MDedge ObGyn

A group of bipartisan lawmakers intends to compel insurers to streamline prior authorization processes for Medicare Advantage plans, including a bid to end the use of faxes and develop systems that can allow for real-time decisions.

Rep. Suzan DelBene (D-Wash.); Rep. Mike Kelly (R-Pa.); Rep. Ami Bera, MD (D-Calif.); and Rep. Larry Bucshon, MD, (R-Ind.) on May 13 introduced a bill that would task federal officials with refining standards regarding prior authorization for Medicare Advantage. Titled the Improving Seniors’ Timely Access to Care Act of 2021, the bill would direct the Department of Health & Human Services to create rules intended to make prior authorization more transparent and speedy for the insurer-run Medicare plans. Known as Medicare Advantage, these plans cover about 24.1 million people of the 62 million enrolled in the giant federal health program, according to the nonprofit Kaiser Family Foundation.

These revamped prior authorization systems could not rely on faxes nor could they employ proprietary payer portals that did not meet HHS’ standards, says the text of the bill released by Rep. DelBene. Insurers would also have to report to the Centers for Medicare & Medicaid Services about the extent of their use of prior authorization and the rate of approvals or denials. The bill seeks to encourage plans to adopt prior authorization programs that adhere to evidence-based medical guidelines in consultation with physicians.

There were several reasons for focusing on Medicare Advantage plans, although prior authorization concerns extend more broadly in the U.S. health care system, said Susan Bailey, MD, president of the American Medical Association.

There’s an ample body of research about issues seen in the Medicare Advantage plans. Dr. Bailey also said that, in her experience, Medicare Advantage plans have had some of the most restrictive policies. And, by starting with Medicare Advantage, there’s a potential for a ripple effect in the industry, easing this issue when physicians work with other insurers as well.

“When Medicare adopts a policy whether it be a payment policy or a coverage policy, private insurers typically follow along,” she said.
 

Strong support among health care groups

There’s strong support for streamlining prior authorization both in the medical community and in Congress.

The bill has the support of about 70 health care organizations, including the AMA and the American Academy of Family Physicians, according to its sponsors. As of May 17, the bill had attracted the backing of 97 members of the House of Representatives, roughly evenly split among Democrats and Republicans.

Rep. DelBene’s previous version of this bill, the Improving Seniors’ Timely Access to Care Act of 2019, attracted 143 Democratic cosponsors and 137 Republican ones, or more than half of the members of the House. This bill was not completed during the previous session of Congress (January 2019–January 2021) because of the more urgent needs of pandemic response, said Rep. Bucshon, who practiced cardiothoracic surgery before joining Congress.

“It wasn’t quite on the radar as much as it might have been if we didn’t have COVID,” Rep. Bucshon said.

Rep. Bucshon added that he expects strong Senate support for a companion measure of the House bill, which could make the difference for efforts to pass it this year.

Insurers have become more aggressive over time in denying payments through prior authorization systems for services that physicians say their patients need, according to Rep. Bucshon. There may be some “bad actors” in medicine who would order unnecessary procedures, Rep. Bucshon allowed, but in most cases, the cumbersome prior authorization processes only put a hurdle for patients seeking needed treatments, he said.

“The premise is that it controls health care costs but actually what it does is it helps insurance company’s bottom line,” Rep. Bucshon said.

In a prepared statement, former Pennsylvania representative Allyson Y. Schwartz, now CEO of the Better Medicare Alliance, said her group had spoken with sponsors of this legislation and appreciates “their receptiveness to feedback in this process.”

“Prior authorization ensures beneficiaries receive clinically appropriate care and reduces exposures to duplicative and unnecessary services,” Ms. Schwartz said. “We share an interest in ensuring prior authorization works as smoothly and effectively as possible for beneficiaries while protecting its essential function of facilitating safe, evidenced-based care.”

The Better Medicare Alliance said its funders include UnitedHealth, Humana, and CVS Health/Aetna, which run Advantage plans. The group also lists as its partners many medical organizations.
 

“Rationing care by hassling”

Like Rep. Bucshon, Dr. Bailey sees a different motivation in insurers’ persistence in keeping the prior authorization process cumbersome.

Phone calls and faxes remain the key methods for handling prior authorization for medical services, according to the results of a survey done by the AMA in December. Phone calls were always or often required for prior authorization for medical services (59%), with faxes the second-most common approach (46%), followed by health plans’ online portals (39%), electronic health records and practice management systems (29%), and email or U.S. mail (26%), according to the AMA’s report on the survey.

“It seems like every step in the process is designed to make the patient less likely to get the therapy that the doctor thinks that the patient needs,” Dr. Bailey said. “It’s almost like rationing care by hassling the patient and the physician.”

The findings of an investigation by HHS’ internal watchdog unit appear to support Dr. Bailey’s view, showing that insurer-run Medicare plans had a pattern of often walking back their initial rejections.

In 2018, the Office of the Inspector General for HHS reported that Medicare Advantage organizations (MAOs) overturned 75% of their own denials during 2014-16. In addition, independent reviewers within the appeals process overturned additional denials in favor of patients and clinicians, OIG said.

“The high number of overturned denials raises concerns that some Medicare Advantage beneficiaries and providers were initially denied services and payments that should have been provided,” the OIG said in the report. “This is especially concerning because beneficiaries and providers rarely used the appeals process, which is designed to ensure access to care and payment.”

During 2014-2016, patients and clinicians appealed only 1% of denials to the first level of appeal, OIG said. In the report, the watchdog group noted that CMS audits had highlighted “widespread and persistent MAO performance problems related to denials of care and payment.” In 2015, for example, CMS cited 56% of audited contracts for making inappropriate denials.

Dr. Bailey also said in an interview that she routinely encounters problems with prior authorization in her own practice as an allergist and immunologist in Fort Worth, Tex.

In late May, for example, a Medicare Advantage plan made a patient whose chronic asthma had been stable for years change to a new inhaler that resulted in him developing a yeast infection in his mouth, Dr. Bailey said.

“We treated the yeast infection, made some changes in the way he uses his inhaler, so hopefully he would tolerate it better,” Dr. Bailey said. “He had a reaction to the medication to treat the yeast infection and ended up in the hospital. How is that helping anyone? It certainly hasn’t helped my patient.”

Dr. Bailey said insurers have also asked to seek prior authorization to prescribe medications that have been generic for years and have used the process to challenge her on cases of what seem to be common sense in medical practice. This included a bid to have Dr. Bailey prescribe a medication in pill form for a 6-month-old baby who had no teeth.

“Every doctor has got absurd stories like that, but unfortunately, every doctor is going to have tragic stories where prior authorization has resulted in death and harm to the patients,” Dr. Bailey said.

Some physicians leave it to the patient to try to overcome insurers’ decisions on prior authorization, seeing this task as falling outside of their duties, Dr. Bailey said.

“I don’t do that. I fight. I spend a lot of time fighting. I don’t like to lose. I don’t like my patients to lose, so I will go to the mat for them,” Dr. Bailey said. “But I’m blessed to be in a specialty where I’ve got loads more control over my schedule than many other specialties do.”

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

A group of bipartisan lawmakers intends to compel insurers to streamline prior authorization processes for Medicare Advantage plans, including a bid to end the use of faxes and develop systems that can allow for real-time decisions.

Rep. Suzan DelBene (D-Wash.); Rep. Mike Kelly (R-Pa.); Rep. Ami Bera, MD (D-Calif.); and Rep. Larry Bucshon, MD, (R-Ind.) on May 13 introduced a bill that would task federal officials with refining standards regarding prior authorization for Medicare Advantage. Titled the Improving Seniors’ Timely Access to Care Act of 2021, the bill would direct the Department of Health & Human Services to create rules intended to make prior authorization more transparent and speedy for the insurer-run Medicare plans. Known as Medicare Advantage, these plans cover about 24.1 million people of the 62 million enrolled in the giant federal health program, according to the nonprofit Kaiser Family Foundation.

These revamped prior authorization systems could not rely on faxes nor could they employ proprietary payer portals that did not meet HHS’ standards, says the text of the bill released by Rep. DelBene. Insurers would also have to report to the Centers for Medicare & Medicaid Services about the extent of their use of prior authorization and the rate of approvals or denials. The bill seeks to encourage plans to adopt prior authorization programs that adhere to evidence-based medical guidelines in consultation with physicians.

There were several reasons for focusing on Medicare Advantage plans, although prior authorization concerns extend more broadly in the U.S. health care system, said Susan Bailey, MD, president of the American Medical Association.

There’s an ample body of research about issues seen in the Medicare Advantage plans. Dr. Bailey also said that, in her experience, Medicare Advantage plans have had some of the most restrictive policies. And, by starting with Medicare Advantage, there’s a potential for a ripple effect in the industry, easing this issue when physicians work with other insurers as well.

“When Medicare adopts a policy whether it be a payment policy or a coverage policy, private insurers typically follow along,” she said.
 

Strong support among health care groups

There’s strong support for streamlining prior authorization both in the medical community and in Congress.

The bill has the support of about 70 health care organizations, including the AMA and the American Academy of Family Physicians, according to its sponsors. As of May 17, the bill had attracted the backing of 97 members of the House of Representatives, roughly evenly split among Democrats and Republicans.

Rep. DelBene’s previous version of this bill, the Improving Seniors’ Timely Access to Care Act of 2019, attracted 143 Democratic cosponsors and 137 Republican ones, or more than half of the members of the House. This bill was not completed during the previous session of Congress (January 2019–January 2021) because of the more urgent needs of pandemic response, said Rep. Bucshon, who practiced cardiothoracic surgery before joining Congress.

“It wasn’t quite on the radar as much as it might have been if we didn’t have COVID,” Rep. Bucshon said.

Rep. Bucshon added that he expects strong Senate support for a companion measure of the House bill, which could make the difference for efforts to pass it this year.

Insurers have become more aggressive over time in denying payments through prior authorization systems for services that physicians say their patients need, according to Rep. Bucshon. There may be some “bad actors” in medicine who would order unnecessary procedures, Rep. Bucshon allowed, but in most cases, the cumbersome prior authorization processes only put a hurdle for patients seeking needed treatments, he said.

“The premise is that it controls health care costs but actually what it does is it helps insurance company’s bottom line,” Rep. Bucshon said.

In a prepared statement, former Pennsylvania representative Allyson Y. Schwartz, now CEO of the Better Medicare Alliance, said her group had spoken with sponsors of this legislation and appreciates “their receptiveness to feedback in this process.”

“Prior authorization ensures beneficiaries receive clinically appropriate care and reduces exposures to duplicative and unnecessary services,” Ms. Schwartz said. “We share an interest in ensuring prior authorization works as smoothly and effectively as possible for beneficiaries while protecting its essential function of facilitating safe, evidenced-based care.”

The Better Medicare Alliance said its funders include UnitedHealth, Humana, and CVS Health/Aetna, which run Advantage plans. The group also lists as its partners many medical organizations.
 

“Rationing care by hassling”

Like Rep. Bucshon, Dr. Bailey sees a different motivation in insurers’ persistence in keeping the prior authorization process cumbersome.

Phone calls and faxes remain the key methods for handling prior authorization for medical services, according to the results of a survey done by the AMA in December. Phone calls were always or often required for prior authorization for medical services (59%), with faxes the second-most common approach (46%), followed by health plans’ online portals (39%), electronic health records and practice management systems (29%), and email or U.S. mail (26%), according to the AMA’s report on the survey.

“It seems like every step in the process is designed to make the patient less likely to get the therapy that the doctor thinks that the patient needs,” Dr. Bailey said. “It’s almost like rationing care by hassling the patient and the physician.”

The findings of an investigation by HHS’ internal watchdog unit appear to support Dr. Bailey’s view, showing that insurer-run Medicare plans had a pattern of often walking back their initial rejections.

In 2018, the Office of the Inspector General for HHS reported that Medicare Advantage organizations (MAOs) overturned 75% of their own denials during 2014-16. In addition, independent reviewers within the appeals process overturned additional denials in favor of patients and clinicians, OIG said.

“The high number of overturned denials raises concerns that some Medicare Advantage beneficiaries and providers were initially denied services and payments that should have been provided,” the OIG said in the report. “This is especially concerning because beneficiaries and providers rarely used the appeals process, which is designed to ensure access to care and payment.”

During 2014-2016, patients and clinicians appealed only 1% of denials to the first level of appeal, OIG said. In the report, the watchdog group noted that CMS audits had highlighted “widespread and persistent MAO performance problems related to denials of care and payment.” In 2015, for example, CMS cited 56% of audited contracts for making inappropriate denials.

Dr. Bailey also said in an interview that she routinely encounters problems with prior authorization in her own practice as an allergist and immunologist in Fort Worth, Tex.

In late May, for example, a Medicare Advantage plan made a patient whose chronic asthma had been stable for years change to a new inhaler that resulted in him developing a yeast infection in his mouth, Dr. Bailey said.

“We treated the yeast infection, made some changes in the way he uses his inhaler, so hopefully he would tolerate it better,” Dr. Bailey said. “He had a reaction to the medication to treat the yeast infection and ended up in the hospital. How is that helping anyone? It certainly hasn’t helped my patient.”

Dr. Bailey said insurers have also asked to seek prior authorization to prescribe medications that have been generic for years and have used the process to challenge her on cases of what seem to be common sense in medical practice. This included a bid to have Dr. Bailey prescribe a medication in pill form for a 6-month-old baby who had no teeth.

“Every doctor has got absurd stories like that, but unfortunately, every doctor is going to have tragic stories where prior authorization has resulted in death and harm to the patients,” Dr. Bailey said.

Some physicians leave it to the patient to try to overcome insurers’ decisions on prior authorization, seeing this task as falling outside of their duties, Dr. Bailey said.

“I don’t do that. I fight. I spend a lot of time fighting. I don’t like to lose. I don’t like my patients to lose, so I will go to the mat for them,” Dr. Bailey said. “But I’m blessed to be in a specialty where I’ve got loads more control over my schedule than many other specialties do.”

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

A group of bipartisan lawmakers intends to compel insurers to streamline prior authorization processes for Medicare Advantage plans, including a bid to end the use of faxes and develop systems that can allow for real-time decisions.

Rep. Suzan DelBene (D-Wash.); Rep. Mike Kelly (R-Pa.); Rep. Ami Bera, MD (D-Calif.); and Rep. Larry Bucshon, MD, (R-Ind.) on May 13 introduced a bill that would task federal officials with refining standards regarding prior authorization for Medicare Advantage. Titled the Improving Seniors’ Timely Access to Care Act of 2021, the bill would direct the Department of Health & Human Services to create rules intended to make prior authorization more transparent and speedy for the insurer-run Medicare plans. Known as Medicare Advantage, these plans cover about 24.1 million people of the 62 million enrolled in the giant federal health program, according to the nonprofit Kaiser Family Foundation.

These revamped prior authorization systems could not rely on faxes nor could they employ proprietary payer portals that did not meet HHS’ standards, says the text of the bill released by Rep. DelBene. Insurers would also have to report to the Centers for Medicare & Medicaid Services about the extent of their use of prior authorization and the rate of approvals or denials. The bill seeks to encourage plans to adopt prior authorization programs that adhere to evidence-based medical guidelines in consultation with physicians.

There were several reasons for focusing on Medicare Advantage plans, although prior authorization concerns extend more broadly in the U.S. health care system, said Susan Bailey, MD, president of the American Medical Association.

There’s an ample body of research about issues seen in the Medicare Advantage plans. Dr. Bailey also said that, in her experience, Medicare Advantage plans have had some of the most restrictive policies. And, by starting with Medicare Advantage, there’s a potential for a ripple effect in the industry, easing this issue when physicians work with other insurers as well.

“When Medicare adopts a policy whether it be a payment policy or a coverage policy, private insurers typically follow along,” she said.
 

Strong support among health care groups

There’s strong support for streamlining prior authorization both in the medical community and in Congress.

The bill has the support of about 70 health care organizations, including the AMA and the American Academy of Family Physicians, according to its sponsors. As of May 17, the bill had attracted the backing of 97 members of the House of Representatives, roughly evenly split among Democrats and Republicans.

Rep. DelBene’s previous version of this bill, the Improving Seniors’ Timely Access to Care Act of 2019, attracted 143 Democratic cosponsors and 137 Republican ones, or more than half of the members of the House. This bill was not completed during the previous session of Congress (January 2019–January 2021) because of the more urgent needs of pandemic response, said Rep. Bucshon, who practiced cardiothoracic surgery before joining Congress.

“It wasn’t quite on the radar as much as it might have been if we didn’t have COVID,” Rep. Bucshon said.

Rep. Bucshon added that he expects strong Senate support for a companion measure of the House bill, which could make the difference for efforts to pass it this year.

Insurers have become more aggressive over time in denying payments through prior authorization systems for services that physicians say their patients need, according to Rep. Bucshon. There may be some “bad actors” in medicine who would order unnecessary procedures, Rep. Bucshon allowed, but in most cases, the cumbersome prior authorization processes only put a hurdle for patients seeking needed treatments, he said.

“The premise is that it controls health care costs but actually what it does is it helps insurance company’s bottom line,” Rep. Bucshon said.

In a prepared statement, former Pennsylvania representative Allyson Y. Schwartz, now CEO of the Better Medicare Alliance, said her group had spoken with sponsors of this legislation and appreciates “their receptiveness to feedback in this process.”

“Prior authorization ensures beneficiaries receive clinically appropriate care and reduces exposures to duplicative and unnecessary services,” Ms. Schwartz said. “We share an interest in ensuring prior authorization works as smoothly and effectively as possible for beneficiaries while protecting its essential function of facilitating safe, evidenced-based care.”

The Better Medicare Alliance said its funders include UnitedHealth, Humana, and CVS Health/Aetna, which run Advantage plans. The group also lists as its partners many medical organizations.
 

“Rationing care by hassling”

Like Rep. Bucshon, Dr. Bailey sees a different motivation in insurers’ persistence in keeping the prior authorization process cumbersome.

Phone calls and faxes remain the key methods for handling prior authorization for medical services, according to the results of a survey done by the AMA in December. Phone calls were always or often required for prior authorization for medical services (59%), with faxes the second-most common approach (46%), followed by health plans’ online portals (39%), electronic health records and practice management systems (29%), and email or U.S. mail (26%), according to the AMA’s report on the survey.

“It seems like every step in the process is designed to make the patient less likely to get the therapy that the doctor thinks that the patient needs,” Dr. Bailey said. “It’s almost like rationing care by hassling the patient and the physician.”

The findings of an investigation by HHS’ internal watchdog unit appear to support Dr. Bailey’s view, showing that insurer-run Medicare plans had a pattern of often walking back their initial rejections.

In 2018, the Office of the Inspector General for HHS reported that Medicare Advantage organizations (MAOs) overturned 75% of their own denials during 2014-16. In addition, independent reviewers within the appeals process overturned additional denials in favor of patients and clinicians, OIG said.

“The high number of overturned denials raises concerns that some Medicare Advantage beneficiaries and providers were initially denied services and payments that should have been provided,” the OIG said in the report. “This is especially concerning because beneficiaries and providers rarely used the appeals process, which is designed to ensure access to care and payment.”

During 2014-2016, patients and clinicians appealed only 1% of denials to the first level of appeal, OIG said. In the report, the watchdog group noted that CMS audits had highlighted “widespread and persistent MAO performance problems related to denials of care and payment.” In 2015, for example, CMS cited 56% of audited contracts for making inappropriate denials.

Dr. Bailey also said in an interview that she routinely encounters problems with prior authorization in her own practice as an allergist and immunologist in Fort Worth, Tex.

In late May, for example, a Medicare Advantage plan made a patient whose chronic asthma had been stable for years change to a new inhaler that resulted in him developing a yeast infection in his mouth, Dr. Bailey said.

“We treated the yeast infection, made some changes in the way he uses his inhaler, so hopefully he would tolerate it better,” Dr. Bailey said. “He had a reaction to the medication to treat the yeast infection and ended up in the hospital. How is that helping anyone? It certainly hasn’t helped my patient.”

Dr. Bailey said insurers have also asked to seek prior authorization to prescribe medications that have been generic for years and have used the process to challenge her on cases of what seem to be common sense in medical practice. This included a bid to have Dr. Bailey prescribe a medication in pill form for a 6-month-old baby who had no teeth.

“Every doctor has got absurd stories like that, but unfortunately, every doctor is going to have tragic stories where prior authorization has resulted in death and harm to the patients,” Dr. Bailey said.

Some physicians leave it to the patient to try to overcome insurers’ decisions on prior authorization, seeing this task as falling outside of their duties, Dr. Bailey said.

“I don’t do that. I fight. I spend a lot of time fighting. I don’t like to lose. I don’t like my patients to lose, so I will go to the mat for them,” Dr. Bailey said. “But I’m blessed to be in a specialty where I’ve got loads more control over my schedule than many other specialties do.”

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

Feminizing gender affirmation surgery is a complex genital surgery that most commonly involves removal of natal male genitalia (testes, penile urethra, a majority of the glans penis, penile shaft) and construction of the vulva and/or neovagina utilizing scrotal and penile shaft tissue. Other surgical procedures can also involve using a peritoneal flap or a portion of the small bowel or sigmoid colon to create the neovaginal canal. As with any major surgical procedure, complications do occur, and these can range from minor to major; intraoperative to postoperative. For the purposes of this article, the focus shall be on postoperative complications. Most postoperative complications occur within the first 4 months of the surgery and include vaginal stenosis, genitourinary fistula formation, urinary stream abnormalities, and sexual dysfunction.¹ Minor complications that can be managed in the office include granulation tissue treatment, vaginitis, and hair growth in the neovagina. It is important to note that, if any complication occurs, it is essential to refer to the patient’s original surgeon or to a surgeon with expertise in vaginoplasty techniques and postoperative management.²

For patients who undergo vaginoplasty, or a creation of a neovaginal canal, postoperative dilation is necessary to maintain patency. The frequency and duration of dilation are often determined by each individual surgeon or surgical practice as there is no universal, evidence-based standard to guide recommendations on dilation. Failure to maintain a dilation schedule can result in neovaginal stenosis and inability to engage in penetrative vaginal intercourse (if patients desire). Dilation can be difficult.

Challenges with dilation can occur for a variety of reasons: pain, history of trauma, pelvic floor dysfunction, lack of privacy or a supportive environment, or change in personal goals.³ If the underlying cause is related to pelvic floor dysfunction, postoperative pelvic floor therapy has demonstrated improvement in dilation.⁴ Additionally, routine douching is required for vaginal hygiene. Unlike natal vaginas, neovaginas do not usually contain mucosa, with the exception of a colonic interposition vaginoplasty, and routine douching with soapy water can help prevent a buildup of lubricant and debris.

If a patient reports abnormal discharge, an exam of the vulva and neovagina is warranted. Many patients are able to tolerate a speculum examination. If a patient has undergone a penile inversion vaginoplasty, the microbiome of the neovagina is quite different than that of a natal vagina and most common causes of abnormal discharge often include retained lubricant, keratin debris, sebum, or semen.⁵ During a speculum exam, the provider may notice granulation tissue, which is often another cause of persistent vaginal discharge, vaginal bleeding, or pain during dilation. Depending on the patient’s symptoms and quantity of granulation tissue present, it can often resolve spontaneously. Persistent granulation tissue can be treated with silver nitrate. An alternative to silver nitrate is using medical grade honey or a course of a mild-strength topical steroid cream or ointment.⁵ In some cases, abnormal discharge may be the result of a fistula. If a fistula is noted the patient should be immediately referred back to the original surgeon or to a urogynecologist and/or colorectal surgeon for evaluation and management.

While this surgery often falls outside of the scope of practice of the general obstetrician-gynecologist, most patients will seek the care of a general obstetrician-gynecologist in the postoperative period. It is therefore imperative that obstetrician-gynecologists have a basic understanding of the surgical procedure and the aftercare involved.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. Email her at [email protected].

References

1. Gaither TW et al. J Urol. 2018;199(3):760-5.

2. Ferrando CA and Bowers ML. In: Ferrando CA, ed. “Comprehensive care of the transgender patient” Philadelphia: Elsevier, 2020, p. 82-92.

3. Chi AC et al. Complications of vaginoplasty. In: Niklavsky D and Blakely SA, eds. “Urological care for the transgender patient: A comprehensive guide” Switzerland: Springer Nature, 2021 p. 83-97.

4. Jiang D et al. Obstet Gynecol. 2019;133(5):1003-11.

5. Obedin-Maliver J and Haan GD. Gynecologic care for transgender patients. In: Ferrando CA, ed. “Comprehensive care of the transgender patient” Philadelphia: Elsevier, 2020, p. 131-51.

Feminizing gender affirmation surgery is a complex genital surgery that most commonly involves removal of natal male genitalia (testes, penile urethra, a majority of the glans penis, penile shaft) and construction of the vulva and/or neovagina utilizing scrotal and penile shaft tissue. Other surgical procedures can also involve using a peritoneal flap or a portion of the small bowel or sigmoid colon to create the neovaginal canal. As with any major surgical procedure, complications do occur, and these can range from minor to major; intraoperative to postoperative. For the purposes of this article, the focus shall be on postoperative complications. Most postoperative complications occur within the first 4 months of the surgery and include vaginal stenosis, genitourinary fistula formation, urinary stream abnormalities, and sexual dysfunction.¹ Minor complications that can be managed in the office include granulation tissue treatment, vaginitis, and hair growth in the neovagina. It is important to note that, if any complication occurs, it is essential to refer to the patient’s original surgeon or to a surgeon with expertise in vaginoplasty techniques and postoperative management.²

For patients who undergo vaginoplasty, or a creation of a neovaginal canal, postoperative dilation is necessary to maintain patency. The frequency and duration of dilation are often determined by each individual surgeon or surgical practice as there is no universal, evidence-based standard to guide recommendations on dilation. Failure to maintain a dilation schedule can result in neovaginal stenosis and inability to engage in penetrative vaginal intercourse (if patients desire). Dilation can be difficult.

Challenges with dilation can occur for a variety of reasons: pain, history of trauma, pelvic floor dysfunction, lack of privacy or a supportive environment, or change in personal goals.³ If the underlying cause is related to pelvic floor dysfunction, postoperative pelvic floor therapy has demonstrated improvement in dilation.⁴ Additionally, routine douching is required for vaginal hygiene. Unlike natal vaginas, neovaginas do not usually contain mucosa, with the exception of a colonic interposition vaginoplasty, and routine douching with soapy water can help prevent a buildup of lubricant and debris.

If a patient reports abnormal discharge, an exam of the vulva and neovagina is warranted. Many patients are able to tolerate a speculum examination. If a patient has undergone a penile inversion vaginoplasty, the microbiome of the neovagina is quite different than that of a natal vagina and most common causes of abnormal discharge often include retained lubricant, keratin debris, sebum, or semen.⁵ During a speculum exam, the provider may notice granulation tissue, which is often another cause of persistent vaginal discharge, vaginal bleeding, or pain during dilation. Depending on the patient’s symptoms and quantity of granulation tissue present, it can often resolve spontaneously. Persistent granulation tissue can be treated with silver nitrate. An alternative to silver nitrate is using medical grade honey or a course of a mild-strength topical steroid cream or ointment.⁵ In some cases, abnormal discharge may be the result of a fistula. If a fistula is noted the patient should be immediately referred back to the original surgeon or to a urogynecologist and/or colorectal surgeon for evaluation and management.

While this surgery often falls outside of the scope of practice of the general obstetrician-gynecologist, most patients will seek the care of a general obstetrician-gynecologist in the postoperative period. It is therefore imperative that obstetrician-gynecologists have a basic understanding of the surgical procedure and the aftercare involved.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. Email her at [email protected].

References

1. Gaither TW et al. J Urol. 2018;199(3):760-5.

2. Ferrando CA and Bowers ML. In: Ferrando CA, ed. “Comprehensive care of the transgender patient” Philadelphia: Elsevier, 2020, p. 82-92.

3. Chi AC et al. Complications of vaginoplasty. In: Niklavsky D and Blakely SA, eds. “Urological care for the transgender patient: A comprehensive guide” Switzerland: Springer Nature, 2021 p. 83-97.

4. Jiang D et al. Obstet Gynecol. 2019;133(5):1003-11.

5. Obedin-Maliver J and Haan GD. Gynecologic care for transgender patients. In: Ferrando CA, ed. “Comprehensive care of the transgender patient” Philadelphia: Elsevier, 2020, p. 131-51.

Feminizing gender affirmation surgery is a complex genital surgery that most commonly involves removal of natal male genitalia (testes, penile urethra, a majority of the glans penis, penile shaft) and construction of the vulva and/or neovagina utilizing scrotal and penile shaft tissue. Other surgical procedures can also involve using a peritoneal flap or a portion of the small bowel or sigmoid colon to create the neovaginal canal. As with any major surgical procedure, complications do occur, and these can range from minor to major; intraoperative to postoperative. For the purposes of this article, the focus shall be on postoperative complications. Most postoperative complications occur within the first 4 months of the surgery and include vaginal stenosis, genitourinary fistula formation, urinary stream abnormalities, and sexual dysfunction.¹ Minor complications that can be managed in the office include granulation tissue treatment, vaginitis, and hair growth in the neovagina. It is important to note that, if any complication occurs, it is essential to refer to the patient’s original surgeon or to a surgeon with expertise in vaginoplasty techniques and postoperative management.²

For patients who undergo vaginoplasty, or a creation of a neovaginal canal, postoperative dilation is necessary to maintain patency. The frequency and duration of dilation are often determined by each individual surgeon or surgical practice as there is no universal, evidence-based standard to guide recommendations on dilation. Failure to maintain a dilation schedule can result in neovaginal stenosis and inability to engage in penetrative vaginal intercourse (if patients desire). Dilation can be difficult.

Challenges with dilation can occur for a variety of reasons: pain, history of trauma, pelvic floor dysfunction, lack of privacy or a supportive environment, or change in personal goals.³ If the underlying cause is related to pelvic floor dysfunction, postoperative pelvic floor therapy has demonstrated improvement in dilation.⁴ Additionally, routine douching is required for vaginal hygiene. Unlike natal vaginas, neovaginas do not usually contain mucosa, with the exception of a colonic interposition vaginoplasty, and routine douching with soapy water can help prevent a buildup of lubricant and debris.

If a patient reports abnormal discharge, an exam of the vulva and neovagina is warranted. Many patients are able to tolerate a speculum examination. If a patient has undergone a penile inversion vaginoplasty, the microbiome of the neovagina is quite different than that of a natal vagina and most common causes of abnormal discharge often include retained lubricant, keratin debris, sebum, or semen.⁵ During a speculum exam, the provider may notice granulation tissue, which is often another cause of persistent vaginal discharge, vaginal bleeding, or pain during dilation. Depending on the patient’s symptoms and quantity of granulation tissue present, it can often resolve spontaneously. Persistent granulation tissue can be treated with silver nitrate. An alternative to silver nitrate is using medical grade honey or a course of a mild-strength topical steroid cream or ointment.⁵ In some cases, abnormal discharge may be the result of a fistula. If a fistula is noted the patient should be immediately referred back to the original surgeon or to a urogynecologist and/or colorectal surgeon for evaluation and management.

While this surgery often falls outside of the scope of practice of the general obstetrician-gynecologist, most patients will seek the care of a general obstetrician-gynecologist in the postoperative period. It is therefore imperative that obstetrician-gynecologists have a basic understanding of the surgical procedure and the aftercare involved.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. Email her at [email protected].

References

1. Gaither TW et al. J Urol. 2018;199(3):760-5.

2. Ferrando CA and Bowers ML. In: Ferrando CA, ed. “Comprehensive care of the transgender patient” Philadelphia: Elsevier, 2020, p. 82-92.

3. Chi AC et al. Complications of vaginoplasty. In: Niklavsky D and Blakely SA, eds. “Urological care for the transgender patient: A comprehensive guide” Switzerland: Springer Nature, 2021 p. 83-97.

4. Jiang D et al. Obstet Gynecol. 2019;133(5):1003-11.

5. Obedin-Maliver J and Haan GD. Gynecologic care for transgender patients. In: Ferrando CA, ed. “Comprehensive care of the transgender patient” Philadelphia: Elsevier, 2020, p. 131-51.

The long-term benefits of endocrine therapy in premenopausal breast cancer appear to differ according to whether patients are categorized as high or low molecular risk using the 70-gene signature (MammaPrint).

Based upon data from patients who had participated in the Stockholm tamoxifen (STO-5) trial, high-risk patients significantly benefited from goserelin treatment, whereas low-risk patients benefited more from tamoxifen treatment when compared with no endocrine therapy.

“Goserelin, tamoxifen, and the combination of the two, reduced the 20-year risk of distant occurrences and fatal breast cancer, compared to no endocrine therapy,” Annelie Johansson, MSc, said at the European Society for Medical Oncology: Breast Cancer virtual meeting.

“Our findings indicate that the long-term endocrine therapy benefit in premenopausal patients is influenced by molecular risk classification and thus tumor characteristics,” she added.

Ms. Johansson, a postdoctoral researcher in genomic breast cancer at the Karolinska Institutet in Stockholm, reported the results of the analysis as a late-breaking abstract at the meeting.

“I think this is an innovative translational study trying to use the multigene assay results to look at differential endocrine therapy effects,” said Prudence Francis, MD, the invited discussant for study.

However, there are relatively few patients in the various subgroups being tested, she added. “We’ve also got short duration of tamoxifen, only 2 years, we’ve got prior chemotherapy in some patients and absence of HER2 therapy, all of which might influence outcomes.”

As a result, Dr. Francis, who is head of medical oncology at the Peter MacCallum Cancer Centre and a consultant Medical Oncologist at St. Vincent’s Hospital Melbourne, called the findings purely “hypothesis generating.”
 

Study details and results

The analysis was based on data from the STO-5 trial, which had recruited just over 900 patients between 1990 and 1997. Patients were stratified according to their lymph node status and some received chemotherapy with or without locoregional radiotherapy before being randomized to one of four study arms: goserelin alone, tamoxifen alone, the combination of the two, or no endocrine therapy.

Ms. Johansson noted that they were able to obtain the primary tumor blocks from 729 patients in the past year, of whom 610 were estrogen receptor positive. The analysis according to the 70-gene signature was then based on data from 465 patients: 131 had been treated with goserelin, 105 with tamoxifen, 120 with both, and 109 had received no endocrine treatment.

We have complete 20-year follow-up from high-quality Swedish National registries,” Ms. Johansson said, observing that the median age in the trial was 46 years.

Before stratifying patients into high and low risk using the 70-gene signature, the risk for having a distant recurrence, compared with no endocrine therapy was reduced by 52% with goserelin (hazard ratio, .48), 41% with tamoxifen (HR, 0.59), and 33% with both in combination (HR, 0.67).

After stratification, however, goserelin was associated with a 78% reduction of distant recurrence versus no endocrine treatment in high-risk patients (HR, 0.22) and a 20% reduction in low-risk patients (HR, 0.80).

Results in high- and low-risk patients with tamoxifen versus no endocrine treatment were a respective 31% reduction (HR, 0.69) and 62% reduction (HR, 0.38), and a respective 36% (HR, 0.64) and 28% (HR, 0.72) for the combination.

A further analysis was performed to compare between the active treatment arms, and this suggested a greater benefit of goserelin in patients at high risk when compared with both tamoxifen (HR, 0.30) and the combination (HR, 0.33).

Dr. Francis commented: “it is a bit surprising to find that goserelin appeared to be also better than the combination,” and it is something that the research team is looking into.

“One hypothesis might be if you look how the different treatments are working,” Ms. Johansson said. “Goserelin is very efficient in lowering the estrogen levels in premenopausal patients, suppressing the ovarian production of estrogen whereas tamoxifen can act both as an antagonist and agonist.

“So, we are thinking that maybe the addition of tamoxifen, with the agonistic properties of tamoxifen, might then make the goserelin not as efficient. But that’s of course, just a hypothesis right now and we need to look into this further,” she said.

The work was funded by The Swedish Research Council (Vetenskapsrådet), The Swedish Research Council for Health, Working life and Welfare, and the Swedish Cancer Society (Cancerfonden). Ms. Johansson had no personal disclosures; one of the coauthors was a coinventor of MammaPrint. Dr. Francis disclosed receiving travel support for overseas lectures from Ipsen and Novartis and acting as a medical oncology editor for Elsevier.

The long-term benefits of endocrine therapy in premenopausal breast cancer appear to differ according to whether patients are categorized as high or low molecular risk using the 70-gene signature (MammaPrint).

Based upon data from patients who had participated in the Stockholm tamoxifen (STO-5) trial, high-risk patients significantly benefited from goserelin treatment, whereas low-risk patients benefited more from tamoxifen treatment when compared with no endocrine therapy.

“Goserelin, tamoxifen, and the combination of the two, reduced the 20-year risk of distant occurrences and fatal breast cancer, compared to no endocrine therapy,” Annelie Johansson, MSc, said at the European Society for Medical Oncology: Breast Cancer virtual meeting.

“Our findings indicate that the long-term endocrine therapy benefit in premenopausal patients is influenced by molecular risk classification and thus tumor characteristics,” she added.

Ms. Johansson, a postdoctoral researcher in genomic breast cancer at the Karolinska Institutet in Stockholm, reported the results of the analysis as a late-breaking abstract at the meeting.

“I think this is an innovative translational study trying to use the multigene assay results to look at differential endocrine therapy effects,” said Prudence Francis, MD, the invited discussant for study.

However, there are relatively few patients in the various subgroups being tested, she added. “We’ve also got short duration of tamoxifen, only 2 years, we’ve got prior chemotherapy in some patients and absence of HER2 therapy, all of which might influence outcomes.”

As a result, Dr. Francis, who is head of medical oncology at the Peter MacCallum Cancer Centre and a consultant Medical Oncologist at St. Vincent’s Hospital Melbourne, called the findings purely “hypothesis generating.”
 

Study details and results

The analysis was based on data from the STO-5 trial, which had recruited just over 900 patients between 1990 and 1997. Patients were stratified according to their lymph node status and some received chemotherapy with or without locoregional radiotherapy before being randomized to one of four study arms: goserelin alone, tamoxifen alone, the combination of the two, or no endocrine therapy.

Ms. Johansson noted that they were able to obtain the primary tumor blocks from 729 patients in the past year, of whom 610 were estrogen receptor positive. The analysis according to the 70-gene signature was then based on data from 465 patients: 131 had been treated with goserelin, 105 with tamoxifen, 120 with both, and 109 had received no endocrine treatment.

We have complete 20-year follow-up from high-quality Swedish National registries,” Ms. Johansson said, observing that the median age in the trial was 46 years.

Before stratifying patients into high and low risk using the 70-gene signature, the risk for having a distant recurrence, compared with no endocrine therapy was reduced by 52% with goserelin (hazard ratio, .48), 41% with tamoxifen (HR, 0.59), and 33% with both in combination (HR, 0.67).

After stratification, however, goserelin was associated with a 78% reduction of distant recurrence versus no endocrine treatment in high-risk patients (HR, 0.22) and a 20% reduction in low-risk patients (HR, 0.80).

Results in high- and low-risk patients with tamoxifen versus no endocrine treatment were a respective 31% reduction (HR, 0.69) and 62% reduction (HR, 0.38), and a respective 36% (HR, 0.64) and 28% (HR, 0.72) for the combination.

A further analysis was performed to compare between the active treatment arms, and this suggested a greater benefit of goserelin in patients at high risk when compared with both tamoxifen (HR, 0.30) and the combination (HR, 0.33).

Dr. Francis commented: “it is a bit surprising to find that goserelin appeared to be also better than the combination,” and it is something that the research team is looking into.

“One hypothesis might be if you look how the different treatments are working,” Ms. Johansson said. “Goserelin is very efficient in lowering the estrogen levels in premenopausal patients, suppressing the ovarian production of estrogen whereas tamoxifen can act both as an antagonist and agonist.

“So, we are thinking that maybe the addition of tamoxifen, with the agonistic properties of tamoxifen, might then make the goserelin not as efficient. But that’s of course, just a hypothesis right now and we need to look into this further,” she said.

The work was funded by The Swedish Research Council (Vetenskapsrådet), The Swedish Research Council for Health, Working life and Welfare, and the Swedish Cancer Society (Cancerfonden). Ms. Johansson had no personal disclosures; one of the coauthors was a coinventor of MammaPrint. Dr. Francis disclosed receiving travel support for overseas lectures from Ipsen and Novartis and acting as a medical oncology editor for Elsevier.

The long-term benefits of endocrine therapy in premenopausal breast cancer appear to differ according to whether patients are categorized as high or low molecular risk using the 70-gene signature (MammaPrint).

Based upon data from patients who had participated in the Stockholm tamoxifen (STO-5) trial, high-risk patients significantly benefited from goserelin treatment, whereas low-risk patients benefited more from tamoxifen treatment when compared with no endocrine therapy.

“Goserelin, tamoxifen, and the combination of the two, reduced the 20-year risk of distant occurrences and fatal breast cancer, compared to no endocrine therapy,” Annelie Johansson, MSc, said at the European Society for Medical Oncology: Breast Cancer virtual meeting.

“Our findings indicate that the long-term endocrine therapy benefit in premenopausal patients is influenced by molecular risk classification and thus tumor characteristics,” she added.

Ms. Johansson, a postdoctoral researcher in genomic breast cancer at the Karolinska Institutet in Stockholm, reported the results of the analysis as a late-breaking abstract at the meeting.

“I think this is an innovative translational study trying to use the multigene assay results to look at differential endocrine therapy effects,” said Prudence Francis, MD, the invited discussant for study.

However, there are relatively few patients in the various subgroups being tested, she added. “We’ve also got short duration of tamoxifen, only 2 years, we’ve got prior chemotherapy in some patients and absence of HER2 therapy, all of which might influence outcomes.”

As a result, Dr. Francis, who is head of medical oncology at the Peter MacCallum Cancer Centre and a consultant Medical Oncologist at St. Vincent’s Hospital Melbourne, called the findings purely “hypothesis generating.”
 

Study details and results

The analysis was based on data from the STO-5 trial, which had recruited just over 900 patients between 1990 and 1997. Patients were stratified according to their lymph node status and some received chemotherapy with or without locoregional radiotherapy before being randomized to one of four study arms: goserelin alone, tamoxifen alone, the combination of the two, or no endocrine therapy.

Ms. Johansson noted that they were able to obtain the primary tumor blocks from 729 patients in the past year, of whom 610 were estrogen receptor positive. The analysis according to the 70-gene signature was then based on data from 465 patients: 131 had been treated with goserelin, 105 with tamoxifen, 120 with both, and 109 had received no endocrine treatment.

We have complete 20-year follow-up from high-quality Swedish National registries,” Ms. Johansson said, observing that the median age in the trial was 46 years.

Before stratifying patients into high and low risk using the 70-gene signature, the risk for having a distant recurrence, compared with no endocrine therapy was reduced by 52% with goserelin (hazard ratio, .48), 41% with tamoxifen (HR, 0.59), and 33% with both in combination (HR, 0.67).

After stratification, however, goserelin was associated with a 78% reduction of distant recurrence versus no endocrine treatment in high-risk patients (HR, 0.22) and a 20% reduction in low-risk patients (HR, 0.80).

Results in high- and low-risk patients with tamoxifen versus no endocrine treatment were a respective 31% reduction (HR, 0.69) and 62% reduction (HR, 0.38), and a respective 36% (HR, 0.64) and 28% (HR, 0.72) for the combination.

A further analysis was performed to compare between the active treatment arms, and this suggested a greater benefit of goserelin in patients at high risk when compared with both tamoxifen (HR, 0.30) and the combination (HR, 0.33).

Dr. Francis commented: “it is a bit surprising to find that goserelin appeared to be also better than the combination,” and it is something that the research team is looking into.

“One hypothesis might be if you look how the different treatments are working,” Ms. Johansson said. “Goserelin is very efficient in lowering the estrogen levels in premenopausal patients, suppressing the ovarian production of estrogen whereas tamoxifen can act both as an antagonist and agonist.

“So, we are thinking that maybe the addition of tamoxifen, with the agonistic properties of tamoxifen, might then make the goserelin not as efficient. But that’s of course, just a hypothesis right now and we need to look into this further,” she said.

The work was funded by The Swedish Research Council (Vetenskapsrådet), The Swedish Research Council for Health, Working life and Welfare, and the Swedish Cancer Society (Cancerfonden). Ms. Johansson had no personal disclosures; one of the coauthors was a coinventor of MammaPrint. Dr. Francis disclosed receiving travel support for overseas lectures from Ipsen and Novartis and acting as a medical oncology editor for Elsevier.

Look ma, I’m writing with no hands

Imagine being able to type every thought you had without using your hands, the words just magically appearing on the screen as fast as you can think of writing them down. Well, with the help of a new brain-computer interface (BCI), you can.

In a recent paper published in Nature, a team of researchers described how they developed a whole new way of communicating that blows previous BCIs, which used a method of pointing and clicking on letters, out of the water as far as accuracy and speed are concerned.

Developed for individuals with medical conditions or other disabilities that prevent them from communicating verbally or manually, the technology involves placing tiny sensors on the brain in the areas that control hand and arm movements. All the individual has to do is think of the process of writing and the system does the rest.

©Thinkstock

Chicken noodle salmonella

Chickens and ducks sure are cute, especially babies, but humans should be extra careful around these animals for risk of salmonella. This isn’t a new thing to loyal readers of Livin’ on the MDedge.

As more people keep such creatures at home – Emily Shoop of Penn State University told the N.Y. Times that raising poultry was “the fastest-growing animal-related hobby in the United States” – the ducks and chickens are being treated more like house pets, which is sweet but not safe.

In the latest outbreak, more than 160 people, mostly children under 5 years old, have fallen ill from salmonella poisoning and more than 30 have been hospitalized across 43 states, and the Centers for Disease Control and Prevention suspects the numbers could be higher because many did not get tested and recovered on their own.

JasonJiron/Thinkstock

This kidney research rocks!

When kids pick teams on the playground, someone is going to get their feelings hurt by being chosen last. There’s no way around it. Someone has to be last.

It’s the same way with research teams. When scientists are trying to cure diseases or pioneer new surgical techniques, they get a team together. And who always gets picked last? That’s right, the geologist, because who needs a geologist when you’re studying brain-computer interfaces?

Turns out, though, that there was a research team that needed a geologist: The one studying kidney stones.

Illinois geology professor Bruce Fouke explains: “The process of kidney stone formation is part of the natural process of the stone formation seen throughout nature. We are bringing together geology, biology, and medicine to map the entire process of kidney stone formation, step by step.”

Mayandi Sivaguru

Gene therapy: What is it good for? Absolutely nothing!

Gene therapy has the potential to permanently cure all sorts of terrible diseases, and one would assume that this would be something we all could agree on. Yes, no more cancer or diabetes or anything like that, no sane person could possibly be against this, right?

Oh, you poor naive fool.

To be fair, the report written by Goldman Sachs does lay out many potential applications for gene therapy, and all the markets it can expand into. But then the writers ask the question that they’re not supposed to say out loud: Is curing patients a sustainable business model?

Pogonic/Getty Images

Look ma, I’m writing with no hands

Imagine being able to type every thought you had without using your hands, the words just magically appearing on the screen as fast as you can think of writing them down. Well, with the help of a new brain-computer interface (BCI), you can.

In a recent paper published in Nature, a team of researchers described how they developed a whole new way of communicating that blows previous BCIs, which used a method of pointing and clicking on letters, out of the water as far as accuracy and speed are concerned.

Developed for individuals with medical conditions or other disabilities that prevent them from communicating verbally or manually, the technology involves placing tiny sensors on the brain in the areas that control hand and arm movements. All the individual has to do is think of the process of writing and the system does the rest.

©Thinkstock

Chicken noodle salmonella

Chickens and ducks sure are cute, especially babies, but humans should be extra careful around these animals for risk of salmonella. This isn’t a new thing to loyal readers of Livin’ on the MDedge.

As more people keep such creatures at home – Emily Shoop of Penn State University told the N.Y. Times that raising poultry was “the fastest-growing animal-related hobby in the United States” – the ducks and chickens are being treated more like house pets, which is sweet but not safe.

In the latest outbreak, more than 160 people, mostly children under 5 years old, have fallen ill from salmonella poisoning and more than 30 have been hospitalized across 43 states, and the Centers for Disease Control and Prevention suspects the numbers could be higher because many did not get tested and recovered on their own.

JasonJiron/Thinkstock

This kidney research rocks!

When kids pick teams on the playground, someone is going to get their feelings hurt by being chosen last. There’s no way around it. Someone has to be last.

It’s the same way with research teams. When scientists are trying to cure diseases or pioneer new surgical techniques, they get a team together. And who always gets picked last? That’s right, the geologist, because who needs a geologist when you’re studying brain-computer interfaces?

Turns out, though, that there was a research team that needed a geologist: The one studying kidney stones.

Illinois geology professor Bruce Fouke explains: “The process of kidney stone formation is part of the natural process of the stone formation seen throughout nature. We are bringing together geology, biology, and medicine to map the entire process of kidney stone formation, step by step.”

Mayandi Sivaguru

Gene therapy: What is it good for? Absolutely nothing!

Gene therapy has the potential to permanently cure all sorts of terrible diseases, and one would assume that this would be something we all could agree on. Yes, no more cancer or diabetes or anything like that, no sane person could possibly be against this, right?

Oh, you poor naive fool.

To be fair, the report written by Goldman Sachs does lay out many potential applications for gene therapy, and all the markets it can expand into. But then the writers ask the question that they’re not supposed to say out loud: Is curing patients a sustainable business model?

Pogonic/Getty Images

Look ma, I’m writing with no hands

Imagine being able to type every thought you had without using your hands, the words just magically appearing on the screen as fast as you can think of writing them down. Well, with the help of a new brain-computer interface (BCI), you can.

In a recent paper published in Nature, a team of researchers described how they developed a whole new way of communicating that blows previous BCIs, which used a method of pointing and clicking on letters, out of the water as far as accuracy and speed are concerned.

Developed for individuals with medical conditions or other disabilities that prevent them from communicating verbally or manually, the technology involves placing tiny sensors on the brain in the areas that control hand and arm movements. All the individual has to do is think of the process of writing and the system does the rest.

©Thinkstock

Chicken noodle salmonella

Chickens and ducks sure are cute, especially babies, but humans should be extra careful around these animals for risk of salmonella. This isn’t a new thing to loyal readers of Livin’ on the MDedge.

As more people keep such creatures at home – Emily Shoop of Penn State University told the N.Y. Times that raising poultry was “the fastest-growing animal-related hobby in the United States” – the ducks and chickens are being treated more like house pets, which is sweet but not safe.

In the latest outbreak, more than 160 people, mostly children under 5 years old, have fallen ill from salmonella poisoning and more than 30 have been hospitalized across 43 states, and the Centers for Disease Control and Prevention suspects the numbers could be higher because many did not get tested and recovered on their own.

JasonJiron/Thinkstock

This kidney research rocks!

When kids pick teams on the playground, someone is going to get their feelings hurt by being chosen last. There’s no way around it. Someone has to be last.

It’s the same way with research teams. When scientists are trying to cure diseases or pioneer new surgical techniques, they get a team together. And who always gets picked last? That’s right, the geologist, because who needs a geologist when you’re studying brain-computer interfaces?

Turns out, though, that there was a research team that needed a geologist: The one studying kidney stones.

Illinois geology professor Bruce Fouke explains: “The process of kidney stone formation is part of the natural process of the stone formation seen throughout nature. We are bringing together geology, biology, and medicine to map the entire process of kidney stone formation, step by step.”

Mayandi Sivaguru

Gene therapy: What is it good for? Absolutely nothing!

Gene therapy has the potential to permanently cure all sorts of terrible diseases, and one would assume that this would be something we all could agree on. Yes, no more cancer or diabetes or anything like that, no sane person could possibly be against this, right?

Oh, you poor naive fool.

To be fair, the report written by Goldman Sachs does lay out many potential applications for gene therapy, and all the markets it can expand into. But then the writers ask the question that they’re not supposed to say out loud: Is curing patients a sustainable business model?

Pogonic/Getty Images

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Considerations for the surgical management of diaphragmatic endometriosis
• Circumferential urethral diverticulum: A surgical conundrum
• The surgical approach to the obliterated anterior cul-de-sac

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Considerations for the surgical management of diaphragmatic endometriosis
• Circumferential urethral diverticulum: A surgical conundrum
• The surgical approach to the obliterated anterior cul-de-sac

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Considerations for the surgical management of diaphragmatic endometriosis
• Circumferential urethral diverticulum: A surgical conundrum
• The surgical approach to the obliterated anterior cul-de-sac

Vaccines have been a lifesaving public health measure since 1000 CE, when the Chinese first used smallpox inoculations to induce immunity.¹ Work by pioneers such as Edward Jenner, Louis Pasteur, and Maurice Hilleman has averted countless millions of vaccine-preventable illnesses and deaths, and vaccines have become a routine part of health maintenance throughout the human life cycle.

Pregnant patients who receive vaccines often have an added benefit of protection provided to their infants through passive transfer of antibodies. Several vaccine platforms have been utilized in pregnancy with well-documented improvements in maternal and obstetric outcomes as well as improved neonatal outcomes in the first several months of life. 

Risks of COVID-19 in pregnancy

The COVID-19 pandemic placed a spotlight on medically at-risk groups. Pregnant women  are 3 times more likely to require admission to the intensive care unit, have increased requirement for extracorporeal membrane oxygenation treatment, and are up to 70% more likely to die than nonpregnant peers—and this risk increases with the presence of additional comorbidities.

In the case of COVID-19, vaccination trials that have shaped worldwide clinical practice unfortunately followed the historical trend of excluding pregnant patients from participation. This has required clinicians to guide their patients through the decision of whether or not to accept vaccination without having the same reassurances regarding safety and effectiveness afforded to their nonpregnant counterparts. With more than 86,000 pregnant women infected with COVID-19 through April 19, 2021, this lack of information regarding vaccine safety in pregnancy is a significant public health gap.²

COVID-19 vaccines

The current COVID-19 vaccines approved for use in the United States under an Emergency Use Authorization issued by the US Food and Drug Administration are nonreplicating and thus cannot cause infection in the mother or fetus. These are the Pfizer-BioNTech mRNA vaccine, the Moderna mRNA-1273 vaccine, and the Janssen Biotech Inc. monovalent vaccine. Furthermore, in animal studies that included the Pfizer-BioNTech, Moderna, or Janssen COVID-19 vaccines, no fetal, embryonal, female reproductive, or postnatal development safety concerns were demonstrated.

As of April 19, 2021, 94,335 pregnant women had received a COVID-19 vaccination, and 4,622 of these enrolled in the Centers for Disease Control and Prevention’s (CDC) V-safe Vaccine Pregnancy Registry.³ The data reported noted no unexpected pregnancy or infant outcomes related to COVID-19 vaccination in pregnancy. Adverse effects of the vaccine were similar to those in nonpregnant cohorts. Additionally, emerging data suggest passage of immunity to neonates, with maternal antibodies demonstrated in cord blood at time of delivery as well as in breast milk.⁴ To date, these data mainly have come from women immunized with the Moderna and Pfizer-BioNTech mRNA vaccines.

Counseling pregnant patients

Our counseling aligns with that of the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the CDC’s Advisory Committee on Immunization Practices in that COVID-19 vaccination should not be withheld from pregnant patients or patients who want to become pregnant. In pregnant patients with comorbidities that place them at higher risk for severe COVID-19 infection, all available formulations of the COVID-19 vaccination should be strongly considered.

As evidence for vaccination safety continues to emerge, patients should continue to discuss their individual needs for vaccination in a shared decision-making format with their obstetric providers.

Vaccines have been a lifesaving public health measure since 1000 CE, when the Chinese first used smallpox inoculations to induce immunity.¹ Work by pioneers such as Edward Jenner, Louis Pasteur, and Maurice Hilleman has averted countless millions of vaccine-preventable illnesses and deaths, and vaccines have become a routine part of health maintenance throughout the human life cycle.

Pregnant patients who receive vaccines often have an added benefit of protection provided to their infants through passive transfer of antibodies. Several vaccine platforms have been utilized in pregnancy with well-documented improvements in maternal and obstetric outcomes as well as improved neonatal outcomes in the first several months of life. 

Risks of COVID-19 in pregnancy

The COVID-19 pandemic placed a spotlight on medically at-risk groups. Pregnant women  are 3 times more likely to require admission to the intensive care unit, have increased requirement for extracorporeal membrane oxygenation treatment, and are up to 70% more likely to die than nonpregnant peers—and this risk increases with the presence of additional comorbidities.

In the case of COVID-19, vaccination trials that have shaped worldwide clinical practice unfortunately followed the historical trend of excluding pregnant patients from participation. This has required clinicians to guide their patients through the decision of whether or not to accept vaccination without having the same reassurances regarding safety and effectiveness afforded to their nonpregnant counterparts. With more than 86,000 pregnant women infected with COVID-19 through April 19, 2021, this lack of information regarding vaccine safety in pregnancy is a significant public health gap.²

COVID-19 vaccines

The current COVID-19 vaccines approved for use in the United States under an Emergency Use Authorization issued by the US Food and Drug Administration are nonreplicating and thus cannot cause infection in the mother or fetus. These are the Pfizer-BioNTech mRNA vaccine, the Moderna mRNA-1273 vaccine, and the Janssen Biotech Inc. monovalent vaccine. Furthermore, in animal studies that included the Pfizer-BioNTech, Moderna, or Janssen COVID-19 vaccines, no fetal, embryonal, female reproductive, or postnatal development safety concerns were demonstrated.

As of April 19, 2021, 94,335 pregnant women had received a COVID-19 vaccination, and 4,622 of these enrolled in the Centers for Disease Control and Prevention’s (CDC) V-safe Vaccine Pregnancy Registry.³ The data reported noted no unexpected pregnancy or infant outcomes related to COVID-19 vaccination in pregnancy. Adverse effects of the vaccine were similar to those in nonpregnant cohorts. Additionally, emerging data suggest passage of immunity to neonates, with maternal antibodies demonstrated in cord blood at time of delivery as well as in breast milk.⁴ To date, these data mainly have come from women immunized with the Moderna and Pfizer-BioNTech mRNA vaccines.

Counseling pregnant patients

Our counseling aligns with that of the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the CDC’s Advisory Committee on Immunization Practices in that COVID-19 vaccination should not be withheld from pregnant patients or patients who want to become pregnant. In pregnant patients with comorbidities that place them at higher risk for severe COVID-19 infection, all available formulations of the COVID-19 vaccination should be strongly considered.

As evidence for vaccination safety continues to emerge, patients should continue to discuss their individual needs for vaccination in a shared decision-making format with their obstetric providers.

Vaccines have been a lifesaving public health measure since 1000 CE, when the Chinese first used smallpox inoculations to induce immunity.¹ Work by pioneers such as Edward Jenner, Louis Pasteur, and Maurice Hilleman has averted countless millions of vaccine-preventable illnesses and deaths, and vaccines have become a routine part of health maintenance throughout the human life cycle.

Pregnant patients who receive vaccines often have an added benefit of protection provided to their infants through passive transfer of antibodies. Several vaccine platforms have been utilized in pregnancy with well-documented improvements in maternal and obstetric outcomes as well as improved neonatal outcomes in the first several months of life. 

Risks of COVID-19 in pregnancy

The COVID-19 pandemic placed a spotlight on medically at-risk groups. Pregnant women  are 3 times more likely to require admission to the intensive care unit, have increased requirement for extracorporeal membrane oxygenation treatment, and are up to 70% more likely to die than nonpregnant peers—and this risk increases with the presence of additional comorbidities.

In the case of COVID-19, vaccination trials that have shaped worldwide clinical practice unfortunately followed the historical trend of excluding pregnant patients from participation. This has required clinicians to guide their patients through the decision of whether or not to accept vaccination without having the same reassurances regarding safety and effectiveness afforded to their nonpregnant counterparts. With more than 86,000 pregnant women infected with COVID-19 through April 19, 2021, this lack of information regarding vaccine safety in pregnancy is a significant public health gap.²

COVID-19 vaccines

The current COVID-19 vaccines approved for use in the United States under an Emergency Use Authorization issued by the US Food and Drug Administration are nonreplicating and thus cannot cause infection in the mother or fetus. These are the Pfizer-BioNTech mRNA vaccine, the Moderna mRNA-1273 vaccine, and the Janssen Biotech Inc. monovalent vaccine. Furthermore, in animal studies that included the Pfizer-BioNTech, Moderna, or Janssen COVID-19 vaccines, no fetal, embryonal, female reproductive, or postnatal development safety concerns were demonstrated.

As of April 19, 2021, 94,335 pregnant women had received a COVID-19 vaccination, and 4,622 of these enrolled in the Centers for Disease Control and Prevention’s (CDC) V-safe Vaccine Pregnancy Registry.³ The data reported noted no unexpected pregnancy or infant outcomes related to COVID-19 vaccination in pregnancy. Adverse effects of the vaccine were similar to those in nonpregnant cohorts. Additionally, emerging data suggest passage of immunity to neonates, with maternal antibodies demonstrated in cord blood at time of delivery as well as in breast milk.⁴ To date, these data mainly have come from women immunized with the Moderna and Pfizer-BioNTech mRNA vaccines.

Counseling pregnant patients

Our counseling aligns with that of the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the CDC’s Advisory Committee on Immunization Practices in that COVID-19 vaccination should not be withheld from pregnant patients or patients who want to become pregnant. In pregnant patients with comorbidities that place them at higher risk for severe COVID-19 infection, all available formulations of the COVID-19 vaccination should be strongly considered.

As evidence for vaccination safety continues to emerge, patients should continue to discuss their individual needs for vaccination in a shared decision-making format with their obstetric providers.

The U.S. Preventive Services Task Force has recommended clinicians counsel their adolescent and adult pregnant patients in primary care settings to use interventions to limit excess gestational weight gain.

Counseling pregnant persons on gestational weight gain (GWG) carries a B recommendation from the U.S. Preventive Services Task Force (USPSTF), meaning there is “moderate certainty that behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess GWG in pregnancy have a moderate net benefit for pregnant persons,” the task force said in its recommendation statement, which was published in JAMA on May 25.

While the USPSTF has made other recommendations on screening for obesity in adults and gestational diabetes, this is the first recommendation from the task force on behavioral counseling interventions for pregnant persons to promote a healthy weight and limit GWG. The recommendation is important, the USPSTF said, because half of individuals entered pregnancy while either overweight (24%) or obese (24%) in 2015, with the prevalence of prepregnancy obesity higher among Alaska Native/American Indian (36.4%), Black (34.7%), and Hispanic (27.3%) women.

To define gestational weight gain, the USPSTF used National Academy of Medicine recommendations of weight change of 28-40 pounds in the underweight category (body mass index [BMI], < 18.5 kg/m²), 25-35 pounds in the normal-weight category (BMI, 18.5-24.9 kg/m²), 15-25 pounds in the overweight category (BMI, 25-29.9 kg/m²), and 11-20 pounds in the obese category (≥ 30 kg/m²).

Implementations of this recommendation include content with a focus on nutrition, physical activity, lifestyle change, or behavioral change. The counseling should be performed at the end of the first trimester or start of the second trimester and should stop shortly before delivery. “The most common types of behavioral counseling interventions included active or supervised exercise or counseling about diet and physical activity,” the USPSTF said.

The average duration of counseling sessions was between 15 and 120 minutes, varying from less than 2 contacts to more than 12 contacts involved in the intervention. Primary care clinicians can deliver these interventions themselves or refer the patient out to an intervention in another setting. “Effective behavioral counseling interventions often referred participants to various interventionists in different settings,” such as a local community fitness center, the authors wrote. “Participants were counseled on healthy diet and exercise through individual or group education sessions. Some interventions provided medically supervised group exercise classes with or without counseling.”

In their evidence report for the USPSTF recommendation, Amy G. Cantor, MD, of the Pacific Northwest Evidence-Based Practice Center, department of medical informatics and clinical epidemiology at Oregon Health & Science University in Portland, and colleagues performed a systematic review of 68 studies in the Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews evaluating the effect of diet, exercise, and/or behavioral counseling interventions for 25,789 pregnant patients with GWG. The results were current up to February 2021 when the last search was performed. The mean ages of patients across all studies were 18.6 to 33.8 years, and 41% of studies contained patients from “diverse backgrounds.”

The results of the systematic review showed use of an intervention to limit GWG decreased the risk of gestational diabetes compared with a control group in 43 trials (relative risk, 0.87; 95% confidence interval, 0.79-0.95), emergency cesarean delivery in 14 trials (RR, 0.85; 95% CI, 0.74-0.96), macrosomia in 25 trials (RR, 0.77; 95% CI, 0.65-0.92), and large for gestational age infants in 26 trials (RR, 0.89; 95% CI, 0.80-0.99). There was not an association between GWG interventions and reduced gestational hypertension in 28 trials (RR, 0.87; 95% CI, 0.70-1.04), preeclampsia in 27 trials (RR, 0.98; 95% CI, 0.84-1.13), and lower risk of preterm birth in 33 trials (RR, 0.93; 95% CI, 0.81-1.07), as well as other outcomes such as respiratory distress syndrome, shoulder dystocia, neonatal intensive care unit admission, neonatal death, or infant growth during the first year.

In terms of the types of interventions used, Dr. Canton and colleagues found the greatest impact on GWG occurred when a high-intensity intervention with 12 or more sessions was used in 28 trials (−1.47 kg; 95% CI, −1.78 to −1.22) than in moderate-intensity interventions in 18 trials (−0.32 kg; 95% CI, −0.71 to −0.04) and low-intensity interventions in 9 trials (−0.64 kg; 94% CI, −1.44 to 0.02).
 

Implementing these interventions could be challenging

D. Yvette LaCoursiere, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, in La Jolla, Calif., wrote in an accompanying editorial that the USPSTF recommendation supports the recommendation of the American College of Obstetricians and Gynecologists (ACOG) of offering nutritional and exercise-based support for patients with “excessive GWG,” but noted that leaving implementation of behavioral counseling interventions to the clinicians “is where challenges lie.”

“The USPSTF recommendations will require lengthening already time-constrained prenatal visits or relying on adjunctive professionals,” she said.

Dr. LaCoursiere highlighted the amount of time the behavioral counseling interventions took to implement, with the shortest intervention lasting 15 minutes. “With the exception of those in group prenatal care practices, clinicians conducting the standard prenatal visit will find it difficult to accommodate moderate- or high-intensity interventions. On a similar note, the topics included in many of the interventions are broad and not necessarily in the purview of clinicians who provide prenatal care,” she said.

In addition, behavioral counseling interventions may not be covered by some patients’ insurance plans, Dr. LaCoursiere explained. “While it is a federal requirement for states to provide pregnant Medicaid enrollees smoking cessation counseling and prescription drugs, there is no such mandate for nutrition or physical activity counseling. Neither is it required that states provide these services to nonpregnant enrollees,” she said. “These are not insurmountable challenges, but more groundwork is necessary to ensure an effective and efficient implementation.”

Commenting on how a clinician could fit a behavioral counseling intervention into the prenatal care model, Dr. LaCoursiere said creativity may be needed. Some researchers in the systematic review used Internet or telehealth-based programs for dietary education, exercise support, health information, and goal setting, for example, which could help with continuity of care during the COVID-19 pandemic. “These types of interventions may help overcome the obstacle of insufficient clinic time by separating the primary implementation phase from the traditional clinical setting,” she said.

While the evidence supports the implementation of these interventions, “additional work remains for clinicians and researchers to identify high-yield components and determine best practices for the delivery of GWG interventions,” she said.

“The success of this intervention will depend on improving resources for clinicians to facilitate provision of direct counseling or to refer patients to skilled professionals and explore novel alternatives. Promising innovative approaches such as the use of telehealth, technology-based delivery systems, and group prenatal care are under investigation and may expand the ability to successfully implement these recommendations and ultimately improve outcomes for pregnant persons and their infants,” Dr. LaCoursiere concluded.

This research was funded by contracts from the Agency for Healthcare Research and Quality and U.S. Department of Health and Human Services. The authors report no relevant conflict of interest.

The U.S. Preventive Services Task Force has recommended clinicians counsel their adolescent and adult pregnant patients in primary care settings to use interventions to limit excess gestational weight gain.

Counseling pregnant persons on gestational weight gain (GWG) carries a B recommendation from the U.S. Preventive Services Task Force (USPSTF), meaning there is “moderate certainty that behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess GWG in pregnancy have a moderate net benefit for pregnant persons,” the task force said in its recommendation statement, which was published in JAMA on May 25.

While the USPSTF has made other recommendations on screening for obesity in adults and gestational diabetes, this is the first recommendation from the task force on behavioral counseling interventions for pregnant persons to promote a healthy weight and limit GWG. The recommendation is important, the USPSTF said, because half of individuals entered pregnancy while either overweight (24%) or obese (24%) in 2015, with the prevalence of prepregnancy obesity higher among Alaska Native/American Indian (36.4%), Black (34.7%), and Hispanic (27.3%) women.

To define gestational weight gain, the USPSTF used National Academy of Medicine recommendations of weight change of 28-40 pounds in the underweight category (body mass index [BMI], < 18.5 kg/m²), 25-35 pounds in the normal-weight category (BMI, 18.5-24.9 kg/m²), 15-25 pounds in the overweight category (BMI, 25-29.9 kg/m²), and 11-20 pounds in the obese category (≥ 30 kg/m²).

Implementations of this recommendation include content with a focus on nutrition, physical activity, lifestyle change, or behavioral change. The counseling should be performed at the end of the first trimester or start of the second trimester and should stop shortly before delivery. “The most common types of behavioral counseling interventions included active or supervised exercise or counseling about diet and physical activity,” the USPSTF said.

The average duration of counseling sessions was between 15 and 120 minutes, varying from less than 2 contacts to more than 12 contacts involved in the intervention. Primary care clinicians can deliver these interventions themselves or refer the patient out to an intervention in another setting. “Effective behavioral counseling interventions often referred participants to various interventionists in different settings,” such as a local community fitness center, the authors wrote. “Participants were counseled on healthy diet and exercise through individual or group education sessions. Some interventions provided medically supervised group exercise classes with or without counseling.”

In their evidence report for the USPSTF recommendation, Amy G. Cantor, MD, of the Pacific Northwest Evidence-Based Practice Center, department of medical informatics and clinical epidemiology at Oregon Health & Science University in Portland, and colleagues performed a systematic review of 68 studies in the Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews evaluating the effect of diet, exercise, and/or behavioral counseling interventions for 25,789 pregnant patients with GWG. The results were current up to February 2021 when the last search was performed. The mean ages of patients across all studies were 18.6 to 33.8 years, and 41% of studies contained patients from “diverse backgrounds.”

The results of the systematic review showed use of an intervention to limit GWG decreased the risk of gestational diabetes compared with a control group in 43 trials (relative risk, 0.87; 95% confidence interval, 0.79-0.95), emergency cesarean delivery in 14 trials (RR, 0.85; 95% CI, 0.74-0.96), macrosomia in 25 trials (RR, 0.77; 95% CI, 0.65-0.92), and large for gestational age infants in 26 trials (RR, 0.89; 95% CI, 0.80-0.99). There was not an association between GWG interventions and reduced gestational hypertension in 28 trials (RR, 0.87; 95% CI, 0.70-1.04), preeclampsia in 27 trials (RR, 0.98; 95% CI, 0.84-1.13), and lower risk of preterm birth in 33 trials (RR, 0.93; 95% CI, 0.81-1.07), as well as other outcomes such as respiratory distress syndrome, shoulder dystocia, neonatal intensive care unit admission, neonatal death, or infant growth during the first year.

In terms of the types of interventions used, Dr. Canton and colleagues found the greatest impact on GWG occurred when a high-intensity intervention with 12 or more sessions was used in 28 trials (−1.47 kg; 95% CI, −1.78 to −1.22) than in moderate-intensity interventions in 18 trials (−0.32 kg; 95% CI, −0.71 to −0.04) and low-intensity interventions in 9 trials (−0.64 kg; 94% CI, −1.44 to 0.02).
 

Implementing these interventions could be challenging

D. Yvette LaCoursiere, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, in La Jolla, Calif., wrote in an accompanying editorial that the USPSTF recommendation supports the recommendation of the American College of Obstetricians and Gynecologists (ACOG) of offering nutritional and exercise-based support for patients with “excessive GWG,” but noted that leaving implementation of behavioral counseling interventions to the clinicians “is where challenges lie.”

“The USPSTF recommendations will require lengthening already time-constrained prenatal visits or relying on adjunctive professionals,” she said.

Dr. LaCoursiere highlighted the amount of time the behavioral counseling interventions took to implement, with the shortest intervention lasting 15 minutes. “With the exception of those in group prenatal care practices, clinicians conducting the standard prenatal visit will find it difficult to accommodate moderate- or high-intensity interventions. On a similar note, the topics included in many of the interventions are broad and not necessarily in the purview of clinicians who provide prenatal care,” she said.

In addition, behavioral counseling interventions may not be covered by some patients’ insurance plans, Dr. LaCoursiere explained. “While it is a federal requirement for states to provide pregnant Medicaid enrollees smoking cessation counseling and prescription drugs, there is no such mandate for nutrition or physical activity counseling. Neither is it required that states provide these services to nonpregnant enrollees,” she said. “These are not insurmountable challenges, but more groundwork is necessary to ensure an effective and efficient implementation.”

Commenting on how a clinician could fit a behavioral counseling intervention into the prenatal care model, Dr. LaCoursiere said creativity may be needed. Some researchers in the systematic review used Internet or telehealth-based programs for dietary education, exercise support, health information, and goal setting, for example, which could help with continuity of care during the COVID-19 pandemic. “These types of interventions may help overcome the obstacle of insufficient clinic time by separating the primary implementation phase from the traditional clinical setting,” she said.

While the evidence supports the implementation of these interventions, “additional work remains for clinicians and researchers to identify high-yield components and determine best practices for the delivery of GWG interventions,” she said.

“The success of this intervention will depend on improving resources for clinicians to facilitate provision of direct counseling or to refer patients to skilled professionals and explore novel alternatives. Promising innovative approaches such as the use of telehealth, technology-based delivery systems, and group prenatal care are under investigation and may expand the ability to successfully implement these recommendations and ultimately improve outcomes for pregnant persons and their infants,” Dr. LaCoursiere concluded.

This research was funded by contracts from the Agency for Healthcare Research and Quality and U.S. Department of Health and Human Services. The authors report no relevant conflict of interest.

The U.S. Preventive Services Task Force has recommended clinicians counsel their adolescent and adult pregnant patients in primary care settings to use interventions to limit excess gestational weight gain.

Counseling pregnant persons on gestational weight gain (GWG) carries a B recommendation from the U.S. Preventive Services Task Force (USPSTF), meaning there is “moderate certainty that behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess GWG in pregnancy have a moderate net benefit for pregnant persons,” the task force said in its recommendation statement, which was published in JAMA on May 25.

While the USPSTF has made other recommendations on screening for obesity in adults and gestational diabetes, this is the first recommendation from the task force on behavioral counseling interventions for pregnant persons to promote a healthy weight and limit GWG. The recommendation is important, the USPSTF said, because half of individuals entered pregnancy while either overweight (24%) or obese (24%) in 2015, with the prevalence of prepregnancy obesity higher among Alaska Native/American Indian (36.4%), Black (34.7%), and Hispanic (27.3%) women.

To define gestational weight gain, the USPSTF used National Academy of Medicine recommendations of weight change of 28-40 pounds in the underweight category (body mass index [BMI], < 18.5 kg/m²), 25-35 pounds in the normal-weight category (BMI, 18.5-24.9 kg/m²), 15-25 pounds in the overweight category (BMI, 25-29.9 kg/m²), and 11-20 pounds in the obese category (≥ 30 kg/m²).

Implementations of this recommendation include content with a focus on nutrition, physical activity, lifestyle change, or behavioral change. The counseling should be performed at the end of the first trimester or start of the second trimester and should stop shortly before delivery. “The most common types of behavioral counseling interventions included active or supervised exercise or counseling about diet and physical activity,” the USPSTF said.

The average duration of counseling sessions was between 15 and 120 minutes, varying from less than 2 contacts to more than 12 contacts involved in the intervention. Primary care clinicians can deliver these interventions themselves or refer the patient out to an intervention in another setting. “Effective behavioral counseling interventions often referred participants to various interventionists in different settings,” such as a local community fitness center, the authors wrote. “Participants were counseled on healthy diet and exercise through individual or group education sessions. Some interventions provided medically supervised group exercise classes with or without counseling.”

In their evidence report for the USPSTF recommendation, Amy G. Cantor, MD, of the Pacific Northwest Evidence-Based Practice Center, department of medical informatics and clinical epidemiology at Oregon Health & Science University in Portland, and colleagues performed a systematic review of 68 studies in the Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews evaluating the effect of diet, exercise, and/or behavioral counseling interventions for 25,789 pregnant patients with GWG. The results were current up to February 2021 when the last search was performed. The mean ages of patients across all studies were 18.6 to 33.8 years, and 41% of studies contained patients from “diverse backgrounds.”

The results of the systematic review showed use of an intervention to limit GWG decreased the risk of gestational diabetes compared with a control group in 43 trials (relative risk, 0.87; 95% confidence interval, 0.79-0.95), emergency cesarean delivery in 14 trials (RR, 0.85; 95% CI, 0.74-0.96), macrosomia in 25 trials (RR, 0.77; 95% CI, 0.65-0.92), and large for gestational age infants in 26 trials (RR, 0.89; 95% CI, 0.80-0.99). There was not an association between GWG interventions and reduced gestational hypertension in 28 trials (RR, 0.87; 95% CI, 0.70-1.04), preeclampsia in 27 trials (RR, 0.98; 95% CI, 0.84-1.13), and lower risk of preterm birth in 33 trials (RR, 0.93; 95% CI, 0.81-1.07), as well as other outcomes such as respiratory distress syndrome, shoulder dystocia, neonatal intensive care unit admission, neonatal death, or infant growth during the first year.

In terms of the types of interventions used, Dr. Canton and colleagues found the greatest impact on GWG occurred when a high-intensity intervention with 12 or more sessions was used in 28 trials (−1.47 kg; 95% CI, −1.78 to −1.22) than in moderate-intensity interventions in 18 trials (−0.32 kg; 95% CI, −0.71 to −0.04) and low-intensity interventions in 9 trials (−0.64 kg; 94% CI, −1.44 to 0.02).
 

Implementing these interventions could be challenging

D. Yvette LaCoursiere, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, in La Jolla, Calif., wrote in an accompanying editorial that the USPSTF recommendation supports the recommendation of the American College of Obstetricians and Gynecologists (ACOG) of offering nutritional and exercise-based support for patients with “excessive GWG,” but noted that leaving implementation of behavioral counseling interventions to the clinicians “is where challenges lie.”

“The USPSTF recommendations will require lengthening already time-constrained prenatal visits or relying on adjunctive professionals,” she said.

Dr. LaCoursiere highlighted the amount of time the behavioral counseling interventions took to implement, with the shortest intervention lasting 15 minutes. “With the exception of those in group prenatal care practices, clinicians conducting the standard prenatal visit will find it difficult to accommodate moderate- or high-intensity interventions. On a similar note, the topics included in many of the interventions are broad and not necessarily in the purview of clinicians who provide prenatal care,” she said.

In addition, behavioral counseling interventions may not be covered by some patients’ insurance plans, Dr. LaCoursiere explained. “While it is a federal requirement for states to provide pregnant Medicaid enrollees smoking cessation counseling and prescription drugs, there is no such mandate for nutrition or physical activity counseling. Neither is it required that states provide these services to nonpregnant enrollees,” she said. “These are not insurmountable challenges, but more groundwork is necessary to ensure an effective and efficient implementation.”

Commenting on how a clinician could fit a behavioral counseling intervention into the prenatal care model, Dr. LaCoursiere said creativity may be needed. Some researchers in the systematic review used Internet or telehealth-based programs for dietary education, exercise support, health information, and goal setting, for example, which could help with continuity of care during the COVID-19 pandemic. “These types of interventions may help overcome the obstacle of insufficient clinic time by separating the primary implementation phase from the traditional clinical setting,” she said.

While the evidence supports the implementation of these interventions, “additional work remains for clinicians and researchers to identify high-yield components and determine best practices for the delivery of GWG interventions,” she said.

“The success of this intervention will depend on improving resources for clinicians to facilitate provision of direct counseling or to refer patients to skilled professionals and explore novel alternatives. Promising innovative approaches such as the use of telehealth, technology-based delivery systems, and group prenatal care are under investigation and may expand the ability to successfully implement these recommendations and ultimately improve outcomes for pregnant persons and their infants,” Dr. LaCoursiere concluded.

This research was funded by contracts from the Agency for Healthcare Research and Quality and U.S. Department of Health and Human Services. The authors report no relevant conflict of interest.

Loop electrosurgical excision procedure (LEEP) or cold knife conization of the cervix (CKC) is the standard of care approach for women with cervical intra-epithelial neoplasia (CIN 3) because it achieves both disease control and diagnostic evaluation to rule out invasive carcinoma. While both techniques are associated with equivalent efficacy in disease control, each has its virtues and advantages, and clinical judgment is necessary when choosing a technique.¹

LEEP, or large loop electrosurgical excision of the transformation zone (LLETZ) involves use of electrosurgical current directed through wire loops to excise pieces of cervical tissue. The equipment for this technique is widely available and this procedure can most often be performed safely and comfortably in an outpatient office setting, making it a cost-effective strategy. Its ease of access means that it can be employed in “see-and-treat” programs where there is concern regarding follow-up. The loop from the device has a tendency to take more shallow pieces of tissue, preserving more cervical stroma. This may be why LEEP has been associated with decreased risk for obstetric complications associated with cervical insufficiency when compared with CKC.^2,3

The shallowness and standardized, preset shapes of the loops present challenges with this technique. It can be more difficult to tailor the shape of the excision for particular lesions, and surgeons may need to add a second “top hat” endocervical LEEP after the first ectocervical excision to adequately excise the endocervical canal. If the “coagulation” setting is used instead of “blend” or “cut,” excessive drag and resistance can develop during the procedure, which can result in the specimen’s being amputated, fragmented, or interrupted mid-sweep. This can severely limit pathologic interpretation of the specimen. Orienting these multiple fragments for pathology to specify margin status can be limited or impossible. Electrosurgical effect (“thermal effect”) at the margins of the specimen can limit accurate interpretation of adequacy of the excision.

CKC of the cervix is a procedure in which a narrow scalpel (typically an 11-blade) is used to excise the ecto- and endocervical tissues in a cone-shaped specimen that ensures maximal inclusion of ectocervical and endocervical mucosa but minimization of stromal excision. Absence of electrosurgery in the primary excision means that pathologists have clean edges to evaluate for margin status. Because the shape of the incision is unique for each patient, the surgeon can tailor the shape and extent of the cone to focus on known or suspected areas of disease. It is particularly useful when there is an endocervical lesion, such as in cases of adenocarcinoma in situ and in postmenopausal women whose transformation zone is frequently within the canal. In cases of a distorted, atrophic cervix, or one that is flush with the vagina, a conization procedure in the operating room affords surgeons greater control and precision. Major limitations of this procedure are that it is typically performed in an operating room setting because of the potential for intraoperative bleeding, and its increased risk for early and late complications. The conization procedure is associated with increased obstetric risk in later pregnancies, possibly because of more significant disturbance of cervical stroma.^2,3

As mentioned earlier, both procedures are associated with equivalent outcomes with respect to control of disease.¹ CKC procedures are associated with more complications, including bleeding (intraoperatively and postoperatively) than are LEEPs. Traditionally, adenocarcinoma in situ (AIS) has been preferentially treated with CKC because of the propensity of this lesion to reside within the endocervical canal, a region more readily and extensively sampled with the CKC. However, provided that the LEEP specimen achieves negative margin status, there is no specific benefit of CKC over LEEP. Guidelines recommend that AIS is excised as a single specimen (without a “top hat”) to achieve accurate pathology regarding margins in the endocervical canal.⁴ Considering that a specimen depth between 10 and 20 mm is ideal in the setting of AIS, it may be difficult to achieve this depth with a single-pass LEEP depending upon the dimensions of the cervix. It is due to these technical challenges associated with LEEP that CKC is typically preferred in the treatment of AIS.

Ultimately, the decision regarding when to choose LEEP versus CKC is nuanced and should be tailored for each patient. Factors to consider include the patient’s ease of follow-up, financial limitations, preexisting distortion of anatomy, and the need to minimize obstetrics risks or achieve wider margins. For example, a young, nulliparous patient with an ectocervical lesion of squamous dysplasia would likely best be served by a LEEP, which preserves her cervical stroma and affords her easy access and affordability of the procedure. A patient with a bleeding diathesis including iatrogenic anticoagulant therapy may also benefit from a LEEP to achieve better hemostasis and lower risk of bleeding complications.

A postmenopausal woman with a narrow upper vagina and cervix flush with the vagina from prior excisional procedures may benefit from a conization in the operating room where adequate retraction and exposure can minimize the risk of damage to adjacent structures, and the shape and size of the excision can be tailored to the long, narrow segment that is indicated. The table highlights some of the factors to consider when choosing these options.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Contact her at [email protected].

References

1. Martin-Hirsch PL et al. Cochrane Database Syst Rev 2000;(2):CD001318.

2. Arbyn M et al. BMJ. 2008;337:a1284.

3. Jin G et al. Arch Gynecol Obstet. 2014 Jan;289(1):85-99.

4. Perkins RB et al. J Low Genit Tract Dis. 2020;24(2):102.

Loop electrosurgical excision procedure (LEEP) or cold knife conization of the cervix (CKC) is the standard of care approach for women with cervical intra-epithelial neoplasia (CIN 3) because it achieves both disease control and diagnostic evaluation to rule out invasive carcinoma. While both techniques are associated with equivalent efficacy in disease control, each has its virtues and advantages, and clinical judgment is necessary when choosing a technique.¹

LEEP, or large loop electrosurgical excision of the transformation zone (LLETZ) involves use of electrosurgical current directed through wire loops to excise pieces of cervical tissue. The equipment for this technique is widely available and this procedure can most often be performed safely and comfortably in an outpatient office setting, making it a cost-effective strategy. Its ease of access means that it can be employed in “see-and-treat” programs where there is concern regarding follow-up. The loop from the device has a tendency to take more shallow pieces of tissue, preserving more cervical stroma. This may be why LEEP has been associated with decreased risk for obstetric complications associated with cervical insufficiency when compared with CKC.^2,3

The shallowness and standardized, preset shapes of the loops present challenges with this technique. It can be more difficult to tailor the shape of the excision for particular lesions, and surgeons may need to add a second “top hat” endocervical LEEP after the first ectocervical excision to adequately excise the endocervical canal. If the “coagulation” setting is used instead of “blend” or “cut,” excessive drag and resistance can develop during the procedure, which can result in the specimen’s being amputated, fragmented, or interrupted mid-sweep. This can severely limit pathologic interpretation of the specimen. Orienting these multiple fragments for pathology to specify margin status can be limited or impossible. Electrosurgical effect (“thermal effect”) at the margins of the specimen can limit accurate interpretation of adequacy of the excision.

CKC of the cervix is a procedure in which a narrow scalpel (typically an 11-blade) is used to excise the ecto- and endocervical tissues in a cone-shaped specimen that ensures maximal inclusion of ectocervical and endocervical mucosa but minimization of stromal excision. Absence of electrosurgery in the primary excision means that pathologists have clean edges to evaluate for margin status. Because the shape of the incision is unique for each patient, the surgeon can tailor the shape and extent of the cone to focus on known or suspected areas of disease. It is particularly useful when there is an endocervical lesion, such as in cases of adenocarcinoma in situ and in postmenopausal women whose transformation zone is frequently within the canal. In cases of a distorted, atrophic cervix, or one that is flush with the vagina, a conization procedure in the operating room affords surgeons greater control and precision. Major limitations of this procedure are that it is typically performed in an operating room setting because of the potential for intraoperative bleeding, and its increased risk for early and late complications. The conization procedure is associated with increased obstetric risk in later pregnancies, possibly because of more significant disturbance of cervical stroma.^2,3

As mentioned earlier, both procedures are associated with equivalent outcomes with respect to control of disease.¹ CKC procedures are associated with more complications, including bleeding (intraoperatively and postoperatively) than are LEEPs. Traditionally, adenocarcinoma in situ (AIS) has been preferentially treated with CKC because of the propensity of this lesion to reside within the endocervical canal, a region more readily and extensively sampled with the CKC. However, provided that the LEEP specimen achieves negative margin status, there is no specific benefit of CKC over LEEP. Guidelines recommend that AIS is excised as a single specimen (without a “top hat”) to achieve accurate pathology regarding margins in the endocervical canal.⁴ Considering that a specimen depth between 10 and 20 mm is ideal in the setting of AIS, it may be difficult to achieve this depth with a single-pass LEEP depending upon the dimensions of the cervix. It is due to these technical challenges associated with LEEP that CKC is typically preferred in the treatment of AIS.

Ultimately, the decision regarding when to choose LEEP versus CKC is nuanced and should be tailored for each patient. Factors to consider include the patient’s ease of follow-up, financial limitations, preexisting distortion of anatomy, and the need to minimize obstetrics risks or achieve wider margins. For example, a young, nulliparous patient with an ectocervical lesion of squamous dysplasia would likely best be served by a LEEP, which preserves her cervical stroma and affords her easy access and affordability of the procedure. A patient with a bleeding diathesis including iatrogenic anticoagulant therapy may also benefit from a LEEP to achieve better hemostasis and lower risk of bleeding complications.

A postmenopausal woman with a narrow upper vagina and cervix flush with the vagina from prior excisional procedures may benefit from a conization in the operating room where adequate retraction and exposure can minimize the risk of damage to adjacent structures, and the shape and size of the excision can be tailored to the long, narrow segment that is indicated. The table highlights some of the factors to consider when choosing these options.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Contact her at [email protected].

References

1. Martin-Hirsch PL et al. Cochrane Database Syst Rev 2000;(2):CD001318.

2. Arbyn M et al. BMJ. 2008;337:a1284.

3. Jin G et al. Arch Gynecol Obstet. 2014 Jan;289(1):85-99.

4. Perkins RB et al. J Low Genit Tract Dis. 2020;24(2):102.

Loop electrosurgical excision procedure (LEEP) or cold knife conization of the cervix (CKC) is the standard of care approach for women with cervical intra-epithelial neoplasia (CIN 3) because it achieves both disease control and diagnostic evaluation to rule out invasive carcinoma. While both techniques are associated with equivalent efficacy in disease control, each has its virtues and advantages, and clinical judgment is necessary when choosing a technique.¹

LEEP, or large loop electrosurgical excision of the transformation zone (LLETZ) involves use of electrosurgical current directed through wire loops to excise pieces of cervical tissue. The equipment for this technique is widely available and this procedure can most often be performed safely and comfortably in an outpatient office setting, making it a cost-effective strategy. Its ease of access means that it can be employed in “see-and-treat” programs where there is concern regarding follow-up. The loop from the device has a tendency to take more shallow pieces of tissue, preserving more cervical stroma. This may be why LEEP has been associated with decreased risk for obstetric complications associated with cervical insufficiency when compared with CKC.^2,3

The shallowness and standardized, preset shapes of the loops present challenges with this technique. It can be more difficult to tailor the shape of the excision for particular lesions, and surgeons may need to add a second “top hat” endocervical LEEP after the first ectocervical excision to adequately excise the endocervical canal. If the “coagulation” setting is used instead of “blend” or “cut,” excessive drag and resistance can develop during the procedure, which can result in the specimen’s being amputated, fragmented, or interrupted mid-sweep. This can severely limit pathologic interpretation of the specimen. Orienting these multiple fragments for pathology to specify margin status can be limited or impossible. Electrosurgical effect (“thermal effect”) at the margins of the specimen can limit accurate interpretation of adequacy of the excision.

CKC of the cervix is a procedure in which a narrow scalpel (typically an 11-blade) is used to excise the ecto- and endocervical tissues in a cone-shaped specimen that ensures maximal inclusion of ectocervical and endocervical mucosa but minimization of stromal excision. Absence of electrosurgery in the primary excision means that pathologists have clean edges to evaluate for margin status. Because the shape of the incision is unique for each patient, the surgeon can tailor the shape and extent of the cone to focus on known or suspected areas of disease. It is particularly useful when there is an endocervical lesion, such as in cases of adenocarcinoma in situ and in postmenopausal women whose transformation zone is frequently within the canal. In cases of a distorted, atrophic cervix, or one that is flush with the vagina, a conization procedure in the operating room affords surgeons greater control and precision. Major limitations of this procedure are that it is typically performed in an operating room setting because of the potential for intraoperative bleeding, and its increased risk for early and late complications. The conization procedure is associated with increased obstetric risk in later pregnancies, possibly because of more significant disturbance of cervical stroma.^2,3

As mentioned earlier, both procedures are associated with equivalent outcomes with respect to control of disease.¹ CKC procedures are associated with more complications, including bleeding (intraoperatively and postoperatively) than are LEEPs. Traditionally, adenocarcinoma in situ (AIS) has been preferentially treated with CKC because of the propensity of this lesion to reside within the endocervical canal, a region more readily and extensively sampled with the CKC. However, provided that the LEEP specimen achieves negative margin status, there is no specific benefit of CKC over LEEP. Guidelines recommend that AIS is excised as a single specimen (without a “top hat”) to achieve accurate pathology regarding margins in the endocervical canal.⁴ Considering that a specimen depth between 10 and 20 mm is ideal in the setting of AIS, it may be difficult to achieve this depth with a single-pass LEEP depending upon the dimensions of the cervix. It is due to these technical challenges associated with LEEP that CKC is typically preferred in the treatment of AIS.

Ultimately, the decision regarding when to choose LEEP versus CKC is nuanced and should be tailored for each patient. Factors to consider include the patient’s ease of follow-up, financial limitations, preexisting distortion of anatomy, and the need to minimize obstetrics risks or achieve wider margins. For example, a young, nulliparous patient with an ectocervical lesion of squamous dysplasia would likely best be served by a LEEP, which preserves her cervical stroma and affords her easy access and affordability of the procedure. A patient with a bleeding diathesis including iatrogenic anticoagulant therapy may also benefit from a LEEP to achieve better hemostasis and lower risk of bleeding complications.

A postmenopausal woman with a narrow upper vagina and cervix flush with the vagina from prior excisional procedures may benefit from a conization in the operating room where adequate retraction and exposure can minimize the risk of damage to adjacent structures, and the shape and size of the excision can be tailored to the long, narrow segment that is indicated. The table highlights some of the factors to consider when choosing these options.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest. Contact her at [email protected].

References

1. Martin-Hirsch PL et al. Cochrane Database Syst Rev 2000;(2):CD001318.

2. Arbyn M et al. BMJ. 2008;337:a1284.

3. Jin G et al. Arch Gynecol Obstet. 2014 Jan;289(1):85-99.

4. Perkins RB et al. J Low Genit Tract Dis. 2020;24(2):102.

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.

No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
 

Anti-infectives

Artesunate (384)

The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.

Ebanga (ansuvimab) (147,000)

Studies on its use in pregnant animals have not been conducted.

Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)

Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.

Veklury (remdesivir) (603)

Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Antineoplastics

Ayvakit (avapritinib) (499)

The drug may cause fetal harm. The drug was teratogenic in animals.

Blenrep (belantamab mafodotin-blmf) (152,000)

A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.

Danyelza (naxitamab-gqgk) (144,000)

This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.

Gavreto (pralsetinib) (534)

Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.

Inqovi (cedazuridine + decitabine) (268,228)

The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.

Margenza (margetuximab-cmkb) (149,000)

Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.

Monjuvi (tafasitamab-cxix) (150,000)

This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.

Pemazyre (pemigatinib) (488)

It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.

Qinlock (ripretinib) (510)

This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.

Retevmo (selpercatinib) (526)

This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.

Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.

Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.

Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.

Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.

Tukysa (tucatinib) (481)

Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.

Zeposia (ozanimod) (441)

Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.

Zepzelca (lurbinectedin) (785)

This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
 

Antiemetics

Barhemsys (amisulpride) (369)

This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.

Antimigraine

Nurtec (rimegepant) (611)

Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.

Vyepti (eptinezumab-jjmr) (143,000)

A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
 

CNS

Byfavo (remimazolam) (493 – free base)

This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
 

Diagnostics

Cerianna (fluoroestradiol F 18) (289)

It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.

Detectnet (copper CU-64 dotatate) (1,497)

All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals

Miscellaneous

Dojolvi (triheptanoin) (429)

This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.

Enspryng (satralizumab-mwge) (143,000)

It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.

Evrysdi (risdiplam) (401)

This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.

Gemtesa (vibegron) (445)

Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.

Imcivree (setmelanotide) (1,117)

This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.

Isturisa (osilodrostat) (325)

Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.

Klisyri (tirbanibulin) (431)

Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.

Koselugo (selumetinib) (556)

This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.

Nexletol (bempedoic acid) (344)

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Olinvyk (oliceridine) (503)

Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.

Ongentys (opicapone) (413)

Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.

Orladeyo (berotralstat) (635)

This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.

Oxlumo (lumasiran) (17,286)

Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.

Pizensy (lactitol) (344)

Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.

Rukobia (fostemsavir) (705; 584 for free acid)

This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Sogroya (somapacitan-beco) (23,305)

This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.

Tepezza (teprotumumab-trbw) (148,000)

Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.

Tauvid (flortaucipir F-18) (262)

This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.

Uplizna (inebilizumab-cdon) (149,000)

Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.

Winlevi (clascoterone) (403)

This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.

Xeglyze (abametapir) (1,840)

Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.

Zokinvy (lonafarnib) (639)

Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.

No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
 

Anti-infectives

Artesunate (384)

The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.

Ebanga (ansuvimab) (147,000)

Studies on its use in pregnant animals have not been conducted.

Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)

Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.

Veklury (remdesivir) (603)

Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Antineoplastics

Ayvakit (avapritinib) (499)

The drug may cause fetal harm. The drug was teratogenic in animals.

Blenrep (belantamab mafodotin-blmf) (152,000)

A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.

Danyelza (naxitamab-gqgk) (144,000)

This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.

Gavreto (pralsetinib) (534)

Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.

Inqovi (cedazuridine + decitabine) (268,228)

The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.

Margenza (margetuximab-cmkb) (149,000)

Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.

Monjuvi (tafasitamab-cxix) (150,000)

This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.

Pemazyre (pemigatinib) (488)

It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.

Qinlock (ripretinib) (510)

This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.

Retevmo (selpercatinib) (526)

This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.

Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.

Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.

Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.

Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.

Tukysa (tucatinib) (481)

Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.

Zeposia (ozanimod) (441)

Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.

Zepzelca (lurbinectedin) (785)

This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
 

Antiemetics

Barhemsys (amisulpride) (369)

This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.

Antimigraine

Nurtec (rimegepant) (611)

Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.

Vyepti (eptinezumab-jjmr) (143,000)

A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
 

CNS

Byfavo (remimazolam) (493 – free base)

This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
 

Diagnostics

Cerianna (fluoroestradiol F 18) (289)

It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.

Detectnet (copper CU-64 dotatate) (1,497)

All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals

Miscellaneous

Dojolvi (triheptanoin) (429)

This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.

Enspryng (satralizumab-mwge) (143,000)

It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.

Evrysdi (risdiplam) (401)

This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.

Gemtesa (vibegron) (445)

Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.

Imcivree (setmelanotide) (1,117)

This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.

Isturisa (osilodrostat) (325)

Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.

Klisyri (tirbanibulin) (431)

Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.

Koselugo (selumetinib) (556)

This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.

Nexletol (bempedoic acid) (344)

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Olinvyk (oliceridine) (503)

Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.

Ongentys (opicapone) (413)

Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.

Orladeyo (berotralstat) (635)

This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.

Oxlumo (lumasiran) (17,286)

Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.

Pizensy (lactitol) (344)

Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.

Rukobia (fostemsavir) (705; 584 for free acid)

This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Sogroya (somapacitan-beco) (23,305)

This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.

Tepezza (teprotumumab-trbw) (148,000)

Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.

Tauvid (flortaucipir F-18) (262)

This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.

Uplizna (inebilizumab-cdon) (149,000)

Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.

Winlevi (clascoterone) (403)

This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.

Xeglyze (abametapir) (1,840)

Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.

Zokinvy (lonafarnib) (639)

Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2020, the Food and Drug Administration approved 53 new drugs for humans. One of these agents, Annovera (segesterone and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. Orgovyx (relugolix) is used for prostate cancer and Lampit (nifurtimox) is drug used in children – neither of these two agents will be covered. The remaining 49 are covered below. The agents with molecular weights less than 1,000 probably cross the placenta in the first half of pregnancy, but nearly all, regardless of MW, will cross in the second half of pregnancy.

No human pregnancy data for these agents has been found, but there are five drugs included in pregnancy registries. It will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in an article that I coauthored, “Should pregnant women be included in phase 4 clinical drug trials?”. The article makes a strong argument for including some pregnant women in these trials.
 

Anti-infectives

Artesunate (384)

The drug appears low risk when used in the second and third trimesters. There is inadequate information regarding its use in the first trimester, so the safest course for the embryo appears to be avoiding its use during this period. A single intravenous dose given to rats early in gestation resulted in embryolethality.

Ebanga (ansuvimab) (147,000)

Studies on its use in pregnant animals have not been conducted.

Inmazeb (atoltivimab, maftivimab, odesivimab) (144,000-146,000)

Inmazeb is a combination of the three agents. Studies on its use in pregnant animals have not been conducted.

Veklury (remdesivir) (603)

Veklury is indicated for the treatment of pregnant women hospitalized with COVID-19 who are at risk for serious morbidity and mortality. The drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Antineoplastics

Ayvakit (avapritinib) (499)

The drug may cause fetal harm. The drug was teratogenic in animals.

Blenrep (belantamab mafodotin-blmf) (152,000)

A B-cell maturation antigen, it is indicated for the treatment of multiple myeloma. No human or animal pregnancy data have been located.

Danyelza (naxitamab-gqgk) (144,000)

This agent is used for the treatment of neuroblastoma. Based on its mechanism of action it may cause fetal harm if used in pregnancy.

Gavreto (pralsetinib) (534)

Gavreto is indicated for the treatment of small cell lung cancer. It may cause embryo-fetal harm if used in pregnancy.

Inqovi (cedazuridine + decitabine) (268,228)

The drug combination can cause fetal harm in human pregnancy. It is toxic in pregnant animals.

Margenza (margetuximab-cmkb) (149,000)

Although there are no data on the use of this drug in human pregnancy, the findings in animals and mechanism of action suggest that it will cause fetal harm.

Monjuvi (tafasitamab-cxix) (150,000)

This drug is a cytolytic antibody that is indicated in combination with lenalidomide. The combination may cause fetal harm.

Pemazyre (pemigatinib) (488)

It is indicated for the treatment of cholangiocarcinoma. In an animal study, the drug caused fetal defects, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure.

Qinlock (ripretinib) (510)

This drug is used for the treatment of patients with advanced gastrointestinal stromal tumor. The drug was teratogenic in pregnant animals.

Retevmo (selpercatinib) (526)

This is a kinase inhibitor used for the treatment of small cell lung cancer. The drug is teratogenic in animals.

Sarclisa (isatuximab-irfc) (148,000)This drug is used in combination with pomalidomide and dexamethasone. The combination would probably cause major toxicity in an embryo or fetus.

Tabrecta (capmatinib) (412 – free base)Capmatinib is a kinase inhibitor used for the treatment of metastatic non–small cell lung cancer. It is teratogenic in animals.

Tazverik (tazemetostat) (654)Tazemetostat is indicated for the treatment of epithelioid sarcoma and follicular lymphoma, The drug is teratogenic in animals.

Trodelvy (sacituzumab govitecan-hziy) (1,602)This agent is used for the treatment of breast cancer. The drug has not been tested in pregnant animals. However, according to the manufacturer, there is a high possibility of human teratogenicity if it is given to a pregnant woman.

Tukysa (tucatinib) (481)

Tukysa is a tyrosine kinase inhibitor that is used in combination with trastuzumab and capecitabine for the treatment of breast cancer. The drug is teratogenic in animals.

Zeposia (ozanimod) (441)

Zeposia is indicated for the treatment of multiple sclerosis. The drug takes about 3 months to eliminate from the body. The drug is teratogenic in animals.

Zepzelca (lurbinectedin) (785)

This agent is used for the treatment of metastatic small cell lung cancer. The drug is teratogenic in animals.
 

Antiemetics

Barhemsys (amisulpride) (369)

This agent is Indicated to prevent nausea and vomiting. Animal data suggest low risk of embryo/fetal birth defects.

Antimigraine

Nurtec (rimegepant) (611)

Nurtec is indicated for acute treatment of migraine. Development toxicity was not observed in animals given doses similar to those used in humans.

Vyepti (eptinezumab-jjmr) (143,000)

A humanized monoclonal antibody that is given every 3 months to prevent migraine. There was no embryo-fetal harm in animals given the drug.
 

CNS

Byfavo (remimazolam) (493 – free base)

This drug is indicated for procedural sedation in adults undergoing procedures lasting 30 minutes or less. No defects were observed in animals.
 

Diagnostics

Cerianna (fluoroestradiol F 18) (289)

It is indicated for use with PET for characterization of estrogen receptor status in patients with ER-positive breast cancer. It has the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. There are no data on its use in pregnant women or animals.

Detectnet (copper CU-64 dotatate) (1,497)

All radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. There are no pregnancy data in humans or animals

Miscellaneous

Dojolvi (triheptanoin) (429)

This agent is indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders. Advise patients that there is a pregnancy safety study that collects pregnancy outcome data in women taking Dojolvi during pregnancy. Pregnant patients can enroll in the study by calling 1-888-756-8657.

Enspryng (satralizumab-mwge) (143,000)

It is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. No information is available on the risks, if any, in pregnancy. No adverse effects on maternal or fetal development were observed in pregnant monkeys and their offspring.

Evrysdi (risdiplam) (401)

This is a prescription medicine used to treat spinal muscular atrophy in adults and children aged 2 months and older. In pregnant animals the drug caused adverse effects on fetal development.

Gemtesa (vibegron) (445)

Gemtesa is used in adults to treat the symptoms of overactive bladder. The drug had no adverse effects on pregnant animals.

Imcivree (setmelanotide) (1,117)

This drug is indicated for chronic weight management in adult and pediatric patients aged 6 years and older with obesity because of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. The drug was not embryo toxic in animals.

Isturisa (osilodrostat) (325)

Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease. No adverse fetal effects were observed in pregnant animals.

Klisyri (tirbanibulin) (431)

Tirbanibulin ointment is a microtubule inhibitor that is used to treat actinic keratosis. Information on its effects in pregnancy is not available.

Koselugo (selumetinib) (556)

This is a kinase inhibitor indicated for the treatment of pediatric patients aged 2 years and older. The drug is toxic in pregnant animals but its effects in human pregnancy are not known.

Nexletol (bempedoic acid) (344)

Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL cholesterol. The drug was not teratogenic in animals. Discontinue Nexletol when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Olinvyk (oliceridine) (503)

Olinvyk injection is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic. Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome. The drug was not teratogenic in animals.

Ongentys (opicapone) (413)

Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The drug was teratogenic in rabbits but not in rats.

Orladeyo (berotralstat) (635)

This drug is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema. It was not teratogenic in animals.

Oxlumo (lumasiran) (17,286)

Oxlumo is a HAO1-directed small interfering ribonucleic acid indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels. No adverse effects on pregnancy or embryo-fetal development related to the drug were observed in animals.

Pizensy (lactitol) (344)

Lactitol is minimally absorbed systemically following oral administration. It is unknown whether maternal use will result in fetal exposure to the drug. No effects on embryo-fetal development were observed in animals at doses much higher than the maximum recommended human dosage.

Rukobia (fostemsavir) (705; 584 for free acid)

This drug is an HIV-1–directed attachment inhibitor, in combination with other antiretrovirals. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy. Health care providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Sogroya (somapacitan-beco) (23,305)

This is a human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency. The drug was not teratogenic in animals.

Tepezza (teprotumumab-trbw) (148,000)

Drug is indicated for the treatment of thyroid eye disease. The drug was teratogenic in cynomolgus monkeys. The manufacturer states that because of the risk, the drug should not be used in pregnancy.

Tauvid (flortaucipir F-18) (262)

This drug is indicated for use with PET imaging of the brain to evaluate for Alzheimer’s disease. It is a radioactive drug and should not be used in pregnant women.

Uplizna (inebilizumab-cdon) (149,000)

Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder in adult patients who are anti-AQP4 antibody positive. It is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. Based on animal data, the drug can cause fetal harm because of B-cell lymphopenia and reduce antibody response in offspring exposed to the drug. Women of childbearing potential should use contraception while receiving Uplizna and for 6 months after the last dose.

Winlevi (clascoterone) (403)

This cream is an androgen receptor inhibitor that is indicated for the topical treatment of acne vulgaris in patients aged 12 years and older. Subcutaneous use in animals was associated with fetal defects.

Xeglyze (abametapir) (1,840)

Xeglyze is indicated for the topical treatment of head lice infestation in patients aged 6 months and older. The drug was not teratogenic in animals.

Zokinvy (lonafarnib) (639)

Zokinvy is indicated in patients 12 months or older to reduce the risk of mortality in several conditions. Animal studies have found embryo-fetal harm.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].