Marcia Frellick

If you’re among those people in the United States who never had COVID-19, how should you think about your risk?

According to the Centers for Disease Control and Prevention (CDC), more than half of people in the United States are in the never-got-COVID category.

The CDC estimated that by the end of January, 43.4% in the United States had developed antibodies to SARS-CoV-2 triggered by infection, not by vaccination — suggesting nearly 60% of people have never been infected.

Now mask mandates are lifting, and daily case and death numbers are plunging. According to the New York Times tracker, new cases are down 51% for the past 2 weeks, and deaths have fallen 30% in that period.

So as those who have so far escaped the virus venture further out into reopened environments, should they worry more or less about risk than their previously infected counterparts?

Some experts weigh in with caution against feeling invincible.
 

No “suit of armor”

William Schaffner, MD, an infectious disease expert at Vanderbilt University School of Medicine in Nashville, Tenn., said in an interview that science has not been able to determine why some people have been able to be stay COVID-free when the virus was raging and exposure was ubiquitous.

He said it’s important to remember that though some people think they have never had COVID, they may have been asymptomatic or attributed mild symptoms to something else.

“People may have conceivably — but we can’t define them yet — different capacities to ward off viruses or bacteria,” Dr. Schaffner said.

Could it be that some people have a better immune system or genetic component or environmental reason that they are less susceptible to infectious disease? “We can’t define that in 2022 medicine, but it could be,” he said.

More is known about why people with the same COVID exposure may have different levels of illness severity.

“They’re more likely to get seriously ill if they have a list of predisposing conditions — if they’re older, if they’re frail, if they have underlying illness or are obese. All of those things clearly impair the body’s response to virus,” Dr. Schaffner said.

He warns those who have never been infected, though, not to assume they have “a suit of armor.”

All should continue to follow guidance on getting vaccinated, and those vaccinated should continue to get boosted, Dr. Schaffner said.

“Clearly, the data show that if you are vaccinated and boosted, you’re protected much more securely against severe disease,” he said.

If the never-COVIDs develop a respiratory infection, they should still get tested for COVID, Dr. Schaffner said.

He said while both vaccines and previous natural infection offer protection, the duration of that protection is not yet known.

“We have to stay tuned,” Dr. Schaffner said. “There may be a recommendation in the future to get a booster annually or something like that. We need to be open to those down the road.”

Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore, says it’s unclear why some people have been able to avoid COVID.

“The explanation is likely multifactorial and involves behaviors as well as possible idiosyncrasies with their immune systems that are genetically based,” he said. “It also may be the case that inapparent infections occurred and went undiagnosed.”

Dr. Adalja agrees, though, that this isn’t the time to get overconfident with risk-taking where COVID is concerned.

“People who have not knowingly been infected with COVID should be vaccinated, and after that, be assured that they are protected against serious disease from this virus,” he said.
 

Genetic protection?

A new study in Nature Genetics explains a potential genetic relationship. Study authors found evidence that levels of expression of angiotensin-converting enzyme 2 (ACE2) – which helps regulate blood pressure, wound healing, and inflammation, but has also been shown to serve as an entry point into cells for some coronaviruses like SARS-CoV-2 — influence COVID-19 risk.

Manuel A. Ferreira, PhD, an executive director for analytic genetics at Regeneron Pharmaceuticals, said in an interview that ACE2 receptors — what he calls the “gateways” for SARS-CoV-2 to enter the body — are different in people who have inherited a particular allele.

The researchers have found that that allele is associated with lower risk of SARS-CoV-2 infection.

“It’s quite substantial -- a 40% risk reduction if you carry the allele that reduces ACE2 expression,” he said. They were not able to discern from this study, however, whether that could predict severity of disease.

The team also looked at a series of six genetic variants elsewhere in the genome and developed a risk score to see if it was possible to predict who might be more susceptible to severe COVID.

Dr. Ferreira said the score only slightly improved predictive abilities beyond factors such as age, sex, weight, and comorbidities. Further information will help hone the ability to predict the likelihood of developing severe disease on the basis of genetics, Ferreira said.

“As we identify more genetic risk factors for COVID — variants like the ACE2 variant that will affect your risk of having COVID — the more informative the risk score will be,” he said.

Several authors of the Nature Genetics article are current and/or former employees of AncestryDNA and may hold equity in AncestryDNA. Several are Regeneron employees and/or hold stock in the company. Dr. Ferreira is an employee of Regeneron and holds stock in the company. Dr. Schaffner and Dr. Adalja report no relevant financial relationships.

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

If you’re among those people in the United States who never had COVID-19, how should you think about your risk?

According to the Centers for Disease Control and Prevention (CDC), more than half of people in the United States are in the never-got-COVID category.

The CDC estimated that by the end of January, 43.4% in the United States had developed antibodies to SARS-CoV-2 triggered by infection, not by vaccination — suggesting nearly 60% of people have never been infected.

Now mask mandates are lifting, and daily case and death numbers are plunging. According to the New York Times tracker, new cases are down 51% for the past 2 weeks, and deaths have fallen 30% in that period.

So as those who have so far escaped the virus venture further out into reopened environments, should they worry more or less about risk than their previously infected counterparts?

Some experts weigh in with caution against feeling invincible.
 

No “suit of armor”

William Schaffner, MD, an infectious disease expert at Vanderbilt University School of Medicine in Nashville, Tenn., said in an interview that science has not been able to determine why some people have been able to be stay COVID-free when the virus was raging and exposure was ubiquitous.

He said it’s important to remember that though some people think they have never had COVID, they may have been asymptomatic or attributed mild symptoms to something else.

“People may have conceivably — but we can’t define them yet — different capacities to ward off viruses or bacteria,” Dr. Schaffner said.

Could it be that some people have a better immune system or genetic component or environmental reason that they are less susceptible to infectious disease? “We can’t define that in 2022 medicine, but it could be,” he said.

More is known about why people with the same COVID exposure may have different levels of illness severity.

“They’re more likely to get seriously ill if they have a list of predisposing conditions — if they’re older, if they’re frail, if they have underlying illness or are obese. All of those things clearly impair the body’s response to virus,” Dr. Schaffner said.

He warns those who have never been infected, though, not to assume they have “a suit of armor.”

All should continue to follow guidance on getting vaccinated, and those vaccinated should continue to get boosted, Dr. Schaffner said.

“Clearly, the data show that if you are vaccinated and boosted, you’re protected much more securely against severe disease,” he said.

If the never-COVIDs develop a respiratory infection, they should still get tested for COVID, Dr. Schaffner said.

He said while both vaccines and previous natural infection offer protection, the duration of that protection is not yet known.

“We have to stay tuned,” Dr. Schaffner said. “There may be a recommendation in the future to get a booster annually or something like that. We need to be open to those down the road.”

Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore, says it’s unclear why some people have been able to avoid COVID.

“The explanation is likely multifactorial and involves behaviors as well as possible idiosyncrasies with their immune systems that are genetically based,” he said. “It also may be the case that inapparent infections occurred and went undiagnosed.”

Dr. Adalja agrees, though, that this isn’t the time to get overconfident with risk-taking where COVID is concerned.

“People who have not knowingly been infected with COVID should be vaccinated, and after that, be assured that they are protected against serious disease from this virus,” he said.
 

Genetic protection?

A new study in Nature Genetics explains a potential genetic relationship. Study authors found evidence that levels of expression of angiotensin-converting enzyme 2 (ACE2) – which helps regulate blood pressure, wound healing, and inflammation, but has also been shown to serve as an entry point into cells for some coronaviruses like SARS-CoV-2 — influence COVID-19 risk.

Manuel A. Ferreira, PhD, an executive director for analytic genetics at Regeneron Pharmaceuticals, said in an interview that ACE2 receptors — what he calls the “gateways” for SARS-CoV-2 to enter the body — are different in people who have inherited a particular allele.

The researchers have found that that allele is associated with lower risk of SARS-CoV-2 infection.

“It’s quite substantial -- a 40% risk reduction if you carry the allele that reduces ACE2 expression,” he said. They were not able to discern from this study, however, whether that could predict severity of disease.

The team also looked at a series of six genetic variants elsewhere in the genome and developed a risk score to see if it was possible to predict who might be more susceptible to severe COVID.

Dr. Ferreira said the score only slightly improved predictive abilities beyond factors such as age, sex, weight, and comorbidities. Further information will help hone the ability to predict the likelihood of developing severe disease on the basis of genetics, Ferreira said.

“As we identify more genetic risk factors for COVID — variants like the ACE2 variant that will affect your risk of having COVID — the more informative the risk score will be,” he said.

Several authors of the Nature Genetics article are current and/or former employees of AncestryDNA and may hold equity in AncestryDNA. Several are Regeneron employees and/or hold stock in the company. Dr. Ferreira is an employee of Regeneron and holds stock in the company. Dr. Schaffner and Dr. Adalja report no relevant financial relationships.

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

If you’re among those people in the United States who never had COVID-19, how should you think about your risk?

According to the Centers for Disease Control and Prevention (CDC), more than half of people in the United States are in the never-got-COVID category.

The CDC estimated that by the end of January, 43.4% in the United States had developed antibodies to SARS-CoV-2 triggered by infection, not by vaccination — suggesting nearly 60% of people have never been infected.

Now mask mandates are lifting, and daily case and death numbers are plunging. According to the New York Times tracker, new cases are down 51% for the past 2 weeks, and deaths have fallen 30% in that period.

So as those who have so far escaped the virus venture further out into reopened environments, should they worry more or less about risk than their previously infected counterparts?

Some experts weigh in with caution against feeling invincible.
 

No “suit of armor”

William Schaffner, MD, an infectious disease expert at Vanderbilt University School of Medicine in Nashville, Tenn., said in an interview that science has not been able to determine why some people have been able to be stay COVID-free when the virus was raging and exposure was ubiquitous.

He said it’s important to remember that though some people think they have never had COVID, they may have been asymptomatic or attributed mild symptoms to something else.

“People may have conceivably — but we can’t define them yet — different capacities to ward off viruses or bacteria,” Dr. Schaffner said.

Could it be that some people have a better immune system or genetic component or environmental reason that they are less susceptible to infectious disease? “We can’t define that in 2022 medicine, but it could be,” he said.

More is known about why people with the same COVID exposure may have different levels of illness severity.

“They’re more likely to get seriously ill if they have a list of predisposing conditions — if they’re older, if they’re frail, if they have underlying illness or are obese. All of those things clearly impair the body’s response to virus,” Dr. Schaffner said.

He warns those who have never been infected, though, not to assume they have “a suit of armor.”

All should continue to follow guidance on getting vaccinated, and those vaccinated should continue to get boosted, Dr. Schaffner said.

“Clearly, the data show that if you are vaccinated and boosted, you’re protected much more securely against severe disease,” he said.

If the never-COVIDs develop a respiratory infection, they should still get tested for COVID, Dr. Schaffner said.

He said while both vaccines and previous natural infection offer protection, the duration of that protection is not yet known.

“We have to stay tuned,” Dr. Schaffner said. “There may be a recommendation in the future to get a booster annually or something like that. We need to be open to those down the road.”

Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore, says it’s unclear why some people have been able to avoid COVID.

“The explanation is likely multifactorial and involves behaviors as well as possible idiosyncrasies with their immune systems that are genetically based,” he said. “It also may be the case that inapparent infections occurred and went undiagnosed.”

Dr. Adalja agrees, though, that this isn’t the time to get overconfident with risk-taking where COVID is concerned.

“People who have not knowingly been infected with COVID should be vaccinated, and after that, be assured that they are protected against serious disease from this virus,” he said.
 

Genetic protection?

A new study in Nature Genetics explains a potential genetic relationship. Study authors found evidence that levels of expression of angiotensin-converting enzyme 2 (ACE2) – which helps regulate blood pressure, wound healing, and inflammation, but has also been shown to serve as an entry point into cells for some coronaviruses like SARS-CoV-2 — influence COVID-19 risk.

Manuel A. Ferreira, PhD, an executive director for analytic genetics at Regeneron Pharmaceuticals, said in an interview that ACE2 receptors — what he calls the “gateways” for SARS-CoV-2 to enter the body — are different in people who have inherited a particular allele.

The researchers have found that that allele is associated with lower risk of SARS-CoV-2 infection.

“It’s quite substantial -- a 40% risk reduction if you carry the allele that reduces ACE2 expression,” he said. They were not able to discern from this study, however, whether that could predict severity of disease.

The team also looked at a series of six genetic variants elsewhere in the genome and developed a risk score to see if it was possible to predict who might be more susceptible to severe COVID.

Dr. Ferreira said the score only slightly improved predictive abilities beyond factors such as age, sex, weight, and comorbidities. Further information will help hone the ability to predict the likelihood of developing severe disease on the basis of genetics, Ferreira said.

“As we identify more genetic risk factors for COVID — variants like the ACE2 variant that will affect your risk of having COVID — the more informative the risk score will be,” he said.

Several authors of the Nature Genetics article are current and/or former employees of AncestryDNA and may hold equity in AncestryDNA. Several are Regeneron employees and/or hold stock in the company. Dr. Ferreira is an employee of Regeneron and holds stock in the company. Dr. Schaffner and Dr. Adalja report no relevant financial relationships.

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

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

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

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

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

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

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

Getting a COVID-19 mRNA vaccine did not affect pregnancy rates for women trying to conceive with in vitro fertilization or ovarian response to treatment, findings of a new study indicate.

The study was led by Sarit Avraham, MD, with the IVF unit, department of obstetrics and gynecology, Shamir Medical Center in Tzrifi, Israel. The findings were published online in Fertility and Sterility in a preproof version.

“Women should be vaccinated for COVID-19 prior to attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women,” the authors wrote.

Doubts arose from “the theoretical concept of the supposed similarity between the SARS-CoV-2 spike protein and the syncytin protein that is speculated to take part in the fertilization process and the formation of the placenta,” the authors wrote.

Some then assumed that the COVID vaccine might kick off an immune response that could affect implantation and pregnancy. But this study and others before it found otherwise.

Researchers included 200 vaccinated women trying to conceive with IVF treatments in the retrospective study, and compared them with 200 unvaccinated patients of similar age (average age in both groups, 36 years) who were not previously infected with COVID-19. All the women were undergoing IVF from January to April 2021 and all the vaccinated women completed two doses of the BNT162b2 (Pfizer/BioNTech) vaccine at least 2 weeks before ovarian stimulation.

Researchers compared the average number of oocytes retrieved and clinical pregnancy rates between the two groups.
 

No difference between groups

Two hundred patients underwent oocyte retrieval 14-68 days after receiving a COVID shot; there was no significant difference by vaccination status in the number retrieved per cycle (10.63 in the vaccinated group vs. 10.72 in the unvaccinated group; P = .93).

There was also no difference in the clinical pregnancy rates after fresh embryo transfers. The rate among 128 vaccinated patients was 32.8% versus 33.1% in the 133 unvaccinated patients (P = .96), with 42 and 44 clinical pregnancies, respectively.

A total of 113 patients (66 in the study group and 47 in the controls) underwent freeze-all cycles to preserve fertility and fertilization rates were similar between vaccinated and unvaccinated (55.43% vaccinated vs. 54.29% unvaccinated; P = .73). The average number of cryopreserved embryos was 3.59 (vaccinated) versus 3.28 (unvaccinated) (P = .80).

In a subanalysis of outcomes by age, researchers found vaccination status had no effect on number of oocytes or pregnancy rates in the 39-and-older group. That’s important because it shows the vaccine did not affect outcomes even in a population with reduced ovarian reserves, the authors wrote.

The authors noted one of the study’s limitations is that it didn’t include information about vaccination or past infection status of the male partners.
 

Question should be put to rest

Sarah Cross, MD, a maternal-fetal medicine specialist at the University of Minnesota, Minneapolis, said the study is the biggest she’s seen that concludes COVID vaccinations are safe and highly encouraged for women before trying to conceive, but other smaller studies have come to the same conclusion.

She pointed to research including a study from 2021 with similar findings that concluded: “Physicians and public health personnel can counsel women of reproductive age that neither previous illness with COVID-19 nor antibodies produced from vaccination to COVID-19 will cause sterility.”

She said she thinks the question of whether COVID shots are safe with IVF has been answered and the results of the latest study add proof to counter misinformation around the issue.

“The COVID-19 vaccine does not affect fertility,” she said. “I don’t know how many more [studies] we need.”

The harm is in not getting vaccinated, she said. Pregnancy significantly increases a woman’s chance of getting severe COVID, the need for hospitalization, mechanical ventilation, and risk of death.

“I personally have never had a hospitalized patient who’s been vaccinated,” Dr. Cross said. “The worst thing for the fetus is to have a critically ill mother.”

Dr. Cross, whose high-risk patients include those seeking counseling before IVF, added: “I would counsel all of them that they should absolutely get vaccinated prior to pregnancy, when they’re pregnant, whenever it is, as soon as they possibly can.”

The study authors and Dr. Cross report no relevant financial relationships.

Getting a COVID-19 mRNA vaccine did not affect pregnancy rates for women trying to conceive with in vitro fertilization or ovarian response to treatment, findings of a new study indicate.

The study was led by Sarit Avraham, MD, with the IVF unit, department of obstetrics and gynecology, Shamir Medical Center in Tzrifi, Israel. The findings were published online in Fertility and Sterility in a preproof version.

“Women should be vaccinated for COVID-19 prior to attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women,” the authors wrote.

Doubts arose from “the theoretical concept of the supposed similarity between the SARS-CoV-2 spike protein and the syncytin protein that is speculated to take part in the fertilization process and the formation of the placenta,” the authors wrote.

Some then assumed that the COVID vaccine might kick off an immune response that could affect implantation and pregnancy. But this study and others before it found otherwise.

Researchers included 200 vaccinated women trying to conceive with IVF treatments in the retrospective study, and compared them with 200 unvaccinated patients of similar age (average age in both groups, 36 years) who were not previously infected with COVID-19. All the women were undergoing IVF from January to April 2021 and all the vaccinated women completed two doses of the BNT162b2 (Pfizer/BioNTech) vaccine at least 2 weeks before ovarian stimulation.

Researchers compared the average number of oocytes retrieved and clinical pregnancy rates between the two groups.
 

No difference between groups

Two hundred patients underwent oocyte retrieval 14-68 days after receiving a COVID shot; there was no significant difference by vaccination status in the number retrieved per cycle (10.63 in the vaccinated group vs. 10.72 in the unvaccinated group; P = .93).

There was also no difference in the clinical pregnancy rates after fresh embryo transfers. The rate among 128 vaccinated patients was 32.8% versus 33.1% in the 133 unvaccinated patients (P = .96), with 42 and 44 clinical pregnancies, respectively.

A total of 113 patients (66 in the study group and 47 in the controls) underwent freeze-all cycles to preserve fertility and fertilization rates were similar between vaccinated and unvaccinated (55.43% vaccinated vs. 54.29% unvaccinated; P = .73). The average number of cryopreserved embryos was 3.59 (vaccinated) versus 3.28 (unvaccinated) (P = .80).

In a subanalysis of outcomes by age, researchers found vaccination status had no effect on number of oocytes or pregnancy rates in the 39-and-older group. That’s important because it shows the vaccine did not affect outcomes even in a population with reduced ovarian reserves, the authors wrote.

The authors noted one of the study’s limitations is that it didn’t include information about vaccination or past infection status of the male partners.
 

Question should be put to rest

Sarah Cross, MD, a maternal-fetal medicine specialist at the University of Minnesota, Minneapolis, said the study is the biggest she’s seen that concludes COVID vaccinations are safe and highly encouraged for women before trying to conceive, but other smaller studies have come to the same conclusion.

She pointed to research including a study from 2021 with similar findings that concluded: “Physicians and public health personnel can counsel women of reproductive age that neither previous illness with COVID-19 nor antibodies produced from vaccination to COVID-19 will cause sterility.”

She said she thinks the question of whether COVID shots are safe with IVF has been answered and the results of the latest study add proof to counter misinformation around the issue.

“The COVID-19 vaccine does not affect fertility,” she said. “I don’t know how many more [studies] we need.”

The harm is in not getting vaccinated, she said. Pregnancy significantly increases a woman’s chance of getting severe COVID, the need for hospitalization, mechanical ventilation, and risk of death.

“I personally have never had a hospitalized patient who’s been vaccinated,” Dr. Cross said. “The worst thing for the fetus is to have a critically ill mother.”

Dr. Cross, whose high-risk patients include those seeking counseling before IVF, added: “I would counsel all of them that they should absolutely get vaccinated prior to pregnancy, when they’re pregnant, whenever it is, as soon as they possibly can.”

The study authors and Dr. Cross report no relevant financial relationships.

Getting a COVID-19 mRNA vaccine did not affect pregnancy rates for women trying to conceive with in vitro fertilization or ovarian response to treatment, findings of a new study indicate.

The study was led by Sarit Avraham, MD, with the IVF unit, department of obstetrics and gynecology, Shamir Medical Center in Tzrifi, Israel. The findings were published online in Fertility and Sterility in a preproof version.

“Women should be vaccinated for COVID-19 prior to attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women,” the authors wrote.

Doubts arose from “the theoretical concept of the supposed similarity between the SARS-CoV-2 spike protein and the syncytin protein that is speculated to take part in the fertilization process and the formation of the placenta,” the authors wrote.

Some then assumed that the COVID vaccine might kick off an immune response that could affect implantation and pregnancy. But this study and others before it found otherwise.

Researchers included 200 vaccinated women trying to conceive with IVF treatments in the retrospective study, and compared them with 200 unvaccinated patients of similar age (average age in both groups, 36 years) who were not previously infected with COVID-19. All the women were undergoing IVF from January to April 2021 and all the vaccinated women completed two doses of the BNT162b2 (Pfizer/BioNTech) vaccine at least 2 weeks before ovarian stimulation.

Researchers compared the average number of oocytes retrieved and clinical pregnancy rates between the two groups.
 

No difference between groups

Two hundred patients underwent oocyte retrieval 14-68 days after receiving a COVID shot; there was no significant difference by vaccination status in the number retrieved per cycle (10.63 in the vaccinated group vs. 10.72 in the unvaccinated group; P = .93).

There was also no difference in the clinical pregnancy rates after fresh embryo transfers. The rate among 128 vaccinated patients was 32.8% versus 33.1% in the 133 unvaccinated patients (P = .96), with 42 and 44 clinical pregnancies, respectively.

A total of 113 patients (66 in the study group and 47 in the controls) underwent freeze-all cycles to preserve fertility and fertilization rates were similar between vaccinated and unvaccinated (55.43% vaccinated vs. 54.29% unvaccinated; P = .73). The average number of cryopreserved embryos was 3.59 (vaccinated) versus 3.28 (unvaccinated) (P = .80).

In a subanalysis of outcomes by age, researchers found vaccination status had no effect on number of oocytes or pregnancy rates in the 39-and-older group. That’s important because it shows the vaccine did not affect outcomes even in a population with reduced ovarian reserves, the authors wrote.

The authors noted one of the study’s limitations is that it didn’t include information about vaccination or past infection status of the male partners.
 

Question should be put to rest

Sarah Cross, MD, a maternal-fetal medicine specialist at the University of Minnesota, Minneapolis, said the study is the biggest she’s seen that concludes COVID vaccinations are safe and highly encouraged for women before trying to conceive, but other smaller studies have come to the same conclusion.

She pointed to research including a study from 2021 with similar findings that concluded: “Physicians and public health personnel can counsel women of reproductive age that neither previous illness with COVID-19 nor antibodies produced from vaccination to COVID-19 will cause sterility.”

She said she thinks the question of whether COVID shots are safe with IVF has been answered and the results of the latest study add proof to counter misinformation around the issue.

“The COVID-19 vaccine does not affect fertility,” she said. “I don’t know how many more [studies] we need.”

The harm is in not getting vaccinated, she said. Pregnancy significantly increases a woman’s chance of getting severe COVID, the need for hospitalization, mechanical ventilation, and risk of death.

“I personally have never had a hospitalized patient who’s been vaccinated,” Dr. Cross said. “The worst thing for the fetus is to have a critically ill mother.”

Dr. Cross, whose high-risk patients include those seeking counseling before IVF, added: “I would counsel all of them that they should absolutely get vaccinated prior to pregnancy, when they’re pregnant, whenever it is, as soon as they possibly can.”

The study authors and Dr. Cross report no relevant financial relationships.

A new scoring system proved more accurate than several other available models at predicting the 30-day mortality risk for patients with alcohol-associated hepatitis (AH), according to new data.

The system, called the Mortality Index for Alcohol-Associated Hepatitis (MIAAH), was created by a team of Mayo Clinic researchers, who published their results in Mayo Clinic Proceedings.

Among the currently available prognostic models for assessing AH severity are the Model for End-Stage Liver Disease (MELD); the Age, serum Bilirubin, International normalized ratio, and serum Creatinine (ABIC) score; the Maddrey Discriminant Function (MDF); and the Glasgow Alcoholic Hepatitis Score (GAHS). However, these models have poor accuracy, with the area under the curve between 0.71 and 0.77.

By comparison, the new model has an accuracy of 86% in predicting 30-day mortality for AH, said coauthor Ashwani K. Singal, MD, MS, professor of medicine at the University of South Dakota Sanford School of Medicine, Sioux Falls.

“It’s a better predictor of the outcome, and that’s what sets it apart,” he told this news organization. “I think providers and patients will benefit.”

He said accuracy in determining the likelihood of death can help clinicians better determine treatment options and prepare patients and their families.

Camille Kezer, MD, a Mayo Clinic resident internist and first author of the paper, said in a statement, “MIAAH also has the advantage of performing well in patients, regardless of whether they’ve been treated with steroids, which makes it generalizable.”
 

Creating and validating the MIAAH

Researchers analyzed the health records of 266 eligible patients diagnosed with AH between 1998 and 2018 at the Mayo Clinic, Rochester, Minn. The patients collectively had a 30-day mortality rate of 19.2%.

They then studied the effect of several variables, of which the following were found to be significantly associated with mortality: age (P = .002), blood urea nitrogen (P = .003), albumin (P = .01), bilirubin (P = .02), and international normalized ratio (P = .001).

Mayo researchers built the MIAAH model using these variables and found that it was able to achieve a C statistic of 0.86, which translates into its being able to accurately predict mortality more than 86% of the time. When tested in the initial cohort of 266 patients, MIAAH had a significantly superior C statistic compared with several other available models, such as the MELD, MDF, and GAHS, although not for the ABIC.

The researchers then tested the MIAAH model in a validation cohort of 249 patients from health care centers at the University of South Dakota, Sioux Falls, and the University of Kansas, Lawrence. In this cohort, the MIAAH’s C statistic decreased to 0.73, which remained significantly more accurate than the MDF but was comparable to that found with the MELD.
 

Helping with transplant decisions

There are no pharmacologic treatments that can reduce 90-day mortality in severe cases of AH, and only a small survival benefit at 30 days has been reported with prednisolone use.

With a shortage of liver donors, many centers still require 6 months of alcohol abstinence for transplant consideration, although exceptions are sometimes made for cases of early transplant.

A model that more accurately predicts who is at the highest risk of dying within a month can help clinicians decide how best to proceed, Dr. Singal said.

Paul Martin, MD, chief of the division of digestive health and liver diseases, Mandel Chair in gastroenterology, and professor of medicine at the University of Miami, told this news organization that the model is potentially important in light of the rising prevalence of AH.

“The numbers of patients with AH are unequivocally increasing and often in young patients,” he noted, presenting difficult choices of who to treat with steroids and who to refer for a transplant.

“This model is certainly timely,” he said. “We need more accuracy in predicting which patients will recover with medical therapy and which patients won’t in the absence of a liver transplant.”

He noted, however, that the study’s retrospective design requires that it’s validated prospectively: “not only looking at the outcome in terms of mortality of patients, but its potential utility in identifying candidates for liver transplantation who are not going to recover on their own.”

He said it was unlikely that the model would replace others, particularly MELD, which is ingrained in practices in the United States and other countries, but may instead have a complementary role.

Dr. Singal, Dr. Kezer, and Dr. Martin report no relevant financial relationships.

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

A new scoring system proved more accurate than several other available models at predicting the 30-day mortality risk for patients with alcohol-associated hepatitis (AH), according to new data.

The system, called the Mortality Index for Alcohol-Associated Hepatitis (MIAAH), was created by a team of Mayo Clinic researchers, who published their results in Mayo Clinic Proceedings.

Among the currently available prognostic models for assessing AH severity are the Model for End-Stage Liver Disease (MELD); the Age, serum Bilirubin, International normalized ratio, and serum Creatinine (ABIC) score; the Maddrey Discriminant Function (MDF); and the Glasgow Alcoholic Hepatitis Score (GAHS). However, these models have poor accuracy, with the area under the curve between 0.71 and 0.77.

By comparison, the new model has an accuracy of 86% in predicting 30-day mortality for AH, said coauthor Ashwani K. Singal, MD, MS, professor of medicine at the University of South Dakota Sanford School of Medicine, Sioux Falls.

“It’s a better predictor of the outcome, and that’s what sets it apart,” he told this news organization. “I think providers and patients will benefit.”

He said accuracy in determining the likelihood of death can help clinicians better determine treatment options and prepare patients and their families.

Camille Kezer, MD, a Mayo Clinic resident internist and first author of the paper, said in a statement, “MIAAH also has the advantage of performing well in patients, regardless of whether they’ve been treated with steroids, which makes it generalizable.”
 

Creating and validating the MIAAH

Researchers analyzed the health records of 266 eligible patients diagnosed with AH between 1998 and 2018 at the Mayo Clinic, Rochester, Minn. The patients collectively had a 30-day mortality rate of 19.2%.

They then studied the effect of several variables, of which the following were found to be significantly associated with mortality: age (P = .002), blood urea nitrogen (P = .003), albumin (P = .01), bilirubin (P = .02), and international normalized ratio (P = .001).

Mayo researchers built the MIAAH model using these variables and found that it was able to achieve a C statistic of 0.86, which translates into its being able to accurately predict mortality more than 86% of the time. When tested in the initial cohort of 266 patients, MIAAH had a significantly superior C statistic compared with several other available models, such as the MELD, MDF, and GAHS, although not for the ABIC.

The researchers then tested the MIAAH model in a validation cohort of 249 patients from health care centers at the University of South Dakota, Sioux Falls, and the University of Kansas, Lawrence. In this cohort, the MIAAH’s C statistic decreased to 0.73, which remained significantly more accurate than the MDF but was comparable to that found with the MELD.
 

Helping with transplant decisions

There are no pharmacologic treatments that can reduce 90-day mortality in severe cases of AH, and only a small survival benefit at 30 days has been reported with prednisolone use.

With a shortage of liver donors, many centers still require 6 months of alcohol abstinence for transplant consideration, although exceptions are sometimes made for cases of early transplant.

A model that more accurately predicts who is at the highest risk of dying within a month can help clinicians decide how best to proceed, Dr. Singal said.

Paul Martin, MD, chief of the division of digestive health and liver diseases, Mandel Chair in gastroenterology, and professor of medicine at the University of Miami, told this news organization that the model is potentially important in light of the rising prevalence of AH.

“The numbers of patients with AH are unequivocally increasing and often in young patients,” he noted, presenting difficult choices of who to treat with steroids and who to refer for a transplant.

“This model is certainly timely,” he said. “We need more accuracy in predicting which patients will recover with medical therapy and which patients won’t in the absence of a liver transplant.”

He noted, however, that the study’s retrospective design requires that it’s validated prospectively: “not only looking at the outcome in terms of mortality of patients, but its potential utility in identifying candidates for liver transplantation who are not going to recover on their own.”

He said it was unlikely that the model would replace others, particularly MELD, which is ingrained in practices in the United States and other countries, but may instead have a complementary role.

Dr. Singal, Dr. Kezer, and Dr. Martin report no relevant financial relationships.

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

A new scoring system proved more accurate than several other available models at predicting the 30-day mortality risk for patients with alcohol-associated hepatitis (AH), according to new data.

The system, called the Mortality Index for Alcohol-Associated Hepatitis (MIAAH), was created by a team of Mayo Clinic researchers, who published their results in Mayo Clinic Proceedings.

Among the currently available prognostic models for assessing AH severity are the Model for End-Stage Liver Disease (MELD); the Age, serum Bilirubin, International normalized ratio, and serum Creatinine (ABIC) score; the Maddrey Discriminant Function (MDF); and the Glasgow Alcoholic Hepatitis Score (GAHS). However, these models have poor accuracy, with the area under the curve between 0.71 and 0.77.

By comparison, the new model has an accuracy of 86% in predicting 30-day mortality for AH, said coauthor Ashwani K. Singal, MD, MS, professor of medicine at the University of South Dakota Sanford School of Medicine, Sioux Falls.

“It’s a better predictor of the outcome, and that’s what sets it apart,” he told this news organization. “I think providers and patients will benefit.”

He said accuracy in determining the likelihood of death can help clinicians better determine treatment options and prepare patients and their families.

Camille Kezer, MD, a Mayo Clinic resident internist and first author of the paper, said in a statement, “MIAAH also has the advantage of performing well in patients, regardless of whether they’ve been treated with steroids, which makes it generalizable.”
 

Creating and validating the MIAAH

Researchers analyzed the health records of 266 eligible patients diagnosed with AH between 1998 and 2018 at the Mayo Clinic, Rochester, Minn. The patients collectively had a 30-day mortality rate of 19.2%.

They then studied the effect of several variables, of which the following were found to be significantly associated with mortality: age (P = .002), blood urea nitrogen (P = .003), albumin (P = .01), bilirubin (P = .02), and international normalized ratio (P = .001).

Mayo researchers built the MIAAH model using these variables and found that it was able to achieve a C statistic of 0.86, which translates into its being able to accurately predict mortality more than 86% of the time. When tested in the initial cohort of 266 patients, MIAAH had a significantly superior C statistic compared with several other available models, such as the MELD, MDF, and GAHS, although not for the ABIC.

The researchers then tested the MIAAH model in a validation cohort of 249 patients from health care centers at the University of South Dakota, Sioux Falls, and the University of Kansas, Lawrence. In this cohort, the MIAAH’s C statistic decreased to 0.73, which remained significantly more accurate than the MDF but was comparable to that found with the MELD.
 

Helping with transplant decisions

There are no pharmacologic treatments that can reduce 90-day mortality in severe cases of AH, and only a small survival benefit at 30 days has been reported with prednisolone use.

With a shortage of liver donors, many centers still require 6 months of alcohol abstinence for transplant consideration, although exceptions are sometimes made for cases of early transplant.

A model that more accurately predicts who is at the highest risk of dying within a month can help clinicians decide how best to proceed, Dr. Singal said.

Paul Martin, MD, chief of the division of digestive health and liver diseases, Mandel Chair in gastroenterology, and professor of medicine at the University of Miami, told this news organization that the model is potentially important in light of the rising prevalence of AH.

“The numbers of patients with AH are unequivocally increasing and often in young patients,” he noted, presenting difficult choices of who to treat with steroids and who to refer for a transplant.

“This model is certainly timely,” he said. “We need more accuracy in predicting which patients will recover with medical therapy and which patients won’t in the absence of a liver transplant.”

He noted, however, that the study’s retrospective design requires that it’s validated prospectively: “not only looking at the outcome in terms of mortality of patients, but its potential utility in identifying candidates for liver transplantation who are not going to recover on their own.”

He said it was unlikely that the model would replace others, particularly MELD, which is ingrained in practices in the United States and other countries, but may instead have a complementary role.

Dr. Singal, Dr. Kezer, and Dr. Martin report no relevant financial relationships.

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

Payments to rheumatologists by pharmaceutical companies, whether through food and beverages or consulting fees, are linked with a higher likelihood of prescribing drugs and higher Medicare spending, according to a new study published Feb. 2 in Mayo Clinic Proceedings.

Alí Duarte-García, MD, of the division of rheumatology in the department of medicine at the Mayo Clinic in Rochester, Minn., led the study.

Courtesy Mayo Clinic

Researchers conducted a cross-sectional analysis of Medicare Part B Public Use File, Medicare Part D Public Use File, and Open Payments data for 2013-2015. They included prescription drugs that accounted for 80% of the total Medicare pharmaceutical expenditures in rheumatology.

They then calculated annual average drug cost per beneficiary per year, the percentage of rheumatologists who received payments, and the average payment per physician per drug per year. Industry payments were categorized as either food/beverage or consulting/compensation.

Multivariable regression models were used to assess links between industry payments, prescribing patterns, and prescription drug spending.
 

‘Directly associated’ with prescribing probability

The authors concluded that “pharmaceutical company payments to rheumatologists were directly associated with the probability of the physician’s prescribing a drug marketed by that company, the proportion of prescriptions that are for that drug, and the resulting Medicare expenditures.”

Thinkstock

The authors noted that food and beverage payments were associated with increased Medicare reimbursement amounts for all drugs except rituximab.

The article includes examples that help quantify the link between payments and prescribing.

The authors wrote that for each $100 in food/beverage payments, Medicare reimbursement increased 6% to 44%. The increases were particularly high for infliximab and rACTH (repository corticotropin injection), “whereby a payment of $100 to a prescriber of these drugs was associated with increases of approximately $72,000 and $30,000 in Medicare reimbursements, respectively. For most of the other drugs, for every $100 in payments, the Medicare reimbursement increased by $8,000 to $13,000.”

The associations were strongest for food and beverage payments even though those were for lower dollar amounts.

The researchers found that every $100 in food and beverage payments, which also include gifts, entertainment, or educational materials, was linked with more than twofold higher probability of prescribing and higher Medicare reimbursements than for every $1,000 paid in consulting fees and compensation.

That finding and findings from previous studies, they say, “suggest that the current approach to regulating industry influence, which focuses on disclosure of large payments, may be inadequate.”

Aaron P. Mitchell, MD, a medical oncologist and health services researcher with Memorial Sloan Kettering Cancer Center in New York, told this news organization that the findings regarding rACTH show the potential harm of industry payments that are linked with prescribing.

Memorial Sloan Kettering Cancer Center

The drug is a naturally produced hormone used for both rheumatologic and neurologic conditions. “Since it is an unpatentable drug – really just a hormone – it’s kind of grandfathered in and never had to get [Food and Drug Administration] approval for its current indications,” Dr. Mitchell said.

The drug, which costs nearly $230,000 per Medicare beneficiary, hasn’t been tested head to head in large randomized trials against much cheaper rheumatology drugs, such as prednisone.

In the case of infliximab, he noted, for every $100 in food/beverage payments, there was an increase of $72,000 in Medicare spending.

Dr. Mitchell studies industry influence in a variety of specialties and said rheumatology follows the universal pattern, although the drugs used in the specialty are more expensive than in many specialties.

He agrees with the authors that focusing on disclosures to address the problem is probably not enough.

“We’ve been in this period of full and open disclosure for going on 10 years, and we haven’t really seen a decline in these payments,” he said.
 

Results won’t surprise rheumatologists

Karen Onel, MD, a pediatric rheumatologist at the Hospital for Special Surgery, New York, and chair of the American College of Rheumatology’s Ethics and Conflict of Interest Committee, who said she was speaking only for herself and not on behalf of the committee, told this news organization that the study will not be surprising to rheumatologists or to physicians in other specialties who are aware of the plethora of studies that concluded that industry payments influence prescribing.*

Physicians are well aware of the problem, but “they all think it’s not them,” she said.

She said a shortcoming of this study is that it is unclear what the payments were for, because many things are lumped together in the categories. In the case of food and beverage payments, she said that could include payments physicians don’t realize are going on their open payments profile.

Dr. Onel gives a personal example. When she goes to a medical conference, she says, “I don’t eat on pharma’s dime.” But because badge numbers are scanned, it appears she accepted the food provided by the pharmaceutical sponsor when she enters a room where food or coffee is being served.

She said that although there are outliers like rACTH that often get highlighted, “the numbers are very low of the physicians who had [industry] money, and the change in prescribing patterns actually was very low.”

She pointed to an important limitation that the authors list: The study was limited to patients with fee-for-service Medicare coverage and did not include those with private insurance.

“For example, Aetna, Cigna, and UnitedHealthcare have restricted reimbursement for rACTH in recent years, citing its lack of proven efficacy and the availability of more affordable options, and rACTH is not in the Veterans Affairs formulary,” the authors wrote.
 

Rapid development of specialty drugs

Still, the authors wrote, the associations described in this article are of high interest because even though rheumatologists make up a small proportion of the physician workforce, they have among the highest costs per prescription in Medicare drug claims.

“Rheumatology, second only to oncology, has entered an era of rapid development of specialty drugs, including biologic disease-modifying antirheumatic drugs (DMARDs),” the authors wrote.

The complex drugs are expensive to produce and require expertise in handling. Most are under patent with no generic or approved biosimilar equivalent.

Nearly half of all U.S. rheumatologists received some payment from a pharmaceutical company in the study period, and most payments to rheumatologists were for low dollar amounts.

The highest per-year annual expenditures were attributed to etanercept ($741 million), adalimumab ($620 million), and infliximab ($539 million).

These drugs were expensive per beneficiary ($20,728 for etanercept, $21,492 for adalimumab, and $15,941 for infliximab) and were prescribed by a large number of rheumatologists (4,068, 3,872, and 1,349, respectively).

Addressing the problem

Dr. Mitchell says the leaders of individual societies need to fill the gaps that leave busy clinicians searching for easy ways to get up-to-date information on drugs.

He says in all specialties, “Industry should not be the most easily and readily available source of information.

“We’re in the age of Zoom now,” he said. “There’s no reason you have to be sitting for an hour at lunch with a sales rep and not a brown-bag lunch getting a 1-hour update from a society on a new drug indication.

“We will get higher-quality information if we’re doing the education ourselves, and we’d be removing the sense of obligation to pay back the industry gift givers,” Dr. Mitchell said.

Dr. Onel said among the most critical work is making sure that the leadership of ACR is free of conflicts of interest.

“They are making decisions for the entire organization. We need to feel safe and comfortable that they are acting in the best interest of the rheumatologists and patients versus corporate partners,” she said.

Guidelines must strictly follow the standards from the Institute of Medicine that fewer than 50% of the regular guideline committee members may have commercial conflicts, Dr. Onel said.

She added that training on real or apparent conflicts of interest must start in medical school, residency, and fellowship, before physicians start to think they know their own practice patterns and that the results don’t apply to them.

However, the reality is that the industry and physicians will always need each other, she said.

Dr. Onel describes a tension between rheumatologists needing industry’s help for research and education, especially when federal money for research can be difficult to get, and managing those relationships to avoid real or apparent conflicts.

“We want the public’s trust,” she said.

A study coauthor has served on advisory boards of Boehringer Ingelheim (> $10,000) and Gilead Sciences (> $10,000); has served on speakers bureaus for Simply Speaking (> $10,000) and Boehringer Ingelheim (< $10,000); and has received royalties from UpToDate (> $10,000). Dr. Mitchell and Dr. Onel reported no relevant financial relationships.

* Update, 2/25/22: This article, which originally attributed comments to Dr. Karen Onel personally, has been updated to further emphasize that these comments were not on behalf of the committee that she leads.

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

Payments to rheumatologists by pharmaceutical companies, whether through food and beverages or consulting fees, are linked with a higher likelihood of prescribing drugs and higher Medicare spending, according to a new study published Feb. 2 in Mayo Clinic Proceedings.

Alí Duarte-García, MD, of the division of rheumatology in the department of medicine at the Mayo Clinic in Rochester, Minn., led the study.

Courtesy Mayo Clinic

Researchers conducted a cross-sectional analysis of Medicare Part B Public Use File, Medicare Part D Public Use File, and Open Payments data for 2013-2015. They included prescription drugs that accounted for 80% of the total Medicare pharmaceutical expenditures in rheumatology.

They then calculated annual average drug cost per beneficiary per year, the percentage of rheumatologists who received payments, and the average payment per physician per drug per year. Industry payments were categorized as either food/beverage or consulting/compensation.

Multivariable regression models were used to assess links between industry payments, prescribing patterns, and prescription drug spending.
 

‘Directly associated’ with prescribing probability

The authors concluded that “pharmaceutical company payments to rheumatologists were directly associated with the probability of the physician’s prescribing a drug marketed by that company, the proportion of prescriptions that are for that drug, and the resulting Medicare expenditures.”

Thinkstock

The authors noted that food and beverage payments were associated with increased Medicare reimbursement amounts for all drugs except rituximab.

The article includes examples that help quantify the link between payments and prescribing.

The authors wrote that for each $100 in food/beverage payments, Medicare reimbursement increased 6% to 44%. The increases were particularly high for infliximab and rACTH (repository corticotropin injection), “whereby a payment of $100 to a prescriber of these drugs was associated with increases of approximately $72,000 and $30,000 in Medicare reimbursements, respectively. For most of the other drugs, for every $100 in payments, the Medicare reimbursement increased by $8,000 to $13,000.”

The associations were strongest for food and beverage payments even though those were for lower dollar amounts.

The researchers found that every $100 in food and beverage payments, which also include gifts, entertainment, or educational materials, was linked with more than twofold higher probability of prescribing and higher Medicare reimbursements than for every $1,000 paid in consulting fees and compensation.

That finding and findings from previous studies, they say, “suggest that the current approach to regulating industry influence, which focuses on disclosure of large payments, may be inadequate.”

Aaron P. Mitchell, MD, a medical oncologist and health services researcher with Memorial Sloan Kettering Cancer Center in New York, told this news organization that the findings regarding rACTH show the potential harm of industry payments that are linked with prescribing.

Memorial Sloan Kettering Cancer Center

The drug is a naturally produced hormone used for both rheumatologic and neurologic conditions. “Since it is an unpatentable drug – really just a hormone – it’s kind of grandfathered in and never had to get [Food and Drug Administration] approval for its current indications,” Dr. Mitchell said.

The drug, which costs nearly $230,000 per Medicare beneficiary, hasn’t been tested head to head in large randomized trials against much cheaper rheumatology drugs, such as prednisone.

In the case of infliximab, he noted, for every $100 in food/beverage payments, there was an increase of $72,000 in Medicare spending.

Dr. Mitchell studies industry influence in a variety of specialties and said rheumatology follows the universal pattern, although the drugs used in the specialty are more expensive than in many specialties.

He agrees with the authors that focusing on disclosures to address the problem is probably not enough.

“We’ve been in this period of full and open disclosure for going on 10 years, and we haven’t really seen a decline in these payments,” he said.
 

Results won’t surprise rheumatologists

Karen Onel, MD, a pediatric rheumatologist at the Hospital for Special Surgery, New York, and chair of the American College of Rheumatology’s Ethics and Conflict of Interest Committee, who said she was speaking only for herself and not on behalf of the committee, told this news organization that the study will not be surprising to rheumatologists or to physicians in other specialties who are aware of the plethora of studies that concluded that industry payments influence prescribing.*

Physicians are well aware of the problem, but “they all think it’s not them,” she said.

She said a shortcoming of this study is that it is unclear what the payments were for, because many things are lumped together in the categories. In the case of food and beverage payments, she said that could include payments physicians don’t realize are going on their open payments profile.

Dr. Onel gives a personal example. When she goes to a medical conference, she says, “I don’t eat on pharma’s dime.” But because badge numbers are scanned, it appears she accepted the food provided by the pharmaceutical sponsor when she enters a room where food or coffee is being served.

She said that although there are outliers like rACTH that often get highlighted, “the numbers are very low of the physicians who had [industry] money, and the change in prescribing patterns actually was very low.”

She pointed to an important limitation that the authors list: The study was limited to patients with fee-for-service Medicare coverage and did not include those with private insurance.

“For example, Aetna, Cigna, and UnitedHealthcare have restricted reimbursement for rACTH in recent years, citing its lack of proven efficacy and the availability of more affordable options, and rACTH is not in the Veterans Affairs formulary,” the authors wrote.
 

Rapid development of specialty drugs

Still, the authors wrote, the associations described in this article are of high interest because even though rheumatologists make up a small proportion of the physician workforce, they have among the highest costs per prescription in Medicare drug claims.

“Rheumatology, second only to oncology, has entered an era of rapid development of specialty drugs, including biologic disease-modifying antirheumatic drugs (DMARDs),” the authors wrote.

The complex drugs are expensive to produce and require expertise in handling. Most are under patent with no generic or approved biosimilar equivalent.

Nearly half of all U.S. rheumatologists received some payment from a pharmaceutical company in the study period, and most payments to rheumatologists were for low dollar amounts.

The highest per-year annual expenditures were attributed to etanercept ($741 million), adalimumab ($620 million), and infliximab ($539 million).

These drugs were expensive per beneficiary ($20,728 for etanercept, $21,492 for adalimumab, and $15,941 for infliximab) and were prescribed by a large number of rheumatologists (4,068, 3,872, and 1,349, respectively).

Addressing the problem

Dr. Mitchell says the leaders of individual societies need to fill the gaps that leave busy clinicians searching for easy ways to get up-to-date information on drugs.

He says in all specialties, “Industry should not be the most easily and readily available source of information.

“We’re in the age of Zoom now,” he said. “There’s no reason you have to be sitting for an hour at lunch with a sales rep and not a brown-bag lunch getting a 1-hour update from a society on a new drug indication.

“We will get higher-quality information if we’re doing the education ourselves, and we’d be removing the sense of obligation to pay back the industry gift givers,” Dr. Mitchell said.

Dr. Onel said among the most critical work is making sure that the leadership of ACR is free of conflicts of interest.

“They are making decisions for the entire organization. We need to feel safe and comfortable that they are acting in the best interest of the rheumatologists and patients versus corporate partners,” she said.

Guidelines must strictly follow the standards from the Institute of Medicine that fewer than 50% of the regular guideline committee members may have commercial conflicts, Dr. Onel said.

She added that training on real or apparent conflicts of interest must start in medical school, residency, and fellowship, before physicians start to think they know their own practice patterns and that the results don’t apply to them.

However, the reality is that the industry and physicians will always need each other, she said.

Dr. Onel describes a tension between rheumatologists needing industry’s help for research and education, especially when federal money for research can be difficult to get, and managing those relationships to avoid real or apparent conflicts.

“We want the public’s trust,” she said.

A study coauthor has served on advisory boards of Boehringer Ingelheim (> $10,000) and Gilead Sciences (> $10,000); has served on speakers bureaus for Simply Speaking (> $10,000) and Boehringer Ingelheim (< $10,000); and has received royalties from UpToDate (> $10,000). Dr. Mitchell and Dr. Onel reported no relevant financial relationships.

* Update, 2/25/22: This article, which originally attributed comments to Dr. Karen Onel personally, has been updated to further emphasize that these comments were not on behalf of the committee that she leads.

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

Payments to rheumatologists by pharmaceutical companies, whether through food and beverages or consulting fees, are linked with a higher likelihood of prescribing drugs and higher Medicare spending, according to a new study published Feb. 2 in Mayo Clinic Proceedings.

Alí Duarte-García, MD, of the division of rheumatology in the department of medicine at the Mayo Clinic in Rochester, Minn., led the study.

Courtesy Mayo Clinic

Researchers conducted a cross-sectional analysis of Medicare Part B Public Use File, Medicare Part D Public Use File, and Open Payments data for 2013-2015. They included prescription drugs that accounted for 80% of the total Medicare pharmaceutical expenditures in rheumatology.

They then calculated annual average drug cost per beneficiary per year, the percentage of rheumatologists who received payments, and the average payment per physician per drug per year. Industry payments were categorized as either food/beverage or consulting/compensation.

Multivariable regression models were used to assess links between industry payments, prescribing patterns, and prescription drug spending.
 

‘Directly associated’ with prescribing probability

The authors concluded that “pharmaceutical company payments to rheumatologists were directly associated with the probability of the physician’s prescribing a drug marketed by that company, the proportion of prescriptions that are for that drug, and the resulting Medicare expenditures.”

Thinkstock

The authors noted that food and beverage payments were associated with increased Medicare reimbursement amounts for all drugs except rituximab.

The article includes examples that help quantify the link between payments and prescribing.

The authors wrote that for each $100 in food/beverage payments, Medicare reimbursement increased 6% to 44%. The increases were particularly high for infliximab and rACTH (repository corticotropin injection), “whereby a payment of $100 to a prescriber of these drugs was associated with increases of approximately $72,000 and $30,000 in Medicare reimbursements, respectively. For most of the other drugs, for every $100 in payments, the Medicare reimbursement increased by $8,000 to $13,000.”

The associations were strongest for food and beverage payments even though those were for lower dollar amounts.

The researchers found that every $100 in food and beverage payments, which also include gifts, entertainment, or educational materials, was linked with more than twofold higher probability of prescribing and higher Medicare reimbursements than for every $1,000 paid in consulting fees and compensation.

That finding and findings from previous studies, they say, “suggest that the current approach to regulating industry influence, which focuses on disclosure of large payments, may be inadequate.”

Aaron P. Mitchell, MD, a medical oncologist and health services researcher with Memorial Sloan Kettering Cancer Center in New York, told this news organization that the findings regarding rACTH show the potential harm of industry payments that are linked with prescribing.

Memorial Sloan Kettering Cancer Center

The drug is a naturally produced hormone used for both rheumatologic and neurologic conditions. “Since it is an unpatentable drug – really just a hormone – it’s kind of grandfathered in and never had to get [Food and Drug Administration] approval for its current indications,” Dr. Mitchell said.

The drug, which costs nearly $230,000 per Medicare beneficiary, hasn’t been tested head to head in large randomized trials against much cheaper rheumatology drugs, such as prednisone.

In the case of infliximab, he noted, for every $100 in food/beverage payments, there was an increase of $72,000 in Medicare spending.

Dr. Mitchell studies industry influence in a variety of specialties and said rheumatology follows the universal pattern, although the drugs used in the specialty are more expensive than in many specialties.

He agrees with the authors that focusing on disclosures to address the problem is probably not enough.

“We’ve been in this period of full and open disclosure for going on 10 years, and we haven’t really seen a decline in these payments,” he said.
 

Results won’t surprise rheumatologists

Karen Onel, MD, a pediatric rheumatologist at the Hospital for Special Surgery, New York, and chair of the American College of Rheumatology’s Ethics and Conflict of Interest Committee, who said she was speaking only for herself and not on behalf of the committee, told this news organization that the study will not be surprising to rheumatologists or to physicians in other specialties who are aware of the plethora of studies that concluded that industry payments influence prescribing.*

Physicians are well aware of the problem, but “they all think it’s not them,” she said.

She said a shortcoming of this study is that it is unclear what the payments were for, because many things are lumped together in the categories. In the case of food and beverage payments, she said that could include payments physicians don’t realize are going on their open payments profile.

Dr. Onel gives a personal example. When she goes to a medical conference, she says, “I don’t eat on pharma’s dime.” But because badge numbers are scanned, it appears she accepted the food provided by the pharmaceutical sponsor when she enters a room where food or coffee is being served.

She said that although there are outliers like rACTH that often get highlighted, “the numbers are very low of the physicians who had [industry] money, and the change in prescribing patterns actually was very low.”

She pointed to an important limitation that the authors list: The study was limited to patients with fee-for-service Medicare coverage and did not include those with private insurance.

“For example, Aetna, Cigna, and UnitedHealthcare have restricted reimbursement for rACTH in recent years, citing its lack of proven efficacy and the availability of more affordable options, and rACTH is not in the Veterans Affairs formulary,” the authors wrote.
 

Rapid development of specialty drugs

Still, the authors wrote, the associations described in this article are of high interest because even though rheumatologists make up a small proportion of the physician workforce, they have among the highest costs per prescription in Medicare drug claims.

“Rheumatology, second only to oncology, has entered an era of rapid development of specialty drugs, including biologic disease-modifying antirheumatic drugs (DMARDs),” the authors wrote.

The complex drugs are expensive to produce and require expertise in handling. Most are under patent with no generic or approved biosimilar equivalent.

Nearly half of all U.S. rheumatologists received some payment from a pharmaceutical company in the study period, and most payments to rheumatologists were for low dollar amounts.

The highest per-year annual expenditures were attributed to etanercept ($741 million), adalimumab ($620 million), and infliximab ($539 million).

These drugs were expensive per beneficiary ($20,728 for etanercept, $21,492 for adalimumab, and $15,941 for infliximab) and were prescribed by a large number of rheumatologists (4,068, 3,872, and 1,349, respectively).

Addressing the problem

Dr. Mitchell says the leaders of individual societies need to fill the gaps that leave busy clinicians searching for easy ways to get up-to-date information on drugs.

He says in all specialties, “Industry should not be the most easily and readily available source of information.

“We’re in the age of Zoom now,” he said. “There’s no reason you have to be sitting for an hour at lunch with a sales rep and not a brown-bag lunch getting a 1-hour update from a society on a new drug indication.

“We will get higher-quality information if we’re doing the education ourselves, and we’d be removing the sense of obligation to pay back the industry gift givers,” Dr. Mitchell said.

Dr. Onel said among the most critical work is making sure that the leadership of ACR is free of conflicts of interest.

“They are making decisions for the entire organization. We need to feel safe and comfortable that they are acting in the best interest of the rheumatologists and patients versus corporate partners,” she said.

Guidelines must strictly follow the standards from the Institute of Medicine that fewer than 50% of the regular guideline committee members may have commercial conflicts, Dr. Onel said.

She added that training on real or apparent conflicts of interest must start in medical school, residency, and fellowship, before physicians start to think they know their own practice patterns and that the results don’t apply to them.

However, the reality is that the industry and physicians will always need each other, she said.

Dr. Onel describes a tension between rheumatologists needing industry’s help for research and education, especially when federal money for research can be difficult to get, and managing those relationships to avoid real or apparent conflicts.

“We want the public’s trust,” she said.

A study coauthor has served on advisory boards of Boehringer Ingelheim (> $10,000) and Gilead Sciences (> $10,000); has served on speakers bureaus for Simply Speaking (> $10,000) and Boehringer Ingelheim (< $10,000); and has received royalties from UpToDate (> $10,000). Dr. Mitchell and Dr. Onel reported no relevant financial relationships.

* Update, 2/25/22: This article, which originally attributed comments to Dr. Karen Onel personally, has been updated to further emphasize that these comments were not on behalf of the committee that she leads.

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

Health authorities in Malawi have declared an outbreak of wild poliovirus type 1 after a case was confirmed in a 3-year-old girl in the capital, Lilongwe. It was the first case in Africa in 5 years, according to the World Health Organization.

Globally, there were only five cases of wild poliovirus in 2021, the WHO states.

“As long as wild polio exists anywhere in the world all countries remain at risk of importation of the virus,” Matshidiso Moeti, MBBS, WHO regional director for Africa, said in the statement.
 

Girl paralyzed in November

The Global Polio Eradication Initiative (GPEI) said in a statement that the 3-year-old girl  experienced paralysis in November, and stool specimens were collected. Sequencing of the virus was conducted in February, 2022, by the National Institute for Communicable Diseases in South Africa, and the Centers for Disease Control and Prevention confirmed the case as WPV1.

According to the WHO announcement, laboratory analysis shows that the strain identified in Malawi is linked to one circulating in Sindh Province in Pakistan. Polio remains endemic only in Afghanistan and Pakistan.

Kacey C. Ernst, PhD, MPH, professor and infectious disease epidemiologist at the University of Arizona’s Zuckerman College of Public Health in Tucson, pointed out that what is not clear from the press release is whether the girl had traveled to Pakistan or was infected in Malawi.

“This is a very significant detail that would indicate whether or not transmission was actively occurring in Malawi. Until that information is released, it is hard to judge the extent of the possible outbreak,” she said in an interview. “The good news is that this case was in fact detected. The surveillance systems are in place and they were able to identify wild-type cases.”

Dr. Ernst said that although there is cause for concern, it is “not a reason to panic. Malawi has very high polio vaccination rates and it is quite possible that this will be a very small defined outbreak that will be well contained.”

She added that the medical community should be alerted that this case has been identified so travelers who have been to affected areas who have any symptoms can be appropriately screened.

The WHO said it is helping Malawi health authorities in the response, including increasing immunizations.

However, a vaccination campaign comes at a time of health system upheaval in Malawi.

“Malawi, like countries all over the world, has seen an interruption in services due to COVID,” Joia S. Mukherjee, MD, MPH, chief medical officer with Partners in Health and associate professor with the division of global health equity at Brigham and Women’s Hospital and in the department of global health and social medicine at Harvard Medical School, Boston, said in an interview. “In addition, Malawi is currently dealing with the aftermath of a cyclone – where nearly a million people were displaced. Vaccination campaigns work best if there is solid infrastructure. Both COVID and the impact of climate change have shaken the health system.”

UN health agencies warned last year that millions of children who have not received immunizations during the pandemic, especially in Africa, “are now at risk from life-threatening diseases such as measles, polio, yellow fever, and diphtheria,” Reuters reported.

Africa was certified as wild poliovirus free on Aug. 25, 2020. The CDC had served as the lead partner over 3 decades in helping Africa reach the milestone. Africa will retain that status, the WHO stated, because the strain originated in Pakistan.

Five of six WHO regions have been certified polio free. The Americas received eradication certification in 1994.

There is no cure for polio, which can cause irreversible paralysis within hours, but the disease has been largely eradicated globally with an effective vaccine.
 

GPEI sending teams

The GPEI is sending a team to Malawi to support emergency operations, communications, and surveillance. Partner organizations will also send teams to support operations and innovative vaccination campaign solutions.

GPEI was launched in 1988 with the combined efforts of national governments, WHO, Rotary International, the CDC, and UNICEF. The GPEI partnership has included the Bill & Melinda Gates Foundation and, in recent years, Gavi, the Vaccine Alliance.

The CDC states, “[G]lobal incidence of polio has decreased by 99.9% since GPEI’s foundation. An estimated 16 million people today are walking who would otherwise have been paralyzed by the disease, and more than 1.5 million people are alive, whose lives would otherwise have been lost. Now the task remains to tackle polio in its last few strongholds and get rid of the final 0.1% of polio cases.”
 

Three wild poliovirus strains

There are three wild poliovirus strains: type 1 (WPV1), type 2 (WPV2), and type 3 (WPV3).

“Symptomatically, all three strains are identical, in that they cause irreversible paralysis or even death. But there are genetic and virologic differences which make these three strains three separate viruses that must each be eradicated individually,” according to WHO.

WPV3 is the second strain to be wiped out, following the certification of the eradication of WPV2 in 2015.

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

Health authorities in Malawi have declared an outbreak of wild poliovirus type 1 after a case was confirmed in a 3-year-old girl in the capital, Lilongwe. It was the first case in Africa in 5 years, according to the World Health Organization.

Globally, there were only five cases of wild poliovirus in 2021, the WHO states.

“As long as wild polio exists anywhere in the world all countries remain at risk of importation of the virus,” Matshidiso Moeti, MBBS, WHO regional director for Africa, said in the statement.
 

Girl paralyzed in November

The Global Polio Eradication Initiative (GPEI) said in a statement that the 3-year-old girl  experienced paralysis in November, and stool specimens were collected. Sequencing of the virus was conducted in February, 2022, by the National Institute for Communicable Diseases in South Africa, and the Centers for Disease Control and Prevention confirmed the case as WPV1.

According to the WHO announcement, laboratory analysis shows that the strain identified in Malawi is linked to one circulating in Sindh Province in Pakistan. Polio remains endemic only in Afghanistan and Pakistan.

Kacey C. Ernst, PhD, MPH, professor and infectious disease epidemiologist at the University of Arizona’s Zuckerman College of Public Health in Tucson, pointed out that what is not clear from the press release is whether the girl had traveled to Pakistan or was infected in Malawi.

“This is a very significant detail that would indicate whether or not transmission was actively occurring in Malawi. Until that information is released, it is hard to judge the extent of the possible outbreak,” she said in an interview. “The good news is that this case was in fact detected. The surveillance systems are in place and they were able to identify wild-type cases.”

Dr. Ernst said that although there is cause for concern, it is “not a reason to panic. Malawi has very high polio vaccination rates and it is quite possible that this will be a very small defined outbreak that will be well contained.”

She added that the medical community should be alerted that this case has been identified so travelers who have been to affected areas who have any symptoms can be appropriately screened.

The WHO said it is helping Malawi health authorities in the response, including increasing immunizations.

However, a vaccination campaign comes at a time of health system upheaval in Malawi.

“Malawi, like countries all over the world, has seen an interruption in services due to COVID,” Joia S. Mukherjee, MD, MPH, chief medical officer with Partners in Health and associate professor with the division of global health equity at Brigham and Women’s Hospital and in the department of global health and social medicine at Harvard Medical School, Boston, said in an interview. “In addition, Malawi is currently dealing with the aftermath of a cyclone – where nearly a million people were displaced. Vaccination campaigns work best if there is solid infrastructure. Both COVID and the impact of climate change have shaken the health system.”

UN health agencies warned last year that millions of children who have not received immunizations during the pandemic, especially in Africa, “are now at risk from life-threatening diseases such as measles, polio, yellow fever, and diphtheria,” Reuters reported.

Africa was certified as wild poliovirus free on Aug. 25, 2020. The CDC had served as the lead partner over 3 decades in helping Africa reach the milestone. Africa will retain that status, the WHO stated, because the strain originated in Pakistan.

Five of six WHO regions have been certified polio free. The Americas received eradication certification in 1994.

There is no cure for polio, which can cause irreversible paralysis within hours, but the disease has been largely eradicated globally with an effective vaccine.
 

GPEI sending teams

The GPEI is sending a team to Malawi to support emergency operations, communications, and surveillance. Partner organizations will also send teams to support operations and innovative vaccination campaign solutions.

GPEI was launched in 1988 with the combined efforts of national governments, WHO, Rotary International, the CDC, and UNICEF. The GPEI partnership has included the Bill & Melinda Gates Foundation and, in recent years, Gavi, the Vaccine Alliance.

The CDC states, “[G]lobal incidence of polio has decreased by 99.9% since GPEI’s foundation. An estimated 16 million people today are walking who would otherwise have been paralyzed by the disease, and more than 1.5 million people are alive, whose lives would otherwise have been lost. Now the task remains to tackle polio in its last few strongholds and get rid of the final 0.1% of polio cases.”
 

Three wild poliovirus strains

There are three wild poliovirus strains: type 1 (WPV1), type 2 (WPV2), and type 3 (WPV3).

“Symptomatically, all three strains are identical, in that they cause irreversible paralysis or even death. But there are genetic and virologic differences which make these three strains three separate viruses that must each be eradicated individually,” according to WHO.

WPV3 is the second strain to be wiped out, following the certification of the eradication of WPV2 in 2015.

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

Health authorities in Malawi have declared an outbreak of wild poliovirus type 1 after a case was confirmed in a 3-year-old girl in the capital, Lilongwe. It was the first case in Africa in 5 years, according to the World Health Organization.

Globally, there were only five cases of wild poliovirus in 2021, the WHO states.

“As long as wild polio exists anywhere in the world all countries remain at risk of importation of the virus,” Matshidiso Moeti, MBBS, WHO regional director for Africa, said in the statement.
 

Girl paralyzed in November

The Global Polio Eradication Initiative (GPEI) said in a statement that the 3-year-old girl  experienced paralysis in November, and stool specimens were collected. Sequencing of the virus was conducted in February, 2022, by the National Institute for Communicable Diseases in South Africa, and the Centers for Disease Control and Prevention confirmed the case as WPV1.

According to the WHO announcement, laboratory analysis shows that the strain identified in Malawi is linked to one circulating in Sindh Province in Pakistan. Polio remains endemic only in Afghanistan and Pakistan.

Kacey C. Ernst, PhD, MPH, professor and infectious disease epidemiologist at the University of Arizona’s Zuckerman College of Public Health in Tucson, pointed out that what is not clear from the press release is whether the girl had traveled to Pakistan or was infected in Malawi.

“This is a very significant detail that would indicate whether or not transmission was actively occurring in Malawi. Until that information is released, it is hard to judge the extent of the possible outbreak,” she said in an interview. “The good news is that this case was in fact detected. The surveillance systems are in place and they were able to identify wild-type cases.”

Dr. Ernst said that although there is cause for concern, it is “not a reason to panic. Malawi has very high polio vaccination rates and it is quite possible that this will be a very small defined outbreak that will be well contained.”

She added that the medical community should be alerted that this case has been identified so travelers who have been to affected areas who have any symptoms can be appropriately screened.

The WHO said it is helping Malawi health authorities in the response, including increasing immunizations.

However, a vaccination campaign comes at a time of health system upheaval in Malawi.

“Malawi, like countries all over the world, has seen an interruption in services due to COVID,” Joia S. Mukherjee, MD, MPH, chief medical officer with Partners in Health and associate professor with the division of global health equity at Brigham and Women’s Hospital and in the department of global health and social medicine at Harvard Medical School, Boston, said in an interview. “In addition, Malawi is currently dealing with the aftermath of a cyclone – where nearly a million people were displaced. Vaccination campaigns work best if there is solid infrastructure. Both COVID and the impact of climate change have shaken the health system.”

UN health agencies warned last year that millions of children who have not received immunizations during the pandemic, especially in Africa, “are now at risk from life-threatening diseases such as measles, polio, yellow fever, and diphtheria,” Reuters reported.

Africa was certified as wild poliovirus free on Aug. 25, 2020. The CDC had served as the lead partner over 3 decades in helping Africa reach the milestone. Africa will retain that status, the WHO stated, because the strain originated in Pakistan.

Five of six WHO regions have been certified polio free. The Americas received eradication certification in 1994.

There is no cure for polio, which can cause irreversible paralysis within hours, but the disease has been largely eradicated globally with an effective vaccine.
 

GPEI sending teams

The GPEI is sending a team to Malawi to support emergency operations, communications, and surveillance. Partner organizations will also send teams to support operations and innovative vaccination campaign solutions.

GPEI was launched in 1988 with the combined efforts of national governments, WHO, Rotary International, the CDC, and UNICEF. The GPEI partnership has included the Bill & Melinda Gates Foundation and, in recent years, Gavi, the Vaccine Alliance.

The CDC states, “[G]lobal incidence of polio has decreased by 99.9% since GPEI’s foundation. An estimated 16 million people today are walking who would otherwise have been paralyzed by the disease, and more than 1.5 million people are alive, whose lives would otherwise have been lost. Now the task remains to tackle polio in its last few strongholds and get rid of the final 0.1% of polio cases.”
 

Three wild poliovirus strains

There are three wild poliovirus strains: type 1 (WPV1), type 2 (WPV2), and type 3 (WPV3).

“Symptomatically, all three strains are identical, in that they cause irreversible paralysis or even death. But there are genetic and virologic differences which make these three strains three separate viruses that must each be eradicated individually,” according to WHO.

WPV3 is the second strain to be wiped out, following the certification of the eradication of WPV2 in 2015.

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

Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.

“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.

The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.

Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.

Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
 

Secondary outcomes

Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.

In all the secondary outcomes, there were no significant differences between groups.

Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).

The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
 

No difference by vaccine status

The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”

Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.

The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”

Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.

Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.

In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.

Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.

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

Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.

“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.

The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.

Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.

Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
 

Secondary outcomes

Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.

In all the secondary outcomes, there were no significant differences between groups.

Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).

The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
 

No difference by vaccine status

The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”

Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.

The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”

Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.

Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.

In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.

Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.

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

Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.

“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.

The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.

Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.

Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
 

Secondary outcomes

Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.

In all the secondary outcomes, there were no significant differences between groups.

Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).

The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
 

No difference by vaccine status

The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”

Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.

The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”

Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.

Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.

In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.

Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.

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

Polycystic ovary syndrome is common in girls with type 2 diabetes, findings of a new study suggest, and authors say screening for PCOS is critical in this group.

In a systematic review and meta-analysis involving 470 girls (average age 12.9-16.1 years) with type 2 diabetes in six studies, the prevalence of PCOS was nearly 1 in 5 (19.58%; 95% confidence interval, 12.02%-27.14%; P = .002), substantially higher than that of PCOS in the general adolescent population.

PCOS, a complex endocrine disorder, occurs in 1.14%-11.04% of adolescent girls globally, according to the paper published online in JAMA Network Open.

The secondary outcome studied links to prevalence of PCOS with race and obesity.

Insulin resistance and compensatory hyperinsulinemia are present in 44%-70% of women with PCOS, suggesting that they are more likely to develop type 2 diabetes, according to the researchers led by Milena Cioana, BHSc, with the department of pediatrics, McMaster University, Hamilton, Ont.

Kelly A. Curran, MD, an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center in Oklahoma City, where she practices adolescent medicine, said in an interview that it has been known that women with PCOS have higher rates of diabetes and many in the field have suspected the relationship is bidirectional.

“In my clinical practice, I’ve seen a high percentage of women with type 2 diabetes present with irregular menses, some of whom have gone on to be diagnosed with PCOS,” said Dr. Curran, who was not involved with the study.

However, she said, she was surprised the prevalence of PCOS reported in this paper – nearly one in five – was so high. Early diagnosis is important for PCOS to prevent complications such as hypertension, hyperglycemia, and dyslipidemia.

Psychiatric conditions are also prevalent in patients with PCOS, including anxiety (18%), depression (16%), and ADHD (9%).

Dr. Curran agreed there is a need to screen for PCOS and to evaluate for other causes of irregular periods in patients with type 2 diabetes.

“Menstrual irregularities are often overlooked in young women without further work-up, especially in patients who have chronic illnesses,” she noted.
 

Results come with a caveat

However, the authors said, results should be viewed with caution because “studies including the larger numbers of girls did not report the criteria used to diagnose PCOS, which is a challenge during adolescence.”

Diagnostic criteria for PCOS during adolescence include the combination of menstrual irregularities according to time since their first period and clinical or biochemical hyperandrogenism after excluding other potential causes.

Dr. Curran explained that PCOS symptoms include irregular periods and acne which can overlap with normal changes in puberty. In her experience, PCOS is often diagnosed without patients meeting full criteria. She agreed further research with standardized criteria is urgently needed.

The European Society of Human Reproduction and Embryology/American Society of Reproductive Medicine, the Pediatric Endocrine Society, and the International Consortium of Paediatric Endocrinology guidelines suggest that using ultrasound to check the size of ovaries could help diagnose PCOS, but other guidelines are more conservative, the authors noted.

They added that “there is a need for a consensus to establish the pediatric criteria for diagnosing PCOS in adolescents to ensure accurate diagnosis and lower the misclassification rates.”
 

Assessing links to obesity and race

Still unclear, the authors wrote, is whether and how obesity and race affect prevalence of PCOS among girls with type 2 diabetes.

The authors wrote: “Although earlier studies suggested that obesity-related insulin resistance and hyperinsulinemia can contribute to PCOS pathogenesis, insulin resistance in patients with PCOS may be present independently of [body mass index]. Obesity seems to increase the risk of PCOS only slightly and might represent a referral bias for PCOS.”

Few studies included in the meta-analysis had race-specific data, so the authors were limited in assessing associations between race and PCOS prevalence.

“However,” they wrote, “our data demonstrate that Indian girls had the highest prevalence, followed by White girls, and then Indigenous girls in Canada.”

Further studies are needed to help define at-risk subgroups and evaluate treatment strategies, the authors noted.

They reported having no relevant financial relationships. Dr. Curran had no conflicts of interest.

Polycystic ovary syndrome is common in girls with type 2 diabetes, findings of a new study suggest, and authors say screening for PCOS is critical in this group.

In a systematic review and meta-analysis involving 470 girls (average age 12.9-16.1 years) with type 2 diabetes in six studies, the prevalence of PCOS was nearly 1 in 5 (19.58%; 95% confidence interval, 12.02%-27.14%; P = .002), substantially higher than that of PCOS in the general adolescent population.

PCOS, a complex endocrine disorder, occurs in 1.14%-11.04% of adolescent girls globally, according to the paper published online in JAMA Network Open.

The secondary outcome studied links to prevalence of PCOS with race and obesity.

Insulin resistance and compensatory hyperinsulinemia are present in 44%-70% of women with PCOS, suggesting that they are more likely to develop type 2 diabetes, according to the researchers led by Milena Cioana, BHSc, with the department of pediatrics, McMaster University, Hamilton, Ont.

Kelly A. Curran, MD, an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center in Oklahoma City, where she practices adolescent medicine, said in an interview that it has been known that women with PCOS have higher rates of diabetes and many in the field have suspected the relationship is bidirectional.

“In my clinical practice, I’ve seen a high percentage of women with type 2 diabetes present with irregular menses, some of whom have gone on to be diagnosed with PCOS,” said Dr. Curran, who was not involved with the study.

However, she said, she was surprised the prevalence of PCOS reported in this paper – nearly one in five – was so high. Early diagnosis is important for PCOS to prevent complications such as hypertension, hyperglycemia, and dyslipidemia.

Psychiatric conditions are also prevalent in patients with PCOS, including anxiety (18%), depression (16%), and ADHD (9%).

Dr. Curran agreed there is a need to screen for PCOS and to evaluate for other causes of irregular periods in patients with type 2 diabetes.

“Menstrual irregularities are often overlooked in young women without further work-up, especially in patients who have chronic illnesses,” she noted.
 

Results come with a caveat

However, the authors said, results should be viewed with caution because “studies including the larger numbers of girls did not report the criteria used to diagnose PCOS, which is a challenge during adolescence.”

Diagnostic criteria for PCOS during adolescence include the combination of menstrual irregularities according to time since their first period and clinical or biochemical hyperandrogenism after excluding other potential causes.

Dr. Curran explained that PCOS symptoms include irregular periods and acne which can overlap with normal changes in puberty. In her experience, PCOS is often diagnosed without patients meeting full criteria. She agreed further research with standardized criteria is urgently needed.

The European Society of Human Reproduction and Embryology/American Society of Reproductive Medicine, the Pediatric Endocrine Society, and the International Consortium of Paediatric Endocrinology guidelines suggest that using ultrasound to check the size of ovaries could help diagnose PCOS, but other guidelines are more conservative, the authors noted.

They added that “there is a need for a consensus to establish the pediatric criteria for diagnosing PCOS in adolescents to ensure accurate diagnosis and lower the misclassification rates.”
 

Assessing links to obesity and race

Still unclear, the authors wrote, is whether and how obesity and race affect prevalence of PCOS among girls with type 2 diabetes.

The authors wrote: “Although earlier studies suggested that obesity-related insulin resistance and hyperinsulinemia can contribute to PCOS pathogenesis, insulin resistance in patients with PCOS may be present independently of [body mass index]. Obesity seems to increase the risk of PCOS only slightly and might represent a referral bias for PCOS.”

Few studies included in the meta-analysis had race-specific data, so the authors were limited in assessing associations between race and PCOS prevalence.

“However,” they wrote, “our data demonstrate that Indian girls had the highest prevalence, followed by White girls, and then Indigenous girls in Canada.”

Further studies are needed to help define at-risk subgroups and evaluate treatment strategies, the authors noted.

They reported having no relevant financial relationships. Dr. Curran had no conflicts of interest.

Polycystic ovary syndrome is common in girls with type 2 diabetes, findings of a new study suggest, and authors say screening for PCOS is critical in this group.

In a systematic review and meta-analysis involving 470 girls (average age 12.9-16.1 years) with type 2 diabetes in six studies, the prevalence of PCOS was nearly 1 in 5 (19.58%; 95% confidence interval, 12.02%-27.14%; P = .002), substantially higher than that of PCOS in the general adolescent population.

PCOS, a complex endocrine disorder, occurs in 1.14%-11.04% of adolescent girls globally, according to the paper published online in JAMA Network Open.

The secondary outcome studied links to prevalence of PCOS with race and obesity.

Insulin resistance and compensatory hyperinsulinemia are present in 44%-70% of women with PCOS, suggesting that they are more likely to develop type 2 diabetes, according to the researchers led by Milena Cioana, BHSc, with the department of pediatrics, McMaster University, Hamilton, Ont.

Kelly A. Curran, MD, an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center in Oklahoma City, where she practices adolescent medicine, said in an interview that it has been known that women with PCOS have higher rates of diabetes and many in the field have suspected the relationship is bidirectional.

“In my clinical practice, I’ve seen a high percentage of women with type 2 diabetes present with irregular menses, some of whom have gone on to be diagnosed with PCOS,” said Dr. Curran, who was not involved with the study.

However, she said, she was surprised the prevalence of PCOS reported in this paper – nearly one in five – was so high. Early diagnosis is important for PCOS to prevent complications such as hypertension, hyperglycemia, and dyslipidemia.

Psychiatric conditions are also prevalent in patients with PCOS, including anxiety (18%), depression (16%), and ADHD (9%).

Dr. Curran agreed there is a need to screen for PCOS and to evaluate for other causes of irregular periods in patients with type 2 diabetes.

“Menstrual irregularities are often overlooked in young women without further work-up, especially in patients who have chronic illnesses,” she noted.
 

Results come with a caveat

However, the authors said, results should be viewed with caution because “studies including the larger numbers of girls did not report the criteria used to diagnose PCOS, which is a challenge during adolescence.”

Diagnostic criteria for PCOS during adolescence include the combination of menstrual irregularities according to time since their first period and clinical or biochemical hyperandrogenism after excluding other potential causes.

Dr. Curran explained that PCOS symptoms include irregular periods and acne which can overlap with normal changes in puberty. In her experience, PCOS is often diagnosed without patients meeting full criteria. She agreed further research with standardized criteria is urgently needed.

The European Society of Human Reproduction and Embryology/American Society of Reproductive Medicine, the Pediatric Endocrine Society, and the International Consortium of Paediatric Endocrinology guidelines suggest that using ultrasound to check the size of ovaries could help diagnose PCOS, but other guidelines are more conservative, the authors noted.

They added that “there is a need for a consensus to establish the pediatric criteria for diagnosing PCOS in adolescents to ensure accurate diagnosis and lower the misclassification rates.”
 

Assessing links to obesity and race

Still unclear, the authors wrote, is whether and how obesity and race affect prevalence of PCOS among girls with type 2 diabetes.

The authors wrote: “Although earlier studies suggested that obesity-related insulin resistance and hyperinsulinemia can contribute to PCOS pathogenesis, insulin resistance in patients with PCOS may be present independently of [body mass index]. Obesity seems to increase the risk of PCOS only slightly and might represent a referral bias for PCOS.”

Few studies included in the meta-analysis had race-specific data, so the authors were limited in assessing associations between race and PCOS prevalence.

“However,” they wrote, “our data demonstrate that Indian girls had the highest prevalence, followed by White girls, and then Indigenous girls in Canada.”

Further studies are needed to help define at-risk subgroups and evaluate treatment strategies, the authors noted.

They reported having no relevant financial relationships. Dr. Curran had no conflicts of interest.

A small study of deceased nonvaccinated men who died of COVID-19 complications suggests the testes may be a sanctuary for the SARS-CoV-2 virus, raising questions about potential consequences for reproductive health among those infected.

The study, published online Feb. 8 on the preprint server MedRxiv, found that “patients who become critically ill exhibit severe damages and may harbor the active virus in testes,” which can “serve as a viral sanctuary.”

Guilherme M.J. Costa, PhD, a professor at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, led the study, which has not yet been peer-reviewed.

“A critical point of this article is that the virus was active in the patient’s testis after a long period of infection, indicating that the testis is able to maintain the viable virus for extended periods. It happens for many kinds of viruses in this genital organ,” Dr. Costa said in an interview.

Brian Keith McNeil, MD, vice-chair, department of urology at SUNY Downstate Health Sciences University in New York, told this news organization that the topic of COVID-19 and fertility has been discussed but data are sparse on the subject.

“The question this raises is whether or not COVID can live in the testes, and based on this it seems it can,” he said, adding that it also raises the question of whether COVID-19 could be transmitted through semen. “It leads one to wonder whether this could have a long-term impact on fertility in men and women.”

The authors wrote that deep testicular evaluation of patients who have been infected with COVID-19 is critical because the testes have one of the highest expressions of angiotensin converting enzyme 2 (ACE2) receptors, which play a large role in entrance of the virus into cells.

“A direct influence of SARS-CoV-2 in testicular cells might deregulate ACE2, elevating the levels of angiotensin II, a potent pro-inflammatory and angiogenic peptide,” the authors wrote.
 

Sperm-producing cells infected

In 2021, the researchers enrolled 11 male patients deceased from COVID-19 complications; none had received a vaccine. Infection was confirmed by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) performed during their hospital stay. All 11 patients were admitted to the intensive care unit with severe pulmonary symptoms.

All but one of the patients had children and none had scrotal symptoms or complaints during their time in the hospital. Their clinical histories revealed no testicular disorders.

Dr. Costa said they found that detecting SARS-CoV-2 mRNA in testes is difficult in a conventional RT-PCR test.

Therefore, “We modified the protocol of the RT-PCR and used nanosensors. We observed that SARS-CoV-2 has a huge tropism for the testes in this context,” he said.

He said the team performed stainings and “discovered that macrophages and germ cells are highly infected.”

That’s important, he said, because an immune cell, which is supposed to fight the virus, is infected in the tissue. Also, the germ cell, responsible for sperm production, is infected.

“This reopens the worries about the presence of SARS-CoV-2 in semen, as other authors mentioned,” he said.
 

New findings

The team also found that the testes are a good place for viral replication.

The authors say they are the first to show:

• The longer the severe condition, the lower the number of surviving germ cells.
• There was fluctuation in several essential testicular genes.
• The intratesticular testosterone levels are 30 times reduced in the testes of COVID-19 patients.

The control group was composed of six patients who had undergone testicle removal after prostate cancer was suspected. Collection of both testicles from the test group was performed within 3 hours of death after a family member signed an informed consent document.

Recent research on semen demonstrates that patients who recovered from COVID-19 reestablish their sperm quality after 3 months of infection.

That study, in Fertility and Sterility, found that sperm quality was initially reduced for months in some men after recovery from COVID-19.

The team studied semen samples from 120 Belgian men (mean age, 35 years) at an average 52 days after their last COVID-19 symptoms. The semen was not found to be infectious.

But among 35 men who provided samples within a month after infection, reductions in sperm motility were evident in 60% and sperm counts were reduced in 37%, according to the report.
 

Testicular damage

The results [of the Costa et al. paper] emphasize the importance of testicular damage in severe COVID-19,” Rafael Kroon Campos, PhD, a postdoctoral fellow in the department of microbiology & immunology at the University of Texas Medical Branch at Galveston, said in an interview.

He noted that other viruses have also been shown to infect or otherwise cause testicular damage or orchitis, such as Zika, Ebola, and the closely related SARS-CoV-1. Sexual transmission has been documented for Zika and Ebola viruses.

Dr. Campos said with SARS-CoV-2, it is unclear whether sexual transmission plays a role.

“Some reports found evidence of viral RNA in semen, but these were rare occurrences. The study by Costa and colleagues used a combination of sensitive techniques and they were able to detect a small amount of viral RNA and viral protein in the testicular tissue of the deceased patients, as well as show viral factories indicating replication of the virus by electron microscopy,” he said.

Dr. Campos said the findings are particularly important and concerning because of the large number of severe cases of COVID-19.

“It is critical to continue to investigate the impact of the disease in testes, including the impact of different variants of concern on testicular damage,” he said.

Dr. McNeil and Dr. Campos have disclosed no relevant financial relationships.

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

A small study of deceased nonvaccinated men who died of COVID-19 complications suggests the testes may be a sanctuary for the SARS-CoV-2 virus, raising questions about potential consequences for reproductive health among those infected.

The study, published online Feb. 8 on the preprint server MedRxiv, found that “patients who become critically ill exhibit severe damages and may harbor the active virus in testes,” which can “serve as a viral sanctuary.”

Guilherme M.J. Costa, PhD, a professor at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, led the study, which has not yet been peer-reviewed.

“A critical point of this article is that the virus was active in the patient’s testis after a long period of infection, indicating that the testis is able to maintain the viable virus for extended periods. It happens for many kinds of viruses in this genital organ,” Dr. Costa said in an interview.

Brian Keith McNeil, MD, vice-chair, department of urology at SUNY Downstate Health Sciences University in New York, told this news organization that the topic of COVID-19 and fertility has been discussed but data are sparse on the subject.

“The question this raises is whether or not COVID can live in the testes, and based on this it seems it can,” he said, adding that it also raises the question of whether COVID-19 could be transmitted through semen. “It leads one to wonder whether this could have a long-term impact on fertility in men and women.”

The authors wrote that deep testicular evaluation of patients who have been infected with COVID-19 is critical because the testes have one of the highest expressions of angiotensin converting enzyme 2 (ACE2) receptors, which play a large role in entrance of the virus into cells.

“A direct influence of SARS-CoV-2 in testicular cells might deregulate ACE2, elevating the levels of angiotensin II, a potent pro-inflammatory and angiogenic peptide,” the authors wrote.
 

Sperm-producing cells infected

In 2021, the researchers enrolled 11 male patients deceased from COVID-19 complications; none had received a vaccine. Infection was confirmed by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) performed during their hospital stay. All 11 patients were admitted to the intensive care unit with severe pulmonary symptoms.

All but one of the patients had children and none had scrotal symptoms or complaints during their time in the hospital. Their clinical histories revealed no testicular disorders.

Dr. Costa said they found that detecting SARS-CoV-2 mRNA in testes is difficult in a conventional RT-PCR test.

Therefore, “We modified the protocol of the RT-PCR and used nanosensors. We observed that SARS-CoV-2 has a huge tropism for the testes in this context,” he said.

He said the team performed stainings and “discovered that macrophages and germ cells are highly infected.”

That’s important, he said, because an immune cell, which is supposed to fight the virus, is infected in the tissue. Also, the germ cell, responsible for sperm production, is infected.

“This reopens the worries about the presence of SARS-CoV-2 in semen, as other authors mentioned,” he said.
 

New findings

The team also found that the testes are a good place for viral replication.

The authors say they are the first to show:

• The longer the severe condition, the lower the number of surviving germ cells.
• There was fluctuation in several essential testicular genes.
• The intratesticular testosterone levels are 30 times reduced in the testes of COVID-19 patients.

The control group was composed of six patients who had undergone testicle removal after prostate cancer was suspected. Collection of both testicles from the test group was performed within 3 hours of death after a family member signed an informed consent document.

Recent research on semen demonstrates that patients who recovered from COVID-19 reestablish their sperm quality after 3 months of infection.

That study, in Fertility and Sterility, found that sperm quality was initially reduced for months in some men after recovery from COVID-19.

The team studied semen samples from 120 Belgian men (mean age, 35 years) at an average 52 days after their last COVID-19 symptoms. The semen was not found to be infectious.

But among 35 men who provided samples within a month after infection, reductions in sperm motility were evident in 60% and sperm counts were reduced in 37%, according to the report.
 

Testicular damage

The results [of the Costa et al. paper] emphasize the importance of testicular damage in severe COVID-19,” Rafael Kroon Campos, PhD, a postdoctoral fellow in the department of microbiology & immunology at the University of Texas Medical Branch at Galveston, said in an interview.

He noted that other viruses have also been shown to infect or otherwise cause testicular damage or orchitis, such as Zika, Ebola, and the closely related SARS-CoV-1. Sexual transmission has been documented for Zika and Ebola viruses.

Dr. Campos said with SARS-CoV-2, it is unclear whether sexual transmission plays a role.

“Some reports found evidence of viral RNA in semen, but these were rare occurrences. The study by Costa and colleagues used a combination of sensitive techniques and they were able to detect a small amount of viral RNA and viral protein in the testicular tissue of the deceased patients, as well as show viral factories indicating replication of the virus by electron microscopy,” he said.

Dr. Campos said the findings are particularly important and concerning because of the large number of severe cases of COVID-19.

“It is critical to continue to investigate the impact of the disease in testes, including the impact of different variants of concern on testicular damage,” he said.

Dr. McNeil and Dr. Campos have disclosed no relevant financial relationships.

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

A small study of deceased nonvaccinated men who died of COVID-19 complications suggests the testes may be a sanctuary for the SARS-CoV-2 virus, raising questions about potential consequences for reproductive health among those infected.

The study, published online Feb. 8 on the preprint server MedRxiv, found that “patients who become critically ill exhibit severe damages and may harbor the active virus in testes,” which can “serve as a viral sanctuary.”

Guilherme M.J. Costa, PhD, a professor at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, led the study, which has not yet been peer-reviewed.

“A critical point of this article is that the virus was active in the patient’s testis after a long period of infection, indicating that the testis is able to maintain the viable virus for extended periods. It happens for many kinds of viruses in this genital organ,” Dr. Costa said in an interview.

Brian Keith McNeil, MD, vice-chair, department of urology at SUNY Downstate Health Sciences University in New York, told this news organization that the topic of COVID-19 and fertility has been discussed but data are sparse on the subject.

“The question this raises is whether or not COVID can live in the testes, and based on this it seems it can,” he said, adding that it also raises the question of whether COVID-19 could be transmitted through semen. “It leads one to wonder whether this could have a long-term impact on fertility in men and women.”

The authors wrote that deep testicular evaluation of patients who have been infected with COVID-19 is critical because the testes have one of the highest expressions of angiotensin converting enzyme 2 (ACE2) receptors, which play a large role in entrance of the virus into cells.

“A direct influence of SARS-CoV-2 in testicular cells might deregulate ACE2, elevating the levels of angiotensin II, a potent pro-inflammatory and angiogenic peptide,” the authors wrote.
 

Sperm-producing cells infected

In 2021, the researchers enrolled 11 male patients deceased from COVID-19 complications; none had received a vaccine. Infection was confirmed by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) performed during their hospital stay. All 11 patients were admitted to the intensive care unit with severe pulmonary symptoms.

All but one of the patients had children and none had scrotal symptoms or complaints during their time in the hospital. Their clinical histories revealed no testicular disorders.

Dr. Costa said they found that detecting SARS-CoV-2 mRNA in testes is difficult in a conventional RT-PCR test.

Therefore, “We modified the protocol of the RT-PCR and used nanosensors. We observed that SARS-CoV-2 has a huge tropism for the testes in this context,” he said.

He said the team performed stainings and “discovered that macrophages and germ cells are highly infected.”

That’s important, he said, because an immune cell, which is supposed to fight the virus, is infected in the tissue. Also, the germ cell, responsible for sperm production, is infected.

“This reopens the worries about the presence of SARS-CoV-2 in semen, as other authors mentioned,” he said.
 

New findings

The team also found that the testes are a good place for viral replication.

The authors say they are the first to show:

• The longer the severe condition, the lower the number of surviving germ cells.
• There was fluctuation in several essential testicular genes.
• The intratesticular testosterone levels are 30 times reduced in the testes of COVID-19 patients.

The control group was composed of six patients who had undergone testicle removal after prostate cancer was suspected. Collection of both testicles from the test group was performed within 3 hours of death after a family member signed an informed consent document.

Recent research on semen demonstrates that patients who recovered from COVID-19 reestablish their sperm quality after 3 months of infection.

That study, in Fertility and Sterility, found that sperm quality was initially reduced for months in some men after recovery from COVID-19.

The team studied semen samples from 120 Belgian men (mean age, 35 years) at an average 52 days after their last COVID-19 symptoms. The semen was not found to be infectious.

But among 35 men who provided samples within a month after infection, reductions in sperm motility were evident in 60% and sperm counts were reduced in 37%, according to the report.
 

Testicular damage

The results [of the Costa et al. paper] emphasize the importance of testicular damage in severe COVID-19,” Rafael Kroon Campos, PhD, a postdoctoral fellow in the department of microbiology & immunology at the University of Texas Medical Branch at Galveston, said in an interview.

He noted that other viruses have also been shown to infect or otherwise cause testicular damage or orchitis, such as Zika, Ebola, and the closely related SARS-CoV-1. Sexual transmission has been documented for Zika and Ebola viruses.

Dr. Campos said with SARS-CoV-2, it is unclear whether sexual transmission plays a role.

“Some reports found evidence of viral RNA in semen, but these were rare occurrences. The study by Costa and colleagues used a combination of sensitive techniques and they were able to detect a small amount of viral RNA and viral protein in the testicular tissue of the deceased patients, as well as show viral factories indicating replication of the virus by electron microscopy,” he said.

Dr. Campos said the findings are particularly important and concerning because of the large number of severe cases of COVID-19.

“It is critical to continue to investigate the impact of the disease in testes, including the impact of different variants of concern on testicular damage,” he said.

Dr. McNeil and Dr. Campos have disclosed no relevant financial relationships.

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

MicroRNAs (miRNAs) that signal hepatocellular carcinoma (HCC), the most common type of liver cancer, have been detected in saliva for the first time, according to results from a pilot study.

The findings were published online in PeerJ.

The small, noncoding RNAs regulate many cellular functions and affect cancer development and progression.

The discovery has the potential to offer a noninvasive alternative or complement to available detection tools – ultrasound and the blood biomarker alpha fetoprotein (AFP) – which lack sensitivity, said Daniel Rotroff, PhD, MSPH, senior author of the study and a researcher in the Department of Quantitative Health Sciences at the Cleveland Clinic.

“Right now, the current clinical tools are not adequate,” he told this news organization. “They miss approximately 40% to 50% of the patients who have HCC.”

Scientists are interested in finding better ways to detect liver cancer, the rates of which are growing rapidly. HCC represents 80% of all liver cancers.

“HCC and liver cancer are the fastest growing cancers in the United States,” Dr. Rotroff said. “They are the fifth and seventh leading cause of cancer death in men and women, respectively.”

Driving the growth are increases in hepatitis C, obesity, fatty liver disease, and alcoholism.

Nancy Reau, MD, the Richard B. Capps Chair of Hepatology and section chief, Hepatology, at Rush Medical College, Chicago, who was not part of the study, told this news organization that despite the study’s being relatively small in scale, the preliminary information it provides is nonetheless “really attractive.”

If larger studies confirm the results, the discovery could open up the possibility of patients mailing in saliva samples from their homes to screen for liver cancer.

The pandemic, she noted, highlighted the shortcomings of ultrasound in screening for liver cancer, as it required patients to come into a facility.

“You’d love to have a biomarker that was more accessible and accurate,” she said. “It would have lots of applicability where cancer surveillance is less available.”

Dr. Rotroff added that “we do know saliva samples can be stable at room temperature. It opens up possibilities to expand the net of being able to screen a wider number of patients.”
 

Differentiating HCC from cirrhosis

Investigators at the Cleveland Clinic performed small RNA sequencing in 20 patients with HCC and compared the findings to sequencing of 19 patients with cirrhosis.

Liver cirrhosis is the primary risk factor for developing HCC, so distinguishing patients with HCC from this cohort of high-risk patients serves as a proof of principle.

The sequencing showed that 4,565 precursor and mature miRNAs were detected in saliva and that 365 were significantly different between those with HCC compared to cirrhosis (false discovery rate, P < .05).

“Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC,” the authors write.

Machine learning found a combination of 10 miRNAs and covariates that accurately classified patients with HCC (area under the curve = 0.87).

The researchers note that miRNAs have been found in saliva and have shown potential as noninvasive biomarkers for a number of other cancers, including breast, oral, and lung cancers.

Additionally, Dr. Rotroff said, microRNAs have been shown to be altered in the tumor tissue of HCC, compared with the surrounding tissue.
 

Catching cancer early

Dr. Reau noted that a strength of the study is that it validated the biomarker in a diverse group of patients already diagnosed with liver cancer, including people with early-stage cancer, those who underwent transplantation, and those with recurrent cancer.

“Everyone searching for biomarkers is looking to make sure that the surveillance tool identifies the patient when it can pay off with early treatment,” Dr. Reau said.

“You don’t want to identify cancer when it’s bad, and you don’t have any options.

This is a little bit where AFP sometimes fails. Even if ultrasound isn’t that accurate, it still generally identifies people when they fit within curative guidelines.”

Dr. Rotroff also stressed the importance of detecting the cancers early, noting that the prognosis for patients with HCC before it has metastasized is greater than 4 years, but the prognosis drops to less than 1 year if it has metastasized.

Dr. Rotroff has an equity stake in Clarified Precision Medicine. He holds intellectual property related to the detection of HCC. Dr. Reau reports no relevant financial relationships.

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

MicroRNAs (miRNAs) that signal hepatocellular carcinoma (HCC), the most common type of liver cancer, have been detected in saliva for the first time, according to results from a pilot study.

The findings were published online in PeerJ.

The small, noncoding RNAs regulate many cellular functions and affect cancer development and progression.

The discovery has the potential to offer a noninvasive alternative or complement to available detection tools – ultrasound and the blood biomarker alpha fetoprotein (AFP) – which lack sensitivity, said Daniel Rotroff, PhD, MSPH, senior author of the study and a researcher in the Department of Quantitative Health Sciences at the Cleveland Clinic.

“Right now, the current clinical tools are not adequate,” he told this news organization. “They miss approximately 40% to 50% of the patients who have HCC.”

Scientists are interested in finding better ways to detect liver cancer, the rates of which are growing rapidly. HCC represents 80% of all liver cancers.

“HCC and liver cancer are the fastest growing cancers in the United States,” Dr. Rotroff said. “They are the fifth and seventh leading cause of cancer death in men and women, respectively.”

Driving the growth are increases in hepatitis C, obesity, fatty liver disease, and alcoholism.

Nancy Reau, MD, the Richard B. Capps Chair of Hepatology and section chief, Hepatology, at Rush Medical College, Chicago, who was not part of the study, told this news organization that despite the study’s being relatively small in scale, the preliminary information it provides is nonetheless “really attractive.”

If larger studies confirm the results, the discovery could open up the possibility of patients mailing in saliva samples from their homes to screen for liver cancer.

The pandemic, she noted, highlighted the shortcomings of ultrasound in screening for liver cancer, as it required patients to come into a facility.

“You’d love to have a biomarker that was more accessible and accurate,” she said. “It would have lots of applicability where cancer surveillance is less available.”

Dr. Rotroff added that “we do know saliva samples can be stable at room temperature. It opens up possibilities to expand the net of being able to screen a wider number of patients.”
 

Differentiating HCC from cirrhosis

Investigators at the Cleveland Clinic performed small RNA sequencing in 20 patients with HCC and compared the findings to sequencing of 19 patients with cirrhosis.

Liver cirrhosis is the primary risk factor for developing HCC, so distinguishing patients with HCC from this cohort of high-risk patients serves as a proof of principle.

The sequencing showed that 4,565 precursor and mature miRNAs were detected in saliva and that 365 were significantly different between those with HCC compared to cirrhosis (false discovery rate, P < .05).

“Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC,” the authors write.

Machine learning found a combination of 10 miRNAs and covariates that accurately classified patients with HCC (area under the curve = 0.87).

The researchers note that miRNAs have been found in saliva and have shown potential as noninvasive biomarkers for a number of other cancers, including breast, oral, and lung cancers.

Additionally, Dr. Rotroff said, microRNAs have been shown to be altered in the tumor tissue of HCC, compared with the surrounding tissue.
 

Catching cancer early

Dr. Reau noted that a strength of the study is that it validated the biomarker in a diverse group of patients already diagnosed with liver cancer, including people with early-stage cancer, those who underwent transplantation, and those with recurrent cancer.

“Everyone searching for biomarkers is looking to make sure that the surveillance tool identifies the patient when it can pay off with early treatment,” Dr. Reau said.

“You don’t want to identify cancer when it’s bad, and you don’t have any options.

This is a little bit where AFP sometimes fails. Even if ultrasound isn’t that accurate, it still generally identifies people when they fit within curative guidelines.”

Dr. Rotroff also stressed the importance of detecting the cancers early, noting that the prognosis for patients with HCC before it has metastasized is greater than 4 years, but the prognosis drops to less than 1 year if it has metastasized.

Dr. Rotroff has an equity stake in Clarified Precision Medicine. He holds intellectual property related to the detection of HCC. Dr. Reau reports no relevant financial relationships.

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

MicroRNAs (miRNAs) that signal hepatocellular carcinoma (HCC), the most common type of liver cancer, have been detected in saliva for the first time, according to results from a pilot study.

The findings were published online in PeerJ.

The small, noncoding RNAs regulate many cellular functions and affect cancer development and progression.

The discovery has the potential to offer a noninvasive alternative or complement to available detection tools – ultrasound and the blood biomarker alpha fetoprotein (AFP) – which lack sensitivity, said Daniel Rotroff, PhD, MSPH, senior author of the study and a researcher in the Department of Quantitative Health Sciences at the Cleveland Clinic.

“Right now, the current clinical tools are not adequate,” he told this news organization. “They miss approximately 40% to 50% of the patients who have HCC.”

Scientists are interested in finding better ways to detect liver cancer, the rates of which are growing rapidly. HCC represents 80% of all liver cancers.

“HCC and liver cancer are the fastest growing cancers in the United States,” Dr. Rotroff said. “They are the fifth and seventh leading cause of cancer death in men and women, respectively.”

Driving the growth are increases in hepatitis C, obesity, fatty liver disease, and alcoholism.

Nancy Reau, MD, the Richard B. Capps Chair of Hepatology and section chief, Hepatology, at Rush Medical College, Chicago, who was not part of the study, told this news organization that despite the study’s being relatively small in scale, the preliminary information it provides is nonetheless “really attractive.”

If larger studies confirm the results, the discovery could open up the possibility of patients mailing in saliva samples from their homes to screen for liver cancer.

The pandemic, she noted, highlighted the shortcomings of ultrasound in screening for liver cancer, as it required patients to come into a facility.

“You’d love to have a biomarker that was more accessible and accurate,” she said. “It would have lots of applicability where cancer surveillance is less available.”

Dr. Rotroff added that “we do know saliva samples can be stable at room temperature. It opens up possibilities to expand the net of being able to screen a wider number of patients.”
 

Differentiating HCC from cirrhosis

Investigators at the Cleveland Clinic performed small RNA sequencing in 20 patients with HCC and compared the findings to sequencing of 19 patients with cirrhosis.

Liver cirrhosis is the primary risk factor for developing HCC, so distinguishing patients with HCC from this cohort of high-risk patients serves as a proof of principle.

The sequencing showed that 4,565 precursor and mature miRNAs were detected in saliva and that 365 were significantly different between those with HCC compared to cirrhosis (false discovery rate, P < .05).

“Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC,” the authors write.

Machine learning found a combination of 10 miRNAs and covariates that accurately classified patients with HCC (area under the curve = 0.87).

The researchers note that miRNAs have been found in saliva and have shown potential as noninvasive biomarkers for a number of other cancers, including breast, oral, and lung cancers.

Additionally, Dr. Rotroff said, microRNAs have been shown to be altered in the tumor tissue of HCC, compared with the surrounding tissue.
 

Catching cancer early

Dr. Reau noted that a strength of the study is that it validated the biomarker in a diverse group of patients already diagnosed with liver cancer, including people with early-stage cancer, those who underwent transplantation, and those with recurrent cancer.

“Everyone searching for biomarkers is looking to make sure that the surveillance tool identifies the patient when it can pay off with early treatment,” Dr. Reau said.

“You don’t want to identify cancer when it’s bad, and you don’t have any options.

This is a little bit where AFP sometimes fails. Even if ultrasound isn’t that accurate, it still generally identifies people when they fit within curative guidelines.”

Dr. Rotroff also stressed the importance of detecting the cancers early, noting that the prognosis for patients with HCC before it has metastasized is greater than 4 years, but the prognosis drops to less than 1 year if it has metastasized.

Dr. Rotroff has an equity stake in Clarified Precision Medicine. He holds intellectual property related to the detection of HCC. Dr. Reau reports no relevant financial relationships.

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