial atypical hyperplasia may certainly wish to consider participation,” Dr. Markman said. He noted the “limited sample size” of the study.

Advanced, recurrent or refractory ovarian, fallopian, and endometrial cancers overexpressing folate receptor (FR)–alpha. Patients with these types of cancers are eligible for a phase 1/2 study of a new-concept targeted therapy called ELU-001. The molecular structure of ELU001 – called a C’Dot drug conjugate – consists of a drug “payload” riding with an FR-alpha–targeting molecule. For the first 28 days of the study, patients will receive escalating intravenous doses of ELU001 to determine the highest tolerated dose of the drug. All participants will then receive the selected dose for up to 12 months until lesions disappear (complete response) or there is a 30% decrease in the sum of the tumors’ longest diameter (partial response). This “basket” study – a trial involving a “basket” of different cancers with one genetic target – is hosted by New Experimental Therapeutics of San Antonio, which started recruitment for 166 patients on Sept. 13. Neither OS nor QoL will be tracked. .

Dr. Markman commented: “There is considerable interest in examining antineoplastic agents directed to tumor antigens overexpressed in ovarian cancer.”

Locally recurrent, unresectable, or metastatic cervical or endometrial cancer positive for PD-L1. Adults with these types of cancers are invited to join another basket trial, this time testing MK-7684A, a new coformulation of pembrolizumab (Keytruda) and the investigational drug vibostolimab. Most participants will receive intravenous infusions of either MK-7684A, MK-7684A plus chemotherapy, or pembrolizumab alone every 3 weeks for up to 3 years. One group will be given MK-7684A every 3 weeks plus paclitaxel weekly. People with endometrial cancer will also take a daily capsule of lenvatinib (Lenvima). The primary outcomes are response rate and progression-free survival; OS and QoL are secondary outcomes. The study opened on Sept. 16 and hopes to recruit 480 participants in eight countries with several different cancers, including cervical and endometrial cancers. U.S. patients can join at the City of Hope National Medical Center, Duarte, Calif. .

Persistent or recurrent rare epithelial tumors of the ovary, fallopian tube, or peritoneum. Adults with these cancers are sought for a phase 2 trial comparing four targeted-therapy regimens. Participants will receive either ipatasertib plus paclitaxel (Taxol); cobimetinib (Cotellic); trastuzumab emtansine (Kadcyla); or atezolizumab (Tecentriq) plus bevacizumab (Avastin) for up to 5 years until disease progression or unacceptable toxicity. Ipatasertib and cobimetinib are oral medications; all the others are administered intravenously on schedules that vary from once every 3 weeks (atezolizumab, trastuzumab) to weekly infusions 3 weeks out of 4 (paclitaxel). The study opened on Oct. 7 and hopes to enroll 200 participants at sites in Arizona, California, Minnesota, Missouri, Texas, Virginia, and worldwide. OS will be tracked, QoL will not. 

Dr. Markman commented: “This is an interesting early study of the potential efficacy of a novel AKT inhibitor [ipatasertib] in rare gynecologic cancers.”

Platinum-resistant or refractory high-grade serous ovarian cancer. Adult women whose high-grade serous ovarian cancer is platinum resistant or refractory and who do not have germline BRCA mutations are sought for a phase 3 study comparing alpelisib (Piqray) plus olaparib (Lynparza) to investigator’s choice of chemotherapy. Alpelisib is approved for breast cancer in combination with fulvestrant; olaparib is approved for advanced ovarian cancer in platinum-responsive patients and/or those with BRCA- or HRD-positive tumors, so this study could lead to labeling changes for these drugs. Participants will either take daily oral doses of alpelisib plus olaparib or receive intravenous chemo on the appropriate schedules for approximately 2 years. Progression-free survival is the primary outcome measure; OS and QoL are secondary outcomes. The trial opened on July 2 and hopes to recruit 358 individuals in Singapore, Australia, Europe, and the United States (Arizona, Illinois, and Texas). .

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

Dr. Markman is not involved with any of these trials. He is a regular contributor to Medscape Oncology. He has received income in an amount equal to or greater than $250 from Genentech, AstraZeneca Celgene, Clovis, Amgen.

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

A number of clinical trials in gynecologic cancers have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Uterine precancer (endometrial intraepithelial neoplasia). A phase 2 study sponsored by the National Cancer Institute is seeking adults with endometrial intraepithelial neoplasia (also called complex atypical hyperplasia or atypical hyperplasia) who are scheduled for hysterectomy within 3 months. Researchers are using the window of opportunity before an already-scheduled hysterectomy to see whether adding metformin to megestrol acetate, a treatment standard for nonsurgical patients, increases the effectiveness of megestrol in slowing this type of neoplasia. Participants will receive twice-daily oral medication for 4 weeks then undergo hysterectomy. The trial aims to enroll 50 participants. It began recruiting on Sept. 21 at its Northwestern University site in Evanston, Ill.; sites in California, Colorado, and North Carolina are also planned. The primary outcome is the change in endometrial cell proliferation. Overall survival (OS) and quality of life (QoL) will not be measured. .

Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, who is not involved in this trial, was approached for comment. “This is an interesting study concept, and patients with endometrial atypical hyperplasia may certainly wish to consider participation,” Dr. Markman said. He noted the “limited sample size” of the study.

Advanced, recurrent or refractory ovarian, fallopian, and endometrial cancers overexpressing folate receptor (FR)–alpha. Patients with these types of cancers are eligible for a phase 1/2 study of a new-concept targeted therapy called ELU-001. The molecular structure of ELU001 – called a C’Dot drug conjugate – consists of a drug “payload” riding with an FR-alpha–targeting molecule. For the first 28 days of the study, patients will receive escalating intravenous doses of ELU001 to determine the highest tolerated dose of the drug. All participants will then receive the selected dose for up to 12 months until lesions disappear (complete response) or there is a 30% decrease in the sum of the tumors’ longest diameter (partial response). This “basket” study – a trial involving a “basket” of different cancers with one genetic target – is hosted by New Experimental Therapeutics of San Antonio, which started recruitment for 166 patients on Sept. 13. Neither OS nor QoL will be tracked. .

Dr. Markman commented: “There is considerable interest in examining antineoplastic agents directed to tumor antigens overexpressed in ovarian cancer.”

Locally recurrent, unresectable, or metastatic cervical or endometrial cancer positive for PD-L1. Adults with these types of cancers are invited to join another basket trial, this time testing MK-7684A, a new coformulation of pembrolizumab (Keytruda) and the investigational drug vibostolimab. Most participants will receive intravenous infusions of either MK-7684A, MK-7684A plus chemotherapy, or pembrolizumab alone every 3 weeks for up to 3 years. One group will be given MK-7684A every 3 weeks plus paclitaxel weekly. People with endometrial cancer will also take a daily capsule of lenvatinib (Lenvima). The primary outcomes are response rate and progression-free survival; OS and QoL are secondary outcomes. The study opened on Sept. 16 and hopes to recruit 480 participants in eight countries with several different cancers, including cervical and endometrial cancers. U.S. patients can join at the City of Hope National Medical Center, Duarte, Calif. .

Persistent or recurrent rare epithelial tumors of the ovary, fallopian tube, or peritoneum. Adults with these cancers are sought for a phase 2 trial comparing four targeted-therapy regimens. Participants will receive either ipatasertib plus paclitaxel (Taxol); cobimetinib (Cotellic); trastuzumab emtansine (Kadcyla); or atezolizumab (Tecentriq) plus bevacizumab (Avastin) for up to 5 years until disease progression or unacceptable toxicity. Ipatasertib and cobimetinib are oral medications; all the others are administered intravenously on schedules that vary from once every 3 weeks (atezolizumab, trastuzumab) to weekly infusions 3 weeks out of 4 (paclitaxel). The study opened on Oct. 7 and hopes to enroll 200 participants at sites in Arizona, California, Minnesota, Missouri, Texas, Virginia, and worldwide. OS will be tracked, QoL will not. 

Dr. Markman commented: “This is an interesting early study of the potential efficacy of a novel AKT inhibitor [ipatasertib] in rare gynecologic cancers.”

Platinum-resistant or refractory high-grade serous ovarian cancer. Adult women whose high-grade serous ovarian cancer is platinum resistant or refractory and who do not have germline BRCA mutations are sought for a phase 3 study comparing alpelisib (Piqray) plus olaparib (Lynparza) to investigator’s choice of chemotherapy. Alpelisib is approved for breast cancer in combination with fulvestrant; olaparib is approved for advanced ovarian cancer in platinum-responsive patients and/or those with BRCA- or HRD-positive tumors, so this study could lead to labeling changes for these drugs. Participants will either take daily oral doses of alpelisib plus olaparib or receive intravenous chemo on the appropriate schedules for approximately 2 years. Progression-free survival is the primary outcome measure; OS and QoL are secondary outcomes. The trial opened on July 2 and hopes to recruit 358 individuals in Singapore, Australia, Europe, and the United States (Arizona, Illinois, and Texas). .

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

Dr. Markman is not involved with any of these trials. He is a regular contributor to Medscape Oncology. He has received income in an amount equal to or greater than $250 from Genentech, AstraZeneca Celgene, Clovis, Amgen.

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

A number of clinical trials in gynecologic cancers have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Uterine precancer (endometrial intraepithelial neoplasia). A phase 2 study sponsored by the National Cancer Institute is seeking adults with endometrial intraepithelial neoplasia (also called complex atypical hyperplasia or atypical hyperplasia) who are scheduled for hysterectomy within 3 months. Researchers are using the window of opportunity before an already-scheduled hysterectomy to see whether adding metformin to megestrol acetate, a treatment standard for nonsurgical patients, increases the effectiveness of megestrol in slowing this type of neoplasia. Participants will receive twice-daily oral medication for 4 weeks then undergo hysterectomy. The trial aims to enroll 50 participants. It began recruiting on Sept. 21 at its Northwestern University site in Evanston, Ill.; sites in California, Colorado, and North Carolina are also planned. The primary outcome is the change in endometrial cell proliferation. Overall survival (OS) and quality of life (QoL) will not be measured. .

Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, who is not involved in this trial, was approached for comment. “This is an interesting study concept, and patients with endometrial atypical hyperplasia may certainly wish to consider participation,” Dr. Markman said. He noted the “limited sample size” of the study.

Advanced, recurrent or refractory ovarian, fallopian, and endometrial cancers overexpressing folate receptor (FR)–alpha. Patients with these types of cancers are eligible for a phase 1/2 study of a new-concept targeted therapy called ELU-001. The molecular structure of ELU001 – called a C’Dot drug conjugate – consists of a drug “payload” riding with an FR-alpha–targeting molecule. For the first 28 days of the study, patients will receive escalating intravenous doses of ELU001 to determine the highest tolerated dose of the drug. All participants will then receive the selected dose for up to 12 months until lesions disappear (complete response) or there is a 30% decrease in the sum of the tumors’ longest diameter (partial response). This “basket” study – a trial involving a “basket” of different cancers with one genetic target – is hosted by New Experimental Therapeutics of San Antonio, which started recruitment for 166 patients on Sept. 13. Neither OS nor QoL will be tracked. .

Dr. Markman commented: “There is considerable interest in examining antineoplastic agents directed to tumor antigens overexpressed in ovarian cancer.”

Locally recurrent, unresectable, or metastatic cervical or endometrial cancer positive for PD-L1. Adults with these types of cancers are invited to join another basket trial, this time testing MK-7684A, a new coformulation of pembrolizumab (Keytruda) and the investigational drug vibostolimab. Most participants will receive intravenous infusions of either MK-7684A, MK-7684A plus chemotherapy, or pembrolizumab alone every 3 weeks for up to 3 years. One group will be given MK-7684A every 3 weeks plus paclitaxel weekly. People with endometrial cancer will also take a daily capsule of lenvatinib (Lenvima). The primary outcomes are response rate and progression-free survival; OS and QoL are secondary outcomes. The study opened on Sept. 16 and hopes to recruit 480 participants in eight countries with several different cancers, including cervical and endometrial cancers. U.S. patients can join at the City of Hope National Medical Center, Duarte, Calif. .

Persistent or recurrent rare epithelial tumors of the ovary, fallopian tube, or peritoneum. Adults with these cancers are sought for a phase 2 trial comparing four targeted-therapy regimens. Participants will receive either ipatasertib plus paclitaxel (Taxol); cobimetinib (Cotellic); trastuzumab emtansine (Kadcyla); or atezolizumab (Tecentriq) plus bevacizumab (Avastin) for up to 5 years until disease progression or unacceptable toxicity. Ipatasertib and cobimetinib are oral medications; all the others are administered intravenously on schedules that vary from once every 3 weeks (atezolizumab, trastuzumab) to weekly infusions 3 weeks out of 4 (paclitaxel). The study opened on Oct. 7 and hopes to enroll 200 participants at sites in Arizona, California, Minnesota, Missouri, Texas, Virginia, and worldwide. OS will be tracked, QoL will not. 

Dr. Markman commented: “This is an interesting early study of the potential efficacy of a novel AKT inhibitor [ipatasertib] in rare gynecologic cancers.”

Platinum-resistant or refractory high-grade serous ovarian cancer. Adult women whose high-grade serous ovarian cancer is platinum resistant or refractory and who do not have germline BRCA mutations are sought for a phase 3 study comparing alpelisib (Piqray) plus olaparib (Lynparza) to investigator’s choice of chemotherapy. Alpelisib is approved for breast cancer in combination with fulvestrant; olaparib is approved for advanced ovarian cancer in platinum-responsive patients and/or those with BRCA- or HRD-positive tumors, so this study could lead to labeling changes for these drugs. Participants will either take daily oral doses of alpelisib plus olaparib or receive intravenous chemo on the appropriate schedules for approximately 2 years. Progression-free survival is the primary outcome measure; OS and QoL are secondary outcomes. The trial opened on July 2 and hopes to recruit 358 individuals in Singapore, Australia, Europe, and the United States (Arizona, Illinois, and Texas). .

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

Dr. Markman is not involved with any of these trials. He is a regular contributor to Medscape Oncology. He has received income in an amount equal to or greater than $250 from Genentech, AstraZeneca Celgene, Clovis, Amgen.

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

COVID-19 cases are rising across 40 states and territories, setting the United States up for a rough fifth surge of the pandemic.

“A significant rise in cases just before Thanksgiving is not what we want to be seeing,” said Stephen Kissler, PhD, a postdoctoral researcher and data modeler at the Harvard TH Chan School of Public Health in Boston.

Dr. Kissler said he’d rather see increases in daily cases coming 2 weeks after busy travel periods, as that would mean they could come back down as people returned to their routines.

Seeing big increases in cases ahead of the holidays, he said, “is sort of like adding fuel to an already raging fire.”

Last winter, vaccines hadn’t been rolled out as the nation prepared for Thanksgiving. COVID-19 was burning through family gatherings.

But now that two-thirds of Americans over age 5 are fully vaccinated and booster doses are approved for all adults, will a rise in cases translate, once again, into a strain on our still thinly stretched healthcare system?

Experts say the vaccines are keeping people out of the hospital, which will help. And new antiviral pills are coming that seem to be able to cut a COVID-19 infection off at the knees, at least according to early data. A U.S. Food and Drug Administration panel meets next week to discuss the first application for a pill by Merck.

But experts caution that the coming surge will almost certainly tax hospitals again, especially in areas with lower vaccination rates.

And even states where blood testing shows that significant numbers of people have antibodies after a COVID-19 infection aren’t out of the woods, in part because we still don’t know how long the immunity generated by infection may last.
 

“Erosion of immunity”

“It’s hard to know how much risk is out there,” said Jeffrey Shaman, PhD, professor of environmental health sciences at Columbia University’s Mailman School of Public Health in New York City, who has been modeling the trajectory of the pandemic.

“We’re estimating, unfortunately, and we have for many weeks now, that there is an erosion of immunity,” Dr. Shaman said. “I think it could get bad. How bad? I’m not sure.”

Ali Mokdad, PhD, a professor of health metrics sciences at the University of Washington’s Institute for Health Metrics and Evaluation in Seattle, agrees.

Because there are so few studies on how long immunity from natural infection lasts, Dr. Mokdad and his colleagues are assuming that waning immunity after infection happens at least as quickly as it does after vaccination.

Their model is predicting that the average number of daily cases will peak at around 100,000, with another 100,000 going undetected, and will stay at that level until the end of January, as some states recover from their surges and others pick up steam.

While the number of daily deaths won’t climb to the heights seen during the summer surge, Dr. Mokdad said their model is predicting that daily deaths will climb again to about 1,200 a day.

“We are almost there right now, and it will be with us for a while,” he said. “We are predicting 881,000 deaths by March 1.”

The United States has currently recorded 773,000 COVID-19 deaths, so Dr. Mokdad is predicting about 120,000 more deaths between now and then.

He said his model shows that more than half of those deaths could be prevented if 95% of Americans wore their masks while in close proximity to strangers.

Currently, only about 36% of Americans are consistently wearing masks, according to surveys. While people are moving around more now, mobility is at prepandemic levels in some states.

“The rise that you are seeing right now is high mobility and low mask wearing in the United States,” Dr. Mokdad said.

The solution, he said, is for all adults to get another dose of vaccine — he doesn’t like calling it a booster.

“Because they’re vaccinated and they have two doses they have a false sense of security that they are protected. We needed to come ahead of it immediately and say you need a third dose, and we were late to do so,” Dr. Mokdad said.

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

COVID-19 cases are rising across 40 states and territories, setting the United States up for a rough fifth surge of the pandemic.

“A significant rise in cases just before Thanksgiving is not what we want to be seeing,” said Stephen Kissler, PhD, a postdoctoral researcher and data modeler at the Harvard TH Chan School of Public Health in Boston.

Dr. Kissler said he’d rather see increases in daily cases coming 2 weeks after busy travel periods, as that would mean they could come back down as people returned to their routines.

Seeing big increases in cases ahead of the holidays, he said, “is sort of like adding fuel to an already raging fire.”

Last winter, vaccines hadn’t been rolled out as the nation prepared for Thanksgiving. COVID-19 was burning through family gatherings.

But now that two-thirds of Americans over age 5 are fully vaccinated and booster doses are approved for all adults, will a rise in cases translate, once again, into a strain on our still thinly stretched healthcare system?

Experts say the vaccines are keeping people out of the hospital, which will help. And new antiviral pills are coming that seem to be able to cut a COVID-19 infection off at the knees, at least according to early data. A U.S. Food and Drug Administration panel meets next week to discuss the first application for a pill by Merck.

But experts caution that the coming surge will almost certainly tax hospitals again, especially in areas with lower vaccination rates.

And even states where blood testing shows that significant numbers of people have antibodies after a COVID-19 infection aren’t out of the woods, in part because we still don’t know how long the immunity generated by infection may last.
 

“Erosion of immunity”

“It’s hard to know how much risk is out there,” said Jeffrey Shaman, PhD, professor of environmental health sciences at Columbia University’s Mailman School of Public Health in New York City, who has been modeling the trajectory of the pandemic.

“We’re estimating, unfortunately, and we have for many weeks now, that there is an erosion of immunity,” Dr. Shaman said. “I think it could get bad. How bad? I’m not sure.”

Ali Mokdad, PhD, a professor of health metrics sciences at the University of Washington’s Institute for Health Metrics and Evaluation in Seattle, agrees.

Because there are so few studies on how long immunity from natural infection lasts, Dr. Mokdad and his colleagues are assuming that waning immunity after infection happens at least as quickly as it does after vaccination.

Their model is predicting that the average number of daily cases will peak at around 100,000, with another 100,000 going undetected, and will stay at that level until the end of January, as some states recover from their surges and others pick up steam.

While the number of daily deaths won’t climb to the heights seen during the summer surge, Dr. Mokdad said their model is predicting that daily deaths will climb again to about 1,200 a day.

“We are almost there right now, and it will be with us for a while,” he said. “We are predicting 881,000 deaths by March 1.”

The United States has currently recorded 773,000 COVID-19 deaths, so Dr. Mokdad is predicting about 120,000 more deaths between now and then.

He said his model shows that more than half of those deaths could be prevented if 95% of Americans wore their masks while in close proximity to strangers.

Currently, only about 36% of Americans are consistently wearing masks, according to surveys. While people are moving around more now, mobility is at prepandemic levels in some states.

“The rise that you are seeing right now is high mobility and low mask wearing in the United States,” Dr. Mokdad said.

The solution, he said, is for all adults to get another dose of vaccine — he doesn’t like calling it a booster.

“Because they’re vaccinated and they have two doses they have a false sense of security that they are protected. We needed to come ahead of it immediately and say you need a third dose, and we were late to do so,” Dr. Mokdad said.

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

COVID-19 cases are rising across 40 states and territories, setting the United States up for a rough fifth surge of the pandemic.

“A significant rise in cases just before Thanksgiving is not what we want to be seeing,” said Stephen Kissler, PhD, a postdoctoral researcher and data modeler at the Harvard TH Chan School of Public Health in Boston.

Dr. Kissler said he’d rather see increases in daily cases coming 2 weeks after busy travel periods, as that would mean they could come back down as people returned to their routines.

Seeing big increases in cases ahead of the holidays, he said, “is sort of like adding fuel to an already raging fire.”

Last winter, vaccines hadn’t been rolled out as the nation prepared for Thanksgiving. COVID-19 was burning through family gatherings.

But now that two-thirds of Americans over age 5 are fully vaccinated and booster doses are approved for all adults, will a rise in cases translate, once again, into a strain on our still thinly stretched healthcare system?

Experts say the vaccines are keeping people out of the hospital, which will help. And new antiviral pills are coming that seem to be able to cut a COVID-19 infection off at the knees, at least according to early data. A U.S. Food and Drug Administration panel meets next week to discuss the first application for a pill by Merck.

But experts caution that the coming surge will almost certainly tax hospitals again, especially in areas with lower vaccination rates.

And even states where blood testing shows that significant numbers of people have antibodies after a COVID-19 infection aren’t out of the woods, in part because we still don’t know how long the immunity generated by infection may last.
 

“Erosion of immunity”

“It’s hard to know how much risk is out there,” said Jeffrey Shaman, PhD, professor of environmental health sciences at Columbia University’s Mailman School of Public Health in New York City, who has been modeling the trajectory of the pandemic.

“We’re estimating, unfortunately, and we have for many weeks now, that there is an erosion of immunity,” Dr. Shaman said. “I think it could get bad. How bad? I’m not sure.”

Ali Mokdad, PhD, a professor of health metrics sciences at the University of Washington’s Institute for Health Metrics and Evaluation in Seattle, agrees.

Because there are so few studies on how long immunity from natural infection lasts, Dr. Mokdad and his colleagues are assuming that waning immunity after infection happens at least as quickly as it does after vaccination.

Their model is predicting that the average number of daily cases will peak at around 100,000, with another 100,000 going undetected, and will stay at that level until the end of January, as some states recover from their surges and others pick up steam.

While the number of daily deaths won’t climb to the heights seen during the summer surge, Dr. Mokdad said their model is predicting that daily deaths will climb again to about 1,200 a day.

“We are almost there right now, and it will be with us for a while,” he said. “We are predicting 881,000 deaths by March 1.”

The United States has currently recorded 773,000 COVID-19 deaths, so Dr. Mokdad is predicting about 120,000 more deaths between now and then.

He said his model shows that more than half of those deaths could be prevented if 95% of Americans wore their masks while in close proximity to strangers.

Currently, only about 36% of Americans are consistently wearing masks, according to surveys. While people are moving around more now, mobility is at prepandemic levels in some states.

“The rise that you are seeing right now is high mobility and low mask wearing in the United States,” Dr. Mokdad said.

The solution, he said, is for all adults to get another dose of vaccine — he doesn’t like calling it a booster.

“Because they’re vaccinated and they have two doses they have a false sense of security that they are protected. We needed to come ahead of it immediately and say you need a third dose, and we were late to do so,” Dr. Mokdad said.

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

Physicians who care for women having difficulty conceiving must understand the devastation their patients feel while knowing how to define infertility, when (and when not) to advise an evaluation, and offer evidence-based treatment options. Analogous to a mother desiring an antibiotic prescription for her child’s common cold, infertility patients can be desperate for an evaluation and treatment, despite the lack of an indication. This month’s article addresses the diagnosis and management of unexplained infertility.

The chronological age of a woman is the leading prognostic factor for successful reproduction. The definition of infertility remains 1 year of an inability to conceive in a couple who have no demonstrable risk factors, such as ovulation dysfunction, prior infertility, or known male factor. In women less than age 30, monthly fecundity rates are between 20% and 37% during the first 3 months of trying to conceive. The chance of success increases to 80% after 1 year and 90% after 2 years of trying to conceive, according to the American Society of Reproductive Medicine. Nevertheless, following unsuccessful attempts at conception by a couple, the physician should offer an evaluation based on the woman’s age – 1 year for women less than age 35, 6 months for women aged 35-39, and 3 months for women aged 40 and older. Testing can be initiated earlier if there are predisposing factors impairing fertility.

The basic infertility evaluation consists of a thorough history of the couple, a review of medical records, and an assessment of ovulation, fallopian tube patency, and sperm parameters on analysis. In the interest of efficiency, given that couples are typically anxious, these three areas can be evaluated within 1 month. In years past, a diagnostic laparoscopy was considered the gold standard of necessity to provide the diagnosis of exclusion, that is, unexplained infertility. This surgical procedure has fallen out of favor given the low diagnostic yield in a woman with a normal hysterosalpingogram, pelvic ultrasound, and no risk for a pelvic factor; for example, prior abdominal myomectomy, bowel surgery, or strong suspicion for endometriosis based on symptoms including significant pelvic pain affecting activities of daily living.

Initial laboratory testing should be judiciously ordered by recommending only those that will affect management, that is, prenatal labs to assess immunity to rubella and varicella along with a baseline thyroid-stimulating hormone, CBC, blood type, and Rh and antibody screen. In a woman with monthly ovulatory menstrual cycles and no signs of hirsutism or galactorrhea, the clinical utility of obtaining follicle-stimulating hormone, luteinizing hormone (LH), estradiol, prolactin, total and free testosterone, and dehydroepiandrosterone lack evidence. Further, a random anti-Müllerian hormone (without prior chemotherapy, radiation, or ovarian surgery) lacks value as the natural pregnancy rate does not appear to be affected, although low AMH has been associated with an increased risk for miscarriage.

Although not typically screened, measles can cause significant complications in pregnancy including an increased risk of maternal hospitalization and pneumonia, as well as miscarriage, stillbirth, low birth weight, and increased risk of preterm delivery.

Education is an important tool to guide patients and begins with an explanation of urine LH timed intercourse. From the onset of the LH surge, the oocyte is released in 24-36 hours, i.e., the actual day of ovulation is estimated to be the day after the urine LH surge. The “fertile window” appears to be the 5 days before plus the day of ovulation but the highest chance of conception occurs within the 2 days before and including the day of ovulation.

Empiric treatment may be offered when no demonstrable etiology has been identified, lifestyle factors have been addressed (for example, elevated female body mass index, tobacco use by the couple), and medical conditions have been optimized. Reproductive capability declines with continued attempts at conception such that, by 2 years, the approximate monthly fecundity rate is 3%-4%.

The first-line treatment of unexplained infertility is clomiphene citrate (CC) with intrauterine insemination. Letrozole, while not Food and Drug Administration approved for infertility treatment, has been shown in multiple studies to be equally effective as CC and to have a good safety profile. In a recent study, the cumulative live-birth rate over three cycles with CC and IUI, compared with expectant management was 31% versus 9%, respectively. Further, multiple studies failed to show a difference in pregnancy outcomes when comparing CC and IUI with letrozole and IUI.

It is vital to note that, for women who ovulate, studies do not support the use of CC without the addition of intrauterine insemination (IUI). The monthly fecundity rate of a cycle of CC without IUI is similar to natural conception attempts with urine LH timed intercourse, that is, without ovarian stimulation.
 

Recommendations (along with the level of evidence) from ASRM guidelines

• 1. Natural cycle, that is, without ovarian stimulation, timed with IUI is equivalent to expectant management (strong)
• 2. CC or letrozole with timed intercourse is no more effective than a natural cycle (good)
• 3. Pregnancy rates using gonadotropins with timed intercourse have not been shown to be superior to oral ovarian stimulating medications but risks multiple gestation (insufficient)
• 4. CC plus standard-dose gonadotropins results in higher pregnancy rates, there is good evidence for an increased risk of multiple gestation (fair)
• 5. Treatment with gonadotropins alone with IUI is superior to CC or letrozole with IUI; the risk of a multiple gestation rate remains significant (insufficient)
• 6. IUI can be performed between 0 and 36 hours following human chorionic gonadotropin trigger and performing one IUI in a cycle has equivalent success as two (fair)
• 7. Immediate IVF in women older than 38 years may be associated with a higher pregnancy rate and shorter time to pregnancy, compared with ovarian stimulation/IUI cycles before IVF (good)

Conclusion

It is recommended that couples with unexplained infertility initially undergo a course (typically three or four cycles) of ovarian stimulation with IUI using oral agents (CC or letrozole). For those unsuccessful with ovarian stimulation and IUI treatments with oral agents, in vitro fertilization is recommended rather than ovarian stimulation and IUI with gonadotropins to reduce the risk of a multiple gestation.

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at [email protected].

Physicians who care for women having difficulty conceiving must understand the devastation their patients feel while knowing how to define infertility, when (and when not) to advise an evaluation, and offer evidence-based treatment options. Analogous to a mother desiring an antibiotic prescription for her child’s common cold, infertility patients can be desperate for an evaluation and treatment, despite the lack of an indication. This month’s article addresses the diagnosis and management of unexplained infertility.

The chronological age of a woman is the leading prognostic factor for successful reproduction. The definition of infertility remains 1 year of an inability to conceive in a couple who have no demonstrable risk factors, such as ovulation dysfunction, prior infertility, or known male factor. In women less than age 30, monthly fecundity rates are between 20% and 37% during the first 3 months of trying to conceive. The chance of success increases to 80% after 1 year and 90% after 2 years of trying to conceive, according to the American Society of Reproductive Medicine. Nevertheless, following unsuccessful attempts at conception by a couple, the physician should offer an evaluation based on the woman’s age – 1 year for women less than age 35, 6 months for women aged 35-39, and 3 months for women aged 40 and older. Testing can be initiated earlier if there are predisposing factors impairing fertility.

The basic infertility evaluation consists of a thorough history of the couple, a review of medical records, and an assessment of ovulation, fallopian tube patency, and sperm parameters on analysis. In the interest of efficiency, given that couples are typically anxious, these three areas can be evaluated within 1 month. In years past, a diagnostic laparoscopy was considered the gold standard of necessity to provide the diagnosis of exclusion, that is, unexplained infertility. This surgical procedure has fallen out of favor given the low diagnostic yield in a woman with a normal hysterosalpingogram, pelvic ultrasound, and no risk for a pelvic factor; for example, prior abdominal myomectomy, bowel surgery, or strong suspicion for endometriosis based on symptoms including significant pelvic pain affecting activities of daily living.

Initial laboratory testing should be judiciously ordered by recommending only those that will affect management, that is, prenatal labs to assess immunity to rubella and varicella along with a baseline thyroid-stimulating hormone, CBC, blood type, and Rh and antibody screen. In a woman with monthly ovulatory menstrual cycles and no signs of hirsutism or galactorrhea, the clinical utility of obtaining follicle-stimulating hormone, luteinizing hormone (LH), estradiol, prolactin, total and free testosterone, and dehydroepiandrosterone lack evidence. Further, a random anti-Müllerian hormone (without prior chemotherapy, radiation, or ovarian surgery) lacks value as the natural pregnancy rate does not appear to be affected, although low AMH has been associated with an increased risk for miscarriage.

Although not typically screened, measles can cause significant complications in pregnancy including an increased risk of maternal hospitalization and pneumonia, as well as miscarriage, stillbirth, low birth weight, and increased risk of preterm delivery.

Education is an important tool to guide patients and begins with an explanation of urine LH timed intercourse. From the onset of the LH surge, the oocyte is released in 24-36 hours, i.e., the actual day of ovulation is estimated to be the day after the urine LH surge. The “fertile window” appears to be the 5 days before plus the day of ovulation but the highest chance of conception occurs within the 2 days before and including the day of ovulation.

Empiric treatment may be offered when no demonstrable etiology has been identified, lifestyle factors have been addressed (for example, elevated female body mass index, tobacco use by the couple), and medical conditions have been optimized. Reproductive capability declines with continued attempts at conception such that, by 2 years, the approximate monthly fecundity rate is 3%-4%.

The first-line treatment of unexplained infertility is clomiphene citrate (CC) with intrauterine insemination. Letrozole, while not Food and Drug Administration approved for infertility treatment, has been shown in multiple studies to be equally effective as CC and to have a good safety profile. In a recent study, the cumulative live-birth rate over three cycles with CC and IUI, compared with expectant management was 31% versus 9%, respectively. Further, multiple studies failed to show a difference in pregnancy outcomes when comparing CC and IUI with letrozole and IUI.

It is vital to note that, for women who ovulate, studies do not support the use of CC without the addition of intrauterine insemination (IUI). The monthly fecundity rate of a cycle of CC without IUI is similar to natural conception attempts with urine LH timed intercourse, that is, without ovarian stimulation.
 

Recommendations (along with the level of evidence) from ASRM guidelines

• 1. Natural cycle, that is, without ovarian stimulation, timed with IUI is equivalent to expectant management (strong)
• 2. CC or letrozole with timed intercourse is no more effective than a natural cycle (good)
• 3. Pregnancy rates using gonadotropins with timed intercourse have not been shown to be superior to oral ovarian stimulating medications but risks multiple gestation (insufficient)
• 4. CC plus standard-dose gonadotropins results in higher pregnancy rates, there is good evidence for an increased risk of multiple gestation (fair)
• 5. Treatment with gonadotropins alone with IUI is superior to CC or letrozole with IUI; the risk of a multiple gestation rate remains significant (insufficient)
• 6. IUI can be performed between 0 and 36 hours following human chorionic gonadotropin trigger and performing one IUI in a cycle has equivalent success as two (fair)
• 7. Immediate IVF in women older than 38 years may be associated with a higher pregnancy rate and shorter time to pregnancy, compared with ovarian stimulation/IUI cycles before IVF (good)

Conclusion

It is recommended that couples with unexplained infertility initially undergo a course (typically three or four cycles) of ovarian stimulation with IUI using oral agents (CC or letrozole). For those unsuccessful with ovarian stimulation and IUI treatments with oral agents, in vitro fertilization is recommended rather than ovarian stimulation and IUI with gonadotropins to reduce the risk of a multiple gestation.

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at [email protected].

Physicians who care for women having difficulty conceiving must understand the devastation their patients feel while knowing how to define infertility, when (and when not) to advise an evaluation, and offer evidence-based treatment options. Analogous to a mother desiring an antibiotic prescription for her child’s common cold, infertility patients can be desperate for an evaluation and treatment, despite the lack of an indication. This month’s article addresses the diagnosis and management of unexplained infertility.

The chronological age of a woman is the leading prognostic factor for successful reproduction. The definition of infertility remains 1 year of an inability to conceive in a couple who have no demonstrable risk factors, such as ovulation dysfunction, prior infertility, or known male factor. In women less than age 30, monthly fecundity rates are between 20% and 37% during the first 3 months of trying to conceive. The chance of success increases to 80% after 1 year and 90% after 2 years of trying to conceive, according to the American Society of Reproductive Medicine. Nevertheless, following unsuccessful attempts at conception by a couple, the physician should offer an evaluation based on the woman’s age – 1 year for women less than age 35, 6 months for women aged 35-39, and 3 months for women aged 40 and older. Testing can be initiated earlier if there are predisposing factors impairing fertility.

The basic infertility evaluation consists of a thorough history of the couple, a review of medical records, and an assessment of ovulation, fallopian tube patency, and sperm parameters on analysis. In the interest of efficiency, given that couples are typically anxious, these three areas can be evaluated within 1 month. In years past, a diagnostic laparoscopy was considered the gold standard of necessity to provide the diagnosis of exclusion, that is, unexplained infertility. This surgical procedure has fallen out of favor given the low diagnostic yield in a woman with a normal hysterosalpingogram, pelvic ultrasound, and no risk for a pelvic factor; for example, prior abdominal myomectomy, bowel surgery, or strong suspicion for endometriosis based on symptoms including significant pelvic pain affecting activities of daily living.

Initial laboratory testing should be judiciously ordered by recommending only those that will affect management, that is, prenatal labs to assess immunity to rubella and varicella along with a baseline thyroid-stimulating hormone, CBC, blood type, and Rh and antibody screen. In a woman with monthly ovulatory menstrual cycles and no signs of hirsutism or galactorrhea, the clinical utility of obtaining follicle-stimulating hormone, luteinizing hormone (LH), estradiol, prolactin, total and free testosterone, and dehydroepiandrosterone lack evidence. Further, a random anti-Müllerian hormone (without prior chemotherapy, radiation, or ovarian surgery) lacks value as the natural pregnancy rate does not appear to be affected, although low AMH has been associated with an increased risk for miscarriage.

Although not typically screened, measles can cause significant complications in pregnancy including an increased risk of maternal hospitalization and pneumonia, as well as miscarriage, stillbirth, low birth weight, and increased risk of preterm delivery.

Education is an important tool to guide patients and begins with an explanation of urine LH timed intercourse. From the onset of the LH surge, the oocyte is released in 24-36 hours, i.e., the actual day of ovulation is estimated to be the day after the urine LH surge. The “fertile window” appears to be the 5 days before plus the day of ovulation but the highest chance of conception occurs within the 2 days before and including the day of ovulation.

Empiric treatment may be offered when no demonstrable etiology has been identified, lifestyle factors have been addressed (for example, elevated female body mass index, tobacco use by the couple), and medical conditions have been optimized. Reproductive capability declines with continued attempts at conception such that, by 2 years, the approximate monthly fecundity rate is 3%-4%.

The first-line treatment of unexplained infertility is clomiphene citrate (CC) with intrauterine insemination. Letrozole, while not Food and Drug Administration approved for infertility treatment, has been shown in multiple studies to be equally effective as CC and to have a good safety profile. In a recent study, the cumulative live-birth rate over three cycles with CC and IUI, compared with expectant management was 31% versus 9%, respectively. Further, multiple studies failed to show a difference in pregnancy outcomes when comparing CC and IUI with letrozole and IUI.

It is vital to note that, for women who ovulate, studies do not support the use of CC without the addition of intrauterine insemination (IUI). The monthly fecundity rate of a cycle of CC without IUI is similar to natural conception attempts with urine LH timed intercourse, that is, without ovarian stimulation.
 

Recommendations (along with the level of evidence) from ASRM guidelines

• 1. Natural cycle, that is, without ovarian stimulation, timed with IUI is equivalent to expectant management (strong)
• 2. CC or letrozole with timed intercourse is no more effective than a natural cycle (good)
• 3. Pregnancy rates using gonadotropins with timed intercourse have not been shown to be superior to oral ovarian stimulating medications but risks multiple gestation (insufficient)
• 4. CC plus standard-dose gonadotropins results in higher pregnancy rates, there is good evidence for an increased risk of multiple gestation (fair)
• 5. Treatment with gonadotropins alone with IUI is superior to CC or letrozole with IUI; the risk of a multiple gestation rate remains significant (insufficient)
• 6. IUI can be performed between 0 and 36 hours following human chorionic gonadotropin trigger and performing one IUI in a cycle has equivalent success as two (fair)
• 7. Immediate IVF in women older than 38 years may be associated with a higher pregnancy rate and shorter time to pregnancy, compared with ovarian stimulation/IUI cycles before IVF (good)

Conclusion

It is recommended that couples with unexplained infertility initially undergo a course (typically three or four cycles) of ovarian stimulation with IUI using oral agents (CC or letrozole). For those unsuccessful with ovarian stimulation and IUI treatments with oral agents, in vitro fertilization is recommended rather than ovarian stimulation and IUI with gonadotropins to reduce the risk of a multiple gestation.

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at [email protected].