Opinion

DDW is now history. While rejoicing that DDW happened (as opposed to when it couldn’t in 2020), the virtual format precluded all those hallway conversations, meetings with mentors and small group (after hour) discussions. This year, AGA saved substantial monies in travel costs. Of note, at Michigan Medicine, we track the miles patients did not have to travel because of our conversion to virtual care (currently about 30% of all ambulatory visits). To date, our “virtual first” protocol has saved over 24 million patient travel-miles since February 2020 (average of 62 miles per patient visit).

The pandemic forced rapid adoption of virtual care and alternative care delivery models. As patients adapted to telehealth, businesses saw opportunities. Health systems have begun to downsize their brick-and-mortar footprints for both clinical and office space. Hospital at Home models are developing as viable alternatives to inpatient care using a hybrid system of on-site nurses and remote physician supervision.

Digital health start-ups are developing rapidly, and equity funding for digital health companies has reached an all-time high of $26.5 billion in 2020. Multiple companies went public through traditional initial public offerings or special purpose acquisition companies. Sameer Berry, MD, recently collected an inventory of major GI digital health companies counted at least 16 with more appearing each month. These companies focus on management of a single condition (for example IBS or Celiac) or full-service virtual GI care that includes “at-risk” financial contracts

I am delighted to announce that Megan Adams, MD, JD, MSc, has been chosen to be the fourth editor in chief of GI & Hepatology News. She and her team will transition into editorial control during Fall 2021. I have known Megan since meeting her at an AGA young faculty function almost 10 years ago. She is extremely talented and knowledgeable about gastroenterology from a variety of viewpoints. She has recruited a strong and dedicated editorial board.

I have enjoyed the last 5 years leading the current board as we have brought breaking news to the GI community. I wish to publicly thank our editorial board and the Frontline staff who monthly publish AGA’s official newspaper.

John I. Allen, MD, MBA, AGAF
Editor in Chief

DDW is now history. While rejoicing that DDW happened (as opposed to when it couldn’t in 2020), the virtual format precluded all those hallway conversations, meetings with mentors and small group (after hour) discussions. This year, AGA saved substantial monies in travel costs. Of note, at Michigan Medicine, we track the miles patients did not have to travel because of our conversion to virtual care (currently about 30% of all ambulatory visits). To date, our “virtual first” protocol has saved over 24 million patient travel-miles since February 2020 (average of 62 miles per patient visit).

The pandemic forced rapid adoption of virtual care and alternative care delivery models. As patients adapted to telehealth, businesses saw opportunities. Health systems have begun to downsize their brick-and-mortar footprints for both clinical and office space. Hospital at Home models are developing as viable alternatives to inpatient care using a hybrid system of on-site nurses and remote physician supervision.

Digital health start-ups are developing rapidly, and equity funding for digital health companies has reached an all-time high of $26.5 billion in 2020. Multiple companies went public through traditional initial public offerings or special purpose acquisition companies. Sameer Berry, MD, recently collected an inventory of major GI digital health companies counted at least 16 with more appearing each month. These companies focus on management of a single condition (for example IBS or Celiac) or full-service virtual GI care that includes “at-risk” financial contracts

I am delighted to announce that Megan Adams, MD, JD, MSc, has been chosen to be the fourth editor in chief of GI & Hepatology News. She and her team will transition into editorial control during Fall 2021. I have known Megan since meeting her at an AGA young faculty function almost 10 years ago. She is extremely talented and knowledgeable about gastroenterology from a variety of viewpoints. She has recruited a strong and dedicated editorial board.

I have enjoyed the last 5 years leading the current board as we have brought breaking news to the GI community. I wish to publicly thank our editorial board and the Frontline staff who monthly publish AGA’s official newspaper.

John I. Allen, MD, MBA, AGAF
Editor in Chief

DDW is now history. While rejoicing that DDW happened (as opposed to when it couldn’t in 2020), the virtual format precluded all those hallway conversations, meetings with mentors and small group (after hour) discussions. This year, AGA saved substantial monies in travel costs. Of note, at Michigan Medicine, we track the miles patients did not have to travel because of our conversion to virtual care (currently about 30% of all ambulatory visits). To date, our “virtual first” protocol has saved over 24 million patient travel-miles since February 2020 (average of 62 miles per patient visit).

The pandemic forced rapid adoption of virtual care and alternative care delivery models. As patients adapted to telehealth, businesses saw opportunities. Health systems have begun to downsize their brick-and-mortar footprints for both clinical and office space. Hospital at Home models are developing as viable alternatives to inpatient care using a hybrid system of on-site nurses and remote physician supervision.

Digital health start-ups are developing rapidly, and equity funding for digital health companies has reached an all-time high of $26.5 billion in 2020. Multiple companies went public through traditional initial public offerings or special purpose acquisition companies. Sameer Berry, MD, recently collected an inventory of major GI digital health companies counted at least 16 with more appearing each month. These companies focus on management of a single condition (for example IBS or Celiac) or full-service virtual GI care that includes “at-risk” financial contracts

I am delighted to announce that Megan Adams, MD, JD, MSc, has been chosen to be the fourth editor in chief of GI & Hepatology News. She and her team will transition into editorial control during Fall 2021. I have known Megan since meeting her at an AGA young faculty function almost 10 years ago. She is extremely talented and knowledgeable about gastroenterology from a variety of viewpoints. She has recruited a strong and dedicated editorial board.

I have enjoyed the last 5 years leading the current board as we have brought breaking news to the GI community. I wish to publicly thank our editorial board and the Frontline staff who monthly publish AGA’s official newspaper.

John I. Allen, MD, MBA, AGAF
Editor in Chief

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.

Remember FOMO (fear of missing out)? The pandemic cured most of us of that! In its place, many are suffering from a new syndrome that has been coined “FOGO” (fear of going out). As the COVID-19 vaccines roll out, restrictions lessen, and cases decline, we face new challenges. The pandemic showed us that “we are all in it together.” Now our patients, family, friends – and even we, ourselves – may face similar anxieties as we transition back.

Our brains love routines. They save energy as we transverse the same pathway with ease. We created new patterns in the first 30 days of quarantine, and we spent more than a year engraining them. Many people remain reluctant to send their children back to school, don’t want to return to the office, and are still avoiding travel and social situations. Many people are feeling even more anxiety as restrictions are lifting and expectations are rising. Those with preexisting anxiety disorders may have an even more difficult time resuming routine activities.

Since the virus is still among us, we need to maintain caution, so some degree of FOGO is wise. But when we limit our activities too much, we create a whole new host of issues. The pandemic gave us all a taste of the agoraphobic lifestyle. It is difficult to know where exactly to draw the line right now between healthy anxiety and anxiety that becomes the disease for ourselves, our families and friends – and our patients.
 

Recommendations for FOGO

• Talk to your families, friends, and patients about what activities you recommend, which they might resume and which they should continue to avoid. People should make plans to optimize their physical and mental health while continuing to protect themselves from COVID-19. If anxiety is becoming the main problem, psychotherapy or medication may be necessary to treat their symptoms.
• Continue to encourage those with FOGO to practice techniques to be calm. Suggest that they take deep breaths with long exhales. This breathing pattern activates the parasympathetic nervous system and will help them feel calmer. We have all been under chronic stress, and our sympathetic nervous system has been in overdrive. We need to be calm to make the best decisions so our frontal lobe can be in charge rather than our primitive, fear-based brain that has been running the show for more a year. Encourage calming activities, such as yoga, meditation, warm baths, spending time in nature, hugging a pet, and more.
• Advise sufferers to start slowly. They should resume activities where they feel the safest. Walking outside with a friend is a good way to start. We now know that transmission is remarkably low or nonexistent if both parties are vaccinated. Exercise is a great way to combat many psychological issues, including FOGO.
• FOGO sufferers should build confidence gradually. Recommend taking one day at a time and trying to find ways to enjoy new ventures out. Soon, our brains will adapt to the new routines and the days of COVID-19 will recede from our thoughts.
• Respect whatever feelings emerge. The closer we and our patients were to trauma, the more challenging it may be to recover. If you or your patients suffered from COVID-19 or had a close family member or friend who did, be prepared to reemerge more slowly. Don’t feel pressured by what others are doing. Go at your own pace. Only you can decide what is the right way to move forward in these times.
• Look for signs of substance overuse or misuse. FOGO sufferers may turn to drugs or alcohol to mask their anxiety. This is a common pothole and should be avoided. Be alert for this problem and discuss it with patients, friends, or family members who may be making unhealthy choices.

Time is a great healer, and remind others that “this too shall pass.” FOGO will give rise to another yet-to-be named syndrome. We seem to be moving in a very positive direction at a remarkable pace. As Alexander Pope so wisely wrote, “Hope springs eternal.” Better times are ahead.
 

Dr. Ritvo, who has almost 30 years’ experience in psychiatry, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa. Momosa Publishing, 2018). Dr. Ritvo has no disclosures.

Remember FOMO (fear of missing out)? The pandemic cured most of us of that! In its place, many are suffering from a new syndrome that has been coined “FOGO” (fear of going out). As the COVID-19 vaccines roll out, restrictions lessen, and cases decline, we face new challenges. The pandemic showed us that “we are all in it together.” Now our patients, family, friends – and even we, ourselves – may face similar anxieties as we transition back.

Our brains love routines. They save energy as we transverse the same pathway with ease. We created new patterns in the first 30 days of quarantine, and we spent more than a year engraining them. Many people remain reluctant to send their children back to school, don’t want to return to the office, and are still avoiding travel and social situations. Many people are feeling even more anxiety as restrictions are lifting and expectations are rising. Those with preexisting anxiety disorders may have an even more difficult time resuming routine activities.

Since the virus is still among us, we need to maintain caution, so some degree of FOGO is wise. But when we limit our activities too much, we create a whole new host of issues. The pandemic gave us all a taste of the agoraphobic lifestyle. It is difficult to know where exactly to draw the line right now between healthy anxiety and anxiety that becomes the disease for ourselves, our families and friends – and our patients.
 

Recommendations for FOGO

• Talk to your families, friends, and patients about what activities you recommend, which they might resume and which they should continue to avoid. People should make plans to optimize their physical and mental health while continuing to protect themselves from COVID-19. If anxiety is becoming the main problem, psychotherapy or medication may be necessary to treat their symptoms.
• Continue to encourage those with FOGO to practice techniques to be calm. Suggest that they take deep breaths with long exhales. This breathing pattern activates the parasympathetic nervous system and will help them feel calmer. We have all been under chronic stress, and our sympathetic nervous system has been in overdrive. We need to be calm to make the best decisions so our frontal lobe can be in charge rather than our primitive, fear-based brain that has been running the show for more a year. Encourage calming activities, such as yoga, meditation, warm baths, spending time in nature, hugging a pet, and more.
• Advise sufferers to start slowly. They should resume activities where they feel the safest. Walking outside with a friend is a good way to start. We now know that transmission is remarkably low or nonexistent if both parties are vaccinated. Exercise is a great way to combat many psychological issues, including FOGO.
• FOGO sufferers should build confidence gradually. Recommend taking one day at a time and trying to find ways to enjoy new ventures out. Soon, our brains will adapt to the new routines and the days of COVID-19 will recede from our thoughts.
• Respect whatever feelings emerge. The closer we and our patients were to trauma, the more challenging it may be to recover. If you or your patients suffered from COVID-19 or had a close family member or friend who did, be prepared to reemerge more slowly. Don’t feel pressured by what others are doing. Go at your own pace. Only you can decide what is the right way to move forward in these times.
• Look for signs of substance overuse or misuse. FOGO sufferers may turn to drugs or alcohol to mask their anxiety. This is a common pothole and should be avoided. Be alert for this problem and discuss it with patients, friends, or family members who may be making unhealthy choices.

Time is a great healer, and remind others that “this too shall pass.” FOGO will give rise to another yet-to-be named syndrome. We seem to be moving in a very positive direction at a remarkable pace. As Alexander Pope so wisely wrote, “Hope springs eternal.” Better times are ahead.
 

Dr. Ritvo, who has almost 30 years’ experience in psychiatry, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa. Momosa Publishing, 2018). Dr. Ritvo has no disclosures.

Remember FOMO (fear of missing out)? The pandemic cured most of us of that! In its place, many are suffering from a new syndrome that has been coined “FOGO” (fear of going out). As the COVID-19 vaccines roll out, restrictions lessen, and cases decline, we face new challenges. The pandemic showed us that “we are all in it together.” Now our patients, family, friends – and even we, ourselves – may face similar anxieties as we transition back.

Our brains love routines. They save energy as we transverse the same pathway with ease. We created new patterns in the first 30 days of quarantine, and we spent more than a year engraining them. Many people remain reluctant to send their children back to school, don’t want to return to the office, and are still avoiding travel and social situations. Many people are feeling even more anxiety as restrictions are lifting and expectations are rising. Those with preexisting anxiety disorders may have an even more difficult time resuming routine activities.

Since the virus is still among us, we need to maintain caution, so some degree of FOGO is wise. But when we limit our activities too much, we create a whole new host of issues. The pandemic gave us all a taste of the agoraphobic lifestyle. It is difficult to know where exactly to draw the line right now between healthy anxiety and anxiety that becomes the disease for ourselves, our families and friends – and our patients.
 

Recommendations for FOGO

• Talk to your families, friends, and patients about what activities you recommend, which they might resume and which they should continue to avoid. People should make plans to optimize their physical and mental health while continuing to protect themselves from COVID-19. If anxiety is becoming the main problem, psychotherapy or medication may be necessary to treat their symptoms.
• Continue to encourage those with FOGO to practice techniques to be calm. Suggest that they take deep breaths with long exhales. This breathing pattern activates the parasympathetic nervous system and will help them feel calmer. We have all been under chronic stress, and our sympathetic nervous system has been in overdrive. We need to be calm to make the best decisions so our frontal lobe can be in charge rather than our primitive, fear-based brain that has been running the show for more a year. Encourage calming activities, such as yoga, meditation, warm baths, spending time in nature, hugging a pet, and more.
• Advise sufferers to start slowly. They should resume activities where they feel the safest. Walking outside with a friend is a good way to start. We now know that transmission is remarkably low or nonexistent if both parties are vaccinated. Exercise is a great way to combat many psychological issues, including FOGO.
• FOGO sufferers should build confidence gradually. Recommend taking one day at a time and trying to find ways to enjoy new ventures out. Soon, our brains will adapt to the new routines and the days of COVID-19 will recede from our thoughts.
• Respect whatever feelings emerge. The closer we and our patients were to trauma, the more challenging it may be to recover. If you or your patients suffered from COVID-19 or had a close family member or friend who did, be prepared to reemerge more slowly. Don’t feel pressured by what others are doing. Go at your own pace. Only you can decide what is the right way to move forward in these times.
• Look for signs of substance overuse or misuse. FOGO sufferers may turn to drugs or alcohol to mask their anxiety. This is a common pothole and should be avoided. Be alert for this problem and discuss it with patients, friends, or family members who may be making unhealthy choices.

Time is a great healer, and remind others that “this too shall pass.” FOGO will give rise to another yet-to-be named syndrome. We seem to be moving in a very positive direction at a remarkable pace. As Alexander Pope so wisely wrote, “Hope springs eternal.” Better times are ahead.
 

Dr. Ritvo, who has almost 30 years’ experience in psychiatry, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa. Momosa Publishing, 2018). Dr. Ritvo has no disclosures.

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.

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].

Approaching the nursing unit, I heard the anxiety in my masked colleagues’ voices. I was starting another rotation on our COVID unit; this week I was trying to develop my emotional awareness in an effort to help with the stress of the job and, just as importantly, take in the moments of positive emotions when they arose. I was making a conscious effort to take in all I saw and felt in the same way I approached my patient examinations: my mind quiet, receptive, and curious.

Seeing my nursing teammates covered with personal protective equipment, I felt a little reverence at the purpose they bring to work. Thinking of our patients, isolated and scared in noisy, ventilated rooms, there was compassion welling up in my chest. Thinking about my role on the team, I felt humbled by the challenges of treating this new disease and meeting the needs of staff and patient.

A few years ago, a period of frustration and disaffectedness had led me to apply my diagnostic eye to myself: I was burning out. Developing a mindfulness practice has transformed my experience at work. Now, the pandemic pushed me to go beyond a few minutes of quieting the mind before work. I was developing my emotional awareness. A growing body of research suggests that emotional awareness helps temper the negative experiences and savor the good. This week on the COVID unit was an opportunity to put this idea to the test.

Across the hall from the desk was Ms. A, 85-year-old woman who always clutched her rosary. My Spanish is not great, but I understood her prayer when I entered the room. She had tested positive for COVID about 7 days before – so had all the people in her multigenerational home. Over the din of the negative-pressure machine, with damp eyes she kept saying she wanted to go home. I felt my body soften and, in my chest, it felt as if my heart moved towards her which is the manifestation of compassion. “I will do my best to get you there soon,” I said in an effort to comfort her.

We often resist strong emotions, especially at work, because they can increase stress in situations where we need to be in control. In high-emotion situations, our brain’s warning centers alert both body and brain. This has helped our ancestors to action over the millennia, but in the hospital, these responses hurt more than help. Our bodies amplifying the emotion, our mind races for solutions and we can feel overwhelmed.

Simply recognizing the emotion and naming it puts the brakes on this process. fMRI data demonstrate that naming the emotions moves the brain activity away from the emotion centers to the appraisal centers in the frontal lobe. Just the perspective to see the emotional process calms it down.

Name it to tame it – this is what those in the field call this act. “This is sadness,” I said to myself as I left Ms. A’s room.

Down the hall was Mr. D; he was an 81-year-old former Vietnamese refugee. He had come in 3 days prior to my coming on service. While he didn’t talk, even with an interpreter, he ate well and had looked comfortable for days on 50% O₂.

Ms. A’s O₂ needs crept up each day as did her anxiety, the plaintive tenor of her prayers and inquiries about going home. I got a priest to visit, not for last rites but just for some support. Over the phone, I updated the family on the prognosis.

A couple of days later, she needed 95% O₂ and with PO₂ was only 70. I told her family it seemed she was losing her battle with the virus. I said we could see how she did on 60% – that’s the max she could get at home with hospice. I called them after 2 hours on 60% to tell them she was up eating and despite slight increased resp rate, she looked okay. “Can you guarantee that she would not make it if she stayed in the hospital? “

My body vibrating with uncertainty – an emotional mix of fear and sadness – I said, “I am sorry, but this is such a new disease, I can’t say that for certain.” On the call, family members voiced different opinions, but in the end, they were unable to give up hope, so we agreed to keep her in hospital.

Down the hall, Mr. D had stopped eating and his sats dropped as did his blood pressure. A nurse exited his room; despite the mask and steamed-up glasses, I could read her body language. “That poor man is dying,” she said. I told her I agreed and called the family with the news and to offer them a chance to visit and to talk about home hospice.

“He has not seen any of us in 10 months,” said his daughter over the phone, “We would love to visit and talk about bringing him home on hospice.” The next morning four of his nine kids showed up with a quart of jook, an Asian rice porridge, for him and pastries for the staff.

They left the room smiling an hour later. “He ate all the jook and he smiled! Yes, let’s work on home with hospice.” That night his blood pressure was better, and we were able to move him to 8 liters oxymizer; the staff was excited by his improvement, too.

The next day Ms. A was less responsive with sats in the 80’s on 100% FiO₂, but she still had this great sense of warmth and dignity about her. When I entered the room, Spanish Catholic hymns were playing, two of her kids stood leaning over the bed and on an iPod, there was a chorus of tears. 20 family members were all crying on a Zoom call. Together this made the most beautiful soundtrack to an end of life I have ever heard. I tried hard not to join the chorus as we talked about turning off the oxygen to help limit her suffering.

We added a bolus of morphine to her drip and removed the oxygen. She looked more beautiful and peaceful without it. Briefly, she closed her eyes then opened them, her breathing calmer. And with the hymns and the chorus of family crying she lived another 20 minutes in the loving presence of her big family.

Leaving the room, I was flooded with “woulda, coulda, shouldas” that accompany work with so much uncertainty and high stakes. “Maybe I should have tried convalescent plasma. Maybe I should have told them she must go home,” and so on my mind went on looking for solutions when there were none. I turned to my body – my chest ached, and I whispered to myself: “This is how sadness feels.”

By thinking about how the emotion feels in the body, we move the mind away from problem solving that can end up leading to unhealthy ruminations. Such thoughts in times of high emotions lead to that pressurized, tightness feeling we get when overwhelmed. Taking in the universal sensations of the emotions is calming and connects us with these deep human experiences in healthy ways. At the same time, the racing and ruminations stop.

Meanwhile, down the hall, Mr. D’s family arrived in great spirits armed with more food for patient and staff. He was to go home later that day with hospice. When they saw him up in the chair without the oxygen, they said: “It is a miracle, Dr. Hass! He is going home on hospice but having beat COVID! We can’t thank you enough!”

“Don’t thank me! He was cured by love and jook! What a lesson for us all. Sometimes there is no better medicine than food from home and love!” With the explosive expansiveness of joy, we shared some “elbow bumps” and took some pictures before he was wheeled home.

Back at the nurse’s station, there were tears. Sometimes life is so full of emotion that it is hard to give it a name – joy? grief? Our bodies almost pulsing, our minds searching for words, it is as if an ancient process is marking a time and place in our souls. “This is what it is to be a human being living with love and creating meaning,” the experience seems to be telling us.

This is awesome work. In fact, awe was what we were feeling then – that sense of wonder we have in the presence of something beautiful or vast that we cannot easily comprehend. Taking in these moments of awe at the power and depth of the human experience is critical to keep us humble, engaged, and emotionally involved.

Cultivating emotional awareness is a simple technique to maintain equanimity as we do the emotionally turbulent work of caring for vulnerable and seriously ill members of our community. It uses the same techniques of attention and diagnosis we use on those we care for. It is a practice that can be seamlessly incorporated into our workday with no time added. Recognizing it, naming it, and feeling it will give us the resilience to handle the challenges this amazing work inevitably brings.

Dr. Hass is a hospitalist at Sutter East Bay Medical Group in Oakland, Calif. He is a member of the clinical faculty at the University of California, Berkeley–UC San Francisco joint medical program, and an adviser on health and health care at the Greater Good Science Center at UC Berkeley.

Approaching the nursing unit, I heard the anxiety in my masked colleagues’ voices. I was starting another rotation on our COVID unit; this week I was trying to develop my emotional awareness in an effort to help with the stress of the job and, just as importantly, take in the moments of positive emotions when they arose. I was making a conscious effort to take in all I saw and felt in the same way I approached my patient examinations: my mind quiet, receptive, and curious.

Seeing my nursing teammates covered with personal protective equipment, I felt a little reverence at the purpose they bring to work. Thinking of our patients, isolated and scared in noisy, ventilated rooms, there was compassion welling up in my chest. Thinking about my role on the team, I felt humbled by the challenges of treating this new disease and meeting the needs of staff and patient.

A few years ago, a period of frustration and disaffectedness had led me to apply my diagnostic eye to myself: I was burning out. Developing a mindfulness practice has transformed my experience at work. Now, the pandemic pushed me to go beyond a few minutes of quieting the mind before work. I was developing my emotional awareness. A growing body of research suggests that emotional awareness helps temper the negative experiences and savor the good. This week on the COVID unit was an opportunity to put this idea to the test.

Across the hall from the desk was Ms. A, 85-year-old woman who always clutched her rosary. My Spanish is not great, but I understood her prayer when I entered the room. She had tested positive for COVID about 7 days before – so had all the people in her multigenerational home. Over the din of the negative-pressure machine, with damp eyes she kept saying she wanted to go home. I felt my body soften and, in my chest, it felt as if my heart moved towards her which is the manifestation of compassion. “I will do my best to get you there soon,” I said in an effort to comfort her.

We often resist strong emotions, especially at work, because they can increase stress in situations where we need to be in control. In high-emotion situations, our brain’s warning centers alert both body and brain. This has helped our ancestors to action over the millennia, but in the hospital, these responses hurt more than help. Our bodies amplifying the emotion, our mind races for solutions and we can feel overwhelmed.

Simply recognizing the emotion and naming it puts the brakes on this process. fMRI data demonstrate that naming the emotions moves the brain activity away from the emotion centers to the appraisal centers in the frontal lobe. Just the perspective to see the emotional process calms it down.

Name it to tame it – this is what those in the field call this act. “This is sadness,” I said to myself as I left Ms. A’s room.

Down the hall was Mr. D; he was an 81-year-old former Vietnamese refugee. He had come in 3 days prior to my coming on service. While he didn’t talk, even with an interpreter, he ate well and had looked comfortable for days on 50% O₂.

Ms. A’s O₂ needs crept up each day as did her anxiety, the plaintive tenor of her prayers and inquiries about going home. I got a priest to visit, not for last rites but just for some support. Over the phone, I updated the family on the prognosis.

A couple of days later, she needed 95% O₂ and with PO₂ was only 70. I told her family it seemed she was losing her battle with the virus. I said we could see how she did on 60% – that’s the max she could get at home with hospice. I called them after 2 hours on 60% to tell them she was up eating and despite slight increased resp rate, she looked okay. “Can you guarantee that she would not make it if she stayed in the hospital? “

My body vibrating with uncertainty – an emotional mix of fear and sadness – I said, “I am sorry, but this is such a new disease, I can’t say that for certain.” On the call, family members voiced different opinions, but in the end, they were unable to give up hope, so we agreed to keep her in hospital.

Down the hall, Mr. D had stopped eating and his sats dropped as did his blood pressure. A nurse exited his room; despite the mask and steamed-up glasses, I could read her body language. “That poor man is dying,” she said. I told her I agreed and called the family with the news and to offer them a chance to visit and to talk about home hospice.

“He has not seen any of us in 10 months,” said his daughter over the phone, “We would love to visit and talk about bringing him home on hospice.” The next morning four of his nine kids showed up with a quart of jook, an Asian rice porridge, for him and pastries for the staff.

They left the room smiling an hour later. “He ate all the jook and he smiled! Yes, let’s work on home with hospice.” That night his blood pressure was better, and we were able to move him to 8 liters oxymizer; the staff was excited by his improvement, too.

The next day Ms. A was less responsive with sats in the 80’s on 100% FiO₂, but she still had this great sense of warmth and dignity about her. When I entered the room, Spanish Catholic hymns were playing, two of her kids stood leaning over the bed and on an iPod, there was a chorus of tears. 20 family members were all crying on a Zoom call. Together this made the most beautiful soundtrack to an end of life I have ever heard. I tried hard not to join the chorus as we talked about turning off the oxygen to help limit her suffering.

We added a bolus of morphine to her drip and removed the oxygen. She looked more beautiful and peaceful without it. Briefly, she closed her eyes then opened them, her breathing calmer. And with the hymns and the chorus of family crying she lived another 20 minutes in the loving presence of her big family.

Leaving the room, I was flooded with “woulda, coulda, shouldas” that accompany work with so much uncertainty and high stakes. “Maybe I should have tried convalescent plasma. Maybe I should have told them she must go home,” and so on my mind went on looking for solutions when there were none. I turned to my body – my chest ached, and I whispered to myself: “This is how sadness feels.”

By thinking about how the emotion feels in the body, we move the mind away from problem solving that can end up leading to unhealthy ruminations. Such thoughts in times of high emotions lead to that pressurized, tightness feeling we get when overwhelmed. Taking in the universal sensations of the emotions is calming and connects us with these deep human experiences in healthy ways. At the same time, the racing and ruminations stop.

Meanwhile, down the hall, Mr. D’s family arrived in great spirits armed with more food for patient and staff. He was to go home later that day with hospice. When they saw him up in the chair without the oxygen, they said: “It is a miracle, Dr. Hass! He is going home on hospice but having beat COVID! We can’t thank you enough!”

“Don’t thank me! He was cured by love and jook! What a lesson for us all. Sometimes there is no better medicine than food from home and love!” With the explosive expansiveness of joy, we shared some “elbow bumps” and took some pictures before he was wheeled home.

Back at the nurse’s station, there were tears. Sometimes life is so full of emotion that it is hard to give it a name – joy? grief? Our bodies almost pulsing, our minds searching for words, it is as if an ancient process is marking a time and place in our souls. “This is what it is to be a human being living with love and creating meaning,” the experience seems to be telling us.

This is awesome work. In fact, awe was what we were feeling then – that sense of wonder we have in the presence of something beautiful or vast that we cannot easily comprehend. Taking in these moments of awe at the power and depth of the human experience is critical to keep us humble, engaged, and emotionally involved.

Cultivating emotional awareness is a simple technique to maintain equanimity as we do the emotionally turbulent work of caring for vulnerable and seriously ill members of our community. It uses the same techniques of attention and diagnosis we use on those we care for. It is a practice that can be seamlessly incorporated into our workday with no time added. Recognizing it, naming it, and feeling it will give us the resilience to handle the challenges this amazing work inevitably brings.

Dr. Hass is a hospitalist at Sutter East Bay Medical Group in Oakland, Calif. He is a member of the clinical faculty at the University of California, Berkeley–UC San Francisco joint medical program, and an adviser on health and health care at the Greater Good Science Center at UC Berkeley.

Approaching the nursing unit, I heard the anxiety in my masked colleagues’ voices. I was starting another rotation on our COVID unit; this week I was trying to develop my emotional awareness in an effort to help with the stress of the job and, just as importantly, take in the moments of positive emotions when they arose. I was making a conscious effort to take in all I saw and felt in the same way I approached my patient examinations: my mind quiet, receptive, and curious.

Seeing my nursing teammates covered with personal protective equipment, I felt a little reverence at the purpose they bring to work. Thinking of our patients, isolated and scared in noisy, ventilated rooms, there was compassion welling up in my chest. Thinking about my role on the team, I felt humbled by the challenges of treating this new disease and meeting the needs of staff and patient.

A few years ago, a period of frustration and disaffectedness had led me to apply my diagnostic eye to myself: I was burning out. Developing a mindfulness practice has transformed my experience at work. Now, the pandemic pushed me to go beyond a few minutes of quieting the mind before work. I was developing my emotional awareness. A growing body of research suggests that emotional awareness helps temper the negative experiences and savor the good. This week on the COVID unit was an opportunity to put this idea to the test.

Across the hall from the desk was Ms. A, 85-year-old woman who always clutched her rosary. My Spanish is not great, but I understood her prayer when I entered the room. She had tested positive for COVID about 7 days before – so had all the people in her multigenerational home. Over the din of the negative-pressure machine, with damp eyes she kept saying she wanted to go home. I felt my body soften and, in my chest, it felt as if my heart moved towards her which is the manifestation of compassion. “I will do my best to get you there soon,” I said in an effort to comfort her.

We often resist strong emotions, especially at work, because they can increase stress in situations where we need to be in control. In high-emotion situations, our brain’s warning centers alert both body and brain. This has helped our ancestors to action over the millennia, but in the hospital, these responses hurt more than help. Our bodies amplifying the emotion, our mind races for solutions and we can feel overwhelmed.

Simply recognizing the emotion and naming it puts the brakes on this process. fMRI data demonstrate that naming the emotions moves the brain activity away from the emotion centers to the appraisal centers in the frontal lobe. Just the perspective to see the emotional process calms it down.

Name it to tame it – this is what those in the field call this act. “This is sadness,” I said to myself as I left Ms. A’s room.

Down the hall was Mr. D; he was an 81-year-old former Vietnamese refugee. He had come in 3 days prior to my coming on service. While he didn’t talk, even with an interpreter, he ate well and had looked comfortable for days on 50% O₂.

Ms. A’s O₂ needs crept up each day as did her anxiety, the plaintive tenor of her prayers and inquiries about going home. I got a priest to visit, not for last rites but just for some support. Over the phone, I updated the family on the prognosis.

A couple of days later, she needed 95% O₂ and with PO₂ was only 70. I told her family it seemed she was losing her battle with the virus. I said we could see how she did on 60% – that’s the max she could get at home with hospice. I called them after 2 hours on 60% to tell them she was up eating and despite slight increased resp rate, she looked okay. “Can you guarantee that she would not make it if she stayed in the hospital? “

My body vibrating with uncertainty – an emotional mix of fear and sadness – I said, “I am sorry, but this is such a new disease, I can’t say that for certain.” On the call, family members voiced different opinions, but in the end, they were unable to give up hope, so we agreed to keep her in hospital.

Down the hall, Mr. D had stopped eating and his sats dropped as did his blood pressure. A nurse exited his room; despite the mask and steamed-up glasses, I could read her body language. “That poor man is dying,” she said. I told her I agreed and called the family with the news and to offer them a chance to visit and to talk about home hospice.

“He has not seen any of us in 10 months,” said his daughter over the phone, “We would love to visit and talk about bringing him home on hospice.” The next morning four of his nine kids showed up with a quart of jook, an Asian rice porridge, for him and pastries for the staff.

They left the room smiling an hour later. “He ate all the jook and he smiled! Yes, let’s work on home with hospice.” That night his blood pressure was better, and we were able to move him to 8 liters oxymizer; the staff was excited by his improvement, too.

The next day Ms. A was less responsive with sats in the 80’s on 100% FiO₂, but she still had this great sense of warmth and dignity about her. When I entered the room, Spanish Catholic hymns were playing, two of her kids stood leaning over the bed and on an iPod, there was a chorus of tears. 20 family members were all crying on a Zoom call. Together this made the most beautiful soundtrack to an end of life I have ever heard. I tried hard not to join the chorus as we talked about turning off the oxygen to help limit her suffering.

We added a bolus of morphine to her drip and removed the oxygen. She looked more beautiful and peaceful without it. Briefly, she closed her eyes then opened them, her breathing calmer. And with the hymns and the chorus of family crying she lived another 20 minutes in the loving presence of her big family.

Leaving the room, I was flooded with “woulda, coulda, shouldas” that accompany work with so much uncertainty and high stakes. “Maybe I should have tried convalescent plasma. Maybe I should have told them she must go home,” and so on my mind went on looking for solutions when there were none. I turned to my body – my chest ached, and I whispered to myself: “This is how sadness feels.”

By thinking about how the emotion feels in the body, we move the mind away from problem solving that can end up leading to unhealthy ruminations. Such thoughts in times of high emotions lead to that pressurized, tightness feeling we get when overwhelmed. Taking in the universal sensations of the emotions is calming and connects us with these deep human experiences in healthy ways. At the same time, the racing and ruminations stop.

Meanwhile, down the hall, Mr. D’s family arrived in great spirits armed with more food for patient and staff. He was to go home later that day with hospice. When they saw him up in the chair without the oxygen, they said: “It is a miracle, Dr. Hass! He is going home on hospice but having beat COVID! We can’t thank you enough!”

“Don’t thank me! He was cured by love and jook! What a lesson for us all. Sometimes there is no better medicine than food from home and love!” With the explosive expansiveness of joy, we shared some “elbow bumps” and took some pictures before he was wheeled home.

Back at the nurse’s station, there were tears. Sometimes life is so full of emotion that it is hard to give it a name – joy? grief? Our bodies almost pulsing, our minds searching for words, it is as if an ancient process is marking a time and place in our souls. “This is what it is to be a human being living with love and creating meaning,” the experience seems to be telling us.

This is awesome work. In fact, awe was what we were feeling then – that sense of wonder we have in the presence of something beautiful or vast that we cannot easily comprehend. Taking in these moments of awe at the power and depth of the human experience is critical to keep us humble, engaged, and emotionally involved.

Cultivating emotional awareness is a simple technique to maintain equanimity as we do the emotionally turbulent work of caring for vulnerable and seriously ill members of our community. It uses the same techniques of attention and diagnosis we use on those we care for. It is a practice that can be seamlessly incorporated into our workday with no time added. Recognizing it, naming it, and feeling it will give us the resilience to handle the challenges this amazing work inevitably brings.

Dr. Hass is a hospitalist at Sutter East Bay Medical Group in Oakland, Calif. He is a member of the clinical faculty at the University of California, Berkeley–UC San Francisco joint medical program, and an adviser on health and health care at the Greater Good Science Center at UC Berkeley.

The publication of the draft sequence for the human genome changed the research and clinical medicine landscape forever. This genetic map created the possibility to develop more personalized health care and targeted therapeutics. It opened the door to the age of “big data” sets in biomedical research, fusing science, computer technology, and mathematics – the “s,” “t,” and “m” of “STEM.”

In the 20 years that followed the publication of the human genome, many advances in biomedicine occurred. Improvements in DNA sequencing technologies, built upon the original sequencing project, made the noninvasive prenatal screening test (NIPT) possible. The ease, speed, and cost effectiveness of sequencing has made diagnosing fetal structural anomalies using whole-exome sequencing a reality.

However, uncovering humanity’s genetic code introduced new quandaries and reopened old wounds: How would a person’s genetic data be used? Could a person’s risk for disease, identified through sequencing, lead to overdiagnosis? Would knowing the human genome reinforce age-old ideas that genes make one group superior or inferior? Could we now create “designer babies”?

This last question has become even more pressing with the advent of human gene editing technology, also known by its acronym “CRISPR.” The ability to pick and choose a gene to replace within an organism could transform how we treat diseases caused by genetic mutations, but it also has the potential for bringing us to the precipice of a Wellsian reality. The alarming claim that scientists had used CRISPR to edit the genes of human babies (Nature. 2020;577[7789]:154-5; doi:10.1038/d41586-020-00001-y) has rippled through the biomedical community and spurred numerous debates on the ethics of using such a powerful tool (Human Genome Editing: Science, Ethics, and Governance; doi: 10.17226/24623).

The passage of the Genetic Information Non-discrimination Act (GINA; https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008) in 2008 ensured that health insurance companies and employers could not use a person’s genome against them, creating a balance between the forces of “can we?” and “should we?” Yet, many ethical questions remain.

We have invited two experts from the University of Maryland (Baltimore) School of Medicine’s department of obstetrics, gynecology & reproductive sciences, Christopher Harman, MD, professor and chair, and Amanda Higgs, MGC, CGC, senior genetic counselor, to address how advances in genomics affect patient care and counseling.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

The publication of the draft sequence for the human genome changed the research and clinical medicine landscape forever. This genetic map created the possibility to develop more personalized health care and targeted therapeutics. It opened the door to the age of “big data” sets in biomedical research, fusing science, computer technology, and mathematics – the “s,” “t,” and “m” of “STEM.”

In the 20 years that followed the publication of the human genome, many advances in biomedicine occurred. Improvements in DNA sequencing technologies, built upon the original sequencing project, made the noninvasive prenatal screening test (NIPT) possible. The ease, speed, and cost effectiveness of sequencing has made diagnosing fetal structural anomalies using whole-exome sequencing a reality.

However, uncovering humanity’s genetic code introduced new quandaries and reopened old wounds: How would a person’s genetic data be used? Could a person’s risk for disease, identified through sequencing, lead to overdiagnosis? Would knowing the human genome reinforce age-old ideas that genes make one group superior or inferior? Could we now create “designer babies”?

This last question has become even more pressing with the advent of human gene editing technology, also known by its acronym “CRISPR.” The ability to pick and choose a gene to replace within an organism could transform how we treat diseases caused by genetic mutations, but it also has the potential for bringing us to the precipice of a Wellsian reality. The alarming claim that scientists had used CRISPR to edit the genes of human babies (Nature. 2020;577[7789]:154-5; doi:10.1038/d41586-020-00001-y) has rippled through the biomedical community and spurred numerous debates on the ethics of using such a powerful tool (Human Genome Editing: Science, Ethics, and Governance; doi: 10.17226/24623).

The passage of the Genetic Information Non-discrimination Act (GINA; https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008) in 2008 ensured that health insurance companies and employers could not use a person’s genome against them, creating a balance between the forces of “can we?” and “should we?” Yet, many ethical questions remain.

We have invited two experts from the University of Maryland (Baltimore) School of Medicine’s department of obstetrics, gynecology & reproductive sciences, Christopher Harman, MD, professor and chair, and Amanda Higgs, MGC, CGC, senior genetic counselor, to address how advances in genomics affect patient care and counseling.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

The publication of the draft sequence for the human genome changed the research and clinical medicine landscape forever. This genetic map created the possibility to develop more personalized health care and targeted therapeutics. It opened the door to the age of “big data” sets in biomedical research, fusing science, computer technology, and mathematics – the “s,” “t,” and “m” of “STEM.”

In the 20 years that followed the publication of the human genome, many advances in biomedicine occurred. Improvements in DNA sequencing technologies, built upon the original sequencing project, made the noninvasive prenatal screening test (NIPT) possible. The ease, speed, and cost effectiveness of sequencing has made diagnosing fetal structural anomalies using whole-exome sequencing a reality.

However, uncovering humanity’s genetic code introduced new quandaries and reopened old wounds: How would a person’s genetic data be used? Could a person’s risk for disease, identified through sequencing, lead to overdiagnosis? Would knowing the human genome reinforce age-old ideas that genes make one group superior or inferior? Could we now create “designer babies”?

This last question has become even more pressing with the advent of human gene editing technology, also known by its acronym “CRISPR.” The ability to pick and choose a gene to replace within an organism could transform how we treat diseases caused by genetic mutations, but it also has the potential for bringing us to the precipice of a Wellsian reality. The alarming claim that scientists had used CRISPR to edit the genes of human babies (Nature. 2020;577[7789]:154-5; doi:10.1038/d41586-020-00001-y) has rippled through the biomedical community and spurred numerous debates on the ethics of using such a powerful tool (Human Genome Editing: Science, Ethics, and Governance; doi: 10.17226/24623).

The passage of the Genetic Information Non-discrimination Act (GINA; https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008) in 2008 ensured that health insurance companies and employers could not use a person’s genome against them, creating a balance between the forces of “can we?” and “should we?” Yet, many ethical questions remain.

We have invited two experts from the University of Maryland (Baltimore) School of Medicine’s department of obstetrics, gynecology & reproductive sciences, Christopher Harman, MD, professor and chair, and Amanda Higgs, MGC, CGC, senior genetic counselor, to address how advances in genomics affect patient care and counseling.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

Patient navigation as a best practice for GI procedures

Colonoscopy is the preferred method for colorectal cancer (CRC) screening. Among scheduled outpatient colonoscopies, key metrics like no-show rates and poor bowel preparation can be as high as 25% in some facilities. These missed appointments and repeated calls with patients have been an important source of wasted resources, poor patient outcomes, and revenue loss for endoscopy facilities (estimated to be up to $1 million dollars for 10-member GI practice).

Studies have shown that patient navigation (PN), a patient-centered approach, overcomes barriers in health care delivery, thus improving adherence to CRC screening. Typically, navigators are specialized health practitioners who fill a variety of functions, including providing updates and instructions to patients, as well as assisting with test-related fears. Despite the overall cost-effectiveness, PN programs require significant resources from hospitals or medical groups. The continued focus in the United States on value-based medicine has provided an urgent need for cost-effective treatments that are also readily available to most physicians.
 

Digital navigation to automate navigation for colonoscopy and other GI procedures

Digital navigation (DN) is a new navigation technique that enables patients to receive appointment updates, resources related to a treatment or condition, stepwise bowel prep directions, and other periprocedural guidance in an automated and convenient manner (see Figure below). Given the widespread use of mobile phones, DN has the ability to change the way doctors and health care providers work. This led to Mount Sinai Health System, New York, conducting a quality improvement program to automate and evaluate the effectiveness of an automated text messaging and web-based “digital navigation” platform for decreasing colonoscopy appointment no-show rates.

Dr. Ashish Atreja/Icahn School of Medicine

If a valid phone number was available in the patient’s electronic medical record chart and they did not opt out of receiving text message communications from the Mount Sinai Health System, patients over the age of 18 years who were scheduled for a colonoscopy at either of Mount Sinai Hospital, Mount Sinai Morningside, or Mount Sinai West were automatically sent DN SMS messages. The RxUniverse software platform (Rx.Health, New York) was used to send DN content through SMS to all eligible patients. The software platform interfaces with the EMR and endoscopy system (Provation) to automatically extract patient phone number and appointment details.
 

Impact of digital navigation and patient engagement

This study at Mount Sinai Health System demonstrated that patient engagement with SMS-based navigation is strongly predictive of colonoscopy completion. Patients with high engagement with digital navigation are about four times more likely to complete colonoscopy. Of all covariates included in the model, high DN engagement level had the largest effect size (odds ratio, 3.97), compared with no engagement. For health systems with patient navigators, targeting patients who are unlikely to engage DN or are low-engagers may be a more efficient use of person-to-person navigation.

Value-based reimbursement and cost-effectiveness have emerged as core principles in American health care reform, possibly requiring the creation of affordable, cost-effective approaches. Our research at Mount Sinai Health System suggested that SMS-based navigation can be a potential cost-effective strategy for reducing no-show rates. Beyond appointment no-shows, adequate bowel preparation is another important component of the preprocedure navigation process. Insufficient bowel preparation requires a repeat procedure, as poor visualization of the colon results in reduced therapeutic benefit from screening colonoscopy. We’ve shown in previous studies that our DN platform can increase bowel preparation efficiency, which results in lower rates of aborted procedures.

Missed colonoscopies not only cause longer wait times for patients, but they also cost the average facility $725 a day in lost revenue. It has been found through studies that traditional PN is cost-effective, with additional revenue generated from increased colonoscopy completion rates exceeding the costs of program implementation. While formal cost analyses have not been conducted on DN, estimates have shown around $1 million in annual savings for an average ambulatory surgery center or 10-member GI practice.
 

Looking ahead: AGA digital transformation network

After positive results for the Rx.Health’s platform were seen at Mount Sinai Health System, the American Gastroenterological Association partnered with Rx.Health to provide the GI community with a GI endoscopy transformation network. The core purpose of this endoscopy transformation network is to take an evidence-based approach and use digital medicine to positively affect key metrics and safety around periprocedural care and support “procedure bundles.” To illustrate the specific case of colonoscopy, these included the following: enhancing colorectal cancer surveillance rates though a comprehensive screening test strategy, decreasing no-show rates through shared decision-making and better preprocedure engagement, improving rates of adequate bowel preparation, benchmarking safety of procedures nationwide, and ensuring patient satisfaction and adequate recall for repeat procedures. These metrics represent key sources of revenue loss for provider organizations and, more importantly, have negative implications on patient care.

This collaboration is now supporting the implementation and expansion of the digital navigation program to all GI procedures at more than 15 different sites across the country.

Dr. Atreja is an adjunct associate professor at the Icahn School of Medicine at Mount Sinai, New York, and chief information officer and chief digital health officer at UC Davis Medical Center, Sacramento. The Icahn School of Medicine has licensed technology to Rx.Health. Dr. Atreja has no other conflicts to disclose

Patient navigation as a best practice for GI procedures

Colonoscopy is the preferred method for colorectal cancer (CRC) screening. Among scheduled outpatient colonoscopies, key metrics like no-show rates and poor bowel preparation can be as high as 25% in some facilities. These missed appointments and repeated calls with patients have been an important source of wasted resources, poor patient outcomes, and revenue loss for endoscopy facilities (estimated to be up to $1 million dollars for 10-member GI practice).

Studies have shown that patient navigation (PN), a patient-centered approach, overcomes barriers in health care delivery, thus improving adherence to CRC screening. Typically, navigators are specialized health practitioners who fill a variety of functions, including providing updates and instructions to patients, as well as assisting with test-related fears. Despite the overall cost-effectiveness, PN programs require significant resources from hospitals or medical groups. The continued focus in the United States on value-based medicine has provided an urgent need for cost-effective treatments that are also readily available to most physicians.
 

Digital navigation to automate navigation for colonoscopy and other GI procedures

Digital navigation (DN) is a new navigation technique that enables patients to receive appointment updates, resources related to a treatment or condition, stepwise bowel prep directions, and other periprocedural guidance in an automated and convenient manner (see Figure below). Given the widespread use of mobile phones, DN has the ability to change the way doctors and health care providers work. This led to Mount Sinai Health System, New York, conducting a quality improvement program to automate and evaluate the effectiveness of an automated text messaging and web-based “digital navigation” platform for decreasing colonoscopy appointment no-show rates.

Dr. Ashish Atreja/Icahn School of Medicine

If a valid phone number was available in the patient’s electronic medical record chart and they did not opt out of receiving text message communications from the Mount Sinai Health System, patients over the age of 18 years who were scheduled for a colonoscopy at either of Mount Sinai Hospital, Mount Sinai Morningside, or Mount Sinai West were automatically sent DN SMS messages. The RxUniverse software platform (Rx.Health, New York) was used to send DN content through SMS to all eligible patients. The software platform interfaces with the EMR and endoscopy system (Provation) to automatically extract patient phone number and appointment details.
 

Impact of digital navigation and patient engagement

This study at Mount Sinai Health System demonstrated that patient engagement with SMS-based navigation is strongly predictive of colonoscopy completion. Patients with high engagement with digital navigation are about four times more likely to complete colonoscopy. Of all covariates included in the model, high DN engagement level had the largest effect size (odds ratio, 3.97), compared with no engagement. For health systems with patient navigators, targeting patients who are unlikely to engage DN or are low-engagers may be a more efficient use of person-to-person navigation.

Value-based reimbursement and cost-effectiveness have emerged as core principles in American health care reform, possibly requiring the creation of affordable, cost-effective approaches. Our research at Mount Sinai Health System suggested that SMS-based navigation can be a potential cost-effective strategy for reducing no-show rates. Beyond appointment no-shows, adequate bowel preparation is another important component of the preprocedure navigation process. Insufficient bowel preparation requires a repeat procedure, as poor visualization of the colon results in reduced therapeutic benefit from screening colonoscopy. We’ve shown in previous studies that our DN platform can increase bowel preparation efficiency, which results in lower rates of aborted procedures.

Missed colonoscopies not only cause longer wait times for patients, but they also cost the average facility $725 a day in lost revenue. It has been found through studies that traditional PN is cost-effective, with additional revenue generated from increased colonoscopy completion rates exceeding the costs of program implementation. While formal cost analyses have not been conducted on DN, estimates have shown around $1 million in annual savings for an average ambulatory surgery center or 10-member GI practice.
 

Looking ahead: AGA digital transformation network

After positive results for the Rx.Health’s platform were seen at Mount Sinai Health System, the American Gastroenterological Association partnered with Rx.Health to provide the GI community with a GI endoscopy transformation network. The core purpose of this endoscopy transformation network is to take an evidence-based approach and use digital medicine to positively affect key metrics and safety around periprocedural care and support “procedure bundles.” To illustrate the specific case of colonoscopy, these included the following: enhancing colorectal cancer surveillance rates though a comprehensive screening test strategy, decreasing no-show rates through shared decision-making and better preprocedure engagement, improving rates of adequate bowel preparation, benchmarking safety of procedures nationwide, and ensuring patient satisfaction and adequate recall for repeat procedures. These metrics represent key sources of revenue loss for provider organizations and, more importantly, have negative implications on patient care.

This collaboration is now supporting the implementation and expansion of the digital navigation program to all GI procedures at more than 15 different sites across the country.

Dr. Atreja is an adjunct associate professor at the Icahn School of Medicine at Mount Sinai, New York, and chief information officer and chief digital health officer at UC Davis Medical Center, Sacramento. The Icahn School of Medicine has licensed technology to Rx.Health. Dr. Atreja has no other conflicts to disclose

Patient navigation as a best practice for GI procedures

Colonoscopy is the preferred method for colorectal cancer (CRC) screening. Among scheduled outpatient colonoscopies, key metrics like no-show rates and poor bowel preparation can be as high as 25% in some facilities. These missed appointments and repeated calls with patients have been an important source of wasted resources, poor patient outcomes, and revenue loss for endoscopy facilities (estimated to be up to $1 million dollars for 10-member GI practice).

Studies have shown that patient navigation (PN), a patient-centered approach, overcomes barriers in health care delivery, thus improving adherence to CRC screening. Typically, navigators are specialized health practitioners who fill a variety of functions, including providing updates and instructions to patients, as well as assisting with test-related fears. Despite the overall cost-effectiveness, PN programs require significant resources from hospitals or medical groups. The continued focus in the United States on value-based medicine has provided an urgent need for cost-effective treatments that are also readily available to most physicians.
 

Digital navigation to automate navigation for colonoscopy and other GI procedures

Digital navigation (DN) is a new navigation technique that enables patients to receive appointment updates, resources related to a treatment or condition, stepwise bowel prep directions, and other periprocedural guidance in an automated and convenient manner (see Figure below). Given the widespread use of mobile phones, DN has the ability to change the way doctors and health care providers work. This led to Mount Sinai Health System, New York, conducting a quality improvement program to automate and evaluate the effectiveness of an automated text messaging and web-based “digital navigation” platform for decreasing colonoscopy appointment no-show rates.

Dr. Ashish Atreja/Icahn School of Medicine

If a valid phone number was available in the patient’s electronic medical record chart and they did not opt out of receiving text message communications from the Mount Sinai Health System, patients over the age of 18 years who were scheduled for a colonoscopy at either of Mount Sinai Hospital, Mount Sinai Morningside, or Mount Sinai West were automatically sent DN SMS messages. The RxUniverse software platform (Rx.Health, New York) was used to send DN content through SMS to all eligible patients. The software platform interfaces with the EMR and endoscopy system (Provation) to automatically extract patient phone number and appointment details.
 

Impact of digital navigation and patient engagement

This study at Mount Sinai Health System demonstrated that patient engagement with SMS-based navigation is strongly predictive of colonoscopy completion. Patients with high engagement with digital navigation are about four times more likely to complete colonoscopy. Of all covariates included in the model, high DN engagement level had the largest effect size (odds ratio, 3.97), compared with no engagement. For health systems with patient navigators, targeting patients who are unlikely to engage DN or are low-engagers may be a more efficient use of person-to-person navigation.

Value-based reimbursement and cost-effectiveness have emerged as core principles in American health care reform, possibly requiring the creation of affordable, cost-effective approaches. Our research at Mount Sinai Health System suggested that SMS-based navigation can be a potential cost-effective strategy for reducing no-show rates. Beyond appointment no-shows, adequate bowel preparation is another important component of the preprocedure navigation process. Insufficient bowel preparation requires a repeat procedure, as poor visualization of the colon results in reduced therapeutic benefit from screening colonoscopy. We’ve shown in previous studies that our DN platform can increase bowel preparation efficiency, which results in lower rates of aborted procedures.

Missed colonoscopies not only cause longer wait times for patients, but they also cost the average facility $725 a day in lost revenue. It has been found through studies that traditional PN is cost-effective, with additional revenue generated from increased colonoscopy completion rates exceeding the costs of program implementation. While formal cost analyses have not been conducted on DN, estimates have shown around $1 million in annual savings for an average ambulatory surgery center or 10-member GI practice.
 

Looking ahead: AGA digital transformation network

After positive results for the Rx.Health’s platform were seen at Mount Sinai Health System, the American Gastroenterological Association partnered with Rx.Health to provide the GI community with a GI endoscopy transformation network. The core purpose of this endoscopy transformation network is to take an evidence-based approach and use digital medicine to positively affect key metrics and safety around periprocedural care and support “procedure bundles.” To illustrate the specific case of colonoscopy, these included the following: enhancing colorectal cancer surveillance rates though a comprehensive screening test strategy, decreasing no-show rates through shared decision-making and better preprocedure engagement, improving rates of adequate bowel preparation, benchmarking safety of procedures nationwide, and ensuring patient satisfaction and adequate recall for repeat procedures. These metrics represent key sources of revenue loss for provider organizations and, more importantly, have negative implications on patient care.

This collaboration is now supporting the implementation and expansion of the digital navigation program to all GI procedures at more than 15 different sites across the country.

Dr. Atreja is an adjunct associate professor at the Icahn School of Medicine at Mount Sinai, New York, and chief information officer and chief digital health officer at UC Davis Medical Center, Sacramento. The Icahn School of Medicine has licensed technology to Rx.Health. Dr. Atreja has no other conflicts to disclose

Polycystic ovary syndrome, the most common endocrinopathy and most common cause of female infertility, affects 8%-13% of reproductive-aged women. PCOS has a profound impact on a woman’s life yet its diagnosis and management remain confusing despite being first described nearly a century ago by Stein and Leventhal.

To illustrate, in a global survey of 1,385 women with PCOS, one-third or more reported a delay of greater than 2 years and nearly half required evaluation by at least three health professionals before a diagnosis was established (J Clin Endocrinol Metab. 2017;102[2]:604-12). A vital health problem that urgently requires a gap analysis and needs assessment, PCOS is not “just about fertility” but has extensive gynecologic and metabolic consequences that require a personalized approach to care coordinated among the fields of internal medicine, pediatrics, dermatology, and, of course, gynecology.
 

Diagnosis in adults and adolescence

Normal menstrual intervals do not always equate with ovulation. Up to 40% of hirsute women with monthly cycles may not ovulate regularly. The Rotterdam criteria are used to confirm PCOS and require two of the following three: 1) ovulation dysfunction (cycle interval > 35 d or < 8 cycles/year); 2) hyperandrogenism (i.e., elevated total or free testosterone, DHEAS, or signs of hirsutism or acne with Ferriman-Gallwey score greater than 6); 3) polycystic ovaries on ultrasound (20 or more 2- to 9-mm follicles on at least one ovary, and/or increased ovarian volume (> 10 mL) – all at the exclusion of other etiologies including hyperprolactinemia, thyroid dysfunction, androgen-secreting tumors including Cushing’s syndrome, and nonclassic adrenal hyperplasia mostly easily screened by obtaining 17-hydroxyprogesterone.

For adolescents, by age 14 most will have adult androgen levels. Ovarian ultrasound should not be used as a criterion in this age group given the frequency of this appearance. Due to frequent menstrual irregularity, it is recommended to wait at least 2 years post menarche before consideration of a diagnosis.

Antimüllerian hormone is two- to threefold higher in women with PCOS but this hormone level has not yet been accepted as a diagnostic criterion.
 

The metabolic connection

A multisystem disorder whose name misdirects its morbidity, PCOS affects the metabolic, reproductive, and psychological system through vicious cycles of distorted feedback signals. Without a consensus of its origin, there appears to be a hypersensitivity of pituitary luteinizing hormone (LH) to hypothalamic gonadotrophin-releasing hormone. Consequently, elevated LH stimulates ovarian theca cells to increase androgens with resultant hyperandrogenic consequences. Parenthetically, the tonic elevation in LH explains the false-positive surges PCOS women experience when testing their urine during ovulation induction.

Elevations in insulin from unexplained damage to the insulin receptor acts synergistically with LH to increase ovarian androgens and inhibit ovulation. Hyperinsulinemia and abdominal fat deposition contribute to impaired glucose tolerance which is threefold higher with PCOS.

The metabolic syndrome, an association of disorders including hypertension, impaired glucose tolerance, dyslipidemia, and obesity, occurs at an increased overall prevalence rate of 43%-47% in women with PCOS, which is twice as high as in women without PCOS. PCOS is associated with low-grade chronic inflammation, which places these women at increased risk of nonalcoholic fatty liver disease. Dyslipidemia is the most common metabolic disorder in PCOS. These metabolic consequences, including obstructive sleep apnea, are worsened by hyperandrogenemia and an elevated BMI.
 

A genetic link

Multigenetic in origin, PCOS has a fivefold higher risk of inheritance from mothers with PCOS to daughters influenced by prenatal androgen exposure in utero. Genetic studies suggest a causal relationship between PCOS with body mass index, insulin resistance, onset of menopause, depression, and male-pattern balding (PLoS Genet 2018;14[12]:e10007813).

Fifteen genetic risk areas in the human genome seem to predispose to PCOS. New results suggest that altering the gut microbiome via prebiotic or probiotic therapies may be a potential treatment option.
 

Reproductive and gynecologic management

Due to chronic anovulation, unopposed estrogen can result in abnormal endometrial bleeding, endometrial hyperplasia, and a fourfold risk of endometrial cancer. This underscores the importance of regular progestin withdrawal, combined oral contraception (COC), or a progestin intrauterine device.

PCOS is a leading cause of infertility and is associated with abnormal bleeding, miscarriage, gestational diabetes, and gestational hypertension, all of which are higher based on a hyperandrogenic phenotype.

The rate of infertility in women with PCOS is 70%-80%, with ovulation dysfunction being the dominant cause. For years, the mainstay for ovulation induction was clomiphene citrate; however, letrozole has shown higher pregnancy success rates, particularly in women who have a BMI greater than 30 kg/m². (N Engl J Med. 2014;371:119-29). Despite multiple studies demonstrating its efficacy and safety, letrozole remains without Food and Drug Administration approval for ovulation induction.

Metformin has been recommended in women with prediabetes or a BMI above 30, and it may improve menstrual regularity but has not been shown to improve live birth rates nor reduce the pregnancy complications of miscarriage or gestational diabetes. Inositol, the ubiquitous endogenous carbohydrate, has not demonstrated clear improvement in reproduction.

Laparoscopic ovarian diathermy (LOD) is a second-line treatment option, as is the use of gonadotropins, to overcome unsuccessful conservative attempts at ovulation induction. LOD is more invasive but outcomes are equivalent to gonadotropin usage while providing a dramatic reduction in multiple gestation, ovarian hyperstimulation syndrome, and cost (not including the surgical procedure). Ultimately, in vitro fertilization is an option for continued infertility in women with PCOS.
 

Metabolic/gynecologic management

Given the multisystem effect of PCOS, health care providers caring for these women should be vigilant and aggressive at ensuring appropriate monitoring and management. For women with PCOS with an elevated BMI, lifestyle modification is the first line of management. Weight loss alone of only 2%-5% may restore ovulation function.

The combination of dyslipidemia, elevated BMI, and impaired glucose tolerance would presumably predict the risk of cardiovascular events, yet the impact is not proven. Despite an increase in carotid intima media thickness, there are data that suggest only an increase in stroke or myocardial infarction (J Clin Endocrinol Metab. 2019;104[4]:1221-31).

Hyperandrogenism is cosmetically and psychologically disrupting to PCOS patients. The topical application of eflornithine hydrochloride may be of value for mild to moderate facial hair growth. Spironolactone is the preferred first-line agent. (Caution: effective contraception is necessary to avoid feminization of a male fetus). Women with PCOS have a higher risk of disordered eating and body image distress as well as a fivefold higher rate of mental distress such as anxiety and depression.

No specific diet has been determined as part of treatment, yet healthy food selection and caloric intake combined with exercise has been shown to improve metabolic and psychological well-being.
 

Conclusion

PCOS is a ubiquitous, frustrating, and life-altering disease. Health care providers, particularly those in women’s health, must ensure appropriate counseling and education with evidence-based medicine to empower patients toward improved health.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interest. Please contact him at [email protected].

Polycystic ovary syndrome, the most common endocrinopathy and most common cause of female infertility, affects 8%-13% of reproductive-aged women. PCOS has a profound impact on a woman’s life yet its diagnosis and management remain confusing despite being first described nearly a century ago by Stein and Leventhal.

To illustrate, in a global survey of 1,385 women with PCOS, one-third or more reported a delay of greater than 2 years and nearly half required evaluation by at least three health professionals before a diagnosis was established (J Clin Endocrinol Metab. 2017;102[2]:604-12). A vital health problem that urgently requires a gap analysis and needs assessment, PCOS is not “just about fertility” but has extensive gynecologic and metabolic consequences that require a personalized approach to care coordinated among the fields of internal medicine, pediatrics, dermatology, and, of course, gynecology.
 

Diagnosis in adults and adolescence

Normal menstrual intervals do not always equate with ovulation. Up to 40% of hirsute women with monthly cycles may not ovulate regularly. The Rotterdam criteria are used to confirm PCOS and require two of the following three: 1) ovulation dysfunction (cycle interval > 35 d or < 8 cycles/year); 2) hyperandrogenism (i.e., elevated total or free testosterone, DHEAS, or signs of hirsutism or acne with Ferriman-Gallwey score greater than 6); 3) polycystic ovaries on ultrasound (20 or more 2- to 9-mm follicles on at least one ovary, and/or increased ovarian volume (> 10 mL) – all at the exclusion of other etiologies including hyperprolactinemia, thyroid dysfunction, androgen-secreting tumors including Cushing’s syndrome, and nonclassic adrenal hyperplasia mostly easily screened by obtaining 17-hydroxyprogesterone.

For adolescents, by age 14 most will have adult androgen levels. Ovarian ultrasound should not be used as a criterion in this age group given the frequency of this appearance. Due to frequent menstrual irregularity, it is recommended to wait at least 2 years post menarche before consideration of a diagnosis.

Antimüllerian hormone is two- to threefold higher in women with PCOS but this hormone level has not yet been accepted as a diagnostic criterion.
 

The metabolic connection

A multisystem disorder whose name misdirects its morbidity, PCOS affects the metabolic, reproductive, and psychological system through vicious cycles of distorted feedback signals. Without a consensus of its origin, there appears to be a hypersensitivity of pituitary luteinizing hormone (LH) to hypothalamic gonadotrophin-releasing hormone. Consequently, elevated LH stimulates ovarian theca cells to increase androgens with resultant hyperandrogenic consequences. Parenthetically, the tonic elevation in LH explains the false-positive surges PCOS women experience when testing their urine during ovulation induction.

Elevations in insulin from unexplained damage to the insulin receptor acts synergistically with LH to increase ovarian androgens and inhibit ovulation. Hyperinsulinemia and abdominal fat deposition contribute to impaired glucose tolerance which is threefold higher with PCOS.

The metabolic syndrome, an association of disorders including hypertension, impaired glucose tolerance, dyslipidemia, and obesity, occurs at an increased overall prevalence rate of 43%-47% in women with PCOS, which is twice as high as in women without PCOS. PCOS is associated with low-grade chronic inflammation, which places these women at increased risk of nonalcoholic fatty liver disease. Dyslipidemia is the most common metabolic disorder in PCOS. These metabolic consequences, including obstructive sleep apnea, are worsened by hyperandrogenemia and an elevated BMI.
 

A genetic link

Multigenetic in origin, PCOS has a fivefold higher risk of inheritance from mothers with PCOS to daughters influenced by prenatal androgen exposure in utero. Genetic studies suggest a causal relationship between PCOS with body mass index, insulin resistance, onset of menopause, depression, and male-pattern balding (PLoS Genet 2018;14[12]:e10007813).

Fifteen genetic risk areas in the human genome seem to predispose to PCOS. New results suggest that altering the gut microbiome via prebiotic or probiotic therapies may be a potential treatment option.
 

Reproductive and gynecologic management

Due to chronic anovulation, unopposed estrogen can result in abnormal endometrial bleeding, endometrial hyperplasia, and a fourfold risk of endometrial cancer. This underscores the importance of regular progestin withdrawal, combined oral contraception (COC), or a progestin intrauterine device.

PCOS is a leading cause of infertility and is associated with abnormal bleeding, miscarriage, gestational diabetes, and gestational hypertension, all of which are higher based on a hyperandrogenic phenotype.

The rate of infertility in women with PCOS is 70%-80%, with ovulation dysfunction being the dominant cause. For years, the mainstay for ovulation induction was clomiphene citrate; however, letrozole has shown higher pregnancy success rates, particularly in women who have a BMI greater than 30 kg/m². (N Engl J Med. 2014;371:119-29). Despite multiple studies demonstrating its efficacy and safety, letrozole remains without Food and Drug Administration approval for ovulation induction.

Metformin has been recommended in women with prediabetes or a BMI above 30, and it may improve menstrual regularity but has not been shown to improve live birth rates nor reduce the pregnancy complications of miscarriage or gestational diabetes. Inositol, the ubiquitous endogenous carbohydrate, has not demonstrated clear improvement in reproduction.

Laparoscopic ovarian diathermy (LOD) is a second-line treatment option, as is the use of gonadotropins, to overcome unsuccessful conservative attempts at ovulation induction. LOD is more invasive but outcomes are equivalent to gonadotropin usage while providing a dramatic reduction in multiple gestation, ovarian hyperstimulation syndrome, and cost (not including the surgical procedure). Ultimately, in vitro fertilization is an option for continued infertility in women with PCOS.
 

Metabolic/gynecologic management

Given the multisystem effect of PCOS, health care providers caring for these women should be vigilant and aggressive at ensuring appropriate monitoring and management. For women with PCOS with an elevated BMI, lifestyle modification is the first line of management. Weight loss alone of only 2%-5% may restore ovulation function.

The combination of dyslipidemia, elevated BMI, and impaired glucose tolerance would presumably predict the risk of cardiovascular events, yet the impact is not proven. Despite an increase in carotid intima media thickness, there are data that suggest only an increase in stroke or myocardial infarction (J Clin Endocrinol Metab. 2019;104[4]:1221-31).

Hyperandrogenism is cosmetically and psychologically disrupting to PCOS patients. The topical application of eflornithine hydrochloride may be of value for mild to moderate facial hair growth. Spironolactone is the preferred first-line agent. (Caution: effective contraception is necessary to avoid feminization of a male fetus). Women with PCOS have a higher risk of disordered eating and body image distress as well as a fivefold higher rate of mental distress such as anxiety and depression.

No specific diet has been determined as part of treatment, yet healthy food selection and caloric intake combined with exercise has been shown to improve metabolic and psychological well-being.
 

Conclusion

PCOS is a ubiquitous, frustrating, and life-altering disease. Health care providers, particularly those in women’s health, must ensure appropriate counseling and education with evidence-based medicine to empower patients toward improved health.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interest. Please contact him at [email protected].

Polycystic ovary syndrome, the most common endocrinopathy and most common cause of female infertility, affects 8%-13% of reproductive-aged women. PCOS has a profound impact on a woman’s life yet its diagnosis and management remain confusing despite being first described nearly a century ago by Stein and Leventhal.

To illustrate, in a global survey of 1,385 women with PCOS, one-third or more reported a delay of greater than 2 years and nearly half required evaluation by at least three health professionals before a diagnosis was established (J Clin Endocrinol Metab. 2017;102[2]:604-12). A vital health problem that urgently requires a gap analysis and needs assessment, PCOS is not “just about fertility” but has extensive gynecologic and metabolic consequences that require a personalized approach to care coordinated among the fields of internal medicine, pediatrics, dermatology, and, of course, gynecology.
 

Diagnosis in adults and adolescence

Normal menstrual intervals do not always equate with ovulation. Up to 40% of hirsute women with monthly cycles may not ovulate regularly. The Rotterdam criteria are used to confirm PCOS and require two of the following three: 1) ovulation dysfunction (cycle interval > 35 d or < 8 cycles/year); 2) hyperandrogenism (i.e., elevated total or free testosterone, DHEAS, or signs of hirsutism or acne with Ferriman-Gallwey score greater than 6); 3) polycystic ovaries on ultrasound (20 or more 2- to 9-mm follicles on at least one ovary, and/or increased ovarian volume (> 10 mL) – all at the exclusion of other etiologies including hyperprolactinemia, thyroid dysfunction, androgen-secreting tumors including Cushing’s syndrome, and nonclassic adrenal hyperplasia mostly easily screened by obtaining 17-hydroxyprogesterone.

For adolescents, by age 14 most will have adult androgen levels. Ovarian ultrasound should not be used as a criterion in this age group given the frequency of this appearance. Due to frequent menstrual irregularity, it is recommended to wait at least 2 years post menarche before consideration of a diagnosis.

Antimüllerian hormone is two- to threefold higher in women with PCOS but this hormone level has not yet been accepted as a diagnostic criterion.
 

The metabolic connection

A multisystem disorder whose name misdirects its morbidity, PCOS affects the metabolic, reproductive, and psychological system through vicious cycles of distorted feedback signals. Without a consensus of its origin, there appears to be a hypersensitivity of pituitary luteinizing hormone (LH) to hypothalamic gonadotrophin-releasing hormone. Consequently, elevated LH stimulates ovarian theca cells to increase androgens with resultant hyperandrogenic consequences. Parenthetically, the tonic elevation in LH explains the false-positive surges PCOS women experience when testing their urine during ovulation induction.

Elevations in insulin from unexplained damage to the insulin receptor acts synergistically with LH to increase ovarian androgens and inhibit ovulation. Hyperinsulinemia and abdominal fat deposition contribute to impaired glucose tolerance which is threefold higher with PCOS.

The metabolic syndrome, an association of disorders including hypertension, impaired glucose tolerance, dyslipidemia, and obesity, occurs at an increased overall prevalence rate of 43%-47% in women with PCOS, which is twice as high as in women without PCOS. PCOS is associated with low-grade chronic inflammation, which places these women at increased risk of nonalcoholic fatty liver disease. Dyslipidemia is the most common metabolic disorder in PCOS. These metabolic consequences, including obstructive sleep apnea, are worsened by hyperandrogenemia and an elevated BMI.
 

A genetic link

Multigenetic in origin, PCOS has a fivefold higher risk of inheritance from mothers with PCOS to daughters influenced by prenatal androgen exposure in utero. Genetic studies suggest a causal relationship between PCOS with body mass index, insulin resistance, onset of menopause, depression, and male-pattern balding (PLoS Genet 2018;14[12]:e10007813).

Fifteen genetic risk areas in the human genome seem to predispose to PCOS. New results suggest that altering the gut microbiome via prebiotic or probiotic therapies may be a potential treatment option.
 

Reproductive and gynecologic management

Due to chronic anovulation, unopposed estrogen can result in abnormal endometrial bleeding, endometrial hyperplasia, and a fourfold risk of endometrial cancer. This underscores the importance of regular progestin withdrawal, combined oral contraception (COC), or a progestin intrauterine device.

PCOS is a leading cause of infertility and is associated with abnormal bleeding, miscarriage, gestational diabetes, and gestational hypertension, all of which are higher based on a hyperandrogenic phenotype.

The rate of infertility in women with PCOS is 70%-80%, with ovulation dysfunction being the dominant cause. For years, the mainstay for ovulation induction was clomiphene citrate; however, letrozole has shown higher pregnancy success rates, particularly in women who have a BMI greater than 30 kg/m². (N Engl J Med. 2014;371:119-29). Despite multiple studies demonstrating its efficacy and safety, letrozole remains without Food and Drug Administration approval for ovulation induction.

Metformin has been recommended in women with prediabetes or a BMI above 30, and it may improve menstrual regularity but has not been shown to improve live birth rates nor reduce the pregnancy complications of miscarriage or gestational diabetes. Inositol, the ubiquitous endogenous carbohydrate, has not demonstrated clear improvement in reproduction.

Laparoscopic ovarian diathermy (LOD) is a second-line treatment option, as is the use of gonadotropins, to overcome unsuccessful conservative attempts at ovulation induction. LOD is more invasive but outcomes are equivalent to gonadotropin usage while providing a dramatic reduction in multiple gestation, ovarian hyperstimulation syndrome, and cost (not including the surgical procedure). Ultimately, in vitro fertilization is an option for continued infertility in women with PCOS.
 

Metabolic/gynecologic management

Given the multisystem effect of PCOS, health care providers caring for these women should be vigilant and aggressive at ensuring appropriate monitoring and management. For women with PCOS with an elevated BMI, lifestyle modification is the first line of management. Weight loss alone of only 2%-5% may restore ovulation function.

The combination of dyslipidemia, elevated BMI, and impaired glucose tolerance would presumably predict the risk of cardiovascular events, yet the impact is not proven. Despite an increase in carotid intima media thickness, there are data that suggest only an increase in stroke or myocardial infarction (J Clin Endocrinol Metab. 2019;104[4]:1221-31).

Hyperandrogenism is cosmetically and psychologically disrupting to PCOS patients. The topical application of eflornithine hydrochloride may be of value for mild to moderate facial hair growth. Spironolactone is the preferred first-line agent. (Caution: effective contraception is necessary to avoid feminization of a male fetus). Women with PCOS have a higher risk of disordered eating and body image distress as well as a fivefold higher rate of mental distress such as anxiety and depression.

No specific diet has been determined as part of treatment, yet healthy food selection and caloric intake combined with exercise has been shown to improve metabolic and psychological well-being.
 

Conclusion

PCOS is a ubiquitous, frustrating, and life-altering disease. Health care providers, particularly those in women’s health, must ensure appropriate counseling and education with evidence-based medicine to empower patients toward improved health.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interest. Please contact him at [email protected].

As the protective effect of the vaccines becomes increasingly apparent, a large number of school systems are beginning to return to prepandemic in-school learning. But anecdotal reports from around the country are making it clear that some children or their families are hesitant to return to the old norm of face to face learning (Goldstein D. “Schools Are Open, but Many Families Remain Hesitant to Return.” New York Times. 2021 May 9). The possible explanations for this hesitancy include a broad list that goes well beyond the obvious concern about the child contracting COVID-19.

I hear from my grandchildren that remote learning has for the most part been unpleasant and lacked the rigor of their in-class experiences. But, they admit that they have found that, in some situations, they prefer the environment at home because it is less distracting. They also acknowledge that, while they miss seeing their friends, at times the isolation has allowed them to be more efficient. Of course, their observations must be viewed in light of their personalities and the support provided by their parents. For these motivated teenagers, the bottom line is that they would prefer to be in school.

However, for the children who have always been a bit ambivalent about school either because they were anxious in social situations or because they found the academics too challenging, one can easily understand why they might prefer to remain in a less-intimidating home environment. For them, missing their friends may have little draw because they may not have had any friends. And, the negative feedback and bullying they have received at school is too overwhelming. A teenager for whom the pandemic has offered the out-of-school free time to explore her independence, feel more like an adult, and enjoy the benefits of having a job may be hesitant to return to the restrictions imposed by what she sees as the childishness of in-school learning.

Compounding the problem is the risk avoidance posture of some school systems and the hesitancy of some teachers to return to an environment that they continue to view as unsafe despite the evidence of the effectiveness of the vaccines and the minimal threat of in-school spread. It is going to be interesting to see how school administrators and politicians deal with this level of institutional hesitancy. Some schools may take what might be considered a hard-line approach and eliminate remote learning completely.

Regardless of how swiftly and thoughtfully schools return to in-class learning, a large number of children will eventually be faced with the stark reality of returning to a place in which they had felt painfully uncomfortable in the past. Pediatricians must be prepared to see this current wave of school hesitancy morph into a full-fledged tsunami of school refusals.

Successful management of a family whose child finds school too challenging emotionally has always required a combination of careful attention to the possible medical causes of the child’s complaints, consultation with a mental health practitioner, and thoughtful coordination with educators sensitive to the child’s school-generated distress.

It has never been easy to reassure the family of a child with frequent headaches or belly pain that his symptoms have no physical basis and then gently point out that the stress of school attendance may be a contributing factor. Some families who buy into the association may be fortunate enough to be able to offer their child home schooling as a solution to school refusal. But this strategy often requires that one parent remain home and has the temperament and the skills to teach.

Now that we have all seen that remote learning has the potential to work in a crisis, will some parents begin to demand it for their children with school refusal? Who will pay for it? I think you and I would prefer to see a solution that targeted therapeutic interventions aimed at getting the child back in school. But you and I also know those strategies don’t always work.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As the protective effect of the vaccines becomes increasingly apparent, a large number of school systems are beginning to return to prepandemic in-school learning. But anecdotal reports from around the country are making it clear that some children or their families are hesitant to return to the old norm of face to face learning (Goldstein D. “Schools Are Open, but Many Families Remain Hesitant to Return.” New York Times. 2021 May 9). The possible explanations for this hesitancy include a broad list that goes well beyond the obvious concern about the child contracting COVID-19.

I hear from my grandchildren that remote learning has for the most part been unpleasant and lacked the rigor of their in-class experiences. But, they admit that they have found that, in some situations, they prefer the environment at home because it is less distracting. They also acknowledge that, while they miss seeing their friends, at times the isolation has allowed them to be more efficient. Of course, their observations must be viewed in light of their personalities and the support provided by their parents. For these motivated teenagers, the bottom line is that they would prefer to be in school.

However, for the children who have always been a bit ambivalent about school either because they were anxious in social situations or because they found the academics too challenging, one can easily understand why they might prefer to remain in a less-intimidating home environment. For them, missing their friends may have little draw because they may not have had any friends. And, the negative feedback and bullying they have received at school is too overwhelming. A teenager for whom the pandemic has offered the out-of-school free time to explore her independence, feel more like an adult, and enjoy the benefits of having a job may be hesitant to return to the restrictions imposed by what she sees as the childishness of in-school learning.

Compounding the problem is the risk avoidance posture of some school systems and the hesitancy of some teachers to return to an environment that they continue to view as unsafe despite the evidence of the effectiveness of the vaccines and the minimal threat of in-school spread. It is going to be interesting to see how school administrators and politicians deal with this level of institutional hesitancy. Some schools may take what might be considered a hard-line approach and eliminate remote learning completely.

Regardless of how swiftly and thoughtfully schools return to in-class learning, a large number of children will eventually be faced with the stark reality of returning to a place in which they had felt painfully uncomfortable in the past. Pediatricians must be prepared to see this current wave of school hesitancy morph into a full-fledged tsunami of school refusals.

Successful management of a family whose child finds school too challenging emotionally has always required a combination of careful attention to the possible medical causes of the child’s complaints, consultation with a mental health practitioner, and thoughtful coordination with educators sensitive to the child’s school-generated distress.

It has never been easy to reassure the family of a child with frequent headaches or belly pain that his symptoms have no physical basis and then gently point out that the stress of school attendance may be a contributing factor. Some families who buy into the association may be fortunate enough to be able to offer their child home schooling as a solution to school refusal. But this strategy often requires that one parent remain home and has the temperament and the skills to teach.

Now that we have all seen that remote learning has the potential to work in a crisis, will some parents begin to demand it for their children with school refusal? Who will pay for it? I think you and I would prefer to see a solution that targeted therapeutic interventions aimed at getting the child back in school. But you and I also know those strategies don’t always work.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As the protective effect of the vaccines becomes increasingly apparent, a large number of school systems are beginning to return to prepandemic in-school learning. But anecdotal reports from around the country are making it clear that some children or their families are hesitant to return to the old norm of face to face learning (Goldstein D. “Schools Are Open, but Many Families Remain Hesitant to Return.” New York Times. 2021 May 9). The possible explanations for this hesitancy include a broad list that goes well beyond the obvious concern about the child contracting COVID-19.

I hear from my grandchildren that remote learning has for the most part been unpleasant and lacked the rigor of their in-class experiences. But, they admit that they have found that, in some situations, they prefer the environment at home because it is less distracting. They also acknowledge that, while they miss seeing their friends, at times the isolation has allowed them to be more efficient. Of course, their observations must be viewed in light of their personalities and the support provided by their parents. For these motivated teenagers, the bottom line is that they would prefer to be in school.

However, for the children who have always been a bit ambivalent about school either because they were anxious in social situations or because they found the academics too challenging, one can easily understand why they might prefer to remain in a less-intimidating home environment. For them, missing their friends may have little draw because they may not have had any friends. And, the negative feedback and bullying they have received at school is too overwhelming. A teenager for whom the pandemic has offered the out-of-school free time to explore her independence, feel more like an adult, and enjoy the benefits of having a job may be hesitant to return to the restrictions imposed by what she sees as the childishness of in-school learning.

Compounding the problem is the risk avoidance posture of some school systems and the hesitancy of some teachers to return to an environment that they continue to view as unsafe despite the evidence of the effectiveness of the vaccines and the minimal threat of in-school spread. It is going to be interesting to see how school administrators and politicians deal with this level of institutional hesitancy. Some schools may take what might be considered a hard-line approach and eliminate remote learning completely.

Regardless of how swiftly and thoughtfully schools return to in-class learning, a large number of children will eventually be faced with the stark reality of returning to a place in which they had felt painfully uncomfortable in the past. Pediatricians must be prepared to see this current wave of school hesitancy morph into a full-fledged tsunami of school refusals.

Successful management of a family whose child finds school too challenging emotionally has always required a combination of careful attention to the possible medical causes of the child’s complaints, consultation with a mental health practitioner, and thoughtful coordination with educators sensitive to the child’s school-generated distress.

It has never been easy to reassure the family of a child with frequent headaches or belly pain that his symptoms have no physical basis and then gently point out that the stress of school attendance may be a contributing factor. Some families who buy into the association may be fortunate enough to be able to offer their child home schooling as a solution to school refusal. But this strategy often requires that one parent remain home and has the temperament and the skills to teach.

Now that we have all seen that remote learning has the potential to work in a crisis, will some parents begin to demand it for their children with school refusal? Who will pay for it? I think you and I would prefer to see a solution that targeted therapeutic interventions aimed at getting the child back in school. But you and I also know those strategies don’t always work.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].