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azzed
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bullturds
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cocaine
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cocainees
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crackwhore
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cum
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cumsluted
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cunthunterer
cunthunteres
cunthuntering
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cunthunters
cunting
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cuntlicked
cuntlicker
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dagos
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damn
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damneder
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dickbag
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dickbags
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dickdippered
dickdipperer
dickdipperes
dickdippering
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dicker
dickes
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dickfaceed
dickfaceer
dickfacees
dickfaceing
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dickflippered
dickflipperer
dickflipperes
dickflippering
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dickheaded
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dickheadser
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dingleed
dingleer
dinglees
dingleing
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dipship
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dipshipes
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dizzyed
dizzyer
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dizzying
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dizzys
doggiestyleed
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dopeyer
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drunker
drunkes
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dumass
dumassed
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dumasses
dumassing
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dumasss
dumbass
dumbassed
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dumbassing
dumbassly
dumbasss
dummy
dummyed
dummyer
dummyes
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dyke
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dykeer
dykees
dykeing
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erotic
eroticed
eroticer
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erotics
extacy
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extacying
extacyly
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extasy
extasyed
extasyer
extasyes
extasying
extasyly
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facked
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faged
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fagged
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faggoted
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fagoted
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faiged
faiger
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faigts
fannybandit
fannybandited
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fannybandits
farted
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fartknockered
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fartly
farts
felch
felched
felcher
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fellateer
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fellateing
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fellatio
fellatioed
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feltched
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floozy
floozyed
floozyer
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foad
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freexes
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friggaer
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fuckined
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fuckinged
fuckinger
fuckinges
fuckinging
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fuckings
fuckining
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Feds lift pause of J&J COVID vaccine, add new warning
Use of the Johnson & Johnson COVID-19 vaccine should resume in the United States for all adults, the Food and Drug Administration and Centers for Disease Contol and Prevention said April 23, although health care providers should warn patients of the risk of developing the rare and serious blood clots that caused the agencies to pause the vaccine’s distribution earlier this month.
“What we are seeing is the overall rate of events was 1.9 cases per million people. In women 18 to 29 years there was an approximate 7 cases per million. The risk is even lower in women over the age of 50 at .9 cases per million,” CDC Director Rochelle Walensky, MD, said in a news briefing the same day.
In the end, the potential benefits of the vaccine far outweighed its risks.
“In terms of benefits, we found that for every 1 million doses of this vaccine, the J&J vaccine could prevent over 650 hospitalizations and 12 deaths among women ages 18-49,” Dr. Walensky said. The potential benefits to women over 50 were even greater: It could prevent 4,700 hospitalizations and 650 deaths.
“In the end, this vaccine was shown to be safe and effective for the vast majority of people,” Dr. Walensky said.
The recommendation to continue the vaccine’s rollout came barely 2 hours after a CDC Advisory Committee on Immunization Practices voted to recommend the pause be lifted. The vote was 10-4 with one abstention.
The decision also includes instructions for the warning directed at women under 50 who have an increased risk of a rare but serious blood clot disorder called thrombosis with thrombocytopenia syndrome (TTS).
As of April 21, 15 cases of TTS, all in women and 13 of them in women under 50, have been confirmed among 7.98 million doses of the J&J vaccine administered in the United States. Three women have died.
The FDA and CDC recommended the pause on April 13 after reports that 6 women developed a blood clotting disorder 6 to 13 days after they received the J&J vaccine.
William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville, and a non-voting ACIP member, said in an interview the panel made the right recommendation.
He applauded both the decision to restart the vaccine and the updated warning information that “will explain [TTS] more fully to people, particularly women, who are coming to be vaccinated.”
As to women in the risk group needing to have a choice of vaccines, Dr. Schaffner said that will be addressed differently across the country.
“Every provider will not have alternative vaccines in their location so there will be many different ways to do this. You may have to get this information and select which site you’re going to depending on which vaccine is available if this matter is important to you,” he noted.
ACIP made the decision after a 6-hour emergency meeting to hear evidence on the Johnson & Johnson vaccine's protective benefits against COVID-19 vs. risk of TTS.
In the CDC-FDA press briefing, Dr. Walensky pointed out that over the past few days, as regulators have reviewed the rare events, newly identified patients had been treated appropriately, without the use of heparin, which is not advised for treating TTS.
As a result, regulators felt as if their messages had gotten out to doctors who now knew how to take special precautions when treating patients with the disorder.
She said the Johnson & Johnson shot remained an important option because it was convenient to give and easier to store than the other vaccines currently authorized in the United States.
Peter Marks, MD, the director of FDA’s Center for Biologics Evaluation and Research, said the agency had already added information describing the risk of the rare clotting disorder to its fact sheets for patients and doctors.
Janet Woodcock, MD, acting commissioner of the FDA, said vaccination centers could resume giving the “one and done” shots as early as April 24.
This article was updated April 24, 2021, and first appeared on WebMD.com.
Use of the Johnson & Johnson COVID-19 vaccine should resume in the United States for all adults, the Food and Drug Administration and Centers for Disease Contol and Prevention said April 23, although health care providers should warn patients of the risk of developing the rare and serious blood clots that caused the agencies to pause the vaccine’s distribution earlier this month.
“What we are seeing is the overall rate of events was 1.9 cases per million people. In women 18 to 29 years there was an approximate 7 cases per million. The risk is even lower in women over the age of 50 at .9 cases per million,” CDC Director Rochelle Walensky, MD, said in a news briefing the same day.
In the end, the potential benefits of the vaccine far outweighed its risks.
“In terms of benefits, we found that for every 1 million doses of this vaccine, the J&J vaccine could prevent over 650 hospitalizations and 12 deaths among women ages 18-49,” Dr. Walensky said. The potential benefits to women over 50 were even greater: It could prevent 4,700 hospitalizations and 650 deaths.
“In the end, this vaccine was shown to be safe and effective for the vast majority of people,” Dr. Walensky said.
The recommendation to continue the vaccine’s rollout came barely 2 hours after a CDC Advisory Committee on Immunization Practices voted to recommend the pause be lifted. The vote was 10-4 with one abstention.
The decision also includes instructions for the warning directed at women under 50 who have an increased risk of a rare but serious blood clot disorder called thrombosis with thrombocytopenia syndrome (TTS).
As of April 21, 15 cases of TTS, all in women and 13 of them in women under 50, have been confirmed among 7.98 million doses of the J&J vaccine administered in the United States. Three women have died.
The FDA and CDC recommended the pause on April 13 after reports that 6 women developed a blood clotting disorder 6 to 13 days after they received the J&J vaccine.
William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville, and a non-voting ACIP member, said in an interview the panel made the right recommendation.
He applauded both the decision to restart the vaccine and the updated warning information that “will explain [TTS] more fully to people, particularly women, who are coming to be vaccinated.”
As to women in the risk group needing to have a choice of vaccines, Dr. Schaffner said that will be addressed differently across the country.
“Every provider will not have alternative vaccines in their location so there will be many different ways to do this. You may have to get this information and select which site you’re going to depending on which vaccine is available if this matter is important to you,” he noted.
ACIP made the decision after a 6-hour emergency meeting to hear evidence on the Johnson & Johnson vaccine's protective benefits against COVID-19 vs. risk of TTS.
In the CDC-FDA press briefing, Dr. Walensky pointed out that over the past few days, as regulators have reviewed the rare events, newly identified patients had been treated appropriately, without the use of heparin, which is not advised for treating TTS.
As a result, regulators felt as if their messages had gotten out to doctors who now knew how to take special precautions when treating patients with the disorder.
She said the Johnson & Johnson shot remained an important option because it was convenient to give and easier to store than the other vaccines currently authorized in the United States.
Peter Marks, MD, the director of FDA’s Center for Biologics Evaluation and Research, said the agency had already added information describing the risk of the rare clotting disorder to its fact sheets for patients and doctors.
Janet Woodcock, MD, acting commissioner of the FDA, said vaccination centers could resume giving the “one and done” shots as early as April 24.
This article was updated April 24, 2021, and first appeared on WebMD.com.
Use of the Johnson & Johnson COVID-19 vaccine should resume in the United States for all adults, the Food and Drug Administration and Centers for Disease Contol and Prevention said April 23, although health care providers should warn patients of the risk of developing the rare and serious blood clots that caused the agencies to pause the vaccine’s distribution earlier this month.
“What we are seeing is the overall rate of events was 1.9 cases per million people. In women 18 to 29 years there was an approximate 7 cases per million. The risk is even lower in women over the age of 50 at .9 cases per million,” CDC Director Rochelle Walensky, MD, said in a news briefing the same day.
In the end, the potential benefits of the vaccine far outweighed its risks.
“In terms of benefits, we found that for every 1 million doses of this vaccine, the J&J vaccine could prevent over 650 hospitalizations and 12 deaths among women ages 18-49,” Dr. Walensky said. The potential benefits to women over 50 were even greater: It could prevent 4,700 hospitalizations and 650 deaths.
“In the end, this vaccine was shown to be safe and effective for the vast majority of people,” Dr. Walensky said.
The recommendation to continue the vaccine’s rollout came barely 2 hours after a CDC Advisory Committee on Immunization Practices voted to recommend the pause be lifted. The vote was 10-4 with one abstention.
The decision also includes instructions for the warning directed at women under 50 who have an increased risk of a rare but serious blood clot disorder called thrombosis with thrombocytopenia syndrome (TTS).
As of April 21, 15 cases of TTS, all in women and 13 of them in women under 50, have been confirmed among 7.98 million doses of the J&J vaccine administered in the United States. Three women have died.
The FDA and CDC recommended the pause on April 13 after reports that 6 women developed a blood clotting disorder 6 to 13 days after they received the J&J vaccine.
William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville, and a non-voting ACIP member, said in an interview the panel made the right recommendation.
He applauded both the decision to restart the vaccine and the updated warning information that “will explain [TTS] more fully to people, particularly women, who are coming to be vaccinated.”
As to women in the risk group needing to have a choice of vaccines, Dr. Schaffner said that will be addressed differently across the country.
“Every provider will not have alternative vaccines in their location so there will be many different ways to do this. You may have to get this information and select which site you’re going to depending on which vaccine is available if this matter is important to you,” he noted.
ACIP made the decision after a 6-hour emergency meeting to hear evidence on the Johnson & Johnson vaccine's protective benefits against COVID-19 vs. risk of TTS.
In the CDC-FDA press briefing, Dr. Walensky pointed out that over the past few days, as regulators have reviewed the rare events, newly identified patients had been treated appropriately, without the use of heparin, which is not advised for treating TTS.
As a result, regulators felt as if their messages had gotten out to doctors who now knew how to take special precautions when treating patients with the disorder.
She said the Johnson & Johnson shot remained an important option because it was convenient to give and easier to store than the other vaccines currently authorized in the United States.
Peter Marks, MD, the director of FDA’s Center for Biologics Evaluation and Research, said the agency had already added information describing the risk of the rare clotting disorder to its fact sheets for patients and doctors.
Janet Woodcock, MD, acting commissioner of the FDA, said vaccination centers could resume giving the “one and done” shots as early as April 24.
This article was updated April 24, 2021, and first appeared on WebMD.com.
How about contraceptives for men?
With the introduction of new technology to vaccinate the world with the Pfizer and Moderna mRNA vaccines, I considered other health conditions that could benefit from new modalities. Unplanned pregnancies are a public health crisis, yet the burden falls solely on women to solve, burdening them with contraceptive practices to prevent unplanned pregnancy. With the insurrection of Row v. Wade and the new bills being pushed through states that are limiting abortion, perhaps the time has come for males to accept the responsibility for contraception to prevent unplanned pregnancy. The methods that currently exist for males are condoms and vasectomy. Other options are being explored – both nonhormonal and reversible contraception including daily pills, gels, and long-acting injections.
The pill for men has been under preliminary trials with promising results. This contraceptive pill contains dimethandrolone undecanoate, which is an androgen anabolic steroid progesterone once-daily pill that suppresses FSH and LH, causing a decrease in the production of testosterone and consequently sperm production.1 (Long, Lee, & Blithe, 2019). This pill is in long-term trials to determine the efficacy and side effects, including the impact on libido, liver, and kidney disease.
The injectable male contraceptive in trials now includes two different options. The first was a long-acting progestin, testosterone, and androgen combination. The male participants received an intramuscular injection every 8 weeks. Although the results of the study were promising – sperm production was effectively reduced, the side effects were too severe for participants to continue use. Side effects much like those of the female Depo-Provera injections included acne and mood disorders. Men experienced erectile dysfunction while at the same time having an increase in sex drive.2 (Em, 2018).
Recently, researchers in India have studied a nonhormonal injectable with promising outcomes. It prevented pregnancy in more than 97% of participants. This injectable polymer gel is placed into the male’s vas deferens to block sperm from leaving the body. This product inactivates sperm, essentially creating temporary sterilization for men. The benefit of this product, called RISUG (reversible inhibition of sperm under guidance), is a single injection that can be effective for 13 years. It can be reversed earlier if needed by injecting a dissolving gel into the male’s vas deferens.1,2 In the United States, there is an identical product called Vasalgel – a polymer injected into the vas deferens – also being studied for temporary infertility.
Another synthetic implanted androgen product being studied is 7 alpha-methyl-19-nortestosterone (MENT), a synthetic steroid that resembles testosterone but does not convert into testosterone and, consequently, does not stimulate prostate growth. It is administered via two subdermal implants and is effective for 12 months. The first subdermal implant releases the synthetic androgen, which is more potent than testosterone, and the other emits LH-releasing hormone.3 Studies demonstrate that MENT suppresses sperm production.1
Finally, studies are underway using transdermal gel applications to suppress sperm concentrations. The daily gel is absorbed through the skin after application to two different areas of the man’s body: the shoulders and upper arms. The daily application of the progestin product, Nestorone, and testosterone gel has been found to reduce sperm concentrations to < 1 x 106/mL. Studies measured gonadal concentrations after 4 weeks.1 Users were happy with the use of a topical gel, with minimal side effects such as lower libido, weight gain, and changes in cholesterol, yet inconsistent use of the product resulted in lower than anticipated results.4
Male contraceptive options are long overdue to dramatically reduce the rate of unplanned pregnancies and the burden of contraception placed on women. Getting these products to market will be half the battle – getting men to commit to using these options and women to trust male compliance may further impede acceptance. Men have not had to carry the burden and economics of single parenting. Men interested in casual sex may now need to accept more responsibility for unplanned pregnancy and be proactive with prevention, particularly as abortion laws are being challenged.
Ms. Thew is medical director of the department of pediatrics division of adolescent medicine at the Medical College of Wisconsin in Milwaukee. She is a member of the editorial board for Pediatric News and has no relevant disclosures.
References
1. Long J E et al. Clin Chem. 2019;65(1):153-60.
2. Male birth control: Current options and new breakthroughs, SingleCare: Health Education. Aug. 6, 2018.
3. Sundaram K et al. Ann Med. 1993;25(2):199-205.
4. Anawalt BD et al. Andrology. 2019;7(6):878-87.
With the introduction of new technology to vaccinate the world with the Pfizer and Moderna mRNA vaccines, I considered other health conditions that could benefit from new modalities. Unplanned pregnancies are a public health crisis, yet the burden falls solely on women to solve, burdening them with contraceptive practices to prevent unplanned pregnancy. With the insurrection of Row v. Wade and the new bills being pushed through states that are limiting abortion, perhaps the time has come for males to accept the responsibility for contraception to prevent unplanned pregnancy. The methods that currently exist for males are condoms and vasectomy. Other options are being explored – both nonhormonal and reversible contraception including daily pills, gels, and long-acting injections.
The pill for men has been under preliminary trials with promising results. This contraceptive pill contains dimethandrolone undecanoate, which is an androgen anabolic steroid progesterone once-daily pill that suppresses FSH and LH, causing a decrease in the production of testosterone and consequently sperm production.1 (Long, Lee, & Blithe, 2019). This pill is in long-term trials to determine the efficacy and side effects, including the impact on libido, liver, and kidney disease.
The injectable male contraceptive in trials now includes two different options. The first was a long-acting progestin, testosterone, and androgen combination. The male participants received an intramuscular injection every 8 weeks. Although the results of the study were promising – sperm production was effectively reduced, the side effects were too severe for participants to continue use. Side effects much like those of the female Depo-Provera injections included acne and mood disorders. Men experienced erectile dysfunction while at the same time having an increase in sex drive.2 (Em, 2018).
Recently, researchers in India have studied a nonhormonal injectable with promising outcomes. It prevented pregnancy in more than 97% of participants. This injectable polymer gel is placed into the male’s vas deferens to block sperm from leaving the body. This product inactivates sperm, essentially creating temporary sterilization for men. The benefit of this product, called RISUG (reversible inhibition of sperm under guidance), is a single injection that can be effective for 13 years. It can be reversed earlier if needed by injecting a dissolving gel into the male’s vas deferens.1,2 In the United States, there is an identical product called Vasalgel – a polymer injected into the vas deferens – also being studied for temporary infertility.
Another synthetic implanted androgen product being studied is 7 alpha-methyl-19-nortestosterone (MENT), a synthetic steroid that resembles testosterone but does not convert into testosterone and, consequently, does not stimulate prostate growth. It is administered via two subdermal implants and is effective for 12 months. The first subdermal implant releases the synthetic androgen, which is more potent than testosterone, and the other emits LH-releasing hormone.3 Studies demonstrate that MENT suppresses sperm production.1
Finally, studies are underway using transdermal gel applications to suppress sperm concentrations. The daily gel is absorbed through the skin after application to two different areas of the man’s body: the shoulders and upper arms. The daily application of the progestin product, Nestorone, and testosterone gel has been found to reduce sperm concentrations to < 1 x 106/mL. Studies measured gonadal concentrations after 4 weeks.1 Users were happy with the use of a topical gel, with minimal side effects such as lower libido, weight gain, and changes in cholesterol, yet inconsistent use of the product resulted in lower than anticipated results.4
Male contraceptive options are long overdue to dramatically reduce the rate of unplanned pregnancies and the burden of contraception placed on women. Getting these products to market will be half the battle – getting men to commit to using these options and women to trust male compliance may further impede acceptance. Men have not had to carry the burden and economics of single parenting. Men interested in casual sex may now need to accept more responsibility for unplanned pregnancy and be proactive with prevention, particularly as abortion laws are being challenged.
Ms. Thew is medical director of the department of pediatrics division of adolescent medicine at the Medical College of Wisconsin in Milwaukee. She is a member of the editorial board for Pediatric News and has no relevant disclosures.
References
1. Long J E et al. Clin Chem. 2019;65(1):153-60.
2. Male birth control: Current options and new breakthroughs, SingleCare: Health Education. Aug. 6, 2018.
3. Sundaram K et al. Ann Med. 1993;25(2):199-205.
4. Anawalt BD et al. Andrology. 2019;7(6):878-87.
With the introduction of new technology to vaccinate the world with the Pfizer and Moderna mRNA vaccines, I considered other health conditions that could benefit from new modalities. Unplanned pregnancies are a public health crisis, yet the burden falls solely on women to solve, burdening them with contraceptive practices to prevent unplanned pregnancy. With the insurrection of Row v. Wade and the new bills being pushed through states that are limiting abortion, perhaps the time has come for males to accept the responsibility for contraception to prevent unplanned pregnancy. The methods that currently exist for males are condoms and vasectomy. Other options are being explored – both nonhormonal and reversible contraception including daily pills, gels, and long-acting injections.
The pill for men has been under preliminary trials with promising results. This contraceptive pill contains dimethandrolone undecanoate, which is an androgen anabolic steroid progesterone once-daily pill that suppresses FSH and LH, causing a decrease in the production of testosterone and consequently sperm production.1 (Long, Lee, & Blithe, 2019). This pill is in long-term trials to determine the efficacy and side effects, including the impact on libido, liver, and kidney disease.
The injectable male contraceptive in trials now includes two different options. The first was a long-acting progestin, testosterone, and androgen combination. The male participants received an intramuscular injection every 8 weeks. Although the results of the study were promising – sperm production was effectively reduced, the side effects were too severe for participants to continue use. Side effects much like those of the female Depo-Provera injections included acne and mood disorders. Men experienced erectile dysfunction while at the same time having an increase in sex drive.2 (Em, 2018).
Recently, researchers in India have studied a nonhormonal injectable with promising outcomes. It prevented pregnancy in more than 97% of participants. This injectable polymer gel is placed into the male’s vas deferens to block sperm from leaving the body. This product inactivates sperm, essentially creating temporary sterilization for men. The benefit of this product, called RISUG (reversible inhibition of sperm under guidance), is a single injection that can be effective for 13 years. It can be reversed earlier if needed by injecting a dissolving gel into the male’s vas deferens.1,2 In the United States, there is an identical product called Vasalgel – a polymer injected into the vas deferens – also being studied for temporary infertility.
Another synthetic implanted androgen product being studied is 7 alpha-methyl-19-nortestosterone (MENT), a synthetic steroid that resembles testosterone but does not convert into testosterone and, consequently, does not stimulate prostate growth. It is administered via two subdermal implants and is effective for 12 months. The first subdermal implant releases the synthetic androgen, which is more potent than testosterone, and the other emits LH-releasing hormone.3 Studies demonstrate that MENT suppresses sperm production.1
Finally, studies are underway using transdermal gel applications to suppress sperm concentrations. The daily gel is absorbed through the skin after application to two different areas of the man’s body: the shoulders and upper arms. The daily application of the progestin product, Nestorone, and testosterone gel has been found to reduce sperm concentrations to < 1 x 106/mL. Studies measured gonadal concentrations after 4 weeks.1 Users were happy with the use of a topical gel, with minimal side effects such as lower libido, weight gain, and changes in cholesterol, yet inconsistent use of the product resulted in lower than anticipated results.4
Male contraceptive options are long overdue to dramatically reduce the rate of unplanned pregnancies and the burden of contraception placed on women. Getting these products to market will be half the battle – getting men to commit to using these options and women to trust male compliance may further impede acceptance. Men have not had to carry the burden and economics of single parenting. Men interested in casual sex may now need to accept more responsibility for unplanned pregnancy and be proactive with prevention, particularly as abortion laws are being challenged.
Ms. Thew is medical director of the department of pediatrics division of adolescent medicine at the Medical College of Wisconsin in Milwaukee. She is a member of the editorial board for Pediatric News and has no relevant disclosures.
References
1. Long J E et al. Clin Chem. 2019;65(1):153-60.
2. Male birth control: Current options and new breakthroughs, SingleCare: Health Education. Aug. 6, 2018.
3. Sundaram K et al. Ann Med. 1993;25(2):199-205.
4. Anawalt BD et al. Andrology. 2019;7(6):878-87.
Study: COVID-19 can kill months after infection
Long-haul COVID-19 patients face many health threats – including a higher chance of dying – up to 6 months after they catch the virus, according to a massive study published in the journal Nature.
Researchers examined more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database. They found COVID-19 patients had a 59% higher risk of death up to 6 months after infection, compared with noninfected people.
Those findings translate into about 8 extra deaths per 1,000 patients over 6 months, because many deaths caused by long-term COVID complications are not recorded as COVID-19 deaths, the researchers said. Among patients who were hospitalized and died after more than 30 days, there were 29 excess deaths per 1,000 patients over 6 months.
“As far as total pandemic death toll, these numbers suggest that the deaths we’re counting due to the immediate viral infection are only the tip of the iceberg,” Ziyad Al-Aly, MD, the senior author of the study and a director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, said in a news release from the Washington University, St. Louis.
Johns Hopkins University in Baltimore says more than 3 million people worldwide and about 570,000 people in the United States have died of coronavirus-related reasons.
Long-haul COVID patients also had a much higher chance of getting sick, and not just in the respiratory system, according to the study.
The patients had a high rate of stroke and other nervous system ailments, mental health problems such as depression, the onset of diabetes, heart disease and other coronary problems, diarrhea and digestive disorders, kidney disease, blood clots, joint pain, hair loss, and general fatigue.
Patients often had clusters of these ailments. And the more severe the case of COVID-19, the higher the chance of long-term health problems, the study said.
Researchers based their study on health care databases of the U.S. Department of Veterans Affairs. Besides the 87,000 COVID patients, the database included about 5 million patients who didn’t catch COVID. The veterans in the study were about 88% men, but the large sample size included 8,880 women with confirmed cases, the news release said.
Dr. Al-Aly, an assistant professor at Washington University, said the study shows that long-haul COVID-19 could be “America’s next big health crisis.”
“Our study demonstrates that, up to 6 months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity,” he said. “Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades.”
A version of this article first appeared on WebMD.com.
Long-haul COVID-19 patients face many health threats – including a higher chance of dying – up to 6 months after they catch the virus, according to a massive study published in the journal Nature.
Researchers examined more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database. They found COVID-19 patients had a 59% higher risk of death up to 6 months after infection, compared with noninfected people.
Those findings translate into about 8 extra deaths per 1,000 patients over 6 months, because many deaths caused by long-term COVID complications are not recorded as COVID-19 deaths, the researchers said. Among patients who were hospitalized and died after more than 30 days, there were 29 excess deaths per 1,000 patients over 6 months.
“As far as total pandemic death toll, these numbers suggest that the deaths we’re counting due to the immediate viral infection are only the tip of the iceberg,” Ziyad Al-Aly, MD, the senior author of the study and a director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, said in a news release from the Washington University, St. Louis.
Johns Hopkins University in Baltimore says more than 3 million people worldwide and about 570,000 people in the United States have died of coronavirus-related reasons.
Long-haul COVID patients also had a much higher chance of getting sick, and not just in the respiratory system, according to the study.
The patients had a high rate of stroke and other nervous system ailments, mental health problems such as depression, the onset of diabetes, heart disease and other coronary problems, diarrhea and digestive disorders, kidney disease, blood clots, joint pain, hair loss, and general fatigue.
Patients often had clusters of these ailments. And the more severe the case of COVID-19, the higher the chance of long-term health problems, the study said.
Researchers based their study on health care databases of the U.S. Department of Veterans Affairs. Besides the 87,000 COVID patients, the database included about 5 million patients who didn’t catch COVID. The veterans in the study were about 88% men, but the large sample size included 8,880 women with confirmed cases, the news release said.
Dr. Al-Aly, an assistant professor at Washington University, said the study shows that long-haul COVID-19 could be “America’s next big health crisis.”
“Our study demonstrates that, up to 6 months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity,” he said. “Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades.”
A version of this article first appeared on WebMD.com.
Long-haul COVID-19 patients face many health threats – including a higher chance of dying – up to 6 months after they catch the virus, according to a massive study published in the journal Nature.
Researchers examined more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database. They found COVID-19 patients had a 59% higher risk of death up to 6 months after infection, compared with noninfected people.
Those findings translate into about 8 extra deaths per 1,000 patients over 6 months, because many deaths caused by long-term COVID complications are not recorded as COVID-19 deaths, the researchers said. Among patients who were hospitalized and died after more than 30 days, there were 29 excess deaths per 1,000 patients over 6 months.
“As far as total pandemic death toll, these numbers suggest that the deaths we’re counting due to the immediate viral infection are only the tip of the iceberg,” Ziyad Al-Aly, MD, the senior author of the study and a director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, said in a news release from the Washington University, St. Louis.
Johns Hopkins University in Baltimore says more than 3 million people worldwide and about 570,000 people in the United States have died of coronavirus-related reasons.
Long-haul COVID patients also had a much higher chance of getting sick, and not just in the respiratory system, according to the study.
The patients had a high rate of stroke and other nervous system ailments, mental health problems such as depression, the onset of diabetes, heart disease and other coronary problems, diarrhea and digestive disorders, kidney disease, blood clots, joint pain, hair loss, and general fatigue.
Patients often had clusters of these ailments. And the more severe the case of COVID-19, the higher the chance of long-term health problems, the study said.
Researchers based their study on health care databases of the U.S. Department of Veterans Affairs. Besides the 87,000 COVID patients, the database included about 5 million patients who didn’t catch COVID. The veterans in the study were about 88% men, but the large sample size included 8,880 women with confirmed cases, the news release said.
Dr. Al-Aly, an assistant professor at Washington University, said the study shows that long-haul COVID-19 could be “America’s next big health crisis.”
“Our study demonstrates that, up to 6 months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity,” he said. “Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades.”
A version of this article first appeared on WebMD.com.
Can we get to ‘COVID zero’? Experts predict the next 8 months
COVID-19 is likely to follow a seasonal pattern – similar to some other respiratory viruses – with fewer cases come summer 2021 followed by a jump next winter, experts predicted in a Thursday briefing.
If that pattern holds, it could mean a need to reinforce the mask-wearing message as the weather gets colder and people once again congregate indoors.
“Right now, we are projecting the United States all the way to Aug. 1 [will have] 619,000 deaths from COVID-19, with 4.7 million globally,” said Ali H. Mokdad, PhD, professor of health metrics sciences at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle, during today’s media briefing sponsored by the Infectious Diseases Society of America and IHME.
The encouraging news is the vaccines appear to be working, and more Americans are getting them. “If you look at the data for these vaccines, they are extremely safe, they are extremely efficacious, and they make you basically impervious – for the most part – to getting serious disease, hospitalization, or death,” said Amesh Adalja, MD, senior scholar at Johns Hopkins University Center for Health Security in Baltimore.
“These vaccines do what they were meant to do: defang this virus,” said Dr. Adalja, who is an IDSA Fellow and adjunct assistant professor at Johns Hopkins Bloomberg School of Public Health. Emerging data out of Israel and other countries suggest a vaccinated person is less likely to transmit the virus as well, he added.
Still aiming for herd immunity
Furthermore, the U.S. Food and Drug Administration is likely to approve emergency use authorization (EUA) among teenagers 12-15 years old “imminently,” thereby expanding the pool of people potentially protected by vaccines.
Such authorization could help with overall public health efforts. “That’s simply a mathematical formula,” Dr. Adalja said. “The more people that are vaccinated, including children, the quicker we’ll get to herd immunity.”
In addition, with lower case numbers expected this summer, herd immunity might become more achievable, said Dr. Mokdad, who is also chief strategy officer for population health at the University of Washington.
As important as herd immunity is, so-called decoupling is “more important to me,” Dr. Adalja said. Decoupling refers to separating infections from the more severe outcomes, so people who get COVID-19 are less likely to need hospitalization or die from it.
Vaccines get the credit here, he added, including with the variants. “Even if you get a breakthrough infection with a variant, it’s not likely to land you in the hospital or cause serious disease or death,” Dr. Adalja said.
Masks and the uncommon cold
Wearing a mask until we reach herd immunity is important because it’s not possible to tell who is vaccinated and who isn’t, Dr. Mokdad said. “Remember, as many people are waiting to get a vaccine, all of us have access to a mask,” he said.
Dr. Adalja agreed, adding that public health guidance on masks will likely stay in place until we cross that herd immunity threshold and community circulation of the virus goes down.
“People are probably going to want to continue wearing masks, at least some proportion, because they see the benefit for other respiratory viruses,” Dr. Adalja said. “How many of you had a common cold this year?”
Variants: Some good news?
Experts are monitoring the spread of variants of concern in the United States and abroad. On a positive note, the B.1.1.7 variant first identified in the United Kingdom appears to be dominant in the United States at this time, which is potentially good for two reasons. One is that the available COVID-19 vaccines show sufficient efficacy against the strain, Dr. Mokdad said.
Second, a predominance of B.1.1.7 makes it more difficult for other emerging variants of concern like P1 [Brazil] or B.1.351 [South Africa] to gain control, Dr. Adalja said.
“B.1.1.7 is such an efficient transmitter,” he said. “That’s kind of an advantage … because the more B.1.1.7, you have the less opportunity B.1.351 and P1 have to set up shop.”
Hesitancy from misinformation
Vaccine hesitancy remains a concern, particularly at a time when some predict a drop in the number of Americans seeking vaccination. Although needle phobia plays a role in dissuading some from vaccination, the bigger issue is vaccine misinformation, Dr. Adalja said.
“Some people are just terrified when they see the needle. That’s a small part of the proportion of people who don’t want to get vaccinated,” Dr. Adalja said. In contrast, he attributed most hesitancy to misinformation about the vaccine, including reports that the vaccines are fake.
Even celebrities are getting drawn into the misinformation.
“I just had to answer something about Mariah Carey’s vaccination,” he said. Someone believed “that it was done with a retractable needle that didn’t really go into her arm.”
Vaccine hesitancy is more about people not understanding the risk-benefit analysis, taking side effects out of out of context if there are side effects, or being influenced by “arbitrary statements about microchips, infertility, or whatever it might be,” Dr. Adalja said.
The future is subject to change
“We’re expecting another rise in cases and more mortality in our winter season here in the United States,” Dr. Mokdad said, adding that the efficacy of the vaccines is likely to attenuate the mortality rate in particular.
However, as the epidemiology of the pandemic evolves, so too will the long-term predictions. Factors that could influence future numbers include the expansion of vaccination to teens 12-15 years old and (eventually) younger children, a need for booster vaccines, emerging variants, and the changing proportion of the population who are fully vaccinated or were previously infected.
Again, getting people to adhere to mask wearing come winter could be challenging if the scenario over the summer is “close to normal with less than 200 deaths a day in the United States,” he added. Asking people to wear masks again will be like “swimming upstream.”
“I think it’s a mistake to think that we’re going to get to ‘COVID zero,’ ” Dr. Adalja said. “This is not an eradicable disease. There’s only been one human infectious disease eradicated from the planet, and that’s smallpox, and it had very different characteristics.”
A version of this article first appeared on Medscape.com.
COVID-19 is likely to follow a seasonal pattern – similar to some other respiratory viruses – with fewer cases come summer 2021 followed by a jump next winter, experts predicted in a Thursday briefing.
If that pattern holds, it could mean a need to reinforce the mask-wearing message as the weather gets colder and people once again congregate indoors.
“Right now, we are projecting the United States all the way to Aug. 1 [will have] 619,000 deaths from COVID-19, with 4.7 million globally,” said Ali H. Mokdad, PhD, professor of health metrics sciences at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle, during today’s media briefing sponsored by the Infectious Diseases Society of America and IHME.
The encouraging news is the vaccines appear to be working, and more Americans are getting them. “If you look at the data for these vaccines, they are extremely safe, they are extremely efficacious, and they make you basically impervious – for the most part – to getting serious disease, hospitalization, or death,” said Amesh Adalja, MD, senior scholar at Johns Hopkins University Center for Health Security in Baltimore.
“These vaccines do what they were meant to do: defang this virus,” said Dr. Adalja, who is an IDSA Fellow and adjunct assistant professor at Johns Hopkins Bloomberg School of Public Health. Emerging data out of Israel and other countries suggest a vaccinated person is less likely to transmit the virus as well, he added.
Still aiming for herd immunity
Furthermore, the U.S. Food and Drug Administration is likely to approve emergency use authorization (EUA) among teenagers 12-15 years old “imminently,” thereby expanding the pool of people potentially protected by vaccines.
Such authorization could help with overall public health efforts. “That’s simply a mathematical formula,” Dr. Adalja said. “The more people that are vaccinated, including children, the quicker we’ll get to herd immunity.”
In addition, with lower case numbers expected this summer, herd immunity might become more achievable, said Dr. Mokdad, who is also chief strategy officer for population health at the University of Washington.
As important as herd immunity is, so-called decoupling is “more important to me,” Dr. Adalja said. Decoupling refers to separating infections from the more severe outcomes, so people who get COVID-19 are less likely to need hospitalization or die from it.
Vaccines get the credit here, he added, including with the variants. “Even if you get a breakthrough infection with a variant, it’s not likely to land you in the hospital or cause serious disease or death,” Dr. Adalja said.
Masks and the uncommon cold
Wearing a mask until we reach herd immunity is important because it’s not possible to tell who is vaccinated and who isn’t, Dr. Mokdad said. “Remember, as many people are waiting to get a vaccine, all of us have access to a mask,” he said.
Dr. Adalja agreed, adding that public health guidance on masks will likely stay in place until we cross that herd immunity threshold and community circulation of the virus goes down.
“People are probably going to want to continue wearing masks, at least some proportion, because they see the benefit for other respiratory viruses,” Dr. Adalja said. “How many of you had a common cold this year?”
Variants: Some good news?
Experts are monitoring the spread of variants of concern in the United States and abroad. On a positive note, the B.1.1.7 variant first identified in the United Kingdom appears to be dominant in the United States at this time, which is potentially good for two reasons. One is that the available COVID-19 vaccines show sufficient efficacy against the strain, Dr. Mokdad said.
Second, a predominance of B.1.1.7 makes it more difficult for other emerging variants of concern like P1 [Brazil] or B.1.351 [South Africa] to gain control, Dr. Adalja said.
“B.1.1.7 is such an efficient transmitter,” he said. “That’s kind of an advantage … because the more B.1.1.7, you have the less opportunity B.1.351 and P1 have to set up shop.”
Hesitancy from misinformation
Vaccine hesitancy remains a concern, particularly at a time when some predict a drop in the number of Americans seeking vaccination. Although needle phobia plays a role in dissuading some from vaccination, the bigger issue is vaccine misinformation, Dr. Adalja said.
“Some people are just terrified when they see the needle. That’s a small part of the proportion of people who don’t want to get vaccinated,” Dr. Adalja said. In contrast, he attributed most hesitancy to misinformation about the vaccine, including reports that the vaccines are fake.
Even celebrities are getting drawn into the misinformation.
“I just had to answer something about Mariah Carey’s vaccination,” he said. Someone believed “that it was done with a retractable needle that didn’t really go into her arm.”
Vaccine hesitancy is more about people not understanding the risk-benefit analysis, taking side effects out of out of context if there are side effects, or being influenced by “arbitrary statements about microchips, infertility, or whatever it might be,” Dr. Adalja said.
The future is subject to change
“We’re expecting another rise in cases and more mortality in our winter season here in the United States,” Dr. Mokdad said, adding that the efficacy of the vaccines is likely to attenuate the mortality rate in particular.
However, as the epidemiology of the pandemic evolves, so too will the long-term predictions. Factors that could influence future numbers include the expansion of vaccination to teens 12-15 years old and (eventually) younger children, a need for booster vaccines, emerging variants, and the changing proportion of the population who are fully vaccinated or were previously infected.
Again, getting people to adhere to mask wearing come winter could be challenging if the scenario over the summer is “close to normal with less than 200 deaths a day in the United States,” he added. Asking people to wear masks again will be like “swimming upstream.”
“I think it’s a mistake to think that we’re going to get to ‘COVID zero,’ ” Dr. Adalja said. “This is not an eradicable disease. There’s only been one human infectious disease eradicated from the planet, and that’s smallpox, and it had very different characteristics.”
A version of this article first appeared on Medscape.com.
COVID-19 is likely to follow a seasonal pattern – similar to some other respiratory viruses – with fewer cases come summer 2021 followed by a jump next winter, experts predicted in a Thursday briefing.
If that pattern holds, it could mean a need to reinforce the mask-wearing message as the weather gets colder and people once again congregate indoors.
“Right now, we are projecting the United States all the way to Aug. 1 [will have] 619,000 deaths from COVID-19, with 4.7 million globally,” said Ali H. Mokdad, PhD, professor of health metrics sciences at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle, during today’s media briefing sponsored by the Infectious Diseases Society of America and IHME.
The encouraging news is the vaccines appear to be working, and more Americans are getting them. “If you look at the data for these vaccines, they are extremely safe, they are extremely efficacious, and they make you basically impervious – for the most part – to getting serious disease, hospitalization, or death,” said Amesh Adalja, MD, senior scholar at Johns Hopkins University Center for Health Security in Baltimore.
“These vaccines do what they were meant to do: defang this virus,” said Dr. Adalja, who is an IDSA Fellow and adjunct assistant professor at Johns Hopkins Bloomberg School of Public Health. Emerging data out of Israel and other countries suggest a vaccinated person is less likely to transmit the virus as well, he added.
Still aiming for herd immunity
Furthermore, the U.S. Food and Drug Administration is likely to approve emergency use authorization (EUA) among teenagers 12-15 years old “imminently,” thereby expanding the pool of people potentially protected by vaccines.
Such authorization could help with overall public health efforts. “That’s simply a mathematical formula,” Dr. Adalja said. “The more people that are vaccinated, including children, the quicker we’ll get to herd immunity.”
In addition, with lower case numbers expected this summer, herd immunity might become more achievable, said Dr. Mokdad, who is also chief strategy officer for population health at the University of Washington.
As important as herd immunity is, so-called decoupling is “more important to me,” Dr. Adalja said. Decoupling refers to separating infections from the more severe outcomes, so people who get COVID-19 are less likely to need hospitalization or die from it.
Vaccines get the credit here, he added, including with the variants. “Even if you get a breakthrough infection with a variant, it’s not likely to land you in the hospital or cause serious disease or death,” Dr. Adalja said.
Masks and the uncommon cold
Wearing a mask until we reach herd immunity is important because it’s not possible to tell who is vaccinated and who isn’t, Dr. Mokdad said. “Remember, as many people are waiting to get a vaccine, all of us have access to a mask,” he said.
Dr. Adalja agreed, adding that public health guidance on masks will likely stay in place until we cross that herd immunity threshold and community circulation of the virus goes down.
“People are probably going to want to continue wearing masks, at least some proportion, because they see the benefit for other respiratory viruses,” Dr. Adalja said. “How many of you had a common cold this year?”
Variants: Some good news?
Experts are monitoring the spread of variants of concern in the United States and abroad. On a positive note, the B.1.1.7 variant first identified in the United Kingdom appears to be dominant in the United States at this time, which is potentially good for two reasons. One is that the available COVID-19 vaccines show sufficient efficacy against the strain, Dr. Mokdad said.
Second, a predominance of B.1.1.7 makes it more difficult for other emerging variants of concern like P1 [Brazil] or B.1.351 [South Africa] to gain control, Dr. Adalja said.
“B.1.1.7 is such an efficient transmitter,” he said. “That’s kind of an advantage … because the more B.1.1.7, you have the less opportunity B.1.351 and P1 have to set up shop.”
Hesitancy from misinformation
Vaccine hesitancy remains a concern, particularly at a time when some predict a drop in the number of Americans seeking vaccination. Although needle phobia plays a role in dissuading some from vaccination, the bigger issue is vaccine misinformation, Dr. Adalja said.
“Some people are just terrified when they see the needle. That’s a small part of the proportion of people who don’t want to get vaccinated,” Dr. Adalja said. In contrast, he attributed most hesitancy to misinformation about the vaccine, including reports that the vaccines are fake.
Even celebrities are getting drawn into the misinformation.
“I just had to answer something about Mariah Carey’s vaccination,” he said. Someone believed “that it was done with a retractable needle that didn’t really go into her arm.”
Vaccine hesitancy is more about people not understanding the risk-benefit analysis, taking side effects out of out of context if there are side effects, or being influenced by “arbitrary statements about microchips, infertility, or whatever it might be,” Dr. Adalja said.
The future is subject to change
“We’re expecting another rise in cases and more mortality in our winter season here in the United States,” Dr. Mokdad said, adding that the efficacy of the vaccines is likely to attenuate the mortality rate in particular.
However, as the epidemiology of the pandemic evolves, so too will the long-term predictions. Factors that could influence future numbers include the expansion of vaccination to teens 12-15 years old and (eventually) younger children, a need for booster vaccines, emerging variants, and the changing proportion of the population who are fully vaccinated or were previously infected.
Again, getting people to adhere to mask wearing come winter could be challenging if the scenario over the summer is “close to normal with less than 200 deaths a day in the United States,” he added. Asking people to wear masks again will be like “swimming upstream.”
“I think it’s a mistake to think that we’re going to get to ‘COVID zero,’ ” Dr. Adalja said. “This is not an eradicable disease. There’s only been one human infectious disease eradicated from the planet, and that’s smallpox, and it had very different characteristics.”
A version of this article first appeared on Medscape.com.
Small clinics, practices key to COVID-19 vaccine success: State officials
Primary care physicians and providers in small offices and clinics are going to be key to ensuring that the remaining half of the nation receives a COVID-19 vaccination, state health officials said Wednesday, and the federal government will soon start shipping smaller packages of the Pfizer/BioNTech vaccine that can be more readily used by individual doctors.
According to the Centers for Disease Control and Prevention, as of April 21, more than 215 million doses have been administered. About 40% – 134 million Americans – have had at least one dose of a vaccine.
Among those who still haven’t received a shot are people who don’t have the time, may be homebound, or who have questions about the vaccine, or might say they will never be vaccinated, said Nirav Shah, MD, JD, president of the Association of State and Territorial Health Officials and director of the Maine Center for Disease Control and Prevention, on a call with reporters.
Especially for those who fall into the “not-ever” category, state officials “are working to find trusted messengers like doctors” who can connect with these individuals and give them information, he said.
Primary care physicians’ offices and other small practice settings are “where we are most likely to reach many of the remaining 50%,” Steven Stack, MD, MBA, FACEP, commissioner of the Kentucky Department for Public Health, said on the briefing.
State officials also “need to support all people to consult their personal physicians in whom they have confidence and trust to be informed of the benefits of COVID vaccination and the safety of this vaccination,” he said, adding that “this is the way we put this pandemic in the rearview mirror and move on with our lives.”
Dr. Stack said the federal government is starting by working with Pfizer to slim down its packages from 1,170 doses to 450 doses. That should happen before June, said Dr. Stack, adding that state health officials will be able to distribute the smaller packages “more widely and to smaller settings.”
Ideally, packaging for all vaccines will get down to single-dose, pre-filled syringes, he said. But that is a “journey” that the federal government has just begun, said Dr. Stack.
The White House had not responded to a request from this news organization for comment by press time.
Having vaccines onsite in a physician’s office is important, Dr. Stack said, adding that doctors “need to reach people in their persuadable moment.”
Bringing pediatricians on board
Illinois state health officials have begun a process that will let pediatricians have weekly vaccination clinics and also have vaccine on hand to meet patients in the moment, said Ngozi Ezike, MD, director of the Illinois Department of Public Health, on the briefing.
She said the distribution can start even before the Pfizer vaccine is shipped in smaller packages – and as soon as the Food and Drug Administration authorizes the vaccine for adolescents. Pfizer applied for emergency use approval for children aged 12-15 on April 9.
Local health departments will store the vaccine in their ultra-cold freezers. Pediatricians will identify how many people they hope to vaccinate each week and receive the doses on Monday, with the understanding that they must use the vaccine within 5 days, said Dr. Ezike.
The aim is to support vaccination clinics but also to ensure doctors have “doses on hand,” so that a parent or adolescent could opt for vaccination during a visit.
Although estimating the number of doses required will be difficult and likely involve some waste, Dr. Ezike said it’s important to be able to offer a vaccine in the office instead of having to refer someone elsewhere.
A version of this article first appeared on Medscape.com.
Primary care physicians and providers in small offices and clinics are going to be key to ensuring that the remaining half of the nation receives a COVID-19 vaccination, state health officials said Wednesday, and the federal government will soon start shipping smaller packages of the Pfizer/BioNTech vaccine that can be more readily used by individual doctors.
According to the Centers for Disease Control and Prevention, as of April 21, more than 215 million doses have been administered. About 40% – 134 million Americans – have had at least one dose of a vaccine.
Among those who still haven’t received a shot are people who don’t have the time, may be homebound, or who have questions about the vaccine, or might say they will never be vaccinated, said Nirav Shah, MD, JD, president of the Association of State and Territorial Health Officials and director of the Maine Center for Disease Control and Prevention, on a call with reporters.
Especially for those who fall into the “not-ever” category, state officials “are working to find trusted messengers like doctors” who can connect with these individuals and give them information, he said.
Primary care physicians’ offices and other small practice settings are “where we are most likely to reach many of the remaining 50%,” Steven Stack, MD, MBA, FACEP, commissioner of the Kentucky Department for Public Health, said on the briefing.
State officials also “need to support all people to consult their personal physicians in whom they have confidence and trust to be informed of the benefits of COVID vaccination and the safety of this vaccination,” he said, adding that “this is the way we put this pandemic in the rearview mirror and move on with our lives.”
Dr. Stack said the federal government is starting by working with Pfizer to slim down its packages from 1,170 doses to 450 doses. That should happen before June, said Dr. Stack, adding that state health officials will be able to distribute the smaller packages “more widely and to smaller settings.”
Ideally, packaging for all vaccines will get down to single-dose, pre-filled syringes, he said. But that is a “journey” that the federal government has just begun, said Dr. Stack.
The White House had not responded to a request from this news organization for comment by press time.
Having vaccines onsite in a physician’s office is important, Dr. Stack said, adding that doctors “need to reach people in their persuadable moment.”
Bringing pediatricians on board
Illinois state health officials have begun a process that will let pediatricians have weekly vaccination clinics and also have vaccine on hand to meet patients in the moment, said Ngozi Ezike, MD, director of the Illinois Department of Public Health, on the briefing.
She said the distribution can start even before the Pfizer vaccine is shipped in smaller packages – and as soon as the Food and Drug Administration authorizes the vaccine for adolescents. Pfizer applied for emergency use approval for children aged 12-15 on April 9.
Local health departments will store the vaccine in their ultra-cold freezers. Pediatricians will identify how many people they hope to vaccinate each week and receive the doses on Monday, with the understanding that they must use the vaccine within 5 days, said Dr. Ezike.
The aim is to support vaccination clinics but also to ensure doctors have “doses on hand,” so that a parent or adolescent could opt for vaccination during a visit.
Although estimating the number of doses required will be difficult and likely involve some waste, Dr. Ezike said it’s important to be able to offer a vaccine in the office instead of having to refer someone elsewhere.
A version of this article first appeared on Medscape.com.
Primary care physicians and providers in small offices and clinics are going to be key to ensuring that the remaining half of the nation receives a COVID-19 vaccination, state health officials said Wednesday, and the federal government will soon start shipping smaller packages of the Pfizer/BioNTech vaccine that can be more readily used by individual doctors.
According to the Centers for Disease Control and Prevention, as of April 21, more than 215 million doses have been administered. About 40% – 134 million Americans – have had at least one dose of a vaccine.
Among those who still haven’t received a shot are people who don’t have the time, may be homebound, or who have questions about the vaccine, or might say they will never be vaccinated, said Nirav Shah, MD, JD, president of the Association of State and Territorial Health Officials and director of the Maine Center for Disease Control and Prevention, on a call with reporters.
Especially for those who fall into the “not-ever” category, state officials “are working to find trusted messengers like doctors” who can connect with these individuals and give them information, he said.
Primary care physicians’ offices and other small practice settings are “where we are most likely to reach many of the remaining 50%,” Steven Stack, MD, MBA, FACEP, commissioner of the Kentucky Department for Public Health, said on the briefing.
State officials also “need to support all people to consult their personal physicians in whom they have confidence and trust to be informed of the benefits of COVID vaccination and the safety of this vaccination,” he said, adding that “this is the way we put this pandemic in the rearview mirror and move on with our lives.”
Dr. Stack said the federal government is starting by working with Pfizer to slim down its packages from 1,170 doses to 450 doses. That should happen before June, said Dr. Stack, adding that state health officials will be able to distribute the smaller packages “more widely and to smaller settings.”
Ideally, packaging for all vaccines will get down to single-dose, pre-filled syringes, he said. But that is a “journey” that the federal government has just begun, said Dr. Stack.
The White House had not responded to a request from this news organization for comment by press time.
Having vaccines onsite in a physician’s office is important, Dr. Stack said, adding that doctors “need to reach people in their persuadable moment.”
Bringing pediatricians on board
Illinois state health officials have begun a process that will let pediatricians have weekly vaccination clinics and also have vaccine on hand to meet patients in the moment, said Ngozi Ezike, MD, director of the Illinois Department of Public Health, on the briefing.
She said the distribution can start even before the Pfizer vaccine is shipped in smaller packages – and as soon as the Food and Drug Administration authorizes the vaccine for adolescents. Pfizer applied for emergency use approval for children aged 12-15 on April 9.
Local health departments will store the vaccine in their ultra-cold freezers. Pediatricians will identify how many people they hope to vaccinate each week and receive the doses on Monday, with the understanding that they must use the vaccine within 5 days, said Dr. Ezike.
The aim is to support vaccination clinics but also to ensure doctors have “doses on hand,” so that a parent or adolescent could opt for vaccination during a visit.
Although estimating the number of doses required will be difficult and likely involve some waste, Dr. Ezike said it’s important to be able to offer a vaccine in the office instead of having to refer someone elsewhere.
A version of this article first appeared on Medscape.com.
Percentage of doctors who are Black barely changed in 120 years
according to a new study.
In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.
The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.
Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.
“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.
Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.
He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.
Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”
The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.
Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.
In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.
The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”
Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.
“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.
Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.
“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”
Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”
The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”
Dr. Ly has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new study.
In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.
The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.
Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.
“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.
Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.
He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.
Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”
The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.
Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.
In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.
The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”
Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.
“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.
Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.
“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”
Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”
The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”
Dr. Ly has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new study.
In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.
The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.
Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.
“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.
Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.
He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.
Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”
The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.
Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.
In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.
The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”
Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.
“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.
Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.
“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”
Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”
The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”
Dr. Ly has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID-19 infection conveys imperfect immunity in young adults
Do your patients think that getting COVID-19 is fully protective against subsequent reinfection? Tell it to the Marines.
A study of U.S. Marine recruits on their way to boot camp at Parris Island, S.C., showed that those who were seropositive at baseline, indicating prior exposure to SARS-CoV-2, remained at some risk for reinfection. They had about one-fifth the risk of subsequent infection, compared with seronegative recruits during basic training, but reinfections did occur.
The study, by Stuart C. Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues, was published in The Lancet Respiratory Medicine.
“Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection,” they wrote.
An infectious disease specialist who was not involved in the study said that the findings provide further evidence about the level of immunity acquired after an infection.
“It’s quite clear that reinfections do occur, they are of public health importance, and they’re something we need to be mindful of in terms of advising patients about whether a prior infection protects them from reinfection,” Mark Siedner, MD, MPH, a clinician and researcher in the division of infectious diseases at Massachusetts General Hospital, Boston, said in an interview.
The study results reinforce that “not all antibodies are the same,” said Sachin Gupta, MD, an attending physician in pulmonary and critical care medicine at Alameda Health System in Oakland, Calif. “We’re seeing still that 10% of folks who have antibodies can get infected again,” he said in an interview.
CHARM initiative
Dr. Sealfon and colleagues presented an analysis of data from the ironically named CHARM (COVID-19 Health Action Response for Marines) prospective study.
CHARM included U.S. Marine recruits, most of them male, aged 18-20 years, who were instructed to follow a 2-week unsupervised quarantine at home, after which they reported to a Marine-supervised facility for an additional 2-week quarantine.
At baseline, participants were tested for SARS-CoV-2 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (ELISA).
The recruits filled out questionnaires asking them to report any of 14 specific COVID-19–related symptoms or any other unspecified symptom, as well as demographic information, risk factors, and a brief medical history.
Investigators tested recruits for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay at weeks 0, 1, and 2 of quarantine, and any who had positive PCR results during quarantine were excluded.
Participants who had three negative swab PCR results during quarantine and a baseline serology test at the beginning of the supervised quarantine period – either seronegative or seropositive – then went on to enjoy their basic training at the Marine Corps Recruit Depot, Parris Island, S.C.
The participants were followed prospectively with PCR tests at weeks 2, 4, and 6 in both the seropositive and seronegative groups, and sera were obtained at the same time.
Holes in immunologic armor
Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.
In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.
Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).
It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).
Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.
“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.
Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.
Lessons
Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.
Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.
Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.
“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.
Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.
“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”
The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”
The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.
Do your patients think that getting COVID-19 is fully protective against subsequent reinfection? Tell it to the Marines.
A study of U.S. Marine recruits on their way to boot camp at Parris Island, S.C., showed that those who were seropositive at baseline, indicating prior exposure to SARS-CoV-2, remained at some risk for reinfection. They had about one-fifth the risk of subsequent infection, compared with seronegative recruits during basic training, but reinfections did occur.
The study, by Stuart C. Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues, was published in The Lancet Respiratory Medicine.
“Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection,” they wrote.
An infectious disease specialist who was not involved in the study said that the findings provide further evidence about the level of immunity acquired after an infection.
“It’s quite clear that reinfections do occur, they are of public health importance, and they’re something we need to be mindful of in terms of advising patients about whether a prior infection protects them from reinfection,” Mark Siedner, MD, MPH, a clinician and researcher in the division of infectious diseases at Massachusetts General Hospital, Boston, said in an interview.
The study results reinforce that “not all antibodies are the same,” said Sachin Gupta, MD, an attending physician in pulmonary and critical care medicine at Alameda Health System in Oakland, Calif. “We’re seeing still that 10% of folks who have antibodies can get infected again,” he said in an interview.
CHARM initiative
Dr. Sealfon and colleagues presented an analysis of data from the ironically named CHARM (COVID-19 Health Action Response for Marines) prospective study.
CHARM included U.S. Marine recruits, most of them male, aged 18-20 years, who were instructed to follow a 2-week unsupervised quarantine at home, after which they reported to a Marine-supervised facility for an additional 2-week quarantine.
At baseline, participants were tested for SARS-CoV-2 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (ELISA).
The recruits filled out questionnaires asking them to report any of 14 specific COVID-19–related symptoms or any other unspecified symptom, as well as demographic information, risk factors, and a brief medical history.
Investigators tested recruits for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay at weeks 0, 1, and 2 of quarantine, and any who had positive PCR results during quarantine were excluded.
Participants who had three negative swab PCR results during quarantine and a baseline serology test at the beginning of the supervised quarantine period – either seronegative or seropositive – then went on to enjoy their basic training at the Marine Corps Recruit Depot, Parris Island, S.C.
The participants were followed prospectively with PCR tests at weeks 2, 4, and 6 in both the seropositive and seronegative groups, and sera were obtained at the same time.
Holes in immunologic armor
Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.
In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.
Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).
It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).
Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.
“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.
Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.
Lessons
Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.
Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.
Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.
“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.
Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.
“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”
The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”
The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.
Do your patients think that getting COVID-19 is fully protective against subsequent reinfection? Tell it to the Marines.
A study of U.S. Marine recruits on their way to boot camp at Parris Island, S.C., showed that those who were seropositive at baseline, indicating prior exposure to SARS-CoV-2, remained at some risk for reinfection. They had about one-fifth the risk of subsequent infection, compared with seronegative recruits during basic training, but reinfections did occur.
The study, by Stuart C. Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues, was published in The Lancet Respiratory Medicine.
“Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection,” they wrote.
An infectious disease specialist who was not involved in the study said that the findings provide further evidence about the level of immunity acquired after an infection.
“It’s quite clear that reinfections do occur, they are of public health importance, and they’re something we need to be mindful of in terms of advising patients about whether a prior infection protects them from reinfection,” Mark Siedner, MD, MPH, a clinician and researcher in the division of infectious diseases at Massachusetts General Hospital, Boston, said in an interview.
The study results reinforce that “not all antibodies are the same,” said Sachin Gupta, MD, an attending physician in pulmonary and critical care medicine at Alameda Health System in Oakland, Calif. “We’re seeing still that 10% of folks who have antibodies can get infected again,” he said in an interview.
CHARM initiative
Dr. Sealfon and colleagues presented an analysis of data from the ironically named CHARM (COVID-19 Health Action Response for Marines) prospective study.
CHARM included U.S. Marine recruits, most of them male, aged 18-20 years, who were instructed to follow a 2-week unsupervised quarantine at home, after which they reported to a Marine-supervised facility for an additional 2-week quarantine.
At baseline, participants were tested for SARS-CoV-2 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (ELISA).
The recruits filled out questionnaires asking them to report any of 14 specific COVID-19–related symptoms or any other unspecified symptom, as well as demographic information, risk factors, and a brief medical history.
Investigators tested recruits for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay at weeks 0, 1, and 2 of quarantine, and any who had positive PCR results during quarantine were excluded.
Participants who had three negative swab PCR results during quarantine and a baseline serology test at the beginning of the supervised quarantine period – either seronegative or seropositive – then went on to enjoy their basic training at the Marine Corps Recruit Depot, Parris Island, S.C.
The participants were followed prospectively with PCR tests at weeks 2, 4, and 6 in both the seropositive and seronegative groups, and sera were obtained at the same time.
Holes in immunologic armor
Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.
In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.
Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).
It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).
Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.
“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.
Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.
Lessons
Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.
Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.
Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.
“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.
Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.
“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”
The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”
The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.
FROM THE LANCET RESPIRATORY MEDICINE
Failure to rescue occurs more often among women of color
In the United States, the rate of mortality caused by severe maternal morbidity has improved over time, but failure to rescue is significantly more common among racial and ethnic minorities.
These failures are a “major contributing factor” to the disproportionately higher rate of maternal mortality among women of color, reported lead author Jean Guglielminotti, MD, PhD, of Columbia University, New York, and colleagues.
“Racial and ethnic disparities in severe maternal morbidity are a growing public health concern in the United States,” the investigators wrote in Obstetrics & Gynecology.
“The reported incidence of severe maternal morbidity is twofold to threefold higher among Black American women, compared with non-Hispanic White women; and although the difference is less pronounced, the incidence of severe maternal morbidity also is higher among Hispanic, Asian and Pacific Islander, and Native American women.”
The ensuant, disproportionate risk of maternal mortality may be further exacerbated by disparities in hospitals, according to the investigators. They noted that non-Hispanic White women tend to give birth in different hospitals than racial and ethnic minorities, and the hospitals serving people of color “are characterized by lower performance on maternal safety indicators.”
Even within hospitals that most often serve minorities, severe maternal morbidity is more common among women of color than women who are White, they added.
“However, the simple severe maternal morbidity rate is insufficient to assess hospital performance and should be complemented with the rate of failure to rescue,” wrote Dr. Guglielminotti and colleagues.
Measuring failure to rescue across racial and ethnic groups
According to the investigators, failure-to-rescue rate advances focus from complications themselves – which can occur when care is appropriate and may stem from patient characteristics – to a hospital’s response to such complications.
Using this metric, a 2016 study by Friedman and colleagues, which included data from 1998 to 2010, showed failure to rescue was more common among Hispanic and non-Hispanic Black women than white women.
The present study built upon these findings with data from almost 74 million delivery hospitalizations in the National Inpatient Sample (1999-2017). The population included 993,864 women with severe maternal morbidity, among whom 4,328 died.
Overall, the failure-to-rescue rate decreased over the course of the study from 13.2% in 1999-2000 to 4.5% in 2017 (P < .001).
Yet racial and ethnic inequities were apparent.
Compared with White women, non-Hispanic Black women had a significantly higher failure-to-rescue rate ratio (1.79; 95% CI, 1.77-1.81), as did Hispanic women (RR, 1.08; 95% CI, 1.06-1.09), women of other non-White racial/ethnic backgrounds (RR, 1.39; 95% CI, 1.37-1.41), and women documented without racial/ethnic designations (RR, 1.43; 95% CI, 1.42-1.45).
“Failure to rescue from severe maternal morbidity remains a major contributing factor to the excess maternal mortality in racial and ethnic minority women in the United States,” the investigators concluded. “This finding underscores the need to identify factors accounting for these disparities and develop hospital-based interventions to reduce excess maternal mortality in racial and ethnic minority women.”
Striving for progress through systemic change
According to Eve Espey, MD, MPH, of the University of New Mexico, Albuquerque, “this study adds to the literature demonstrating that structural racism and implicit bias have profound negative impacts,” which “has implications for action.”
“We must increase efforts to improve maternal safety, including the rollout of Alliance for Innovation on Maternal Health [AIM] bundles through statewide perinatal quality collaboratives,” Dr. Espey said. “AIM bundle implementation must focus on the context of health inequities related to racism and bias. Similarly, we must consider large scale public policy changes building on the Affordable Care Act, such as universal health coverage throughout the life span, [which] equitably increases access to quality health care for all.”
Constance Bohon, MD, of Sibley Memorial Hospital, Washington, offered a similar viewpoint, and suggested that further analyses could reveal the impacts of systemic changes, thereby guiding future interventions.
“It would be interesting to determine if declines in failure to rescue rates were greatest in states that implemented AIM safety bundles [in 2012] as compared with the states that did not,” Dr. Bohon said. “The same assessment could be made with a comparison between the states that did and those that did not approve the Medicaid expansion [in 2014]. Other beneficial data would be a comparison of the failure-to-rescue rates in hospitals that provide the same obstetrical level of care. Further studies need to be done in order to identify factors that have the greatest impact on the failure-to-rescue rate. Subsequently, proposals can be suggested for actions that can be taken to decrease the excess maternal mortality in racial and ethnic minorities.”
Comparing the U.S. with the rest of the world
In an accompanying editorial, Marian F. MacDorman, PhD, of the University of Maryland, College Park, and Eugene Declercq, PhD, of Boston University, put the findings in a global context.
They noted that, in the United States over the past 2 decades, the rate of maternal mortality has either remained flat or increased, depending on study methodology; however, the relative state of affairs between the United States and the rest of the world is more straightforward.
“What is clear is that U.S. maternal mortality did not decline from 2000 to 2018,” wrote Dr. MacDorman and Dr. Declercq. “This contrasts with World Health Organization data showing that maternal mortality declined by 38% worldwide and by 53% in Europe from 2000 to 2017. In fact, North America was the only world region to not show substantial declines in maternal mortality during the period, and U.S. maternal mortality rates are nearly twice those in Europe.”
Within the US, these shortcomings are felt most acutely among racial and ethnic minorities, they noted, as the present study suggests.
“The U.S. is still plagued by wide racial disparities, with similar or larger Black-White maternal mortality disparities in 2018 than existed in the 1940s,” they wrote. “Thus, any euphoria generated by the lack of increase in maternal mortality (if accurate) must be set in the context of worldwide improvements, in which the U.S. is an outlier with no improvement. The U.S. can and should do better!”
To this end, Dr. MacDorman and Dr. Declercq wrote, “additional training and vigilance among clinicians can help to avert these largely preventable deaths. In addition, applying this same rigor to preventing deaths that occur in the community before and after birth, combined with a focus on social determinants among women during the reproductive years, will be essential to lowering U.S. maternal mortality overall and eliminating longstanding racial inequities.”
The study received no external funding. The investigators reported no conflicts of interest.
In the United States, the rate of mortality caused by severe maternal morbidity has improved over time, but failure to rescue is significantly more common among racial and ethnic minorities.
These failures are a “major contributing factor” to the disproportionately higher rate of maternal mortality among women of color, reported lead author Jean Guglielminotti, MD, PhD, of Columbia University, New York, and colleagues.
“Racial and ethnic disparities in severe maternal morbidity are a growing public health concern in the United States,” the investigators wrote in Obstetrics & Gynecology.
“The reported incidence of severe maternal morbidity is twofold to threefold higher among Black American women, compared with non-Hispanic White women; and although the difference is less pronounced, the incidence of severe maternal morbidity also is higher among Hispanic, Asian and Pacific Islander, and Native American women.”
The ensuant, disproportionate risk of maternal mortality may be further exacerbated by disparities in hospitals, according to the investigators. They noted that non-Hispanic White women tend to give birth in different hospitals than racial and ethnic minorities, and the hospitals serving people of color “are characterized by lower performance on maternal safety indicators.”
Even within hospitals that most often serve minorities, severe maternal morbidity is more common among women of color than women who are White, they added.
“However, the simple severe maternal morbidity rate is insufficient to assess hospital performance and should be complemented with the rate of failure to rescue,” wrote Dr. Guglielminotti and colleagues.
Measuring failure to rescue across racial and ethnic groups
According to the investigators, failure-to-rescue rate advances focus from complications themselves – which can occur when care is appropriate and may stem from patient characteristics – to a hospital’s response to such complications.
Using this metric, a 2016 study by Friedman and colleagues, which included data from 1998 to 2010, showed failure to rescue was more common among Hispanic and non-Hispanic Black women than white women.
The present study built upon these findings with data from almost 74 million delivery hospitalizations in the National Inpatient Sample (1999-2017). The population included 993,864 women with severe maternal morbidity, among whom 4,328 died.
Overall, the failure-to-rescue rate decreased over the course of the study from 13.2% in 1999-2000 to 4.5% in 2017 (P < .001).
Yet racial and ethnic inequities were apparent.
Compared with White women, non-Hispanic Black women had a significantly higher failure-to-rescue rate ratio (1.79; 95% CI, 1.77-1.81), as did Hispanic women (RR, 1.08; 95% CI, 1.06-1.09), women of other non-White racial/ethnic backgrounds (RR, 1.39; 95% CI, 1.37-1.41), and women documented without racial/ethnic designations (RR, 1.43; 95% CI, 1.42-1.45).
“Failure to rescue from severe maternal morbidity remains a major contributing factor to the excess maternal mortality in racial and ethnic minority women in the United States,” the investigators concluded. “This finding underscores the need to identify factors accounting for these disparities and develop hospital-based interventions to reduce excess maternal mortality in racial and ethnic minority women.”
Striving for progress through systemic change
According to Eve Espey, MD, MPH, of the University of New Mexico, Albuquerque, “this study adds to the literature demonstrating that structural racism and implicit bias have profound negative impacts,” which “has implications for action.”
“We must increase efforts to improve maternal safety, including the rollout of Alliance for Innovation on Maternal Health [AIM] bundles through statewide perinatal quality collaboratives,” Dr. Espey said. “AIM bundle implementation must focus on the context of health inequities related to racism and bias. Similarly, we must consider large scale public policy changes building on the Affordable Care Act, such as universal health coverage throughout the life span, [which] equitably increases access to quality health care for all.”
Constance Bohon, MD, of Sibley Memorial Hospital, Washington, offered a similar viewpoint, and suggested that further analyses could reveal the impacts of systemic changes, thereby guiding future interventions.
“It would be interesting to determine if declines in failure to rescue rates were greatest in states that implemented AIM safety bundles [in 2012] as compared with the states that did not,” Dr. Bohon said. “The same assessment could be made with a comparison between the states that did and those that did not approve the Medicaid expansion [in 2014]. Other beneficial data would be a comparison of the failure-to-rescue rates in hospitals that provide the same obstetrical level of care. Further studies need to be done in order to identify factors that have the greatest impact on the failure-to-rescue rate. Subsequently, proposals can be suggested for actions that can be taken to decrease the excess maternal mortality in racial and ethnic minorities.”
Comparing the U.S. with the rest of the world
In an accompanying editorial, Marian F. MacDorman, PhD, of the University of Maryland, College Park, and Eugene Declercq, PhD, of Boston University, put the findings in a global context.
They noted that, in the United States over the past 2 decades, the rate of maternal mortality has either remained flat or increased, depending on study methodology; however, the relative state of affairs between the United States and the rest of the world is more straightforward.
“What is clear is that U.S. maternal mortality did not decline from 2000 to 2018,” wrote Dr. MacDorman and Dr. Declercq. “This contrasts with World Health Organization data showing that maternal mortality declined by 38% worldwide and by 53% in Europe from 2000 to 2017. In fact, North America was the only world region to not show substantial declines in maternal mortality during the period, and U.S. maternal mortality rates are nearly twice those in Europe.”
Within the US, these shortcomings are felt most acutely among racial and ethnic minorities, they noted, as the present study suggests.
“The U.S. is still plagued by wide racial disparities, with similar or larger Black-White maternal mortality disparities in 2018 than existed in the 1940s,” they wrote. “Thus, any euphoria generated by the lack of increase in maternal mortality (if accurate) must be set in the context of worldwide improvements, in which the U.S. is an outlier with no improvement. The U.S. can and should do better!”
To this end, Dr. MacDorman and Dr. Declercq wrote, “additional training and vigilance among clinicians can help to avert these largely preventable deaths. In addition, applying this same rigor to preventing deaths that occur in the community before and after birth, combined with a focus on social determinants among women during the reproductive years, will be essential to lowering U.S. maternal mortality overall and eliminating longstanding racial inequities.”
The study received no external funding. The investigators reported no conflicts of interest.
In the United States, the rate of mortality caused by severe maternal morbidity has improved over time, but failure to rescue is significantly more common among racial and ethnic minorities.
These failures are a “major contributing factor” to the disproportionately higher rate of maternal mortality among women of color, reported lead author Jean Guglielminotti, MD, PhD, of Columbia University, New York, and colleagues.
“Racial and ethnic disparities in severe maternal morbidity are a growing public health concern in the United States,” the investigators wrote in Obstetrics & Gynecology.
“The reported incidence of severe maternal morbidity is twofold to threefold higher among Black American women, compared with non-Hispanic White women; and although the difference is less pronounced, the incidence of severe maternal morbidity also is higher among Hispanic, Asian and Pacific Islander, and Native American women.”
The ensuant, disproportionate risk of maternal mortality may be further exacerbated by disparities in hospitals, according to the investigators. They noted that non-Hispanic White women tend to give birth in different hospitals than racial and ethnic minorities, and the hospitals serving people of color “are characterized by lower performance on maternal safety indicators.”
Even within hospitals that most often serve minorities, severe maternal morbidity is more common among women of color than women who are White, they added.
“However, the simple severe maternal morbidity rate is insufficient to assess hospital performance and should be complemented with the rate of failure to rescue,” wrote Dr. Guglielminotti and colleagues.
Measuring failure to rescue across racial and ethnic groups
According to the investigators, failure-to-rescue rate advances focus from complications themselves – which can occur when care is appropriate and may stem from patient characteristics – to a hospital’s response to such complications.
Using this metric, a 2016 study by Friedman and colleagues, which included data from 1998 to 2010, showed failure to rescue was more common among Hispanic and non-Hispanic Black women than white women.
The present study built upon these findings with data from almost 74 million delivery hospitalizations in the National Inpatient Sample (1999-2017). The population included 993,864 women with severe maternal morbidity, among whom 4,328 died.
Overall, the failure-to-rescue rate decreased over the course of the study from 13.2% in 1999-2000 to 4.5% in 2017 (P < .001).
Yet racial and ethnic inequities were apparent.
Compared with White women, non-Hispanic Black women had a significantly higher failure-to-rescue rate ratio (1.79; 95% CI, 1.77-1.81), as did Hispanic women (RR, 1.08; 95% CI, 1.06-1.09), women of other non-White racial/ethnic backgrounds (RR, 1.39; 95% CI, 1.37-1.41), and women documented without racial/ethnic designations (RR, 1.43; 95% CI, 1.42-1.45).
“Failure to rescue from severe maternal morbidity remains a major contributing factor to the excess maternal mortality in racial and ethnic minority women in the United States,” the investigators concluded. “This finding underscores the need to identify factors accounting for these disparities and develop hospital-based interventions to reduce excess maternal mortality in racial and ethnic minority women.”
Striving for progress through systemic change
According to Eve Espey, MD, MPH, of the University of New Mexico, Albuquerque, “this study adds to the literature demonstrating that structural racism and implicit bias have profound negative impacts,” which “has implications for action.”
“We must increase efforts to improve maternal safety, including the rollout of Alliance for Innovation on Maternal Health [AIM] bundles through statewide perinatal quality collaboratives,” Dr. Espey said. “AIM bundle implementation must focus on the context of health inequities related to racism and bias. Similarly, we must consider large scale public policy changes building on the Affordable Care Act, such as universal health coverage throughout the life span, [which] equitably increases access to quality health care for all.”
Constance Bohon, MD, of Sibley Memorial Hospital, Washington, offered a similar viewpoint, and suggested that further analyses could reveal the impacts of systemic changes, thereby guiding future interventions.
“It would be interesting to determine if declines in failure to rescue rates were greatest in states that implemented AIM safety bundles [in 2012] as compared with the states that did not,” Dr. Bohon said. “The same assessment could be made with a comparison between the states that did and those that did not approve the Medicaid expansion [in 2014]. Other beneficial data would be a comparison of the failure-to-rescue rates in hospitals that provide the same obstetrical level of care. Further studies need to be done in order to identify factors that have the greatest impact on the failure-to-rescue rate. Subsequently, proposals can be suggested for actions that can be taken to decrease the excess maternal mortality in racial and ethnic minorities.”
Comparing the U.S. with the rest of the world
In an accompanying editorial, Marian F. MacDorman, PhD, of the University of Maryland, College Park, and Eugene Declercq, PhD, of Boston University, put the findings in a global context.
They noted that, in the United States over the past 2 decades, the rate of maternal mortality has either remained flat or increased, depending on study methodology; however, the relative state of affairs between the United States and the rest of the world is more straightforward.
“What is clear is that U.S. maternal mortality did not decline from 2000 to 2018,” wrote Dr. MacDorman and Dr. Declercq. “This contrasts with World Health Organization data showing that maternal mortality declined by 38% worldwide and by 53% in Europe from 2000 to 2017. In fact, North America was the only world region to not show substantial declines in maternal mortality during the period, and U.S. maternal mortality rates are nearly twice those in Europe.”
Within the US, these shortcomings are felt most acutely among racial and ethnic minorities, they noted, as the present study suggests.
“The U.S. is still plagued by wide racial disparities, with similar or larger Black-White maternal mortality disparities in 2018 than existed in the 1940s,” they wrote. “Thus, any euphoria generated by the lack of increase in maternal mortality (if accurate) must be set in the context of worldwide improvements, in which the U.S. is an outlier with no improvement. The U.S. can and should do better!”
To this end, Dr. MacDorman and Dr. Declercq wrote, “additional training and vigilance among clinicians can help to avert these largely preventable deaths. In addition, applying this same rigor to preventing deaths that occur in the community before and after birth, combined with a focus on social determinants among women during the reproductive years, will be essential to lowering U.S. maternal mortality overall and eliminating longstanding racial inequities.”
The study received no external funding. The investigators reported no conflicts of interest.
FROM OBSTETRICS & GYNECOLOGY
Surgery for early-stage cervical cancer: Are we still too radical?
It has been more than 120 years since Ernst Wertheim, a Viennese surgeon, performed and described what is considered to have been the first radical total hysterectomy with lymphadenectomy for early-stage cervical cancer, yet this morbid procedure remains the standard of care for most early-stage cervical cancers. The rationale for this procedure, which included removal of the parametrial tissue, uterosacral and cardinal ligaments, and upper vagina en bloc with the cervix and uterus, was to obtain margins around a cancer that has a dominant radial growth pattern. The morbidity associated with this procedure is substantial. The parametrium houses important vascular, neural, and urologic structures. Unlike extrafascial hysterectomy, often referred to as “simple” hysterectomy, in which surgeons follow a fascial plane, and therefore a relatively avascular dissection, surgeons performing radical hysterectomy must venture outside of these embryologic fusion planes into less well–defined anatomy. Therefore, surgical complications are relatively common including hemorrhage, ureteral and bladder injury, as well as late-onset devastating complications such as fistula, urinary retention, or incontinence, and sexual dysfunction.1 More recently, variations of the Wertheim-Meigs radical hysterectomy have been described, and objective classifications created, which include modified radical procedures (removing less parametria) and nerve-sparing procedures to facilitate standardized nomenclature for tailoring the most appropriate procedure for any given tumor.2
The trend, and a positive one at that, over the course of the past century, has been a move away from routine radical surgical procedures for most clinical stage 1 cancers. No better example exists than breast cancer, in which the Halsted radical mastectomy has been largely replaced by less morbid breast-conserving or nonradical procedures with adjunct medical and radiation therapies offered to achieve high rates of cure with far more acceptable patient-centered outcomes.3 And so why is it that radical hysterectomy is still considered the standard of care for all but the smallest of microscopic cervical cancers?
The risk of lymph node metastases or recurrence is exceptionally low for women with microscopic (stage IA1) cervical cancers that are less than 3 mm in depth. Therefore, the National Comprehensive Cancer Network guidelines recommend nonradical surgical remedies (such as extrafascial hysterectomy, or cone biopsy or trachelectomy if fertility preservation is desired) for this earlier stage of disease.4 If there is lymphovascular space invasion (an indicator of poor prognosis and potential lymphatic involvement), a lymphadenectomy or sentinel lymph node biopsy is also recommended. For women with stage IA2 or IB lesions, radical excisions (either trachelectomy or hysterectomy) are considered the standard of care. However, this “gold standard” was achieved largely through legacy, and not a result of randomized trials comparing its outcomes with nonradical procedures.
Initial strides away from radical cervical cancer surgery focused on the goal of fertility preservation via radical trachelectomy which allowed women to preserve an intact uterine fundus. This was initially met with skepticism and concern that surgeons could be sacrificing oncologic outcomes in order to preserve a woman’s fertility. Thanks to pioneering work, including prospective research studies by surgeon innovators it has been shown that, in appropriately selected candidates with tumors less than 2 cm, it is an accepted standard of care.4 Radical vaginal or abdominal trachelectomy is associated with cancer recurrence rates of less than 5% and successful pregnancy in approximately three-quarters of patients in whom this is desired.5,6 However, full-term pregnancy is achieved in 50%-75% of cases, reflecting increased obstetric risk, and radical trachelectomy still subjects patients to the morbidity of a radical parametrial resection, despite the fact that many of them will have no residual carcinoma in their final pathological specimens.
Therefore, can we be even more conservative in our surgery for these patients? Are simple hysterectomy or conization potentially adequate treatments for small (<2 cm) stage IA2 and IB1 lesions that have favorable histology (<10 mm stromal invasion, low-risk histology, no lymphovascular space involvement, negative margins on conization and no lymph node metastases)? In patients whose tumor exhibits these histologic features, the likelihood of parametrial involvement is approximately 1%, calling into question the virtue of parametrial resection.7 Observational studies have identified mixed results on the safety of conservative surgical techniques in early-stage cervical cancer. In a study of the National Cancer Database, the outcomes of 2,543 radical hysterectomies and 1,388 extrafascial hysterectomies for women with stage IB1 disease were evaluated and observed a difference in 5-year survival (92.4% vs. 95.3%) favoring the radical procedure.8 Unfortunately, database analyses such as these are limited by potential confounders and discordance between the groups such as rates of lymphadenectomy, known involvement of oncologic surgeon specialists, and margin status. An alternative evaluation of the Surveillance, Epidemiology, and End Results database including 2,571 patients with stage IB1 disease, all of whom had lymphadenectomy performed, showed no difference in 10-year disease-specific survival between the two surgical approaches.9
Ultimately, whether conservative procedures (such as conization or extrafascial hysterectomy) can be offered to women with small, low-risk IB1 or IA2 cervical cancers will be best determined by prospective single-arm or randomized trials. Fortunately, these are underway. Preliminary results from the ConCerv trial in which 100 women with early-stage, low-risk stage IA2 and IB1 cervical cancer were treated with either repeat conization or extrafascial hysterectomy with sentinel lymph node biopsy showed acceptably low rates of recurrence (3%) with this approach.10 If the mature data supports this finding, it seems that, for appropriately selected and well-counseled patients, conservative surgery may become more broadly accepted as a reasonable option for treatment that spares women not only loss of fertility, but also the early and late surgical morbidity from radical procedures.
In the meantime, until more is known about the oncologic safety of nonradical procedures for stage IA2 and IB1 cervical cancer, this option should not be considered standard of care, and only offered to patients with favorable tumor factors who are well counseled regarding the uncertainty of this approach. It is critical that patients with early-stage cervical cancer be evaluated by a gynecologic cancer specialist prior to definitive surgical treatment as they are best equipped to evaluate risk profiles and counsel about her options for surgery, its known and unknown consequences, and the appropriateness of fertility preservation or radicality of surgery. We eagerly await the results of trials evaluating the safety of conservative cervical cancer surgery, which promise to advance us from 19th-century practices, preserving not only fertility, but also quality of life.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no disclosures and can be contacted at [email protected].
References
1. Trimbos JB et al. Eur J Cancer. 2004;40(3):375-8.
2. Querleu D and Morrow CP. Lancet Oncol. 2008;9:297-303.
3. Sakorafas GH and Safioleas M. Eur J Cancer Care. 2010 Mar;19(2):145-66.
4. National Comprehensive Cancer Network. Cervical Cancer (Version 1.2021). https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed 2021 Apr 21.
5. Plante M et al. Gynecol Oncol. 2011;121:290-7.
6. Wethington SL et al. Int J Gynecol Cancer. 2012;22:1251-7.
7. Domgue J and Schmeler K. Best Pract Res Clin Obstet Gynaecol. 2019 Feb;55:79-92.
8. Sia TY et al. Obstet Gyenecol. 2019;134(6):1132.
9. Tseng J et al. Gynecol Oncol. 2018;150(1):44.
10. Schmeler K et al. Int J Gynecol Cancer. 2019;29:A14-5.
It has been more than 120 years since Ernst Wertheim, a Viennese surgeon, performed and described what is considered to have been the first radical total hysterectomy with lymphadenectomy for early-stage cervical cancer, yet this morbid procedure remains the standard of care for most early-stage cervical cancers. The rationale for this procedure, which included removal of the parametrial tissue, uterosacral and cardinal ligaments, and upper vagina en bloc with the cervix and uterus, was to obtain margins around a cancer that has a dominant radial growth pattern. The morbidity associated with this procedure is substantial. The parametrium houses important vascular, neural, and urologic structures. Unlike extrafascial hysterectomy, often referred to as “simple” hysterectomy, in which surgeons follow a fascial plane, and therefore a relatively avascular dissection, surgeons performing radical hysterectomy must venture outside of these embryologic fusion planes into less well–defined anatomy. Therefore, surgical complications are relatively common including hemorrhage, ureteral and bladder injury, as well as late-onset devastating complications such as fistula, urinary retention, or incontinence, and sexual dysfunction.1 More recently, variations of the Wertheim-Meigs radical hysterectomy have been described, and objective classifications created, which include modified radical procedures (removing less parametria) and nerve-sparing procedures to facilitate standardized nomenclature for tailoring the most appropriate procedure for any given tumor.2
The trend, and a positive one at that, over the course of the past century, has been a move away from routine radical surgical procedures for most clinical stage 1 cancers. No better example exists than breast cancer, in which the Halsted radical mastectomy has been largely replaced by less morbid breast-conserving or nonradical procedures with adjunct medical and radiation therapies offered to achieve high rates of cure with far more acceptable patient-centered outcomes.3 And so why is it that radical hysterectomy is still considered the standard of care for all but the smallest of microscopic cervical cancers?
The risk of lymph node metastases or recurrence is exceptionally low for women with microscopic (stage IA1) cervical cancers that are less than 3 mm in depth. Therefore, the National Comprehensive Cancer Network guidelines recommend nonradical surgical remedies (such as extrafascial hysterectomy, or cone biopsy or trachelectomy if fertility preservation is desired) for this earlier stage of disease.4 If there is lymphovascular space invasion (an indicator of poor prognosis and potential lymphatic involvement), a lymphadenectomy or sentinel lymph node biopsy is also recommended. For women with stage IA2 or IB lesions, radical excisions (either trachelectomy or hysterectomy) are considered the standard of care. However, this “gold standard” was achieved largely through legacy, and not a result of randomized trials comparing its outcomes with nonradical procedures.
Initial strides away from radical cervical cancer surgery focused on the goal of fertility preservation via radical trachelectomy which allowed women to preserve an intact uterine fundus. This was initially met with skepticism and concern that surgeons could be sacrificing oncologic outcomes in order to preserve a woman’s fertility. Thanks to pioneering work, including prospective research studies by surgeon innovators it has been shown that, in appropriately selected candidates with tumors less than 2 cm, it is an accepted standard of care.4 Radical vaginal or abdominal trachelectomy is associated with cancer recurrence rates of less than 5% and successful pregnancy in approximately three-quarters of patients in whom this is desired.5,6 However, full-term pregnancy is achieved in 50%-75% of cases, reflecting increased obstetric risk, and radical trachelectomy still subjects patients to the morbidity of a radical parametrial resection, despite the fact that many of them will have no residual carcinoma in their final pathological specimens.
Therefore, can we be even more conservative in our surgery for these patients? Are simple hysterectomy or conization potentially adequate treatments for small (<2 cm) stage IA2 and IB1 lesions that have favorable histology (<10 mm stromal invasion, low-risk histology, no lymphovascular space involvement, negative margins on conization and no lymph node metastases)? In patients whose tumor exhibits these histologic features, the likelihood of parametrial involvement is approximately 1%, calling into question the virtue of parametrial resection.7 Observational studies have identified mixed results on the safety of conservative surgical techniques in early-stage cervical cancer. In a study of the National Cancer Database, the outcomes of 2,543 radical hysterectomies and 1,388 extrafascial hysterectomies for women with stage IB1 disease were evaluated and observed a difference in 5-year survival (92.4% vs. 95.3%) favoring the radical procedure.8 Unfortunately, database analyses such as these are limited by potential confounders and discordance between the groups such as rates of lymphadenectomy, known involvement of oncologic surgeon specialists, and margin status. An alternative evaluation of the Surveillance, Epidemiology, and End Results database including 2,571 patients with stage IB1 disease, all of whom had lymphadenectomy performed, showed no difference in 10-year disease-specific survival between the two surgical approaches.9
Ultimately, whether conservative procedures (such as conization or extrafascial hysterectomy) can be offered to women with small, low-risk IB1 or IA2 cervical cancers will be best determined by prospective single-arm or randomized trials. Fortunately, these are underway. Preliminary results from the ConCerv trial in which 100 women with early-stage, low-risk stage IA2 and IB1 cervical cancer were treated with either repeat conization or extrafascial hysterectomy with sentinel lymph node biopsy showed acceptably low rates of recurrence (3%) with this approach.10 If the mature data supports this finding, it seems that, for appropriately selected and well-counseled patients, conservative surgery may become more broadly accepted as a reasonable option for treatment that spares women not only loss of fertility, but also the early and late surgical morbidity from radical procedures.
In the meantime, until more is known about the oncologic safety of nonradical procedures for stage IA2 and IB1 cervical cancer, this option should not be considered standard of care, and only offered to patients with favorable tumor factors who are well counseled regarding the uncertainty of this approach. It is critical that patients with early-stage cervical cancer be evaluated by a gynecologic cancer specialist prior to definitive surgical treatment as they are best equipped to evaluate risk profiles and counsel about her options for surgery, its known and unknown consequences, and the appropriateness of fertility preservation or radicality of surgery. We eagerly await the results of trials evaluating the safety of conservative cervical cancer surgery, which promise to advance us from 19th-century practices, preserving not only fertility, but also quality of life.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no disclosures and can be contacted at [email protected].
References
1. Trimbos JB et al. Eur J Cancer. 2004;40(3):375-8.
2. Querleu D and Morrow CP. Lancet Oncol. 2008;9:297-303.
3. Sakorafas GH and Safioleas M. Eur J Cancer Care. 2010 Mar;19(2):145-66.
4. National Comprehensive Cancer Network. Cervical Cancer (Version 1.2021). https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed 2021 Apr 21.
5. Plante M et al. Gynecol Oncol. 2011;121:290-7.
6. Wethington SL et al. Int J Gynecol Cancer. 2012;22:1251-7.
7. Domgue J and Schmeler K. Best Pract Res Clin Obstet Gynaecol. 2019 Feb;55:79-92.
8. Sia TY et al. Obstet Gyenecol. 2019;134(6):1132.
9. Tseng J et al. Gynecol Oncol. 2018;150(1):44.
10. Schmeler K et al. Int J Gynecol Cancer. 2019;29:A14-5.
It has been more than 120 years since Ernst Wertheim, a Viennese surgeon, performed and described what is considered to have been the first radical total hysterectomy with lymphadenectomy for early-stage cervical cancer, yet this morbid procedure remains the standard of care for most early-stage cervical cancers. The rationale for this procedure, which included removal of the parametrial tissue, uterosacral and cardinal ligaments, and upper vagina en bloc with the cervix and uterus, was to obtain margins around a cancer that has a dominant radial growth pattern. The morbidity associated with this procedure is substantial. The parametrium houses important vascular, neural, and urologic structures. Unlike extrafascial hysterectomy, often referred to as “simple” hysterectomy, in which surgeons follow a fascial plane, and therefore a relatively avascular dissection, surgeons performing radical hysterectomy must venture outside of these embryologic fusion planes into less well–defined anatomy. Therefore, surgical complications are relatively common including hemorrhage, ureteral and bladder injury, as well as late-onset devastating complications such as fistula, urinary retention, or incontinence, and sexual dysfunction.1 More recently, variations of the Wertheim-Meigs radical hysterectomy have been described, and objective classifications created, which include modified radical procedures (removing less parametria) and nerve-sparing procedures to facilitate standardized nomenclature for tailoring the most appropriate procedure for any given tumor.2
The trend, and a positive one at that, over the course of the past century, has been a move away from routine radical surgical procedures for most clinical stage 1 cancers. No better example exists than breast cancer, in which the Halsted radical mastectomy has been largely replaced by less morbid breast-conserving or nonradical procedures with adjunct medical and radiation therapies offered to achieve high rates of cure with far more acceptable patient-centered outcomes.3 And so why is it that radical hysterectomy is still considered the standard of care for all but the smallest of microscopic cervical cancers?
The risk of lymph node metastases or recurrence is exceptionally low for women with microscopic (stage IA1) cervical cancers that are less than 3 mm in depth. Therefore, the National Comprehensive Cancer Network guidelines recommend nonradical surgical remedies (such as extrafascial hysterectomy, or cone biopsy or trachelectomy if fertility preservation is desired) for this earlier stage of disease.4 If there is lymphovascular space invasion (an indicator of poor prognosis and potential lymphatic involvement), a lymphadenectomy or sentinel lymph node biopsy is also recommended. For women with stage IA2 or IB lesions, radical excisions (either trachelectomy or hysterectomy) are considered the standard of care. However, this “gold standard” was achieved largely through legacy, and not a result of randomized trials comparing its outcomes with nonradical procedures.
Initial strides away from radical cervical cancer surgery focused on the goal of fertility preservation via radical trachelectomy which allowed women to preserve an intact uterine fundus. This was initially met with skepticism and concern that surgeons could be sacrificing oncologic outcomes in order to preserve a woman’s fertility. Thanks to pioneering work, including prospective research studies by surgeon innovators it has been shown that, in appropriately selected candidates with tumors less than 2 cm, it is an accepted standard of care.4 Radical vaginal or abdominal trachelectomy is associated with cancer recurrence rates of less than 5% and successful pregnancy in approximately three-quarters of patients in whom this is desired.5,6 However, full-term pregnancy is achieved in 50%-75% of cases, reflecting increased obstetric risk, and radical trachelectomy still subjects patients to the morbidity of a radical parametrial resection, despite the fact that many of them will have no residual carcinoma in their final pathological specimens.
Therefore, can we be even more conservative in our surgery for these patients? Are simple hysterectomy or conization potentially adequate treatments for small (<2 cm) stage IA2 and IB1 lesions that have favorable histology (<10 mm stromal invasion, low-risk histology, no lymphovascular space involvement, negative margins on conization and no lymph node metastases)? In patients whose tumor exhibits these histologic features, the likelihood of parametrial involvement is approximately 1%, calling into question the virtue of parametrial resection.7 Observational studies have identified mixed results on the safety of conservative surgical techniques in early-stage cervical cancer. In a study of the National Cancer Database, the outcomes of 2,543 radical hysterectomies and 1,388 extrafascial hysterectomies for women with stage IB1 disease were evaluated and observed a difference in 5-year survival (92.4% vs. 95.3%) favoring the radical procedure.8 Unfortunately, database analyses such as these are limited by potential confounders and discordance between the groups such as rates of lymphadenectomy, known involvement of oncologic surgeon specialists, and margin status. An alternative evaluation of the Surveillance, Epidemiology, and End Results database including 2,571 patients with stage IB1 disease, all of whom had lymphadenectomy performed, showed no difference in 10-year disease-specific survival between the two surgical approaches.9
Ultimately, whether conservative procedures (such as conization or extrafascial hysterectomy) can be offered to women with small, low-risk IB1 or IA2 cervical cancers will be best determined by prospective single-arm or randomized trials. Fortunately, these are underway. Preliminary results from the ConCerv trial in which 100 women with early-stage, low-risk stage IA2 and IB1 cervical cancer were treated with either repeat conization or extrafascial hysterectomy with sentinel lymph node biopsy showed acceptably low rates of recurrence (3%) with this approach.10 If the mature data supports this finding, it seems that, for appropriately selected and well-counseled patients, conservative surgery may become more broadly accepted as a reasonable option for treatment that spares women not only loss of fertility, but also the early and late surgical morbidity from radical procedures.
In the meantime, until more is known about the oncologic safety of nonradical procedures for stage IA2 and IB1 cervical cancer, this option should not be considered standard of care, and only offered to patients with favorable tumor factors who are well counseled regarding the uncertainty of this approach. It is critical that patients with early-stage cervical cancer be evaluated by a gynecologic cancer specialist prior to definitive surgical treatment as they are best equipped to evaluate risk profiles and counsel about her options for surgery, its known and unknown consequences, and the appropriateness of fertility preservation or radicality of surgery. We eagerly await the results of trials evaluating the safety of conservative cervical cancer surgery, which promise to advance us from 19th-century practices, preserving not only fertility, but also quality of life.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no disclosures and can be contacted at [email protected].
References
1. Trimbos JB et al. Eur J Cancer. 2004;40(3):375-8.
2. Querleu D and Morrow CP. Lancet Oncol. 2008;9:297-303.
3. Sakorafas GH and Safioleas M. Eur J Cancer Care. 2010 Mar;19(2):145-66.
4. National Comprehensive Cancer Network. Cervical Cancer (Version 1.2021). https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed 2021 Apr 21.
5. Plante M et al. Gynecol Oncol. 2011;121:290-7.
6. Wethington SL et al. Int J Gynecol Cancer. 2012;22:1251-7.
7. Domgue J and Schmeler K. Best Pract Res Clin Obstet Gynaecol. 2019 Feb;55:79-92.
8. Sia TY et al. Obstet Gyenecol. 2019;134(6):1132.
9. Tseng J et al. Gynecol Oncol. 2018;150(1):44.
10. Schmeler K et al. Int J Gynecol Cancer. 2019;29:A14-5.
FDA approves new immunotherapy for endometrial cancer
Use limited to patients with biomarker
Usage of the new checkpoint inhibitor is limited to patients who have progressed on or following prior treatment with a platinum-containing chemotherapy. Eligibility must also be determined by an FDA-approved test for the dMMR biomarker. Approximately 25%-30% of patients with advanced endometrial cancer have dMMR tumors, according to the FDA.
The approval is “evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
He explained that the immunotherapy was “specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response.”
The new drug also addresses an unmet medical need, as there are limited therapeutic options in this setting following frontline standard treatment with a platinum-containing chemotherapy.
The approval is based on safety and efficacy data from a single-arm, multicohort clinical trial. Of the 71 patients with dMMR recurrent or advanced endometrial cancer who received dostarlimab, 42.3% had a response. For 93% of that group, the response lasted 6 months or longer.
The drug’s maker, GlaxoSmithKline, is currently conducting additional, larger trials in more patients with dMMR endometrial tumors to verify and further describe clinical benefits.
Common side effects of dostarlimab include fatigue, nausea, diarrhea, anemia, and constipation. Like other checkpoint inhibitors, the new drug can cause immune-mediated side effects such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Dostarlimab is contraindicated in women who are pregnant or breastfeeding because it may cause harm to a developing fetus or newborn baby.
The FDA approval comes a month after the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended granting conditional marketing authorization for dostarlimab for use as monotherapy in this same patient group.
In the United States, dostarlimab received Priority Review designation and Breakthrough Therapy designation for this indication.
A version of this article first appeared on Medscape.com.
Use limited to patients with biomarker
Use limited to patients with biomarker
Usage of the new checkpoint inhibitor is limited to patients who have progressed on or following prior treatment with a platinum-containing chemotherapy. Eligibility must also be determined by an FDA-approved test for the dMMR biomarker. Approximately 25%-30% of patients with advanced endometrial cancer have dMMR tumors, according to the FDA.
The approval is “evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
He explained that the immunotherapy was “specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response.”
The new drug also addresses an unmet medical need, as there are limited therapeutic options in this setting following frontline standard treatment with a platinum-containing chemotherapy.
The approval is based on safety and efficacy data from a single-arm, multicohort clinical trial. Of the 71 patients with dMMR recurrent or advanced endometrial cancer who received dostarlimab, 42.3% had a response. For 93% of that group, the response lasted 6 months or longer.
The drug’s maker, GlaxoSmithKline, is currently conducting additional, larger trials in more patients with dMMR endometrial tumors to verify and further describe clinical benefits.
Common side effects of dostarlimab include fatigue, nausea, diarrhea, anemia, and constipation. Like other checkpoint inhibitors, the new drug can cause immune-mediated side effects such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Dostarlimab is contraindicated in women who are pregnant or breastfeeding because it may cause harm to a developing fetus or newborn baby.
The FDA approval comes a month after the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended granting conditional marketing authorization for dostarlimab for use as monotherapy in this same patient group.
In the United States, dostarlimab received Priority Review designation and Breakthrough Therapy designation for this indication.
A version of this article first appeared on Medscape.com.
Usage of the new checkpoint inhibitor is limited to patients who have progressed on or following prior treatment with a platinum-containing chemotherapy. Eligibility must also be determined by an FDA-approved test for the dMMR biomarker. Approximately 25%-30% of patients with advanced endometrial cancer have dMMR tumors, according to the FDA.
The approval is “evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
He explained that the immunotherapy was “specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response.”
The new drug also addresses an unmet medical need, as there are limited therapeutic options in this setting following frontline standard treatment with a platinum-containing chemotherapy.
The approval is based on safety and efficacy data from a single-arm, multicohort clinical trial. Of the 71 patients with dMMR recurrent or advanced endometrial cancer who received dostarlimab, 42.3% had a response. For 93% of that group, the response lasted 6 months or longer.
The drug’s maker, GlaxoSmithKline, is currently conducting additional, larger trials in more patients with dMMR endometrial tumors to verify and further describe clinical benefits.
Common side effects of dostarlimab include fatigue, nausea, diarrhea, anemia, and constipation. Like other checkpoint inhibitors, the new drug can cause immune-mediated side effects such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Dostarlimab is contraindicated in women who are pregnant or breastfeeding because it may cause harm to a developing fetus or newborn baby.
The FDA approval comes a month after the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended granting conditional marketing authorization for dostarlimab for use as monotherapy in this same patient group.
In the United States, dostarlimab received Priority Review designation and Breakthrough Therapy designation for this indication.
A version of this article first appeared on Medscape.com.