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COVID-19 experiences from the ob.gyn. front line
As the COVID-19 pandemic continues to spread across the United States, several members of the Ob.Gyn. News Editorial Advisory Board shared their experiences.
Catherine Cansino, MD, MPH, who is an associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis, discussed the changes COVID-19 has had on local and regional practice in Sacramento and northern California.
There has been a dramatic increase in telehealth, using video, phone, and apps such as Zoom. Although ob.gyns. at the university are limiting outpatient appointments to essential visits only, we are continuing to offer telehealth to a few nonessential visits. This will be readdressed when the COVID-19 cases peak, Dr. Cansino said.
All patients admitted to labor & delivery undergo COVID-19 testing regardless of symptoms. For patients in the clinic who are expected to be induced or scheduled for cesarean delivery, we are screening them within 72 hours before admission.
In gynecology, only essential or urgent surgeries at UC Davis are being performed and include indications such as cancer, serious benign conditions unresponsive to conservative treatment (e.g., tubo-ovarian abscess, large symptomatic adnexal mass), and pregnancy termination. We are preserving access to abortion and reproductive health services since these are essential services.
We limit the number of providers involved in direct contact with inpatients to one or two, including a physician, nurse, and/or resident, Dr. Cansino said in an interview. Based on recent Liaison Committee on Medical Education policies related to concerns about educational experience during the pandemic, no medical students are allowed at the hospital at present. We also severely restrict the number of visitors in the inpatient and outpatient settings, including only two attendants (partner, doula, and such) during labor and delivery, and consider the impact on patients’ well-being when we restrict their visitors.
We are following University of California guidelines regarding face mask use, which have been in evolution over the last month. Face masks are used for patients and the health care providers primarily when patients either have known COVID-19 infection or are considered as patients under investigation or if the employee had a high-risk exposure. The use of face masks is becoming more permissive, rather than mandatory, to conserve personal protective equipment (PPE) for when the surge arrives.
Education is ongoing about caring for our families and ourselves if we get infected and need to isolate within our own homes. The department and health system is trying to balance the challenges of urgent patient care needs against the wellness concerns for the faculty, staff, and residents. Many physicians are also struggling with childcare problems, which add to our personal stress. There is anxiety among many physicians about exposure to asymptomatic carriers, including themselves, patients, and their families, Dr. Cansino said.
David Forstein, DO, dean and professor of obstetrics and gynecology at Touro College of Osteopathic Medicine, New York, said in an interview that the COVID-19 pandemic has “totally disrupted medical education. At almost all medical schools, didactics have moved completely online – ZOOM sessions abound, but labs become demonstrations, if at all, during the preclinical years. The clinical years have been put on hold, as well as student rotations suspended, out of caution for the students because hospitals needed to conserve PPE for the essential personnel and because administrators knew there would be less time for teaching. After initially requesting a pause, many hospitals now are asking students to come back because so many physicians, nurses, and residents have become ill with COVID-19 and either are quarantined or are patients in the hospital themselves.
“There has been a state-by-state call to consider graduating health professions students early, and press them into service, before their residencies actually begin. Some locations are looking for these new graduates to volunteer; some are willing to pay them a resident’s salary level. Medical schools are auditing their student records now to see which students would qualify to graduate early,” Dr. Forstein noted.
David M. Jaspan, DO, chairman of the department of obstetrics and gynecology at the Einstein Health Care Network in Philadelphia, described in an email interview how COVID-19 has changed practice.
To minimize the number of providers on the front line, we have developed a Monday to Friday rotating schedule of three teams of five members, he explained. There will be a hospital-based team, an office-based team, and a telehealth-based team who will provide their services from home. On-call responsibilities remain the same.
The hospital team, working 7 a.m. to 5 p.m., will rotate through assignments each day:
- One person will cover labor and delivery.
- One person will cover triage and help on labor and delivery.
- One person will be assigned to the resident office.
- One person will be assigned to cover the team of the post call attending (Sunday through Thursday call).
- One person will be assigned to gynecology coverage, consults, and postpartum rounds.
To further minimize the patient interactions, when possible, each patient should be seen by the attending physician with the resident. This is a change from usual practice, where the patient is first seen by the resident, who reports back to the attending, and then both physicians see the patient together.
The network’s offices now open from 9 a.m. (many offices had been offering early-morning hours starting at 7 a.m.), and the physicians and advanced practice providers will work through the last scheduled patient appointment, Dr. Jaspan explained. “The office-based team will preferentially see in-person visits.”
Several offices have been closed so that ob.gyns. and staff can be reassigned to telehealth. The remaining five offices generally have one attending physician and one advanced practice provider.
The remaining team of ob.gyns. provides telehealth with the help of staff members. This involves an initial call to the patient by staff letting them know the doctor will be calling, checking them in, verifying insurance, and collecting payment, followed by the actual telehealth visit. If follow-up is needed, the staff member schedules the follow-up.
Dr. Jaspan called the new approach to prenatal care because of COVID-19 a “cataclysmic change in how we care for our patients. We have decided to further limit our obstetrical in-person visits. It is our feeling that these changes will enable patients to remain outside of the office and in the safety of their homes, provide appropriate social distancing, and diminish potential exposures to the office staff providers and patients.”
In-person visits will occur at: the initial visit, between 24 and 28 weeks, at 32 weeks, and at 36 or 37 weeks; if the patient at 36/37 has a blood pressure cuff, they will not have additional scheduled in-patient visits. We have partnered with the insurance companies to provide more than 88% of obstetrical patients with home blood pressure cuffs.
Obstetrical visits via telehealth will continue at our standard intervals: monthly until 26 weeks; twice monthly during 26-36 weeks; and weekly from 37 weeks to delivery. These visits should use a video component such as Zoom, Doxy.me, or FaceTime.
“If the patient has concerns or problems, we will see them at any time. However, the new standard will be telehealth visits and the exception will be the in-person visit,” Dr. Jaspan said.
In addition, we have worked our division of maternal-fetal medicine to adjust the antenatal testing schedules, and we have curtailed the frequency of ultrasound, he noted.
He emphasized the importance of documenting telehealth interactions with obstetrical patients, in addition to “providing adequate teaching and education for patients regarding kick counts to ensure fetal well-being.” It also is key to “properly document conversations with patients regarding bleeding, rupture of membranes, fetal movement, headache, visual changes, fevers, cough, nausea and vomiting, diarrhea, fatigue, muscle aches, etc.”
The residents’ schedule also has been modified to diminish their exposure. Within our new paradigm, we have scheduled video conferences to enable our program to maintain our commitment to academics.
It is imperative that we keep our patients safe, and it is critical to protect our staff members. Those who provide women’s health cannot be replaced by other nurses or physicians.
Mark P. Trolice, MD, 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 related in an email interview that, on March 17, 2020, the American Society for Reproductive Medicine (ASRM) released “Patient Management and Clinical Recommendations During the Coronavirus (COVID-19) Pandemic.” This document serves as guidance on fertility care during the current crisis. Specifically, the recommendations include the following:
- Suspend initiation of new treatment cycles, including ovulation induction, intrauterine inseminations, in vitro fertilization including retrievals and frozen embryo transfers, and nonurgent gamete cryopreservation.
- Strongly consider cancellation of all embryo transfers, whether fresh or frozen.
- Continue to care for patients who are currently “in cycle” or who require urgent stimulation and cryopreservation.
- Suspend elective surgeries and nonurgent diagnostic procedures.
- Minimize in-person interactions and increase utilization of telehealth.
As a member of ASRM for more than 2 decades and a participant of several of their committees, my practice immediately ceased treatment cycles to comply with this guidance.
Then on March 20, 2020, the Florida governor’s executive order 20-72 was released, stating, “All hospitals, ambulatory surgical centers, office surgery centers, dental, orthodontic and endodontic offices, and other health care practitioners’ offices in the State of Florida are prohibited from providing any medically unnecessary, nonurgent or nonemergency procedure or surgery which, if delayed, does not place a patient’s immediate health, safety, or well-being at risk, or will, if delayed, not contribute to the worsening of a serious or life-threatening medical condition.”
As a result, my practice has been limited to telemedicine consultations. While the ASRM guidance and the gubernatorial executive order pose a significant financial hardship on my center and all applicable medical clinics in my state, resulting in expected layoffs, salary reductions, and requests for government stimulus loans, the greater good takes priority and we pray for all the victims of this devastating pandemic.
The governor’s current executive order is set to expire on May 9, 2020, unless it is extended.
ASRM released an update of their guidance on March 30, 2020, offering no change from their prior recommendations. The organization plans to reevaluate the guidance at 2-week intervals.
Sangeeta Sinha, MD, an ob.gyn. in private practice at Stone Springs Hospital Center, Dulles, Va. said in an interview, “COVID 19 has put fear in all aspects of our daily activities which we are attempting to cope with.”
She related several changes made to her office and hospital environments. “In our office, we are now wearing a mask at all times, gloves to examine every patient. We have staggered physicians in the office to take televisits and in-office patients. We are screening all new patients on the phone to determine if they are sick, have traveled to high-risk, hot spot areas of the country, or have had contact with someone who tested positive for COVID-19. We are only seeing our pregnant women and have also pushed out their return appointments to 4 weeks if possible. There are several staff who are not working due to fear or are in self quarantine so we have shortage of staff in the office. At the hospital as well we are wearing a mask at all times, using personal protective equipment for deliveries and C-sections.
“We have had several scares, including a new transfer of an 18-year-old pregnant patient at 30 weeks with cough and sore throat, who later reported that her roommate is very sick and he works with someone who has tested positive for COVID-19. Thankfully she is healthy and well. We learned several lessons from this one.”
As the COVID-19 pandemic continues to spread across the United States, several members of the Ob.Gyn. News Editorial Advisory Board shared their experiences.
Catherine Cansino, MD, MPH, who is an associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis, discussed the changes COVID-19 has had on local and regional practice in Sacramento and northern California.
There has been a dramatic increase in telehealth, using video, phone, and apps such as Zoom. Although ob.gyns. at the university are limiting outpatient appointments to essential visits only, we are continuing to offer telehealth to a few nonessential visits. This will be readdressed when the COVID-19 cases peak, Dr. Cansino said.
All patients admitted to labor & delivery undergo COVID-19 testing regardless of symptoms. For patients in the clinic who are expected to be induced or scheduled for cesarean delivery, we are screening them within 72 hours before admission.
In gynecology, only essential or urgent surgeries at UC Davis are being performed and include indications such as cancer, serious benign conditions unresponsive to conservative treatment (e.g., tubo-ovarian abscess, large symptomatic adnexal mass), and pregnancy termination. We are preserving access to abortion and reproductive health services since these are essential services.
We limit the number of providers involved in direct contact with inpatients to one or two, including a physician, nurse, and/or resident, Dr. Cansino said in an interview. Based on recent Liaison Committee on Medical Education policies related to concerns about educational experience during the pandemic, no medical students are allowed at the hospital at present. We also severely restrict the number of visitors in the inpatient and outpatient settings, including only two attendants (partner, doula, and such) during labor and delivery, and consider the impact on patients’ well-being when we restrict their visitors.
We are following University of California guidelines regarding face mask use, which have been in evolution over the last month. Face masks are used for patients and the health care providers primarily when patients either have known COVID-19 infection or are considered as patients under investigation or if the employee had a high-risk exposure. The use of face masks is becoming more permissive, rather than mandatory, to conserve personal protective equipment (PPE) for when the surge arrives.
Education is ongoing about caring for our families and ourselves if we get infected and need to isolate within our own homes. The department and health system is trying to balance the challenges of urgent patient care needs against the wellness concerns for the faculty, staff, and residents. Many physicians are also struggling with childcare problems, which add to our personal stress. There is anxiety among many physicians about exposure to asymptomatic carriers, including themselves, patients, and their families, Dr. Cansino said.
David Forstein, DO, dean and professor of obstetrics and gynecology at Touro College of Osteopathic Medicine, New York, said in an interview that the COVID-19 pandemic has “totally disrupted medical education. At almost all medical schools, didactics have moved completely online – ZOOM sessions abound, but labs become demonstrations, if at all, during the preclinical years. The clinical years have been put on hold, as well as student rotations suspended, out of caution for the students because hospitals needed to conserve PPE for the essential personnel and because administrators knew there would be less time for teaching. After initially requesting a pause, many hospitals now are asking students to come back because so many physicians, nurses, and residents have become ill with COVID-19 and either are quarantined or are patients in the hospital themselves.
“There has been a state-by-state call to consider graduating health professions students early, and press them into service, before their residencies actually begin. Some locations are looking for these new graduates to volunteer; some are willing to pay them a resident’s salary level. Medical schools are auditing their student records now to see which students would qualify to graduate early,” Dr. Forstein noted.
David M. Jaspan, DO, chairman of the department of obstetrics and gynecology at the Einstein Health Care Network in Philadelphia, described in an email interview how COVID-19 has changed practice.
To minimize the number of providers on the front line, we have developed a Monday to Friday rotating schedule of three teams of five members, he explained. There will be a hospital-based team, an office-based team, and a telehealth-based team who will provide their services from home. On-call responsibilities remain the same.
The hospital team, working 7 a.m. to 5 p.m., will rotate through assignments each day:
- One person will cover labor and delivery.
- One person will cover triage and help on labor and delivery.
- One person will be assigned to the resident office.
- One person will be assigned to cover the team of the post call attending (Sunday through Thursday call).
- One person will be assigned to gynecology coverage, consults, and postpartum rounds.
To further minimize the patient interactions, when possible, each patient should be seen by the attending physician with the resident. This is a change from usual practice, where the patient is first seen by the resident, who reports back to the attending, and then both physicians see the patient together.
The network’s offices now open from 9 a.m. (many offices had been offering early-morning hours starting at 7 a.m.), and the physicians and advanced practice providers will work through the last scheduled patient appointment, Dr. Jaspan explained. “The office-based team will preferentially see in-person visits.”
Several offices have been closed so that ob.gyns. and staff can be reassigned to telehealth. The remaining five offices generally have one attending physician and one advanced practice provider.
The remaining team of ob.gyns. provides telehealth with the help of staff members. This involves an initial call to the patient by staff letting them know the doctor will be calling, checking them in, verifying insurance, and collecting payment, followed by the actual telehealth visit. If follow-up is needed, the staff member schedules the follow-up.
Dr. Jaspan called the new approach to prenatal care because of COVID-19 a “cataclysmic change in how we care for our patients. We have decided to further limit our obstetrical in-person visits. It is our feeling that these changes will enable patients to remain outside of the office and in the safety of their homes, provide appropriate social distancing, and diminish potential exposures to the office staff providers and patients.”
In-person visits will occur at: the initial visit, between 24 and 28 weeks, at 32 weeks, and at 36 or 37 weeks; if the patient at 36/37 has a blood pressure cuff, they will not have additional scheduled in-patient visits. We have partnered with the insurance companies to provide more than 88% of obstetrical patients with home blood pressure cuffs.
Obstetrical visits via telehealth will continue at our standard intervals: monthly until 26 weeks; twice monthly during 26-36 weeks; and weekly from 37 weeks to delivery. These visits should use a video component such as Zoom, Doxy.me, or FaceTime.
“If the patient has concerns or problems, we will see them at any time. However, the new standard will be telehealth visits and the exception will be the in-person visit,” Dr. Jaspan said.
In addition, we have worked our division of maternal-fetal medicine to adjust the antenatal testing schedules, and we have curtailed the frequency of ultrasound, he noted.
He emphasized the importance of documenting telehealth interactions with obstetrical patients, in addition to “providing adequate teaching and education for patients regarding kick counts to ensure fetal well-being.” It also is key to “properly document conversations with patients regarding bleeding, rupture of membranes, fetal movement, headache, visual changes, fevers, cough, nausea and vomiting, diarrhea, fatigue, muscle aches, etc.”
The residents’ schedule also has been modified to diminish their exposure. Within our new paradigm, we have scheduled video conferences to enable our program to maintain our commitment to academics.
It is imperative that we keep our patients safe, and it is critical to protect our staff members. Those who provide women’s health cannot be replaced by other nurses or physicians.
Mark P. Trolice, MD, 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 related in an email interview that, on March 17, 2020, the American Society for Reproductive Medicine (ASRM) released “Patient Management and Clinical Recommendations During the Coronavirus (COVID-19) Pandemic.” This document serves as guidance on fertility care during the current crisis. Specifically, the recommendations include the following:
- Suspend initiation of new treatment cycles, including ovulation induction, intrauterine inseminations, in vitro fertilization including retrievals and frozen embryo transfers, and nonurgent gamete cryopreservation.
- Strongly consider cancellation of all embryo transfers, whether fresh or frozen.
- Continue to care for patients who are currently “in cycle” or who require urgent stimulation and cryopreservation.
- Suspend elective surgeries and nonurgent diagnostic procedures.
- Minimize in-person interactions and increase utilization of telehealth.
As a member of ASRM for more than 2 decades and a participant of several of their committees, my practice immediately ceased treatment cycles to comply with this guidance.
Then on March 20, 2020, the Florida governor’s executive order 20-72 was released, stating, “All hospitals, ambulatory surgical centers, office surgery centers, dental, orthodontic and endodontic offices, and other health care practitioners’ offices in the State of Florida are prohibited from providing any medically unnecessary, nonurgent or nonemergency procedure or surgery which, if delayed, does not place a patient’s immediate health, safety, or well-being at risk, or will, if delayed, not contribute to the worsening of a serious or life-threatening medical condition.”
As a result, my practice has been limited to telemedicine consultations. While the ASRM guidance and the gubernatorial executive order pose a significant financial hardship on my center and all applicable medical clinics in my state, resulting in expected layoffs, salary reductions, and requests for government stimulus loans, the greater good takes priority and we pray for all the victims of this devastating pandemic.
The governor’s current executive order is set to expire on May 9, 2020, unless it is extended.
ASRM released an update of their guidance on March 30, 2020, offering no change from their prior recommendations. The organization plans to reevaluate the guidance at 2-week intervals.
Sangeeta Sinha, MD, an ob.gyn. in private practice at Stone Springs Hospital Center, Dulles, Va. said in an interview, “COVID 19 has put fear in all aspects of our daily activities which we are attempting to cope with.”
She related several changes made to her office and hospital environments. “In our office, we are now wearing a mask at all times, gloves to examine every patient. We have staggered physicians in the office to take televisits and in-office patients. We are screening all new patients on the phone to determine if they are sick, have traveled to high-risk, hot spot areas of the country, or have had contact with someone who tested positive for COVID-19. We are only seeing our pregnant women and have also pushed out their return appointments to 4 weeks if possible. There are several staff who are not working due to fear or are in self quarantine so we have shortage of staff in the office. At the hospital as well we are wearing a mask at all times, using personal protective equipment for deliveries and C-sections.
“We have had several scares, including a new transfer of an 18-year-old pregnant patient at 30 weeks with cough and sore throat, who later reported that her roommate is very sick and he works with someone who has tested positive for COVID-19. Thankfully she is healthy and well. We learned several lessons from this one.”
As the COVID-19 pandemic continues to spread across the United States, several members of the Ob.Gyn. News Editorial Advisory Board shared their experiences.
Catherine Cansino, MD, MPH, who is an associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis, discussed the changes COVID-19 has had on local and regional practice in Sacramento and northern California.
There has been a dramatic increase in telehealth, using video, phone, and apps such as Zoom. Although ob.gyns. at the university are limiting outpatient appointments to essential visits only, we are continuing to offer telehealth to a few nonessential visits. This will be readdressed when the COVID-19 cases peak, Dr. Cansino said.
All patients admitted to labor & delivery undergo COVID-19 testing regardless of symptoms. For patients in the clinic who are expected to be induced or scheduled for cesarean delivery, we are screening them within 72 hours before admission.
In gynecology, only essential or urgent surgeries at UC Davis are being performed and include indications such as cancer, serious benign conditions unresponsive to conservative treatment (e.g., tubo-ovarian abscess, large symptomatic adnexal mass), and pregnancy termination. We are preserving access to abortion and reproductive health services since these are essential services.
We limit the number of providers involved in direct contact with inpatients to one or two, including a physician, nurse, and/or resident, Dr. Cansino said in an interview. Based on recent Liaison Committee on Medical Education policies related to concerns about educational experience during the pandemic, no medical students are allowed at the hospital at present. We also severely restrict the number of visitors in the inpatient and outpatient settings, including only two attendants (partner, doula, and such) during labor and delivery, and consider the impact on patients’ well-being when we restrict their visitors.
We are following University of California guidelines regarding face mask use, which have been in evolution over the last month. Face masks are used for patients and the health care providers primarily when patients either have known COVID-19 infection or are considered as patients under investigation or if the employee had a high-risk exposure. The use of face masks is becoming more permissive, rather than mandatory, to conserve personal protective equipment (PPE) for when the surge arrives.
Education is ongoing about caring for our families and ourselves if we get infected and need to isolate within our own homes. The department and health system is trying to balance the challenges of urgent patient care needs against the wellness concerns for the faculty, staff, and residents. Many physicians are also struggling with childcare problems, which add to our personal stress. There is anxiety among many physicians about exposure to asymptomatic carriers, including themselves, patients, and their families, Dr. Cansino said.
David Forstein, DO, dean and professor of obstetrics and gynecology at Touro College of Osteopathic Medicine, New York, said in an interview that the COVID-19 pandemic has “totally disrupted medical education. At almost all medical schools, didactics have moved completely online – ZOOM sessions abound, but labs become demonstrations, if at all, during the preclinical years. The clinical years have been put on hold, as well as student rotations suspended, out of caution for the students because hospitals needed to conserve PPE for the essential personnel and because administrators knew there would be less time for teaching. After initially requesting a pause, many hospitals now are asking students to come back because so many physicians, nurses, and residents have become ill with COVID-19 and either are quarantined or are patients in the hospital themselves.
“There has been a state-by-state call to consider graduating health professions students early, and press them into service, before their residencies actually begin. Some locations are looking for these new graduates to volunteer; some are willing to pay them a resident’s salary level. Medical schools are auditing their student records now to see which students would qualify to graduate early,” Dr. Forstein noted.
David M. Jaspan, DO, chairman of the department of obstetrics and gynecology at the Einstein Health Care Network in Philadelphia, described in an email interview how COVID-19 has changed practice.
To minimize the number of providers on the front line, we have developed a Monday to Friday rotating schedule of three teams of five members, he explained. There will be a hospital-based team, an office-based team, and a telehealth-based team who will provide their services from home. On-call responsibilities remain the same.
The hospital team, working 7 a.m. to 5 p.m., will rotate through assignments each day:
- One person will cover labor and delivery.
- One person will cover triage and help on labor and delivery.
- One person will be assigned to the resident office.
- One person will be assigned to cover the team of the post call attending (Sunday through Thursday call).
- One person will be assigned to gynecology coverage, consults, and postpartum rounds.
To further minimize the patient interactions, when possible, each patient should be seen by the attending physician with the resident. This is a change from usual practice, where the patient is first seen by the resident, who reports back to the attending, and then both physicians see the patient together.
The network’s offices now open from 9 a.m. (many offices had been offering early-morning hours starting at 7 a.m.), and the physicians and advanced practice providers will work through the last scheduled patient appointment, Dr. Jaspan explained. “The office-based team will preferentially see in-person visits.”
Several offices have been closed so that ob.gyns. and staff can be reassigned to telehealth. The remaining five offices generally have one attending physician and one advanced practice provider.
The remaining team of ob.gyns. provides telehealth with the help of staff members. This involves an initial call to the patient by staff letting them know the doctor will be calling, checking them in, verifying insurance, and collecting payment, followed by the actual telehealth visit. If follow-up is needed, the staff member schedules the follow-up.
Dr. Jaspan called the new approach to prenatal care because of COVID-19 a “cataclysmic change in how we care for our patients. We have decided to further limit our obstetrical in-person visits. It is our feeling that these changes will enable patients to remain outside of the office and in the safety of their homes, provide appropriate social distancing, and diminish potential exposures to the office staff providers and patients.”
In-person visits will occur at: the initial visit, between 24 and 28 weeks, at 32 weeks, and at 36 or 37 weeks; if the patient at 36/37 has a blood pressure cuff, they will not have additional scheduled in-patient visits. We have partnered with the insurance companies to provide more than 88% of obstetrical patients with home blood pressure cuffs.
Obstetrical visits via telehealth will continue at our standard intervals: monthly until 26 weeks; twice monthly during 26-36 weeks; and weekly from 37 weeks to delivery. These visits should use a video component such as Zoom, Doxy.me, or FaceTime.
“If the patient has concerns or problems, we will see them at any time. However, the new standard will be telehealth visits and the exception will be the in-person visit,” Dr. Jaspan said.
In addition, we have worked our division of maternal-fetal medicine to adjust the antenatal testing schedules, and we have curtailed the frequency of ultrasound, he noted.
He emphasized the importance of documenting telehealth interactions with obstetrical patients, in addition to “providing adequate teaching and education for patients regarding kick counts to ensure fetal well-being.” It also is key to “properly document conversations with patients regarding bleeding, rupture of membranes, fetal movement, headache, visual changes, fevers, cough, nausea and vomiting, diarrhea, fatigue, muscle aches, etc.”
The residents’ schedule also has been modified to diminish their exposure. Within our new paradigm, we have scheduled video conferences to enable our program to maintain our commitment to academics.
It is imperative that we keep our patients safe, and it is critical to protect our staff members. Those who provide women’s health cannot be replaced by other nurses or physicians.
Mark P. Trolice, MD, 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 related in an email interview that, on March 17, 2020, the American Society for Reproductive Medicine (ASRM) released “Patient Management and Clinical Recommendations During the Coronavirus (COVID-19) Pandemic.” This document serves as guidance on fertility care during the current crisis. Specifically, the recommendations include the following:
- Suspend initiation of new treatment cycles, including ovulation induction, intrauterine inseminations, in vitro fertilization including retrievals and frozen embryo transfers, and nonurgent gamete cryopreservation.
- Strongly consider cancellation of all embryo transfers, whether fresh or frozen.
- Continue to care for patients who are currently “in cycle” or who require urgent stimulation and cryopreservation.
- Suspend elective surgeries and nonurgent diagnostic procedures.
- Minimize in-person interactions and increase utilization of telehealth.
As a member of ASRM for more than 2 decades and a participant of several of their committees, my practice immediately ceased treatment cycles to comply with this guidance.
Then on March 20, 2020, the Florida governor’s executive order 20-72 was released, stating, “All hospitals, ambulatory surgical centers, office surgery centers, dental, orthodontic and endodontic offices, and other health care practitioners’ offices in the State of Florida are prohibited from providing any medically unnecessary, nonurgent or nonemergency procedure or surgery which, if delayed, does not place a patient’s immediate health, safety, or well-being at risk, or will, if delayed, not contribute to the worsening of a serious or life-threatening medical condition.”
As a result, my practice has been limited to telemedicine consultations. While the ASRM guidance and the gubernatorial executive order pose a significant financial hardship on my center and all applicable medical clinics in my state, resulting in expected layoffs, salary reductions, and requests for government stimulus loans, the greater good takes priority and we pray for all the victims of this devastating pandemic.
The governor’s current executive order is set to expire on May 9, 2020, unless it is extended.
ASRM released an update of their guidance on March 30, 2020, offering no change from their prior recommendations. The organization plans to reevaluate the guidance at 2-week intervals.
Sangeeta Sinha, MD, an ob.gyn. in private practice at Stone Springs Hospital Center, Dulles, Va. said in an interview, “COVID 19 has put fear in all aspects of our daily activities which we are attempting to cope with.”
She related several changes made to her office and hospital environments. “In our office, we are now wearing a mask at all times, gloves to examine every patient. We have staggered physicians in the office to take televisits and in-office patients. We are screening all new patients on the phone to determine if they are sick, have traveled to high-risk, hot spot areas of the country, or have had contact with someone who tested positive for COVID-19. We are only seeing our pregnant women and have also pushed out their return appointments to 4 weeks if possible. There are several staff who are not working due to fear or are in self quarantine so we have shortage of staff in the office. At the hospital as well we are wearing a mask at all times, using personal protective equipment for deliveries and C-sections.
“We have had several scares, including a new transfer of an 18-year-old pregnant patient at 30 weeks with cough and sore throat, who later reported that her roommate is very sick and he works with someone who has tested positive for COVID-19. Thankfully she is healthy and well. We learned several lessons from this one.”
Barriers to clinical trial participation revealed by gynecologic cancer patients
A survey of gynecologic cancer survivors has revealed why some of these patients don’t participate in clinical trials.
Half of survey respondents with no history of trial participation said their medical team never mentioned the possibility of a trial. About 27% of respondents who never enrolled in a trial said they were interested in trial participation but didn’t qualify, the trial they wanted wasn’t available, their insurance didn’t cover participation, or the trial site was too far away.
Annie Ellis and Mary (Dicey) Jackson Scroggins, who are both ovarian cancer survivors and patient advocates, reported these findings in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
“We thought it was important to hear and learn directly from gynecologic cancer survivors,” Ms. Ellis said in an interview. “So we decided to conduct a survey that would expand knowledge about clinical trial participation from a gynecologic cancer patient–specific perspective.”
Ms. Ellis and Ms. Scroggins used survivor networks and social media to distribute a 26-question survey on trial participation. The survey was completed by 189 survivors of gynecologic cancers, 49.19% of whom experienced recurrent disease. The most common diagnoses were ovarian cancer (69.84%) and endometrial or uterine cancer (23.28%).
Perspectives of nonparticipants
Most respondents (65.61%) had never participated in a clinical trial. The most common reason was that the patient’s doctor or medical team never discussed trial participation (50.40%).
There were patients who were interested in trial participation but couldn’t enroll because they didn’t qualify (14.40%), the location was too far away (7.20%), the trial they wanted wasn’t available (4.00%), or their insurance didn’t cover trial participation (1.60%).
Patients who were not interested in trial participation said they didn’t want to receive a placebo (11.20%), they weren’t interested in experimental therapies (3.20%), or they didn’t want to be randomized (2.40%). One patient (1.60%) said she does not trust the medical system.
“Given the frequent conversations about distrust in the medical system, we were surprised that only 1 of the 189 respondents indicated distrust in the medical system as a reason for not participating in a clinical trial,” Ms. Ellis said.
Perspectives of trial participants
Roughly a third of respondents (34.39%) had participated in a clinical trial. Most (86.15%) said they learned about the trial from their doctor. Other sources included the patient’s own research (13.85%), a trial matching service (3.08%), a family member or friend (3.08%), and a support group (1.54%).
The most common reasons patients participated in trials were: “my doctor recommended it,” “to help women in the future,” “to expand my treatment options,” and “to have a chance to benefit personally.”
Additional responses indicated that patients viewed their trial participation in a positive light.
“We were surprised to find that 100% of the respondents who had participated in a clinical trial indicated either that they would participate again (84.62%) or that they were not sure about future participation (15.38%),” Ms. Ellis said. “No respondent indicated that she would not consider another trial. From open comments in the survey, it was clear that even if they did not obtain the result they hoped for or if the experience wasn’t optimal, they maintained the option of participating again.”
Implications and next steps
The survey results suggest there is a need for more discussions about clinical trials with patients who have gynecologic cancers, according to Ms. Ellis and Ms. Scroggins.
“We feel that conversations about clinical trials, with health care team members, should be included at every care decision point, even if – or perhaps especially if – the patient belongs to a group perceived to be unlikely to agree to participate in a trial,” Ms. Ellis said.
“These conversations are necessary with all patients-survivors,” she said, “but they are particularly important and necessary with patients from populations underrepresented in the clinical trial system if we want more representative trial populations, more generalizable results, and the potential for better outcomes for all.”
For their part, Ms. Ellis and Ms. Scroggins plan to conduct more research on this topic to gain additional insights.
“We’d like to conduct a larger survey looking deeper into barriers to and reasons for participation, and to work with medical professionals to develop models of communication to encourage consideration of clinical trials,” Ms. Ellis said. “Additionally, we will work to have a more diverse respondent pool across many dimensions.”
Ms. Ellis is a research advocate on the scientific advisory committee of the Ovarian Cancer National Alliance in Washington. Ms. Scroggins is the director of global outreach and engagement at the International Gynecologic Cancer Society in Louisville, Ken. They have no conflicts of interest.
SOURCE: Ellis A and Scroggins MJ. SGO 2020, Abstract 540.
A survey of gynecologic cancer survivors has revealed why some of these patients don’t participate in clinical trials.
Half of survey respondents with no history of trial participation said their medical team never mentioned the possibility of a trial. About 27% of respondents who never enrolled in a trial said they were interested in trial participation but didn’t qualify, the trial they wanted wasn’t available, their insurance didn’t cover participation, or the trial site was too far away.
Annie Ellis and Mary (Dicey) Jackson Scroggins, who are both ovarian cancer survivors and patient advocates, reported these findings in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
“We thought it was important to hear and learn directly from gynecologic cancer survivors,” Ms. Ellis said in an interview. “So we decided to conduct a survey that would expand knowledge about clinical trial participation from a gynecologic cancer patient–specific perspective.”
Ms. Ellis and Ms. Scroggins used survivor networks and social media to distribute a 26-question survey on trial participation. The survey was completed by 189 survivors of gynecologic cancers, 49.19% of whom experienced recurrent disease. The most common diagnoses were ovarian cancer (69.84%) and endometrial or uterine cancer (23.28%).
Perspectives of nonparticipants
Most respondents (65.61%) had never participated in a clinical trial. The most common reason was that the patient’s doctor or medical team never discussed trial participation (50.40%).
There were patients who were interested in trial participation but couldn’t enroll because they didn’t qualify (14.40%), the location was too far away (7.20%), the trial they wanted wasn’t available (4.00%), or their insurance didn’t cover trial participation (1.60%).
Patients who were not interested in trial participation said they didn’t want to receive a placebo (11.20%), they weren’t interested in experimental therapies (3.20%), or they didn’t want to be randomized (2.40%). One patient (1.60%) said she does not trust the medical system.
“Given the frequent conversations about distrust in the medical system, we were surprised that only 1 of the 189 respondents indicated distrust in the medical system as a reason for not participating in a clinical trial,” Ms. Ellis said.
Perspectives of trial participants
Roughly a third of respondents (34.39%) had participated in a clinical trial. Most (86.15%) said they learned about the trial from their doctor. Other sources included the patient’s own research (13.85%), a trial matching service (3.08%), a family member or friend (3.08%), and a support group (1.54%).
The most common reasons patients participated in trials were: “my doctor recommended it,” “to help women in the future,” “to expand my treatment options,” and “to have a chance to benefit personally.”
Additional responses indicated that patients viewed their trial participation in a positive light.
“We were surprised to find that 100% of the respondents who had participated in a clinical trial indicated either that they would participate again (84.62%) or that they were not sure about future participation (15.38%),” Ms. Ellis said. “No respondent indicated that she would not consider another trial. From open comments in the survey, it was clear that even if they did not obtain the result they hoped for or if the experience wasn’t optimal, they maintained the option of participating again.”
Implications and next steps
The survey results suggest there is a need for more discussions about clinical trials with patients who have gynecologic cancers, according to Ms. Ellis and Ms. Scroggins.
“We feel that conversations about clinical trials, with health care team members, should be included at every care decision point, even if – or perhaps especially if – the patient belongs to a group perceived to be unlikely to agree to participate in a trial,” Ms. Ellis said.
“These conversations are necessary with all patients-survivors,” she said, “but they are particularly important and necessary with patients from populations underrepresented in the clinical trial system if we want more representative trial populations, more generalizable results, and the potential for better outcomes for all.”
For their part, Ms. Ellis and Ms. Scroggins plan to conduct more research on this topic to gain additional insights.
“We’d like to conduct a larger survey looking deeper into barriers to and reasons for participation, and to work with medical professionals to develop models of communication to encourage consideration of clinical trials,” Ms. Ellis said. “Additionally, we will work to have a more diverse respondent pool across many dimensions.”
Ms. Ellis is a research advocate on the scientific advisory committee of the Ovarian Cancer National Alliance in Washington. Ms. Scroggins is the director of global outreach and engagement at the International Gynecologic Cancer Society in Louisville, Ken. They have no conflicts of interest.
SOURCE: Ellis A and Scroggins MJ. SGO 2020, Abstract 540.
A survey of gynecologic cancer survivors has revealed why some of these patients don’t participate in clinical trials.
Half of survey respondents with no history of trial participation said their medical team never mentioned the possibility of a trial. About 27% of respondents who never enrolled in a trial said they were interested in trial participation but didn’t qualify, the trial they wanted wasn’t available, their insurance didn’t cover participation, or the trial site was too far away.
Annie Ellis and Mary (Dicey) Jackson Scroggins, who are both ovarian cancer survivors and patient advocates, reported these findings in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
“We thought it was important to hear and learn directly from gynecologic cancer survivors,” Ms. Ellis said in an interview. “So we decided to conduct a survey that would expand knowledge about clinical trial participation from a gynecologic cancer patient–specific perspective.”
Ms. Ellis and Ms. Scroggins used survivor networks and social media to distribute a 26-question survey on trial participation. The survey was completed by 189 survivors of gynecologic cancers, 49.19% of whom experienced recurrent disease. The most common diagnoses were ovarian cancer (69.84%) and endometrial or uterine cancer (23.28%).
Perspectives of nonparticipants
Most respondents (65.61%) had never participated in a clinical trial. The most common reason was that the patient’s doctor or medical team never discussed trial participation (50.40%).
There were patients who were interested in trial participation but couldn’t enroll because they didn’t qualify (14.40%), the location was too far away (7.20%), the trial they wanted wasn’t available (4.00%), or their insurance didn’t cover trial participation (1.60%).
Patients who were not interested in trial participation said they didn’t want to receive a placebo (11.20%), they weren’t interested in experimental therapies (3.20%), or they didn’t want to be randomized (2.40%). One patient (1.60%) said she does not trust the medical system.
“Given the frequent conversations about distrust in the medical system, we were surprised that only 1 of the 189 respondents indicated distrust in the medical system as a reason for not participating in a clinical trial,” Ms. Ellis said.
Perspectives of trial participants
Roughly a third of respondents (34.39%) had participated in a clinical trial. Most (86.15%) said they learned about the trial from their doctor. Other sources included the patient’s own research (13.85%), a trial matching service (3.08%), a family member or friend (3.08%), and a support group (1.54%).
The most common reasons patients participated in trials were: “my doctor recommended it,” “to help women in the future,” “to expand my treatment options,” and “to have a chance to benefit personally.”
Additional responses indicated that patients viewed their trial participation in a positive light.
“We were surprised to find that 100% of the respondents who had participated in a clinical trial indicated either that they would participate again (84.62%) or that they were not sure about future participation (15.38%),” Ms. Ellis said. “No respondent indicated that she would not consider another trial. From open comments in the survey, it was clear that even if they did not obtain the result they hoped for or if the experience wasn’t optimal, they maintained the option of participating again.”
Implications and next steps
The survey results suggest there is a need for more discussions about clinical trials with patients who have gynecologic cancers, according to Ms. Ellis and Ms. Scroggins.
“We feel that conversations about clinical trials, with health care team members, should be included at every care decision point, even if – or perhaps especially if – the patient belongs to a group perceived to be unlikely to agree to participate in a trial,” Ms. Ellis said.
“These conversations are necessary with all patients-survivors,” she said, “but they are particularly important and necessary with patients from populations underrepresented in the clinical trial system if we want more representative trial populations, more generalizable results, and the potential for better outcomes for all.”
For their part, Ms. Ellis and Ms. Scroggins plan to conduct more research on this topic to gain additional insights.
“We’d like to conduct a larger survey looking deeper into barriers to and reasons for participation, and to work with medical professionals to develop models of communication to encourage consideration of clinical trials,” Ms. Ellis said. “Additionally, we will work to have a more diverse respondent pool across many dimensions.”
Ms. Ellis is a research advocate on the scientific advisory committee of the Ovarian Cancer National Alliance in Washington. Ms. Scroggins is the director of global outreach and engagement at the International Gynecologic Cancer Society in Louisville, Ken. They have no conflicts of interest.
SOURCE: Ellis A and Scroggins MJ. SGO 2020, Abstract 540.
FROM SGO 2020
How long is it safe to delay gynecologic cancer surgery?
As I write this column, there are more than 25,000 current cases of COVID-19 in the United States with an expected exponential rise in these numbers. Hospitals are issuing directives to cancel or postpone “elective” surgery to preserve the finite essential personal protective equipment (PPE), encourage social distancing, prevent exposure of at-risk patients within the hospital, and ensure bed and ventilator capacity for the impending surge in COVID-19 patients.
Many health systems have defined which surgeries they consider permissible, typically by using time parameters such as would not cause patient harm if not performed within 4 weeks, or 7 days, or 24 hours. This leaves surgeons in the unfamiliar position of rationing health care, a role with which, over the coming months, we may have to become increasingly comfortable. This is an enormous responsibility, the shift of resources between one population in need and another, and decisions should be based on data, not bias or hunch. We know that untreated cancer is life threatening, but there is a difference between untreated and delayed. What is a safe time to wait for gynecologic cancer surgery after diagnosis without negatively affecting survival from that cancer?
As I looked through my own upcoming surgical schedule, I sought guidance from the American College of Surgeons’ website, updated on March 17, 2020. In this site they tabulate an “Elective Surgery Acuity Scale” in which “most cancers” fit into tier 3a, which corresponds to high acuity surgery – “do not postpone.” This definition is fairly generalized and blunt; it does not account for the differences in cancers and occasional voluntary needs to postpone a patient’s cancer surgery for health optimization. There are limited data that measure the impact of surgical wait times on survival from gynecologic cancer. Most of this research is observational, and therefore, is influenced by confounders causing delay in surgery (e.g., comorbid conditions or socioeconomic factors that limit access to care). However, the current enforced delays are involuntary; driven by the system, not the patient; and access is universally restricted.
Endometrial cancer
Most data regarding outcomes and gynecologic cancer delay come from endometrial cancer. In 2016, Shalowitz et al. evaluated 182,000 endometrial cancer cases documented within the National Cancer Database (NCDB), which captures approximately 70% of cancer surgeries in the United States.1 They separated these patients into groups of low-grade (grade 1 and 2 endometrioid) and high-grade (grade 3 endometrioid and nonendometrioid) cancers, and evaluated the groups for their overall survival, stratified by the time period between diagnosis and surgery. Interestingly, those whose surgery was performed under 2 weeks from diagnosis had worse perioperative mortality and long-term survival. This seems to be a function of lack of medical optimization; low-volume, nonspecialized centers having less wait time; and the presentation of more advanced and symptomatic disease demanding a more urgent surgery. After those initial 2 weeks of worse outcomes, there was a period of stable outcomes and safety in waiting that extended up to 8 weeks for patients with low-grade cancers and up to 18 weeks for patients with high-grade cancers.
It may be counterintuitive to think that surgical delay affects patients with high-grade endometrial cancers less. These are more aggressive cancers, and there is patient and provider concern for metastatic spread with time elapsed. But an expedited surgery does not appear to be necessary for this group. The Shalowitz study demonstrated no risk for upstaging with surgical delay, meaning that advanced stage was not more likely to be identified in patients whose surgery was delayed, compared with those performed earlier. This observation suggests that the survival from high-grade endometrial cancers is largely determined by factors that cannot be controlled by the surgeon such as the stage at diagnosis, occult spread, and decreased responsiveness of the tumor to adjuvant therapy. In other words, fast-tracking these patients to surgery has limited influence on the outcomes for high-grade endometrial cancers.
For low-grade cancers, adverse outcomes were seen with a surgical delay of more than 8 weeks. But this may not have been caused by progression of disease (low-grade cancers also were not upstaged with delays), but rather may reflect that, in normal times, elective delays of more than 8 weeks are a function of necessary complex medical optimization of comorbidities (such as obesity-related disease). The survival that is measured by NCDB is not disease specific, and patients with comorbidities will be more likely to have impaired overall survival.
A systematic review of all papers that looked at endometrial cancer outcomes associated with surgical delay determined that it is reasonable to delay surgery for up to 8 weeks.2
Ovarian cancer
The data for ovarian cancer surgery is more limited. Most literature discusses the impact of delay in the time between surgery and the receipt of adjuvant chemotherapy, but there are limited data exploring how a delay in primary debulking negatively affects patients. This is perhaps because advanced ovarian cancer surgery rarely is delayed because of symptoms and apparent advanced stage at diagnosis. When a patient’s surgery does need to be voluntarily delayed, for example for medical optimization, there is the option of neoadjuvant chemotherapy (NACT) in which surgery is performed after three or more cycles of chemotherapy. NACT has been shown in multiple studies to have noninferior cancer outcomes, compared with primary debulking surgery.3,4
Perhaps in this current environment in which access to operating rooms and supplies is rationed, we should consider offering more, or all, patients NACT? Hospital stays after primary cytoreductive surgeries are typically 3-7 days in length, and these patients are at a higher risk, compared with other gynecologic cancer surgeries, of ICU admission and blood transfusions, both limited resources in this current environment. The disadvantage of this approach is that, while chemotherapy can keep patients out of the hospital so that they can practice social distancing, this particular therapy adds to the immunocompromised population. However, even patients who undergo primary surgical cytoreductive surgery will need to rapidly transition to immunosuppressive cytotoxic therapy; therefore it is unlikely that this can be avoided entirely during this time.
Lower genital tract cancers
Surgery for patients with lower genital tract cancers – such as cervical and vulvar cancer – also can probably be safely delayed for a 4-week period, and possibly longer. A Canadian retrospective study looked collectively at cervical, vaginal, and vulvar cancers evaluating for disease progression associated with delay to surgery, using 28 days as a benchmark for delayed surgery.5 They found no significant increased progression associated with surgical delay greater than 28 days. This study evaluated progression of cancer and did not measure cancer survival, although it is unlikely we would see impaired survival without a significant increase in disease progression.
We also can look to outcomes from delayed radical hysterectomy for stage I cervical cancer in pregnancy to provided us with some data. A retrospective cohort study observed no difference in survival when 28 women with early-stage cervical cancer who were diagnosed in pregnancy (average wait time 20 weeks from diagnosis to treatment) were compared with the outcomes of 52 matched nonpregnant control patients (average wait time 8 weeks). Their survival was 89% versus 94% respectively (P = .08).6
Summary
Synthesizing this data, it appears that, in an environment of competing needs and resources, it is reasonable and safe to delay surgery for patients with gynecologic cancers for 4-6 weeks and potentially longer. This includes patients with high-grade endometrial cancers. Clearly, these decisions should be individualized to patients and different health systems. For example, a patient who presents with a cancer-associated life-threatening bowel obstruction or hemorrhage may need an immediate intervention, and communities minimally affected by the coronavirus pandemic may have more allowances for surgery. With respect to patient anxiety, most patients with cancer are keen to have surgery promptly, and breaking the news to them that their surgery may be delayed because of institutional and public health needs will be difficult. However, the data support that this is likely safe.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email Dr. Rossi at [email protected].
References
1. Am J Obstet Gynecol 2017;216(3):268 e1-68 e18.
2. Eur J Obstet Gynecol Reprod Biol 2020;246:1-6. doi: 10.1016/j.ejogrb.2020.01.004.
3. N Engl J Med 2010;363(10):943-53.
4. Lancet 2015;386(9990):249-57.
5. J Obstet Gynaecol Can 2015;37(4):338-44.
6. Am J Obstet Gynecol 2017;216(3):276 e1-76 e6. doi: 10.1016/j.ajog.2016.10.034.
As I write this column, there are more than 25,000 current cases of COVID-19 in the United States with an expected exponential rise in these numbers. Hospitals are issuing directives to cancel or postpone “elective” surgery to preserve the finite essential personal protective equipment (PPE), encourage social distancing, prevent exposure of at-risk patients within the hospital, and ensure bed and ventilator capacity for the impending surge in COVID-19 patients.
Many health systems have defined which surgeries they consider permissible, typically by using time parameters such as would not cause patient harm if not performed within 4 weeks, or 7 days, or 24 hours. This leaves surgeons in the unfamiliar position of rationing health care, a role with which, over the coming months, we may have to become increasingly comfortable. This is an enormous responsibility, the shift of resources between one population in need and another, and decisions should be based on data, not bias or hunch. We know that untreated cancer is life threatening, but there is a difference between untreated and delayed. What is a safe time to wait for gynecologic cancer surgery after diagnosis without negatively affecting survival from that cancer?
As I looked through my own upcoming surgical schedule, I sought guidance from the American College of Surgeons’ website, updated on March 17, 2020. In this site they tabulate an “Elective Surgery Acuity Scale” in which “most cancers” fit into tier 3a, which corresponds to high acuity surgery – “do not postpone.” This definition is fairly generalized and blunt; it does not account for the differences in cancers and occasional voluntary needs to postpone a patient’s cancer surgery for health optimization. There are limited data that measure the impact of surgical wait times on survival from gynecologic cancer. Most of this research is observational, and therefore, is influenced by confounders causing delay in surgery (e.g., comorbid conditions or socioeconomic factors that limit access to care). However, the current enforced delays are involuntary; driven by the system, not the patient; and access is universally restricted.
Endometrial cancer
Most data regarding outcomes and gynecologic cancer delay come from endometrial cancer. In 2016, Shalowitz et al. evaluated 182,000 endometrial cancer cases documented within the National Cancer Database (NCDB), which captures approximately 70% of cancer surgeries in the United States.1 They separated these patients into groups of low-grade (grade 1 and 2 endometrioid) and high-grade (grade 3 endometrioid and nonendometrioid) cancers, and evaluated the groups for their overall survival, stratified by the time period between diagnosis and surgery. Interestingly, those whose surgery was performed under 2 weeks from diagnosis had worse perioperative mortality and long-term survival. This seems to be a function of lack of medical optimization; low-volume, nonspecialized centers having less wait time; and the presentation of more advanced and symptomatic disease demanding a more urgent surgery. After those initial 2 weeks of worse outcomes, there was a period of stable outcomes and safety in waiting that extended up to 8 weeks for patients with low-grade cancers and up to 18 weeks for patients with high-grade cancers.
It may be counterintuitive to think that surgical delay affects patients with high-grade endometrial cancers less. These are more aggressive cancers, and there is patient and provider concern for metastatic spread with time elapsed. But an expedited surgery does not appear to be necessary for this group. The Shalowitz study demonstrated no risk for upstaging with surgical delay, meaning that advanced stage was not more likely to be identified in patients whose surgery was delayed, compared with those performed earlier. This observation suggests that the survival from high-grade endometrial cancers is largely determined by factors that cannot be controlled by the surgeon such as the stage at diagnosis, occult spread, and decreased responsiveness of the tumor to adjuvant therapy. In other words, fast-tracking these patients to surgery has limited influence on the outcomes for high-grade endometrial cancers.
For low-grade cancers, adverse outcomes were seen with a surgical delay of more than 8 weeks. But this may not have been caused by progression of disease (low-grade cancers also were not upstaged with delays), but rather may reflect that, in normal times, elective delays of more than 8 weeks are a function of necessary complex medical optimization of comorbidities (such as obesity-related disease). The survival that is measured by NCDB is not disease specific, and patients with comorbidities will be more likely to have impaired overall survival.
A systematic review of all papers that looked at endometrial cancer outcomes associated with surgical delay determined that it is reasonable to delay surgery for up to 8 weeks.2
Ovarian cancer
The data for ovarian cancer surgery is more limited. Most literature discusses the impact of delay in the time between surgery and the receipt of adjuvant chemotherapy, but there are limited data exploring how a delay in primary debulking negatively affects patients. This is perhaps because advanced ovarian cancer surgery rarely is delayed because of symptoms and apparent advanced stage at diagnosis. When a patient’s surgery does need to be voluntarily delayed, for example for medical optimization, there is the option of neoadjuvant chemotherapy (NACT) in which surgery is performed after three or more cycles of chemotherapy. NACT has been shown in multiple studies to have noninferior cancer outcomes, compared with primary debulking surgery.3,4
Perhaps in this current environment in which access to operating rooms and supplies is rationed, we should consider offering more, or all, patients NACT? Hospital stays after primary cytoreductive surgeries are typically 3-7 days in length, and these patients are at a higher risk, compared with other gynecologic cancer surgeries, of ICU admission and blood transfusions, both limited resources in this current environment. The disadvantage of this approach is that, while chemotherapy can keep patients out of the hospital so that they can practice social distancing, this particular therapy adds to the immunocompromised population. However, even patients who undergo primary surgical cytoreductive surgery will need to rapidly transition to immunosuppressive cytotoxic therapy; therefore it is unlikely that this can be avoided entirely during this time.
Lower genital tract cancers
Surgery for patients with lower genital tract cancers – such as cervical and vulvar cancer – also can probably be safely delayed for a 4-week period, and possibly longer. A Canadian retrospective study looked collectively at cervical, vaginal, and vulvar cancers evaluating for disease progression associated with delay to surgery, using 28 days as a benchmark for delayed surgery.5 They found no significant increased progression associated with surgical delay greater than 28 days. This study evaluated progression of cancer and did not measure cancer survival, although it is unlikely we would see impaired survival without a significant increase in disease progression.
We also can look to outcomes from delayed radical hysterectomy for stage I cervical cancer in pregnancy to provided us with some data. A retrospective cohort study observed no difference in survival when 28 women with early-stage cervical cancer who were diagnosed in pregnancy (average wait time 20 weeks from diagnosis to treatment) were compared with the outcomes of 52 matched nonpregnant control patients (average wait time 8 weeks). Their survival was 89% versus 94% respectively (P = .08).6
Summary
Synthesizing this data, it appears that, in an environment of competing needs and resources, it is reasonable and safe to delay surgery for patients with gynecologic cancers for 4-6 weeks and potentially longer. This includes patients with high-grade endometrial cancers. Clearly, these decisions should be individualized to patients and different health systems. For example, a patient who presents with a cancer-associated life-threatening bowel obstruction or hemorrhage may need an immediate intervention, and communities minimally affected by the coronavirus pandemic may have more allowances for surgery. With respect to patient anxiety, most patients with cancer are keen to have surgery promptly, and breaking the news to them that their surgery may be delayed because of institutional and public health needs will be difficult. However, the data support that this is likely safe.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email Dr. Rossi at [email protected].
References
1. Am J Obstet Gynecol 2017;216(3):268 e1-68 e18.
2. Eur J Obstet Gynecol Reprod Biol 2020;246:1-6. doi: 10.1016/j.ejogrb.2020.01.004.
3. N Engl J Med 2010;363(10):943-53.
4. Lancet 2015;386(9990):249-57.
5. J Obstet Gynaecol Can 2015;37(4):338-44.
6. Am J Obstet Gynecol 2017;216(3):276 e1-76 e6. doi: 10.1016/j.ajog.2016.10.034.
As I write this column, there are more than 25,000 current cases of COVID-19 in the United States with an expected exponential rise in these numbers. Hospitals are issuing directives to cancel or postpone “elective” surgery to preserve the finite essential personal protective equipment (PPE), encourage social distancing, prevent exposure of at-risk patients within the hospital, and ensure bed and ventilator capacity for the impending surge in COVID-19 patients.
Many health systems have defined which surgeries they consider permissible, typically by using time parameters such as would not cause patient harm if not performed within 4 weeks, or 7 days, or 24 hours. This leaves surgeons in the unfamiliar position of rationing health care, a role with which, over the coming months, we may have to become increasingly comfortable. This is an enormous responsibility, the shift of resources between one population in need and another, and decisions should be based on data, not bias or hunch. We know that untreated cancer is life threatening, but there is a difference between untreated and delayed. What is a safe time to wait for gynecologic cancer surgery after diagnosis without negatively affecting survival from that cancer?
As I looked through my own upcoming surgical schedule, I sought guidance from the American College of Surgeons’ website, updated on March 17, 2020. In this site they tabulate an “Elective Surgery Acuity Scale” in which “most cancers” fit into tier 3a, which corresponds to high acuity surgery – “do not postpone.” This definition is fairly generalized and blunt; it does not account for the differences in cancers and occasional voluntary needs to postpone a patient’s cancer surgery for health optimization. There are limited data that measure the impact of surgical wait times on survival from gynecologic cancer. Most of this research is observational, and therefore, is influenced by confounders causing delay in surgery (e.g., comorbid conditions or socioeconomic factors that limit access to care). However, the current enforced delays are involuntary; driven by the system, not the patient; and access is universally restricted.
Endometrial cancer
Most data regarding outcomes and gynecologic cancer delay come from endometrial cancer. In 2016, Shalowitz et al. evaluated 182,000 endometrial cancer cases documented within the National Cancer Database (NCDB), which captures approximately 70% of cancer surgeries in the United States.1 They separated these patients into groups of low-grade (grade 1 and 2 endometrioid) and high-grade (grade 3 endometrioid and nonendometrioid) cancers, and evaluated the groups for their overall survival, stratified by the time period between diagnosis and surgery. Interestingly, those whose surgery was performed under 2 weeks from diagnosis had worse perioperative mortality and long-term survival. This seems to be a function of lack of medical optimization; low-volume, nonspecialized centers having less wait time; and the presentation of more advanced and symptomatic disease demanding a more urgent surgery. After those initial 2 weeks of worse outcomes, there was a period of stable outcomes and safety in waiting that extended up to 8 weeks for patients with low-grade cancers and up to 18 weeks for patients with high-grade cancers.
It may be counterintuitive to think that surgical delay affects patients with high-grade endometrial cancers less. These are more aggressive cancers, and there is patient and provider concern for metastatic spread with time elapsed. But an expedited surgery does not appear to be necessary for this group. The Shalowitz study demonstrated no risk for upstaging with surgical delay, meaning that advanced stage was not more likely to be identified in patients whose surgery was delayed, compared with those performed earlier. This observation suggests that the survival from high-grade endometrial cancers is largely determined by factors that cannot be controlled by the surgeon such as the stage at diagnosis, occult spread, and decreased responsiveness of the tumor to adjuvant therapy. In other words, fast-tracking these patients to surgery has limited influence on the outcomes for high-grade endometrial cancers.
For low-grade cancers, adverse outcomes were seen with a surgical delay of more than 8 weeks. But this may not have been caused by progression of disease (low-grade cancers also were not upstaged with delays), but rather may reflect that, in normal times, elective delays of more than 8 weeks are a function of necessary complex medical optimization of comorbidities (such as obesity-related disease). The survival that is measured by NCDB is not disease specific, and patients with comorbidities will be more likely to have impaired overall survival.
A systematic review of all papers that looked at endometrial cancer outcomes associated with surgical delay determined that it is reasonable to delay surgery for up to 8 weeks.2
Ovarian cancer
The data for ovarian cancer surgery is more limited. Most literature discusses the impact of delay in the time between surgery and the receipt of adjuvant chemotherapy, but there are limited data exploring how a delay in primary debulking negatively affects patients. This is perhaps because advanced ovarian cancer surgery rarely is delayed because of symptoms and apparent advanced stage at diagnosis. When a patient’s surgery does need to be voluntarily delayed, for example for medical optimization, there is the option of neoadjuvant chemotherapy (NACT) in which surgery is performed after three or more cycles of chemotherapy. NACT has been shown in multiple studies to have noninferior cancer outcomes, compared with primary debulking surgery.3,4
Perhaps in this current environment in which access to operating rooms and supplies is rationed, we should consider offering more, or all, patients NACT? Hospital stays after primary cytoreductive surgeries are typically 3-7 days in length, and these patients are at a higher risk, compared with other gynecologic cancer surgeries, of ICU admission and blood transfusions, both limited resources in this current environment. The disadvantage of this approach is that, while chemotherapy can keep patients out of the hospital so that they can practice social distancing, this particular therapy adds to the immunocompromised population. However, even patients who undergo primary surgical cytoreductive surgery will need to rapidly transition to immunosuppressive cytotoxic therapy; therefore it is unlikely that this can be avoided entirely during this time.
Lower genital tract cancers
Surgery for patients with lower genital tract cancers – such as cervical and vulvar cancer – also can probably be safely delayed for a 4-week period, and possibly longer. A Canadian retrospective study looked collectively at cervical, vaginal, and vulvar cancers evaluating for disease progression associated with delay to surgery, using 28 days as a benchmark for delayed surgery.5 They found no significant increased progression associated with surgical delay greater than 28 days. This study evaluated progression of cancer and did not measure cancer survival, although it is unlikely we would see impaired survival without a significant increase in disease progression.
We also can look to outcomes from delayed radical hysterectomy for stage I cervical cancer in pregnancy to provided us with some data. A retrospective cohort study observed no difference in survival when 28 women with early-stage cervical cancer who were diagnosed in pregnancy (average wait time 20 weeks from diagnosis to treatment) were compared with the outcomes of 52 matched nonpregnant control patients (average wait time 8 weeks). Their survival was 89% versus 94% respectively (P = .08).6
Summary
Synthesizing this data, it appears that, in an environment of competing needs and resources, it is reasonable and safe to delay surgery for patients with gynecologic cancers for 4-6 weeks and potentially longer. This includes patients with high-grade endometrial cancers. Clearly, these decisions should be individualized to patients and different health systems. For example, a patient who presents with a cancer-associated life-threatening bowel obstruction or hemorrhage may need an immediate intervention, and communities minimally affected by the coronavirus pandemic may have more allowances for surgery. With respect to patient anxiety, most patients with cancer are keen to have surgery promptly, and breaking the news to them that their surgery may be delayed because of institutional and public health needs will be difficult. However, the data support that this is likely safe.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email Dr. Rossi at [email protected].
References
1. Am J Obstet Gynecol 2017;216(3):268 e1-68 e18.
2. Eur J Obstet Gynecol Reprod Biol 2020;246:1-6. doi: 10.1016/j.ejogrb.2020.01.004.
3. N Engl J Med 2010;363(10):943-53.
4. Lancet 2015;386(9990):249-57.
5. J Obstet Gynaecol Can 2015;37(4):338-44.
6. Am J Obstet Gynecol 2017;216(3):276 e1-76 e6. doi: 10.1016/j.ajog.2016.10.034.
Chlamydia trachomatis infections
CASE Pregnant woman with symptoms of genital infection
A 23-year-old primigravid woman at 15 weeks and 2 days’ gestation reported having a 2-week history of increased urinary frequency and vaginal discharge. She said she experienced similar symptoms 6 weeks previously that resolved within a week. The patient has had 3 sexual partners in the past year. Her current partner was experiencing a yellow urethral discharge and dysuria. On the patient’s speculum examination, the clinician noted a yellow-green discharge emanating from the cervix as well as cervical motion tenderness.
What is the most likely diagnosis, and how would you treat this patient?
The culprit was chlamydia
Chlamydia trachomatis is an obligate intracellular bacterium that does not stain with Gram staining. A rigid cell wall encloses its intracellular component. C trachomatis infection begins when the chlamydial elementary body enters a susceptible host cell.
Once ingested, the organism’s surface antigens (major outer membrane protein and lipopolysaccharide antigens) provide intracellular sanctuary for the bacterium by inhibiting phagolysosomal fusion. Subsequently, the elementary body morphs into a reticular body, which replicates through adenosine triphosphate (ATP)–dependent binary fission. After approximately 48 hours of replication, the organism again morphs into an elementary body and is released to infect additional cells and acquire new ATP stores for further replication.
Chlamydia can be transmitted horizontally during oral, vaginal, or anal intercourse or vertically to the infant during vaginal delivery.
The US’s most common notifiable disease
According to the Centers for Disease Control and Prevention (CDC), the incidence of chlamydia infection in the United States increased considerably in recent years: from 976,455 cases in 2005 to 1,758,668 cases in 2018.1 In 2018, rates of chlamydia infection in women were nearly double the rates in men, with an incidence of 688.2 versus 377.5 per 100,000 cases, and a prevalence of 1,150,672 versus 612,020.1
Young adults have a higher frequency of chlamydia infection than any other age group. From 2017 to 2018, reported cases in women aged 15–19 years increased by 1.3%, to 3,306.8 per 100,000; in women aged 20–24 years, cases increased by 0.8%, to 4,064.6 per 100,000. In young men in the same age ranges, reported cases increased by 3.7%, to 959.0 cases per 100,000, and by 3.3%, to 1,784.5 per 100,000 cases, respectively.1
Both the incidence and prevalence of chlamydia infection are higher in African Americans than in whites, while Asians have the lowest rates.1 The prevalence of infection also is increased with incarceration, lower socioeconomic status, and residence in the southern United States.
The prevalence of chlamydia infection in pregnant women is approximately 2% to 3%, but it may be as high as 30% in high-risk populations, such as women who are unmarried, have multiple sex partners, are coinfected with another sexually transmitted disease (STD), have partners with nongonococcal urethritis, have mucopurulent discharge, have acute urethral syndrome, and have late or no prenatal care.2 Since chlamydia infection often is asymptomatic and some infections resolve spontaneously, the true prevalence of infection probably is underreported.
Continue to: Chlamydia infection can cause serious clinical manifestations...
Chlamydia infection can cause serious clinical manifestations
The 15 serotypes of C trachomatis are grouped into 3 categories according to clinical manifestations:
- Serotypes A, B, Ba, and C cause endemic trachoma, characterized by bilateral irritation of the eyelids that progresses to eyelid thickening and scarring, eventually leading to corneal abrasion and blindness.
- Serotypes D–K manifest as conjunctivitis and pneumonia in newborns, proctitis in men (especially in men who have sex with men), and genitourinary infections in women. Reactive arthritis and inclusion conjunctivitis also can occur with D–K serotypes.
- Serotypes L1–L3 cause lymphogranuloma venereum.
About 70% of women with chlamydia infection are asymptomatic. Those who have symptoms often present with endocervicitis or acute urethral syndrome (acute urethritis). Manifestations of these 2 conditions include a frothy yellow-green vaginal and/or urethral discharge, dysuria, and frequency. Women who engage in rectal intercourse also may notice a purulent discharge from the anus. Untreated, C trachomatis organisms may ascend the reproductive tract, causing both endometritis and pelvic inflammatory disease (PID).
While a single episode of PID increases tubal infertility risk by 10%, a second episode increases the risk by 40%.3 Over time, recurrent and/or chronic PID causes scarring and adhesion formation, which may result in chronic pelvic pain. In addition, chronic infection is the single most important risk factor for ectopic pregnancy. Finally, chlamydia infection is a risk factor for Fitz-Hugh-Cutis syndrome (perihepatitis). In this condition, organisms ascend from the site of pelvic infection along the pericolic gutter to ultimately infect the liver capsule.
Specific complications in pregnancy
Chlamydia infection in pregnant women is associated with preterm delivery and preterm premature rupture of membranes. Infants born to mothers with untreated chlamydia infection are at risk for pneumonia, conjunctivitis, and even perinatal death.2 Acquisition of infection occurs at the time of delivery rather than in the antepartum period.
The significant morbidity associated with chlamydia infection underscores the importance of regular screening, especially in pregnant women. The current United States Preventive Service Task Force guidelines recommend annual screening of all sexually active women who are 24 years of age or younger, as well as of older, high-risk women.
The CDC recommends routine screening of all pregnant women for chlamydia at the first prenatal visit. Repeat screening is recommended in the third trimester for all pregnant women younger than 25 years, those at increased risk, and those infected within the past 3 to 6 months or during the first trimester. Those who test positive should be retested 3 weeks after completion of treatment.1
Chlamydia screening strategies
Historically, a chlamydia diagnosis was made by isolating the organisms in tissue culture. In the 1990s, however, that extremely time-consuming and resource-intensive procedure was replaced by nucleic acid amplification testing (NAAT).
NAAT methodology. NAAT is the gold standard for diagnosing C trachomatis infection; this methodology utilizes various assays, including polymerase chain reaction, ligase chain reaction, and transcription-mediated amplification.
Continue to: Compared with previous culture and antigen detection techniques...
Compared with previous culture and antigen detection techniques, NAAT’s advantages include excellent sensitivity and specificity (>90% and ≥99%, respectively), enabling detection of a low inoculum of organisms in a sample obtained by noninvasive methods, such as first-void urine collection or vaginal swab.2,4,5 Furthermore, NAAT does not impose any specific storage regulations on collected specimens, is cost effective, and can jointly test for Neisseria gonorrhoeae, which commonly co-infects with C trachomatis.6
Screening in pregnancy. In 2012, Blatt and colleagues examined testing patterns in nearly 1.3 million obstetric patients and found that only 59% (761,315) of women were tested for chlamydia at least once in pregnancy.7 Only 1 in 3 women were tested during the first prenatal visit, as CDC guidelines recommend. Testing rates declined with increasing age. Of women screened, 3.5% tested positive for chlamydia.7 Of these, 3 of 4 were retested at least once, with almost 20% having at least 1 subsequent positive result.7
Of note, in a study of women who reported receptive anal intercourse (n = 2,818), 292 women tested positive for chlamydia; 10.4% tested positive in genital-only sites, 58.6% in genital and rectal sites, and 20.5% at the rectal site only.8
It is alarming that only 59% of pregnant women are screened for chlamydia given the significant perinatal complications associated with this infection. Barriers to screening pregnant women may include clinician discomfort in discussing STDs and patient refusal of screening. Furthermore, clinicians should routinely ask women about receptive anal sex. Women who report this risk factor should be tested for chlamydia in both the endocervix and rectum.
Retesting and follow-up. After the initial diagnosis of chlamydia, a test of cure 3 weeks after treatment is an important aspect of care. Thus, identifying and overcoming barriers to retesting is important. Clinicians should educate patients about the importance of follow-up. Also consider incorporating the use of home-based, self-obtained vaginal swabs for retesting. Results from 2 randomized trials showed that eliminating a patient’s transportation barriers and providing a home-based alternative to a follow-up visit significantly increased rescreening rates by 33% in STD clinic patients and by 59.2% in family planning clinic patients.9
Reinfection risk. The rate of venereal chlamydia transmission in heterosexual partners is 70%. Since sexually active chlamydia-positive patients are at risk for reinfection by their partner after treatment completion, clinicians should refer the sex partners for evaluation. If the sex partners are reluctant to have testing, it is reasonable to provide empiric antibiotic treatment to decrease the risk of re-infection in the patient.7 Before doing so, however, make certain that state law permits this practice, and be sure to document the prescribed treatment in the patient’s record.
Treatment options
Prompt treatment of C trachomatis infection is essential to decrease the risk of disease sequelae. Nonpregnant adults can be treated with oral doxycycline 100 mg twice daily for 7 days.
In a head-to-head study performed in a controlled environment that ensured treatment adherence, 97% efficacy was achieved with one oral dose of azithromycin (1 g) compared with 100% efficacy with doxycycline.10 However, in the real-world setting, imperfect adherence to the multi-day doxycycline regimen is associated with treatment failures. Thus, a single dose of azithromycin is preferable for patients with questionable compliance.11
In obstetric patients, azithromycin and amoxicillin are preferred as first-line agents for treatment of C trachomatis due to their improved safety profile in this demographic. Amoxicillin 500 mg orally 3 times daily for 7 days has 95% efficacy.2
Women allergic to these agents may be treated with an alternative regimen of erythromycin base, 500 mg orally 4 times daily for 7 days, or erythromycin ethylsuccinate, 800 mg orally 4 times daily for 7 days. Erythromycin should be reserved for second-line therapy because of its lower efficacy (64%) and frequent gastrointestinal adverse effects.2 Doxycycline is contraindicated in pregnancy because of possible teratogenic effects on the teeth and bone of the fetus.
- Centers for Disease Control and Prevention Division of STD Prevention. Sexually transmitted disease surveillance 2018. October 2019. https://www.cdc.gov/std/stats18/default.htm. 2019. Accessed January 4, 2020.
- Duff P. Maternal and fetal infections. In: Creasy RK, Resnik R, Iams JD, et al, eds. Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Philadelphia, PA: Elsevier Saunders; 2019:869.
- Ljubin-Sternak S, Meštrović T. Chlamydia trachomatis and genital mycoplasmas: pathogens with an impact on human reproductive health. J Pathog. 2014. doi: 10.1155/2014/183167.
- Meyer T. Diagnostic procedures to detect Chlamydia trachomatis infections. Microorganisms. 2016:4(3).
- Centers for Disease Control and Prevention.. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae. MMWR Recomm Rep. 2014;63:1-19.
- Wiesenfeld HC. Screening for Chlamydia trachomatis infections in women. N Engl J Med. 2017;376:765-773.
- Blatt AJ, Lieberman JM, Hoover DR, et al. Chlamydial and gonococcal testing during pregnancy in the United States. Am J Obstet Gynecol. 2012;207:55.e1-8.
- Llata E, Braxton J, Asbel L, et al. Rectal Chlamydia trachomatis and Neisseria gonorrhoeae infections among women reporting anal intercourse. Obstet Gynecol. 2018;132:692-697.
- Xu F, Stoner BP, Taylor SN, et al. Use of home-obtained vaginal swabs to facilitate rescreening for Chlamydia trachomatis infections: two randomized controlled trials. Obstet Gynecol. 2011;118(2 pt 1):231-239.
- Geisler WM, Uniyal A, Lee JY, et al. Azithromycin versus doxycycline for urogenital Chlamydia trachomatis infection. N Engl J Med. 2015;373:2512-2521.
- Quinn TC, Gaydos CA. Treatment for chlamydia infection—doxycycline versus azithromycin. N Engl J Med. 2015;373:2573-2575.
CASE Pregnant woman with symptoms of genital infection
A 23-year-old primigravid woman at 15 weeks and 2 days’ gestation reported having a 2-week history of increased urinary frequency and vaginal discharge. She said she experienced similar symptoms 6 weeks previously that resolved within a week. The patient has had 3 sexual partners in the past year. Her current partner was experiencing a yellow urethral discharge and dysuria. On the patient’s speculum examination, the clinician noted a yellow-green discharge emanating from the cervix as well as cervical motion tenderness.
What is the most likely diagnosis, and how would you treat this patient?
The culprit was chlamydia
Chlamydia trachomatis is an obligate intracellular bacterium that does not stain with Gram staining. A rigid cell wall encloses its intracellular component. C trachomatis infection begins when the chlamydial elementary body enters a susceptible host cell.
Once ingested, the organism’s surface antigens (major outer membrane protein and lipopolysaccharide antigens) provide intracellular sanctuary for the bacterium by inhibiting phagolysosomal fusion. Subsequently, the elementary body morphs into a reticular body, which replicates through adenosine triphosphate (ATP)–dependent binary fission. After approximately 48 hours of replication, the organism again morphs into an elementary body and is released to infect additional cells and acquire new ATP stores for further replication.
Chlamydia can be transmitted horizontally during oral, vaginal, or anal intercourse or vertically to the infant during vaginal delivery.
The US’s most common notifiable disease
According to the Centers for Disease Control and Prevention (CDC), the incidence of chlamydia infection in the United States increased considerably in recent years: from 976,455 cases in 2005 to 1,758,668 cases in 2018.1 In 2018, rates of chlamydia infection in women were nearly double the rates in men, with an incidence of 688.2 versus 377.5 per 100,000 cases, and a prevalence of 1,150,672 versus 612,020.1
Young adults have a higher frequency of chlamydia infection than any other age group. From 2017 to 2018, reported cases in women aged 15–19 years increased by 1.3%, to 3,306.8 per 100,000; in women aged 20–24 years, cases increased by 0.8%, to 4,064.6 per 100,000. In young men in the same age ranges, reported cases increased by 3.7%, to 959.0 cases per 100,000, and by 3.3%, to 1,784.5 per 100,000 cases, respectively.1
Both the incidence and prevalence of chlamydia infection are higher in African Americans than in whites, while Asians have the lowest rates.1 The prevalence of infection also is increased with incarceration, lower socioeconomic status, and residence in the southern United States.
The prevalence of chlamydia infection in pregnant women is approximately 2% to 3%, but it may be as high as 30% in high-risk populations, such as women who are unmarried, have multiple sex partners, are coinfected with another sexually transmitted disease (STD), have partners with nongonococcal urethritis, have mucopurulent discharge, have acute urethral syndrome, and have late or no prenatal care.2 Since chlamydia infection often is asymptomatic and some infections resolve spontaneously, the true prevalence of infection probably is underreported.
Continue to: Chlamydia infection can cause serious clinical manifestations...
Chlamydia infection can cause serious clinical manifestations
The 15 serotypes of C trachomatis are grouped into 3 categories according to clinical manifestations:
- Serotypes A, B, Ba, and C cause endemic trachoma, characterized by bilateral irritation of the eyelids that progresses to eyelid thickening and scarring, eventually leading to corneal abrasion and blindness.
- Serotypes D–K manifest as conjunctivitis and pneumonia in newborns, proctitis in men (especially in men who have sex with men), and genitourinary infections in women. Reactive arthritis and inclusion conjunctivitis also can occur with D–K serotypes.
- Serotypes L1–L3 cause lymphogranuloma venereum.
About 70% of women with chlamydia infection are asymptomatic. Those who have symptoms often present with endocervicitis or acute urethral syndrome (acute urethritis). Manifestations of these 2 conditions include a frothy yellow-green vaginal and/or urethral discharge, dysuria, and frequency. Women who engage in rectal intercourse also may notice a purulent discharge from the anus. Untreated, C trachomatis organisms may ascend the reproductive tract, causing both endometritis and pelvic inflammatory disease (PID).
While a single episode of PID increases tubal infertility risk by 10%, a second episode increases the risk by 40%.3 Over time, recurrent and/or chronic PID causes scarring and adhesion formation, which may result in chronic pelvic pain. In addition, chronic infection is the single most important risk factor for ectopic pregnancy. Finally, chlamydia infection is a risk factor for Fitz-Hugh-Cutis syndrome (perihepatitis). In this condition, organisms ascend from the site of pelvic infection along the pericolic gutter to ultimately infect the liver capsule.
Specific complications in pregnancy
Chlamydia infection in pregnant women is associated with preterm delivery and preterm premature rupture of membranes. Infants born to mothers with untreated chlamydia infection are at risk for pneumonia, conjunctivitis, and even perinatal death.2 Acquisition of infection occurs at the time of delivery rather than in the antepartum period.
The significant morbidity associated with chlamydia infection underscores the importance of regular screening, especially in pregnant women. The current United States Preventive Service Task Force guidelines recommend annual screening of all sexually active women who are 24 years of age or younger, as well as of older, high-risk women.
The CDC recommends routine screening of all pregnant women for chlamydia at the first prenatal visit. Repeat screening is recommended in the third trimester for all pregnant women younger than 25 years, those at increased risk, and those infected within the past 3 to 6 months or during the first trimester. Those who test positive should be retested 3 weeks after completion of treatment.1
Chlamydia screening strategies
Historically, a chlamydia diagnosis was made by isolating the organisms in tissue culture. In the 1990s, however, that extremely time-consuming and resource-intensive procedure was replaced by nucleic acid amplification testing (NAAT).
NAAT methodology. NAAT is the gold standard for diagnosing C trachomatis infection; this methodology utilizes various assays, including polymerase chain reaction, ligase chain reaction, and transcription-mediated amplification.
Continue to: Compared with previous culture and antigen detection techniques...
Compared with previous culture and antigen detection techniques, NAAT’s advantages include excellent sensitivity and specificity (>90% and ≥99%, respectively), enabling detection of a low inoculum of organisms in a sample obtained by noninvasive methods, such as first-void urine collection or vaginal swab.2,4,5 Furthermore, NAAT does not impose any specific storage regulations on collected specimens, is cost effective, and can jointly test for Neisseria gonorrhoeae, which commonly co-infects with C trachomatis.6
Screening in pregnancy. In 2012, Blatt and colleagues examined testing patterns in nearly 1.3 million obstetric patients and found that only 59% (761,315) of women were tested for chlamydia at least once in pregnancy.7 Only 1 in 3 women were tested during the first prenatal visit, as CDC guidelines recommend. Testing rates declined with increasing age. Of women screened, 3.5% tested positive for chlamydia.7 Of these, 3 of 4 were retested at least once, with almost 20% having at least 1 subsequent positive result.7
Of note, in a study of women who reported receptive anal intercourse (n = 2,818), 292 women tested positive for chlamydia; 10.4% tested positive in genital-only sites, 58.6% in genital and rectal sites, and 20.5% at the rectal site only.8
It is alarming that only 59% of pregnant women are screened for chlamydia given the significant perinatal complications associated with this infection. Barriers to screening pregnant women may include clinician discomfort in discussing STDs and patient refusal of screening. Furthermore, clinicians should routinely ask women about receptive anal sex. Women who report this risk factor should be tested for chlamydia in both the endocervix and rectum.
Retesting and follow-up. After the initial diagnosis of chlamydia, a test of cure 3 weeks after treatment is an important aspect of care. Thus, identifying and overcoming barriers to retesting is important. Clinicians should educate patients about the importance of follow-up. Also consider incorporating the use of home-based, self-obtained vaginal swabs for retesting. Results from 2 randomized trials showed that eliminating a patient’s transportation barriers and providing a home-based alternative to a follow-up visit significantly increased rescreening rates by 33% in STD clinic patients and by 59.2% in family planning clinic patients.9
Reinfection risk. The rate of venereal chlamydia transmission in heterosexual partners is 70%. Since sexually active chlamydia-positive patients are at risk for reinfection by their partner after treatment completion, clinicians should refer the sex partners for evaluation. If the sex partners are reluctant to have testing, it is reasonable to provide empiric antibiotic treatment to decrease the risk of re-infection in the patient.7 Before doing so, however, make certain that state law permits this practice, and be sure to document the prescribed treatment in the patient’s record.
Treatment options
Prompt treatment of C trachomatis infection is essential to decrease the risk of disease sequelae. Nonpregnant adults can be treated with oral doxycycline 100 mg twice daily for 7 days.
In a head-to-head study performed in a controlled environment that ensured treatment adherence, 97% efficacy was achieved with one oral dose of azithromycin (1 g) compared with 100% efficacy with doxycycline.10 However, in the real-world setting, imperfect adherence to the multi-day doxycycline regimen is associated with treatment failures. Thus, a single dose of azithromycin is preferable for patients with questionable compliance.11
In obstetric patients, azithromycin and amoxicillin are preferred as first-line agents for treatment of C trachomatis due to their improved safety profile in this demographic. Amoxicillin 500 mg orally 3 times daily for 7 days has 95% efficacy.2
Women allergic to these agents may be treated with an alternative regimen of erythromycin base, 500 mg orally 4 times daily for 7 days, or erythromycin ethylsuccinate, 800 mg orally 4 times daily for 7 days. Erythromycin should be reserved for second-line therapy because of its lower efficacy (64%) and frequent gastrointestinal adverse effects.2 Doxycycline is contraindicated in pregnancy because of possible teratogenic effects on the teeth and bone of the fetus.
CASE Pregnant woman with symptoms of genital infection
A 23-year-old primigravid woman at 15 weeks and 2 days’ gestation reported having a 2-week history of increased urinary frequency and vaginal discharge. She said she experienced similar symptoms 6 weeks previously that resolved within a week. The patient has had 3 sexual partners in the past year. Her current partner was experiencing a yellow urethral discharge and dysuria. On the patient’s speculum examination, the clinician noted a yellow-green discharge emanating from the cervix as well as cervical motion tenderness.
What is the most likely diagnosis, and how would you treat this patient?
The culprit was chlamydia
Chlamydia trachomatis is an obligate intracellular bacterium that does not stain with Gram staining. A rigid cell wall encloses its intracellular component. C trachomatis infection begins when the chlamydial elementary body enters a susceptible host cell.
Once ingested, the organism’s surface antigens (major outer membrane protein and lipopolysaccharide antigens) provide intracellular sanctuary for the bacterium by inhibiting phagolysosomal fusion. Subsequently, the elementary body morphs into a reticular body, which replicates through adenosine triphosphate (ATP)–dependent binary fission. After approximately 48 hours of replication, the organism again morphs into an elementary body and is released to infect additional cells and acquire new ATP stores for further replication.
Chlamydia can be transmitted horizontally during oral, vaginal, or anal intercourse or vertically to the infant during vaginal delivery.
The US’s most common notifiable disease
According to the Centers for Disease Control and Prevention (CDC), the incidence of chlamydia infection in the United States increased considerably in recent years: from 976,455 cases in 2005 to 1,758,668 cases in 2018.1 In 2018, rates of chlamydia infection in women were nearly double the rates in men, with an incidence of 688.2 versus 377.5 per 100,000 cases, and a prevalence of 1,150,672 versus 612,020.1
Young adults have a higher frequency of chlamydia infection than any other age group. From 2017 to 2018, reported cases in women aged 15–19 years increased by 1.3%, to 3,306.8 per 100,000; in women aged 20–24 years, cases increased by 0.8%, to 4,064.6 per 100,000. In young men in the same age ranges, reported cases increased by 3.7%, to 959.0 cases per 100,000, and by 3.3%, to 1,784.5 per 100,000 cases, respectively.1
Both the incidence and prevalence of chlamydia infection are higher in African Americans than in whites, while Asians have the lowest rates.1 The prevalence of infection also is increased with incarceration, lower socioeconomic status, and residence in the southern United States.
The prevalence of chlamydia infection in pregnant women is approximately 2% to 3%, but it may be as high as 30% in high-risk populations, such as women who are unmarried, have multiple sex partners, are coinfected with another sexually transmitted disease (STD), have partners with nongonococcal urethritis, have mucopurulent discharge, have acute urethral syndrome, and have late or no prenatal care.2 Since chlamydia infection often is asymptomatic and some infections resolve spontaneously, the true prevalence of infection probably is underreported.
Continue to: Chlamydia infection can cause serious clinical manifestations...
Chlamydia infection can cause serious clinical manifestations
The 15 serotypes of C trachomatis are grouped into 3 categories according to clinical manifestations:
- Serotypes A, B, Ba, and C cause endemic trachoma, characterized by bilateral irritation of the eyelids that progresses to eyelid thickening and scarring, eventually leading to corneal abrasion and blindness.
- Serotypes D–K manifest as conjunctivitis and pneumonia in newborns, proctitis in men (especially in men who have sex with men), and genitourinary infections in women. Reactive arthritis and inclusion conjunctivitis also can occur with D–K serotypes.
- Serotypes L1–L3 cause lymphogranuloma venereum.
About 70% of women with chlamydia infection are asymptomatic. Those who have symptoms often present with endocervicitis or acute urethral syndrome (acute urethritis). Manifestations of these 2 conditions include a frothy yellow-green vaginal and/or urethral discharge, dysuria, and frequency. Women who engage in rectal intercourse also may notice a purulent discharge from the anus. Untreated, C trachomatis organisms may ascend the reproductive tract, causing both endometritis and pelvic inflammatory disease (PID).
While a single episode of PID increases tubal infertility risk by 10%, a second episode increases the risk by 40%.3 Over time, recurrent and/or chronic PID causes scarring and adhesion formation, which may result in chronic pelvic pain. In addition, chronic infection is the single most important risk factor for ectopic pregnancy. Finally, chlamydia infection is a risk factor for Fitz-Hugh-Cutis syndrome (perihepatitis). In this condition, organisms ascend from the site of pelvic infection along the pericolic gutter to ultimately infect the liver capsule.
Specific complications in pregnancy
Chlamydia infection in pregnant women is associated with preterm delivery and preterm premature rupture of membranes. Infants born to mothers with untreated chlamydia infection are at risk for pneumonia, conjunctivitis, and even perinatal death.2 Acquisition of infection occurs at the time of delivery rather than in the antepartum period.
The significant morbidity associated with chlamydia infection underscores the importance of regular screening, especially in pregnant women. The current United States Preventive Service Task Force guidelines recommend annual screening of all sexually active women who are 24 years of age or younger, as well as of older, high-risk women.
The CDC recommends routine screening of all pregnant women for chlamydia at the first prenatal visit. Repeat screening is recommended in the third trimester for all pregnant women younger than 25 years, those at increased risk, and those infected within the past 3 to 6 months or during the first trimester. Those who test positive should be retested 3 weeks after completion of treatment.1
Chlamydia screening strategies
Historically, a chlamydia diagnosis was made by isolating the organisms in tissue culture. In the 1990s, however, that extremely time-consuming and resource-intensive procedure was replaced by nucleic acid amplification testing (NAAT).
NAAT methodology. NAAT is the gold standard for diagnosing C trachomatis infection; this methodology utilizes various assays, including polymerase chain reaction, ligase chain reaction, and transcription-mediated amplification.
Continue to: Compared with previous culture and antigen detection techniques...
Compared with previous culture and antigen detection techniques, NAAT’s advantages include excellent sensitivity and specificity (>90% and ≥99%, respectively), enabling detection of a low inoculum of organisms in a sample obtained by noninvasive methods, such as first-void urine collection or vaginal swab.2,4,5 Furthermore, NAAT does not impose any specific storage regulations on collected specimens, is cost effective, and can jointly test for Neisseria gonorrhoeae, which commonly co-infects with C trachomatis.6
Screening in pregnancy. In 2012, Blatt and colleagues examined testing patterns in nearly 1.3 million obstetric patients and found that only 59% (761,315) of women were tested for chlamydia at least once in pregnancy.7 Only 1 in 3 women were tested during the first prenatal visit, as CDC guidelines recommend. Testing rates declined with increasing age. Of women screened, 3.5% tested positive for chlamydia.7 Of these, 3 of 4 were retested at least once, with almost 20% having at least 1 subsequent positive result.7
Of note, in a study of women who reported receptive anal intercourse (n = 2,818), 292 women tested positive for chlamydia; 10.4% tested positive in genital-only sites, 58.6% in genital and rectal sites, and 20.5% at the rectal site only.8
It is alarming that only 59% of pregnant women are screened for chlamydia given the significant perinatal complications associated with this infection. Barriers to screening pregnant women may include clinician discomfort in discussing STDs and patient refusal of screening. Furthermore, clinicians should routinely ask women about receptive anal sex. Women who report this risk factor should be tested for chlamydia in both the endocervix and rectum.
Retesting and follow-up. After the initial diagnosis of chlamydia, a test of cure 3 weeks after treatment is an important aspect of care. Thus, identifying and overcoming barriers to retesting is important. Clinicians should educate patients about the importance of follow-up. Also consider incorporating the use of home-based, self-obtained vaginal swabs for retesting. Results from 2 randomized trials showed that eliminating a patient’s transportation barriers and providing a home-based alternative to a follow-up visit significantly increased rescreening rates by 33% in STD clinic patients and by 59.2% in family planning clinic patients.9
Reinfection risk. The rate of venereal chlamydia transmission in heterosexual partners is 70%. Since sexually active chlamydia-positive patients are at risk for reinfection by their partner after treatment completion, clinicians should refer the sex partners for evaluation. If the sex partners are reluctant to have testing, it is reasonable to provide empiric antibiotic treatment to decrease the risk of re-infection in the patient.7 Before doing so, however, make certain that state law permits this practice, and be sure to document the prescribed treatment in the patient’s record.
Treatment options
Prompt treatment of C trachomatis infection is essential to decrease the risk of disease sequelae. Nonpregnant adults can be treated with oral doxycycline 100 mg twice daily for 7 days.
In a head-to-head study performed in a controlled environment that ensured treatment adherence, 97% efficacy was achieved with one oral dose of azithromycin (1 g) compared with 100% efficacy with doxycycline.10 However, in the real-world setting, imperfect adherence to the multi-day doxycycline regimen is associated with treatment failures. Thus, a single dose of azithromycin is preferable for patients with questionable compliance.11
In obstetric patients, azithromycin and amoxicillin are preferred as first-line agents for treatment of C trachomatis due to their improved safety profile in this demographic. Amoxicillin 500 mg orally 3 times daily for 7 days has 95% efficacy.2
Women allergic to these agents may be treated with an alternative regimen of erythromycin base, 500 mg orally 4 times daily for 7 days, or erythromycin ethylsuccinate, 800 mg orally 4 times daily for 7 days. Erythromycin should be reserved for second-line therapy because of its lower efficacy (64%) and frequent gastrointestinal adverse effects.2 Doxycycline is contraindicated in pregnancy because of possible teratogenic effects on the teeth and bone of the fetus.
- Centers for Disease Control and Prevention Division of STD Prevention. Sexually transmitted disease surveillance 2018. October 2019. https://www.cdc.gov/std/stats18/default.htm. 2019. Accessed January 4, 2020.
- Duff P. Maternal and fetal infections. In: Creasy RK, Resnik R, Iams JD, et al, eds. Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Philadelphia, PA: Elsevier Saunders; 2019:869.
- Ljubin-Sternak S, Meštrović T. Chlamydia trachomatis and genital mycoplasmas: pathogens with an impact on human reproductive health. J Pathog. 2014. doi: 10.1155/2014/183167.
- Meyer T. Diagnostic procedures to detect Chlamydia trachomatis infections. Microorganisms. 2016:4(3).
- Centers for Disease Control and Prevention.. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae. MMWR Recomm Rep. 2014;63:1-19.
- Wiesenfeld HC. Screening for Chlamydia trachomatis infections in women. N Engl J Med. 2017;376:765-773.
- Blatt AJ, Lieberman JM, Hoover DR, et al. Chlamydial and gonococcal testing during pregnancy in the United States. Am J Obstet Gynecol. 2012;207:55.e1-8.
- Llata E, Braxton J, Asbel L, et al. Rectal Chlamydia trachomatis and Neisseria gonorrhoeae infections among women reporting anal intercourse. Obstet Gynecol. 2018;132:692-697.
- Xu F, Stoner BP, Taylor SN, et al. Use of home-obtained vaginal swabs to facilitate rescreening for Chlamydia trachomatis infections: two randomized controlled trials. Obstet Gynecol. 2011;118(2 pt 1):231-239.
- Geisler WM, Uniyal A, Lee JY, et al. Azithromycin versus doxycycline for urogenital Chlamydia trachomatis infection. N Engl J Med. 2015;373:2512-2521.
- Quinn TC, Gaydos CA. Treatment for chlamydia infection—doxycycline versus azithromycin. N Engl J Med. 2015;373:2573-2575.
- Centers for Disease Control and Prevention Division of STD Prevention. Sexually transmitted disease surveillance 2018. October 2019. https://www.cdc.gov/std/stats18/default.htm. 2019. Accessed January 4, 2020.
- Duff P. Maternal and fetal infections. In: Creasy RK, Resnik R, Iams JD, et al, eds. Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Philadelphia, PA: Elsevier Saunders; 2019:869.
- Ljubin-Sternak S, Meštrović T. Chlamydia trachomatis and genital mycoplasmas: pathogens with an impact on human reproductive health. J Pathog. 2014. doi: 10.1155/2014/183167.
- Meyer T. Diagnostic procedures to detect Chlamydia trachomatis infections. Microorganisms. 2016:4(3).
- Centers for Disease Control and Prevention.. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae. MMWR Recomm Rep. 2014;63:1-19.
- Wiesenfeld HC. Screening for Chlamydia trachomatis infections in women. N Engl J Med. 2017;376:765-773.
- Blatt AJ, Lieberman JM, Hoover DR, et al. Chlamydial and gonococcal testing during pregnancy in the United States. Am J Obstet Gynecol. 2012;207:55.e1-8.
- Llata E, Braxton J, Asbel L, et al. Rectal Chlamydia trachomatis and Neisseria gonorrhoeae infections among women reporting anal intercourse. Obstet Gynecol. 2018;132:692-697.
- Xu F, Stoner BP, Taylor SN, et al. Use of home-obtained vaginal swabs to facilitate rescreening for Chlamydia trachomatis infections: two randomized controlled trials. Obstet Gynecol. 2011;118(2 pt 1):231-239.
- Geisler WM, Uniyal A, Lee JY, et al. Azithromycin versus doxycycline for urogenital Chlamydia trachomatis infection. N Engl J Med. 2015;373:2512-2521.
- Quinn TC, Gaydos CA. Treatment for chlamydia infection—doxycycline versus azithromycin. N Engl J Med. 2015;373:2573-2575.
COVID-19 during pregnancy: How would you proceed in this case of a novel and ominous emerging pathogen?
CASE Pregnant patient with fever who has travel history to Italy
A 28-year-old primigravid woman at 12 weeks’ gestation just returned from a 2-week vacation in Italy. She requests medical evaluation because of malaise; fever; chills; rhinorrhea; mild dyspnea; a dry, nonproductive cough; and diarrhea. On physical examination, her temperature is 38.6° C (101.5° F), pulse 104 bpm, respirations 22/minute, and blood pressure 100/70 mm Hg. Auscultation of the lungs demonstrates scattered rales, rhonchi, and expiratory wheezes in both posterior lung fields. The fetal heart rate is 168 bpm. What are the most likely diagnoses? What diagnostic tests are indicated? And what clinical treatment is indicated?
In the presented case scenario, the patient’s symptoms are consistent with a viral influenza. Her recent travel history certainly makes coronavirus disease 2019 (COVID-19) the most likely diagnosis.
COVID-19, caused by a novel new coronavirus, has evolved with lightning speed since it was first identified in early December 2019.1 The disease originated in Wuhan, China. Its epicenter is now in Europe, and over 100 countries and regions have reported cases. New cases in the United States are being identified daily, and there is no clear end to the outbreak. Several areas of the United States have been particularly hard hit by this disease: Seattle, New Orleans, and New York City.
COVID-19 has provoked widespread unsettledness in many populations and an extraordinary response from public health officials, large corporations, professional organizations, and financial markets. We are learning more about somewhat unfamiliar public health concepts such as quarantine, containment, mitigation, reproduction number (R), and “flattening the curve.” Disneyland and Walt Disney World are now temporarily closed. Professional and collegiate sports organizations have cancelled or suspended games and tournaments. Scientific and trade association meetings have been postponed or cancelled. Broadway, Carnegie Hall, and the Metropolitan Museum of Art have now “turned out the lights.” The Centers for Disease Control and Prevention has recommended that everyone avoid gatherings that include more than 10 other persons.
This article will review the evolving epidemiology of COVID-19, describe the usual clinical manifestations of the disease, highlight the key diagnostic tests, and present guidelines for treatment. It will review the limited information currently available about the impact of COVID-19 in pregnant women. The review will conclude by describing measures that individuals can employ to prevent acquisition or transmission of infection and then by highlighting key “unanswered questions” about this new and ominous pathogen (TABLE).
Continue to: What we know about epidemiology...
What we know about epidemiology
COVID-19 is caused by a novel new coronavirus that shares some genetic overlap with the viruses that caused Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).2 The first case of COVID-19 was reported on December 1, 2019, from Wuhan, China.1 Within a very short period of time the disease has spread throughout the world, and on March 11, 2020, the World Health Organization (WHO) declared the infection to be a true pandemic. The countries with the highest prevalence of COVID-19 include China, South Korea, Iran, Italy, France, Spain, and the United States. However, more than 100 other countries and regions have reported cases. As of the first week of April, approximately 1 million persons in the world have been diagnosed with COVID-19. Of those infected, slightly more than 50,000 deaths have occurred. At the time of this writing, 234,483 cases have been documented in the United States, and current estimates indicate that approximately 7% of the population in the country could become infected.1,3,4
The virus responsible for COVID-19 is a single-stranded, enveloped RNA virus. Like its counterparts that caused SARS and MERS, this virus originates in animals, primarily bats. The early cases seem to have resulted from patient contact with exotic animals displayed in the Huanan Seafood Wholesale Market.1
The virus is transmitted directly by respiratory droplets and by close surface-to-hand contact with infected respiratory secretions. The virus appears to remain viable on environmental surfaces for 1 to 3 days, although the degree of infectivity over time is not well delineated. With direct exposure to respiratory droplets, the infectivity is relatively high; approximately 2 to 3 individuals become infected as the result of contact with an infected patient. By contrast, the “reproduction number (R)” for influenza is closer to 1.2,5
Certain persons appear to be at increased risk for developing infection and becoming seriously ill2,6:
- persons older than age 60
- persons with underlying medical illness
- persons who are immunosuppressed.
The reported range in the case fatality rate (CFR) varies from 1% to 13%, with the higher rates concentrated in older patients with comorbidities.3 These initial reports of high CFRs may be misleading because in the initial phases of this pandemic many patients with mild or no symptoms were not tested, and, thus, the overall prevalence of infection is not clear. By way of comparison, the CRF for influenza A and B is about 0.1%.2
Of note, the number of reported cases in the pediatric population is low, and the outcomes in these individuals are much better than in the older population.2,3,6 At present, there are only two reports of COVID-19 in pregnancy; these two studies include 18 women and 19 infants.7,8 The frequency of preterm delivery was 50% in these reports. Sixteen of the 18 patients were delivered by cesarean delivery; at least 6 of these procedures were performed for a non-reassuring fetal heart rate tracing. No maternal deaths were identified, and no cases of vertical transmission occurred.
We must remember that the number of patients described in these two reports is very small. Although the initial reports are favorable, in other influenza epidemics, pregnant women have not fared so well and have experienced disproportionately higher rates of morbidity and mortality.2
Reported clinical manifestations
The incubation period of COVID-19 ranges from 2 to 14 days; the median is 5.2 days. Many patients with proven COVID-19 infection are asymptomatic. When clinical findings are present, they usually are relatively mild and include low-grade fever, myalgias, arthralgias, sore throat, mild dyspnea, and a dry nonproductive cough. Some patients also may experience diarrhea. Of course, these findings are also consistent with influenza A or B or atypical pneumonia. One key to differentiation is the patient’s history of recent travel to an area of high COVID-19 prevalence or contact with a person who has been in one of these areas and who is clinically ill.2,3,9,10
In some patients, notably those who are older than 65 years of age and/or who have underlying medical illnesses, the respiratory manifestations are more prominent.6 These patients may develop severe dyspnea, pneumonia, adult respiratory distress syndrome (ARDS), multiorgan failure, and septic shock. Interestingly, the more severe manifestations tend to occur during the second week of the illness. In this group of more severely ill patients requiring hospitalization, 17% to 29% develop ARDS, and 23% to 32% require admission to the intensive care unit.2,6
Pregnant patients who become severely ill may be at risk for spontaneous miscarriage and preterm labor. With profound maternal hypoxia, fetal heart rate abnormalities may become apparent. To date, no clearly proven cases of vertical transmission of infection to the newborn have been identified. However, as noted above, current reports only include 18 pregnancies and 19 infants.2,3,7,8,11
Continue to: Diagnostic testing...
Diagnostic testing
Infected patients may have a decreased peripheral white blood cell count, with a specific decrease in the number of lymphocytes. Thrombocytopenia may be present, as well as an elevation in the hepatic transaminase enzymes (ALT, AST).2
X-ray, chest CT, and RT-PCR. The three most important diagnostic tests are chest x-ray, chest computed tomography (CT) scan, and real-time PCR (RT-PCR) or nucleic acid amplification test (NAAT).2,6 Specimens for RT-PCR or NAAT should be obtained from the oropharynx and nasopharynx using a synthetic-tipped applicator with an aluminum shaft. Patients who are intubated should have specimens obtained by broncho-alveolar lavage. The virus also has been recovered from blood and stool, but not yet from urine, amniotic fluid, placenta, cord blood, or breast milk.2
CT and chest x-ray show characteristic ground-glass opacities in both lung fields, combined with multiple areas of consolidation. Chest imaging is particularly helpful when the patient has all the major clinical manifestations, but the initial RT-PCR or NAAT is negative.
Treatment
Fortunately, most infected persons can be treated as outpatients. Because this condition may be confused with influenza A or B, initial treatment with a drug such as oseltamivir 75 mg orally twice daily for five days is very reasonable.9 Supportive therapy is critically important in this clinical setting. Acetaminophen, up to 3,000 mg/d in divided doses, or ibuprofen, up to 2,400 mg/d in divided doses, can be used to reduce fever and relieve myalgias and arthralgias. The latter drug, of course, should not be used in pregnant women. The patient should be encouraged to rest and to stay well hydrated. Loperamide can be used to treat diarrhea, 4 mg orally initially, then 2 mg orally after each loose stool up to a maximum of 16 mg/d. Pregnant patients should be cautioned to watch for signs of preterm labor.9,12 Patients should remain in relative isolation at home until they are free of signs of illness and they test negative for COVID-19.
For patients who are more severely ill at initial evaluation or who deteriorate while undergoing outpatient management, hospitalization is indicated.2,6 Patients should be placed in rooms that provide protection against aerosolized infection. They should receive supplemental oxygen and be observed closely for signs of superimposed bacterial infection. Depending upon the suspected bacterial pathogen, appropriate antibiotics may include ceftriaxone, which targets Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis; azithromycin, which targets mycoplasmas; and vancomycin, which specifically covers Staphylococcus aureus. Health care workers should wear appropriate personal protective equipment when interacting with these patients, including cap, N95 mask, face shield, gloves, gown, and shoe covers. If a woman with COVID-19 has delivered, and the pediatrician permits rooming in, the isolette should be positioned at least 6 feet away from the mother. The mother should use a mechanical breast pump to obtain milk and then have another family member feed the baby until the mother tests negative for the virus. The breast pump needs to be cleaned meticulously after each use. The number of visitors to the mother’s room should be strictly limited.3,9
At the present time, there is no specific antiviral drug approved by the US Food and Drug Administration for treatment of COVID-19. The National Institutes of Health is currently conducting a trial of remdesivir for affected patients.13 The drug is also available from the manufacturer outside of this trial on a “compassionate use” basis. Another treatment regimen receiving extensive publicity is the combination of azithromycin and hydroxychloroquine. Its effectiveness has not been confirmed in a properly designed randomized trial.
Prevention hinges on commonsense precautions
Although vaccine trials are underway, public health authorities estimate that a vaccine will not be commercially available for at least 12 to 18 months. Therefore, independent of “community/organizational” mitigation programs, individuals should observe the following commonsense precautions to minimize their risk of contracting or transmitting COVID-192,3,5,14:
- Eliminate any nonessential travel, particularly by plane or cruise ship.
- Avoid events that draw large crowds, such as concerts, theater performances, movies, and even religious services.
- When out in public, try to maintain a distance of 6 feet from others
- Remain at home if you feel ill, particularly if you have respiratory symptoms.
- Cough or sneeze into your sleeve rather than your bare hand.
- Avoid handshakes.
- Wash your hands frequently in warm soapy water for at least 20 seconds, particularly after touching environmental surfaces such as counter tops and handrails.
- If you use hand sanitizers, they should have an alcohol content of at least 60%.
- Clean environmental surfaces frequently with a dilute bleach solution.
CASE Resolved
The clinical manifestations displayed by this patient are consistent with viral influenza. The recent travel history to one of the European epicenters makes COVID-19 the most likely diagnosis. The patient should have a chest CT scan and a RT-PCR or NAAT to confirm the diagnosis. If the diagnosis is confirmed, she and her close contacts should be self-quarantined at home for 14 days. She should receive appropriate supportive care with anti-pyretics, analgesics, and anti-diarrhea agents. If she develops signs of serious respiratory compromise, she should be admitted to an isolation room in the hospital for intensive respiratory therapy and close observation for superimposed bacterial pneumonia.
- Holshue ML, DeBolt C, Lindquist S, et al; Washington State 2019-nCoV Case Investigation Team. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382:929-936.
- Rasmussen SA, Smulian JC, Lednicky JA, et al. Coronavirus disease 2019 (COVID-19) and pregnancy: what obstetricians need to know. Am J Obstet Gynecol. February 24, 2020. doi: 10.1016/j.ajog.2020.02.017.
- Rasmussen SA, Jamieson DJ. Coronavirus disease 2019 (COVID-19) and pregnancy: responding to a rapidly evolving situation [in press]. Obstet Gynecol. 2020.
- Centers for Disease Control and Prevention. Coronavirus disease 2019: Cases in US. CDC website. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html. Accessed March 18, 2020.
- Wang H, Wang Z, Dong Y, et al. Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China. Cell Discov. 2020;6:10.
- Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-733.
- Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395;809-815.
- Lei D, Wang C, Li C, et al. Clinical characteristics of pregnancy with the 2019 novel coronavirus disease (COVID-19) infection. Chin J Perinat Med. 2020:23.
- Dotters-Katz S, Hughes BL. Coronavirus (COVID-19) and pregnancy: what maternal-fetal medicine subspecialists need to know. Society for Maternal-Fetal Medicine. March 17, 2020. https://s3.amazonaws.com/cdn.smfm.org/media/2267/COVID19-_updated_3-17-20_PDF.pdf. Accessed March 17, 2020.
- Perlman S. Another decade, another coronavirus. N Engl J Med. 2020;382:760-762.
- Yang H, Wang C, Poon LC. Novel coronavirus infection and pregnancy. Ultrasound Obstet Gynecol. March 5, 2020. doi:10.1002/uog.22006.
- American College of Obstetricians and Gynecologists. Practice Advisory: novel coronavirus 2019 (COVID-19). March 13, 2020. https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Novel-Coronavirus2019?IsMobileSet=false. Accessed March 17, 2020.
- National Institutes of Health. NIH clinical trial of remdesivir to treat COVID-19 begins. February 25, 2020. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins. Accessed March 17, 2020.
- Munster VJ, Koopmans M, Van Doremalen N, et al. A novel coronavirus emerging in China – key questions for impact assessment. N Engl J Med. 2020;382:692-694.
CASE Pregnant patient with fever who has travel history to Italy
A 28-year-old primigravid woman at 12 weeks’ gestation just returned from a 2-week vacation in Italy. She requests medical evaluation because of malaise; fever; chills; rhinorrhea; mild dyspnea; a dry, nonproductive cough; and diarrhea. On physical examination, her temperature is 38.6° C (101.5° F), pulse 104 bpm, respirations 22/minute, and blood pressure 100/70 mm Hg. Auscultation of the lungs demonstrates scattered rales, rhonchi, and expiratory wheezes in both posterior lung fields. The fetal heart rate is 168 bpm. What are the most likely diagnoses? What diagnostic tests are indicated? And what clinical treatment is indicated?
In the presented case scenario, the patient’s symptoms are consistent with a viral influenza. Her recent travel history certainly makes coronavirus disease 2019 (COVID-19) the most likely diagnosis.
COVID-19, caused by a novel new coronavirus, has evolved with lightning speed since it was first identified in early December 2019.1 The disease originated in Wuhan, China. Its epicenter is now in Europe, and over 100 countries and regions have reported cases. New cases in the United States are being identified daily, and there is no clear end to the outbreak. Several areas of the United States have been particularly hard hit by this disease: Seattle, New Orleans, and New York City.
COVID-19 has provoked widespread unsettledness in many populations and an extraordinary response from public health officials, large corporations, professional organizations, and financial markets. We are learning more about somewhat unfamiliar public health concepts such as quarantine, containment, mitigation, reproduction number (R), and “flattening the curve.” Disneyland and Walt Disney World are now temporarily closed. Professional and collegiate sports organizations have cancelled or suspended games and tournaments. Scientific and trade association meetings have been postponed or cancelled. Broadway, Carnegie Hall, and the Metropolitan Museum of Art have now “turned out the lights.” The Centers for Disease Control and Prevention has recommended that everyone avoid gatherings that include more than 10 other persons.
This article will review the evolving epidemiology of COVID-19, describe the usual clinical manifestations of the disease, highlight the key diagnostic tests, and present guidelines for treatment. It will review the limited information currently available about the impact of COVID-19 in pregnant women. The review will conclude by describing measures that individuals can employ to prevent acquisition or transmission of infection and then by highlighting key “unanswered questions” about this new and ominous pathogen (TABLE).
Continue to: What we know about epidemiology...
What we know about epidemiology
COVID-19 is caused by a novel new coronavirus that shares some genetic overlap with the viruses that caused Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).2 The first case of COVID-19 was reported on December 1, 2019, from Wuhan, China.1 Within a very short period of time the disease has spread throughout the world, and on March 11, 2020, the World Health Organization (WHO) declared the infection to be a true pandemic. The countries with the highest prevalence of COVID-19 include China, South Korea, Iran, Italy, France, Spain, and the United States. However, more than 100 other countries and regions have reported cases. As of the first week of April, approximately 1 million persons in the world have been diagnosed with COVID-19. Of those infected, slightly more than 50,000 deaths have occurred. At the time of this writing, 234,483 cases have been documented in the United States, and current estimates indicate that approximately 7% of the population in the country could become infected.1,3,4
The virus responsible for COVID-19 is a single-stranded, enveloped RNA virus. Like its counterparts that caused SARS and MERS, this virus originates in animals, primarily bats. The early cases seem to have resulted from patient contact with exotic animals displayed in the Huanan Seafood Wholesale Market.1
The virus is transmitted directly by respiratory droplets and by close surface-to-hand contact with infected respiratory secretions. The virus appears to remain viable on environmental surfaces for 1 to 3 days, although the degree of infectivity over time is not well delineated. With direct exposure to respiratory droplets, the infectivity is relatively high; approximately 2 to 3 individuals become infected as the result of contact with an infected patient. By contrast, the “reproduction number (R)” for influenza is closer to 1.2,5
Certain persons appear to be at increased risk for developing infection and becoming seriously ill2,6:
- persons older than age 60
- persons with underlying medical illness
- persons who are immunosuppressed.
The reported range in the case fatality rate (CFR) varies from 1% to 13%, with the higher rates concentrated in older patients with comorbidities.3 These initial reports of high CFRs may be misleading because in the initial phases of this pandemic many patients with mild or no symptoms were not tested, and, thus, the overall prevalence of infection is not clear. By way of comparison, the CRF for influenza A and B is about 0.1%.2
Of note, the number of reported cases in the pediatric population is low, and the outcomes in these individuals are much better than in the older population.2,3,6 At present, there are only two reports of COVID-19 in pregnancy; these two studies include 18 women and 19 infants.7,8 The frequency of preterm delivery was 50% in these reports. Sixteen of the 18 patients were delivered by cesarean delivery; at least 6 of these procedures were performed for a non-reassuring fetal heart rate tracing. No maternal deaths were identified, and no cases of vertical transmission occurred.
We must remember that the number of patients described in these two reports is very small. Although the initial reports are favorable, in other influenza epidemics, pregnant women have not fared so well and have experienced disproportionately higher rates of morbidity and mortality.2
Reported clinical manifestations
The incubation period of COVID-19 ranges from 2 to 14 days; the median is 5.2 days. Many patients with proven COVID-19 infection are asymptomatic. When clinical findings are present, they usually are relatively mild and include low-grade fever, myalgias, arthralgias, sore throat, mild dyspnea, and a dry nonproductive cough. Some patients also may experience diarrhea. Of course, these findings are also consistent with influenza A or B or atypical pneumonia. One key to differentiation is the patient’s history of recent travel to an area of high COVID-19 prevalence or contact with a person who has been in one of these areas and who is clinically ill.2,3,9,10
In some patients, notably those who are older than 65 years of age and/or who have underlying medical illnesses, the respiratory manifestations are more prominent.6 These patients may develop severe dyspnea, pneumonia, adult respiratory distress syndrome (ARDS), multiorgan failure, and septic shock. Interestingly, the more severe manifestations tend to occur during the second week of the illness. In this group of more severely ill patients requiring hospitalization, 17% to 29% develop ARDS, and 23% to 32% require admission to the intensive care unit.2,6
Pregnant patients who become severely ill may be at risk for spontaneous miscarriage and preterm labor. With profound maternal hypoxia, fetal heart rate abnormalities may become apparent. To date, no clearly proven cases of vertical transmission of infection to the newborn have been identified. However, as noted above, current reports only include 18 pregnancies and 19 infants.2,3,7,8,11
Continue to: Diagnostic testing...
Diagnostic testing
Infected patients may have a decreased peripheral white blood cell count, with a specific decrease in the number of lymphocytes. Thrombocytopenia may be present, as well as an elevation in the hepatic transaminase enzymes (ALT, AST).2
X-ray, chest CT, and RT-PCR. The three most important diagnostic tests are chest x-ray, chest computed tomography (CT) scan, and real-time PCR (RT-PCR) or nucleic acid amplification test (NAAT).2,6 Specimens for RT-PCR or NAAT should be obtained from the oropharynx and nasopharynx using a synthetic-tipped applicator with an aluminum shaft. Patients who are intubated should have specimens obtained by broncho-alveolar lavage. The virus also has been recovered from blood and stool, but not yet from urine, amniotic fluid, placenta, cord blood, or breast milk.2
CT and chest x-ray show characteristic ground-glass opacities in both lung fields, combined with multiple areas of consolidation. Chest imaging is particularly helpful when the patient has all the major clinical manifestations, but the initial RT-PCR or NAAT is negative.
Treatment
Fortunately, most infected persons can be treated as outpatients. Because this condition may be confused with influenza A or B, initial treatment with a drug such as oseltamivir 75 mg orally twice daily for five days is very reasonable.9 Supportive therapy is critically important in this clinical setting. Acetaminophen, up to 3,000 mg/d in divided doses, or ibuprofen, up to 2,400 mg/d in divided doses, can be used to reduce fever and relieve myalgias and arthralgias. The latter drug, of course, should not be used in pregnant women. The patient should be encouraged to rest and to stay well hydrated. Loperamide can be used to treat diarrhea, 4 mg orally initially, then 2 mg orally after each loose stool up to a maximum of 16 mg/d. Pregnant patients should be cautioned to watch for signs of preterm labor.9,12 Patients should remain in relative isolation at home until they are free of signs of illness and they test negative for COVID-19.
For patients who are more severely ill at initial evaluation or who deteriorate while undergoing outpatient management, hospitalization is indicated.2,6 Patients should be placed in rooms that provide protection against aerosolized infection. They should receive supplemental oxygen and be observed closely for signs of superimposed bacterial infection. Depending upon the suspected bacterial pathogen, appropriate antibiotics may include ceftriaxone, which targets Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis; azithromycin, which targets mycoplasmas; and vancomycin, which specifically covers Staphylococcus aureus. Health care workers should wear appropriate personal protective equipment when interacting with these patients, including cap, N95 mask, face shield, gloves, gown, and shoe covers. If a woman with COVID-19 has delivered, and the pediatrician permits rooming in, the isolette should be positioned at least 6 feet away from the mother. The mother should use a mechanical breast pump to obtain milk and then have another family member feed the baby until the mother tests negative for the virus. The breast pump needs to be cleaned meticulously after each use. The number of visitors to the mother’s room should be strictly limited.3,9
At the present time, there is no specific antiviral drug approved by the US Food and Drug Administration for treatment of COVID-19. The National Institutes of Health is currently conducting a trial of remdesivir for affected patients.13 The drug is also available from the manufacturer outside of this trial on a “compassionate use” basis. Another treatment regimen receiving extensive publicity is the combination of azithromycin and hydroxychloroquine. Its effectiveness has not been confirmed in a properly designed randomized trial.
Prevention hinges on commonsense precautions
Although vaccine trials are underway, public health authorities estimate that a vaccine will not be commercially available for at least 12 to 18 months. Therefore, independent of “community/organizational” mitigation programs, individuals should observe the following commonsense precautions to minimize their risk of contracting or transmitting COVID-192,3,5,14:
- Eliminate any nonessential travel, particularly by plane or cruise ship.
- Avoid events that draw large crowds, such as concerts, theater performances, movies, and even religious services.
- When out in public, try to maintain a distance of 6 feet from others
- Remain at home if you feel ill, particularly if you have respiratory symptoms.
- Cough or sneeze into your sleeve rather than your bare hand.
- Avoid handshakes.
- Wash your hands frequently in warm soapy water for at least 20 seconds, particularly after touching environmental surfaces such as counter tops and handrails.
- If you use hand sanitizers, they should have an alcohol content of at least 60%.
- Clean environmental surfaces frequently with a dilute bleach solution.
CASE Resolved
The clinical manifestations displayed by this patient are consistent with viral influenza. The recent travel history to one of the European epicenters makes COVID-19 the most likely diagnosis. The patient should have a chest CT scan and a RT-PCR or NAAT to confirm the diagnosis. If the diagnosis is confirmed, she and her close contacts should be self-quarantined at home for 14 days. She should receive appropriate supportive care with anti-pyretics, analgesics, and anti-diarrhea agents. If she develops signs of serious respiratory compromise, she should be admitted to an isolation room in the hospital for intensive respiratory therapy and close observation for superimposed bacterial pneumonia.
CASE Pregnant patient with fever who has travel history to Italy
A 28-year-old primigravid woman at 12 weeks’ gestation just returned from a 2-week vacation in Italy. She requests medical evaluation because of malaise; fever; chills; rhinorrhea; mild dyspnea; a dry, nonproductive cough; and diarrhea. On physical examination, her temperature is 38.6° C (101.5° F), pulse 104 bpm, respirations 22/minute, and blood pressure 100/70 mm Hg. Auscultation of the lungs demonstrates scattered rales, rhonchi, and expiratory wheezes in both posterior lung fields. The fetal heart rate is 168 bpm. What are the most likely diagnoses? What diagnostic tests are indicated? And what clinical treatment is indicated?
In the presented case scenario, the patient’s symptoms are consistent with a viral influenza. Her recent travel history certainly makes coronavirus disease 2019 (COVID-19) the most likely diagnosis.
COVID-19, caused by a novel new coronavirus, has evolved with lightning speed since it was first identified in early December 2019.1 The disease originated in Wuhan, China. Its epicenter is now in Europe, and over 100 countries and regions have reported cases. New cases in the United States are being identified daily, and there is no clear end to the outbreak. Several areas of the United States have been particularly hard hit by this disease: Seattle, New Orleans, and New York City.
COVID-19 has provoked widespread unsettledness in many populations and an extraordinary response from public health officials, large corporations, professional organizations, and financial markets. We are learning more about somewhat unfamiliar public health concepts such as quarantine, containment, mitigation, reproduction number (R), and “flattening the curve.” Disneyland and Walt Disney World are now temporarily closed. Professional and collegiate sports organizations have cancelled or suspended games and tournaments. Scientific and trade association meetings have been postponed or cancelled. Broadway, Carnegie Hall, and the Metropolitan Museum of Art have now “turned out the lights.” The Centers for Disease Control and Prevention has recommended that everyone avoid gatherings that include more than 10 other persons.
This article will review the evolving epidemiology of COVID-19, describe the usual clinical manifestations of the disease, highlight the key diagnostic tests, and present guidelines for treatment. It will review the limited information currently available about the impact of COVID-19 in pregnant women. The review will conclude by describing measures that individuals can employ to prevent acquisition or transmission of infection and then by highlighting key “unanswered questions” about this new and ominous pathogen (TABLE).
Continue to: What we know about epidemiology...
What we know about epidemiology
COVID-19 is caused by a novel new coronavirus that shares some genetic overlap with the viruses that caused Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).2 The first case of COVID-19 was reported on December 1, 2019, from Wuhan, China.1 Within a very short period of time the disease has spread throughout the world, and on March 11, 2020, the World Health Organization (WHO) declared the infection to be a true pandemic. The countries with the highest prevalence of COVID-19 include China, South Korea, Iran, Italy, France, Spain, and the United States. However, more than 100 other countries and regions have reported cases. As of the first week of April, approximately 1 million persons in the world have been diagnosed with COVID-19. Of those infected, slightly more than 50,000 deaths have occurred. At the time of this writing, 234,483 cases have been documented in the United States, and current estimates indicate that approximately 7% of the population in the country could become infected.1,3,4
The virus responsible for COVID-19 is a single-stranded, enveloped RNA virus. Like its counterparts that caused SARS and MERS, this virus originates in animals, primarily bats. The early cases seem to have resulted from patient contact with exotic animals displayed in the Huanan Seafood Wholesale Market.1
The virus is transmitted directly by respiratory droplets and by close surface-to-hand contact with infected respiratory secretions. The virus appears to remain viable on environmental surfaces for 1 to 3 days, although the degree of infectivity over time is not well delineated. With direct exposure to respiratory droplets, the infectivity is relatively high; approximately 2 to 3 individuals become infected as the result of contact with an infected patient. By contrast, the “reproduction number (R)” for influenza is closer to 1.2,5
Certain persons appear to be at increased risk for developing infection and becoming seriously ill2,6:
- persons older than age 60
- persons with underlying medical illness
- persons who are immunosuppressed.
The reported range in the case fatality rate (CFR) varies from 1% to 13%, with the higher rates concentrated in older patients with comorbidities.3 These initial reports of high CFRs may be misleading because in the initial phases of this pandemic many patients with mild or no symptoms were not tested, and, thus, the overall prevalence of infection is not clear. By way of comparison, the CRF for influenza A and B is about 0.1%.2
Of note, the number of reported cases in the pediatric population is low, and the outcomes in these individuals are much better than in the older population.2,3,6 At present, there are only two reports of COVID-19 in pregnancy; these two studies include 18 women and 19 infants.7,8 The frequency of preterm delivery was 50% in these reports. Sixteen of the 18 patients were delivered by cesarean delivery; at least 6 of these procedures were performed for a non-reassuring fetal heart rate tracing. No maternal deaths were identified, and no cases of vertical transmission occurred.
We must remember that the number of patients described in these two reports is very small. Although the initial reports are favorable, in other influenza epidemics, pregnant women have not fared so well and have experienced disproportionately higher rates of morbidity and mortality.2
Reported clinical manifestations
The incubation period of COVID-19 ranges from 2 to 14 days; the median is 5.2 days. Many patients with proven COVID-19 infection are asymptomatic. When clinical findings are present, they usually are relatively mild and include low-grade fever, myalgias, arthralgias, sore throat, mild dyspnea, and a dry nonproductive cough. Some patients also may experience diarrhea. Of course, these findings are also consistent with influenza A or B or atypical pneumonia. One key to differentiation is the patient’s history of recent travel to an area of high COVID-19 prevalence or contact with a person who has been in one of these areas and who is clinically ill.2,3,9,10
In some patients, notably those who are older than 65 years of age and/or who have underlying medical illnesses, the respiratory manifestations are more prominent.6 These patients may develop severe dyspnea, pneumonia, adult respiratory distress syndrome (ARDS), multiorgan failure, and septic shock. Interestingly, the more severe manifestations tend to occur during the second week of the illness. In this group of more severely ill patients requiring hospitalization, 17% to 29% develop ARDS, and 23% to 32% require admission to the intensive care unit.2,6
Pregnant patients who become severely ill may be at risk for spontaneous miscarriage and preterm labor. With profound maternal hypoxia, fetal heart rate abnormalities may become apparent. To date, no clearly proven cases of vertical transmission of infection to the newborn have been identified. However, as noted above, current reports only include 18 pregnancies and 19 infants.2,3,7,8,11
Continue to: Diagnostic testing...
Diagnostic testing
Infected patients may have a decreased peripheral white blood cell count, with a specific decrease in the number of lymphocytes. Thrombocytopenia may be present, as well as an elevation in the hepatic transaminase enzymes (ALT, AST).2
X-ray, chest CT, and RT-PCR. The three most important diagnostic tests are chest x-ray, chest computed tomography (CT) scan, and real-time PCR (RT-PCR) or nucleic acid amplification test (NAAT).2,6 Specimens for RT-PCR or NAAT should be obtained from the oropharynx and nasopharynx using a synthetic-tipped applicator with an aluminum shaft. Patients who are intubated should have specimens obtained by broncho-alveolar lavage. The virus also has been recovered from blood and stool, but not yet from urine, amniotic fluid, placenta, cord blood, or breast milk.2
CT and chest x-ray show characteristic ground-glass opacities in both lung fields, combined with multiple areas of consolidation. Chest imaging is particularly helpful when the patient has all the major clinical manifestations, but the initial RT-PCR or NAAT is negative.
Treatment
Fortunately, most infected persons can be treated as outpatients. Because this condition may be confused with influenza A or B, initial treatment with a drug such as oseltamivir 75 mg orally twice daily for five days is very reasonable.9 Supportive therapy is critically important in this clinical setting. Acetaminophen, up to 3,000 mg/d in divided doses, or ibuprofen, up to 2,400 mg/d in divided doses, can be used to reduce fever and relieve myalgias and arthralgias. The latter drug, of course, should not be used in pregnant women. The patient should be encouraged to rest and to stay well hydrated. Loperamide can be used to treat diarrhea, 4 mg orally initially, then 2 mg orally after each loose stool up to a maximum of 16 mg/d. Pregnant patients should be cautioned to watch for signs of preterm labor.9,12 Patients should remain in relative isolation at home until they are free of signs of illness and they test negative for COVID-19.
For patients who are more severely ill at initial evaluation or who deteriorate while undergoing outpatient management, hospitalization is indicated.2,6 Patients should be placed in rooms that provide protection against aerosolized infection. They should receive supplemental oxygen and be observed closely for signs of superimposed bacterial infection. Depending upon the suspected bacterial pathogen, appropriate antibiotics may include ceftriaxone, which targets Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis; azithromycin, which targets mycoplasmas; and vancomycin, which specifically covers Staphylococcus aureus. Health care workers should wear appropriate personal protective equipment when interacting with these patients, including cap, N95 mask, face shield, gloves, gown, and shoe covers. If a woman with COVID-19 has delivered, and the pediatrician permits rooming in, the isolette should be positioned at least 6 feet away from the mother. The mother should use a mechanical breast pump to obtain milk and then have another family member feed the baby until the mother tests negative for the virus. The breast pump needs to be cleaned meticulously after each use. The number of visitors to the mother’s room should be strictly limited.3,9
At the present time, there is no specific antiviral drug approved by the US Food and Drug Administration for treatment of COVID-19. The National Institutes of Health is currently conducting a trial of remdesivir for affected patients.13 The drug is also available from the manufacturer outside of this trial on a “compassionate use” basis. Another treatment regimen receiving extensive publicity is the combination of azithromycin and hydroxychloroquine. Its effectiveness has not been confirmed in a properly designed randomized trial.
Prevention hinges on commonsense precautions
Although vaccine trials are underway, public health authorities estimate that a vaccine will not be commercially available for at least 12 to 18 months. Therefore, independent of “community/organizational” mitigation programs, individuals should observe the following commonsense precautions to minimize their risk of contracting or transmitting COVID-192,3,5,14:
- Eliminate any nonessential travel, particularly by plane or cruise ship.
- Avoid events that draw large crowds, such as concerts, theater performances, movies, and even religious services.
- When out in public, try to maintain a distance of 6 feet from others
- Remain at home if you feel ill, particularly if you have respiratory symptoms.
- Cough or sneeze into your sleeve rather than your bare hand.
- Avoid handshakes.
- Wash your hands frequently in warm soapy water for at least 20 seconds, particularly after touching environmental surfaces such as counter tops and handrails.
- If you use hand sanitizers, they should have an alcohol content of at least 60%.
- Clean environmental surfaces frequently with a dilute bleach solution.
CASE Resolved
The clinical manifestations displayed by this patient are consistent with viral influenza. The recent travel history to one of the European epicenters makes COVID-19 the most likely diagnosis. The patient should have a chest CT scan and a RT-PCR or NAAT to confirm the diagnosis. If the diagnosis is confirmed, she and her close contacts should be self-quarantined at home for 14 days. She should receive appropriate supportive care with anti-pyretics, analgesics, and anti-diarrhea agents. If she develops signs of serious respiratory compromise, she should be admitted to an isolation room in the hospital for intensive respiratory therapy and close observation for superimposed bacterial pneumonia.
- Holshue ML, DeBolt C, Lindquist S, et al; Washington State 2019-nCoV Case Investigation Team. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382:929-936.
- Rasmussen SA, Smulian JC, Lednicky JA, et al. Coronavirus disease 2019 (COVID-19) and pregnancy: what obstetricians need to know. Am J Obstet Gynecol. February 24, 2020. doi: 10.1016/j.ajog.2020.02.017.
- Rasmussen SA, Jamieson DJ. Coronavirus disease 2019 (COVID-19) and pregnancy: responding to a rapidly evolving situation [in press]. Obstet Gynecol. 2020.
- Centers for Disease Control and Prevention. Coronavirus disease 2019: Cases in US. CDC website. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html. Accessed March 18, 2020.
- Wang H, Wang Z, Dong Y, et al. Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China. Cell Discov. 2020;6:10.
- Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-733.
- Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395;809-815.
- Lei D, Wang C, Li C, et al. Clinical characteristics of pregnancy with the 2019 novel coronavirus disease (COVID-19) infection. Chin J Perinat Med. 2020:23.
- Dotters-Katz S, Hughes BL. Coronavirus (COVID-19) and pregnancy: what maternal-fetal medicine subspecialists need to know. Society for Maternal-Fetal Medicine. March 17, 2020. https://s3.amazonaws.com/cdn.smfm.org/media/2267/COVID19-_updated_3-17-20_PDF.pdf. Accessed March 17, 2020.
- Perlman S. Another decade, another coronavirus. N Engl J Med. 2020;382:760-762.
- Yang H, Wang C, Poon LC. Novel coronavirus infection and pregnancy. Ultrasound Obstet Gynecol. March 5, 2020. doi:10.1002/uog.22006.
- American College of Obstetricians and Gynecologists. Practice Advisory: novel coronavirus 2019 (COVID-19). March 13, 2020. https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Novel-Coronavirus2019?IsMobileSet=false. Accessed March 17, 2020.
- National Institutes of Health. NIH clinical trial of remdesivir to treat COVID-19 begins. February 25, 2020. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins. Accessed March 17, 2020.
- Munster VJ, Koopmans M, Van Doremalen N, et al. A novel coronavirus emerging in China – key questions for impact assessment. N Engl J Med. 2020;382:692-694.
- Holshue ML, DeBolt C, Lindquist S, et al; Washington State 2019-nCoV Case Investigation Team. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382:929-936.
- Rasmussen SA, Smulian JC, Lednicky JA, et al. Coronavirus disease 2019 (COVID-19) and pregnancy: what obstetricians need to know. Am J Obstet Gynecol. February 24, 2020. doi: 10.1016/j.ajog.2020.02.017.
- Rasmussen SA, Jamieson DJ. Coronavirus disease 2019 (COVID-19) and pregnancy: responding to a rapidly evolving situation [in press]. Obstet Gynecol. 2020.
- Centers for Disease Control and Prevention. Coronavirus disease 2019: Cases in US. CDC website. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html. Accessed March 18, 2020.
- Wang H, Wang Z, Dong Y, et al. Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China. Cell Discov. 2020;6:10.
- Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-733.
- Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395;809-815.
- Lei D, Wang C, Li C, et al. Clinical characteristics of pregnancy with the 2019 novel coronavirus disease (COVID-19) infection. Chin J Perinat Med. 2020:23.
- Dotters-Katz S, Hughes BL. Coronavirus (COVID-19) and pregnancy: what maternal-fetal medicine subspecialists need to know. Society for Maternal-Fetal Medicine. March 17, 2020. https://s3.amazonaws.com/cdn.smfm.org/media/2267/COVID19-_updated_3-17-20_PDF.pdf. Accessed March 17, 2020.
- Perlman S. Another decade, another coronavirus. N Engl J Med. 2020;382:760-762.
- Yang H, Wang C, Poon LC. Novel coronavirus infection and pregnancy. Ultrasound Obstet Gynecol. March 5, 2020. doi:10.1002/uog.22006.
- American College of Obstetricians and Gynecologists. Practice Advisory: novel coronavirus 2019 (COVID-19). March 13, 2020. https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Novel-Coronavirus2019?IsMobileSet=false. Accessed March 17, 2020.
- National Institutes of Health. NIH clinical trial of remdesivir to treat COVID-19 begins. February 25, 2020. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins. Accessed March 17, 2020.
- Munster VJ, Koopmans M, Van Doremalen N, et al. A novel coronavirus emerging in China – key questions for impact assessment. N Engl J Med. 2020;382:692-694.
Nearly half of STI events go without HIV testing
according to Danielle Petsis, MPH, of the Children’s Hospital of Philadelphia, and associates.
In a study published in Pediatrics, the investigators conducted a retrospective analysis of 1,816 acute STI events from 1,313 patients aged 13-24 years admitted between July 2014 and Dec. 2017 at two urban health care clinics. The most common STIs in the analysis were Chlamydia, gonorrhea, trichomoniasis, and syphilis; the mean age at diagnosis was 17 years, 71% of episodes occurred in females, and 97% occurred in African American patients.
Of the 1,816 events, HIV testing was completed within 90 days of the STI diagnosis for only 55%; there was 1 confirmed HIV diagnosis among the completed tests. When HIV testing did occur, in 38% of cases it was completed concurrently with STI testing or HIV testing was performed in 35% of the 872 follow-up cases. Of the 815 events where HIV testing was not performed, 27% had a test ordered by the provider but not completed by the patient; the patient leaving the laboratory before the test could be performed was the most common reason for test noncompletion (67%), followed by not showing up at all (18%) and errors in the medical record or laboratory (5%); the remaining patients gave as reasons for test noncompletion: declining an HIV test, a closed lab, or no reason.
Logistic regression showed that participants who were female and those with a previous history of STIs had significantly lower adjusted odds of HIV test completion, compared with males and those with no previous history of STIs, respectively, the investigators said. In addition, having insurance and having a family planning visit were associated with decreased odds of HIV testing, compared with not having insurance or a family planning visit.
“As we enter the fourth decade of the HIV epidemic, it remains clear that missed opportunities for diagnosis have the potential to delay HIV diagnosis and linkage to antiretroviral therapy or PrEP and prevention services, thus increasing the population risk of HIV transmission. Our data underscore the need for improved HIV testing education for providers of all levels of training and the need for public health agencies to clearly communicate the need for testing at the time of STI infection to reduce the number of missed opportunities for testing,” Ms. Petsis and colleagues concluded.
The study was supported by the National Institutes of Mental Health and the Children’s Hospital of Philadelphia Research Institute K-Readiness Award. One coauthor reported receiving funding from Bayer Healthcare, the Templeton Foundation, the National Institutes of Health, and Janssen Biotech. She also serves on expert advisory boards for Mylan Pharmaceuticals and Merck. The other authors have no relevant financial disclosures.
SOURCE: Wood S et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2019-2265.
according to Danielle Petsis, MPH, of the Children’s Hospital of Philadelphia, and associates.
In a study published in Pediatrics, the investigators conducted a retrospective analysis of 1,816 acute STI events from 1,313 patients aged 13-24 years admitted between July 2014 and Dec. 2017 at two urban health care clinics. The most common STIs in the analysis were Chlamydia, gonorrhea, trichomoniasis, and syphilis; the mean age at diagnosis was 17 years, 71% of episodes occurred in females, and 97% occurred in African American patients.
Of the 1,816 events, HIV testing was completed within 90 days of the STI diagnosis for only 55%; there was 1 confirmed HIV diagnosis among the completed tests. When HIV testing did occur, in 38% of cases it was completed concurrently with STI testing or HIV testing was performed in 35% of the 872 follow-up cases. Of the 815 events where HIV testing was not performed, 27% had a test ordered by the provider but not completed by the patient; the patient leaving the laboratory before the test could be performed was the most common reason for test noncompletion (67%), followed by not showing up at all (18%) and errors in the medical record or laboratory (5%); the remaining patients gave as reasons for test noncompletion: declining an HIV test, a closed lab, or no reason.
Logistic regression showed that participants who were female and those with a previous history of STIs had significantly lower adjusted odds of HIV test completion, compared with males and those with no previous history of STIs, respectively, the investigators said. In addition, having insurance and having a family planning visit were associated with decreased odds of HIV testing, compared with not having insurance or a family planning visit.
“As we enter the fourth decade of the HIV epidemic, it remains clear that missed opportunities for diagnosis have the potential to delay HIV diagnosis and linkage to antiretroviral therapy or PrEP and prevention services, thus increasing the population risk of HIV transmission. Our data underscore the need for improved HIV testing education for providers of all levels of training and the need for public health agencies to clearly communicate the need for testing at the time of STI infection to reduce the number of missed opportunities for testing,” Ms. Petsis and colleagues concluded.
The study was supported by the National Institutes of Mental Health and the Children’s Hospital of Philadelphia Research Institute K-Readiness Award. One coauthor reported receiving funding from Bayer Healthcare, the Templeton Foundation, the National Institutes of Health, and Janssen Biotech. She also serves on expert advisory boards for Mylan Pharmaceuticals and Merck. The other authors have no relevant financial disclosures.
SOURCE: Wood S et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2019-2265.
according to Danielle Petsis, MPH, of the Children’s Hospital of Philadelphia, and associates.
In a study published in Pediatrics, the investigators conducted a retrospective analysis of 1,816 acute STI events from 1,313 patients aged 13-24 years admitted between July 2014 and Dec. 2017 at two urban health care clinics. The most common STIs in the analysis were Chlamydia, gonorrhea, trichomoniasis, and syphilis; the mean age at diagnosis was 17 years, 71% of episodes occurred in females, and 97% occurred in African American patients.
Of the 1,816 events, HIV testing was completed within 90 days of the STI diagnosis for only 55%; there was 1 confirmed HIV diagnosis among the completed tests. When HIV testing did occur, in 38% of cases it was completed concurrently with STI testing or HIV testing was performed in 35% of the 872 follow-up cases. Of the 815 events where HIV testing was not performed, 27% had a test ordered by the provider but not completed by the patient; the patient leaving the laboratory before the test could be performed was the most common reason for test noncompletion (67%), followed by not showing up at all (18%) and errors in the medical record or laboratory (5%); the remaining patients gave as reasons for test noncompletion: declining an HIV test, a closed lab, or no reason.
Logistic regression showed that participants who were female and those with a previous history of STIs had significantly lower adjusted odds of HIV test completion, compared with males and those with no previous history of STIs, respectively, the investigators said. In addition, having insurance and having a family planning visit were associated with decreased odds of HIV testing, compared with not having insurance or a family planning visit.
“As we enter the fourth decade of the HIV epidemic, it remains clear that missed opportunities for diagnosis have the potential to delay HIV diagnosis and linkage to antiretroviral therapy or PrEP and prevention services, thus increasing the population risk of HIV transmission. Our data underscore the need for improved HIV testing education for providers of all levels of training and the need for public health agencies to clearly communicate the need for testing at the time of STI infection to reduce the number of missed opportunities for testing,” Ms. Petsis and colleagues concluded.
The study was supported by the National Institutes of Mental Health and the Children’s Hospital of Philadelphia Research Institute K-Readiness Award. One coauthor reported receiving funding from Bayer Healthcare, the Templeton Foundation, the National Institutes of Health, and Janssen Biotech. She also serves on expert advisory boards for Mylan Pharmaceuticals and Merck. The other authors have no relevant financial disclosures.
SOURCE: Wood S et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2019-2265.
FROM PEDIATRICS
In the management of cesarean scar defects, is there a superior surgical method for treatment?
He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: a systematic review and network meta-analysis. J Minim Invasive Gynecol. 2020;27:593-602.
EXPERT COMMENTARY
With the increase in cesarean deliveries performed over the decades, the sequelae of the surgery are now arising. Cesarean scar defects (CSDs) are a complication seen when the endometrium and muscular layers from a prior uterine scar are damaged. This damage in the uterine scar can lead to abnormal uterine bleeding and the implantation of an ectopic pregnancy, which can be life-threatening. Ultrasonography can be used to diagnose this defect, which can appear as a hypoechoic space filled with postmenstrual blood, representing a myometrial tear at the wound site.1 There are several risk factors for CSD, including multiple cesarean deliveries, cesarean delivery during advanced stages of labor, and uterine incisions near the cervix. Elevated body mass index as well as gestational diabetes also have been found to be associated with inadequate healing of the prior cesarean incision.2 Studies have shown that both single- and double-layer closure of the hysterotomy during a cesarean delivery have similar incidences of CSDs.3,4 There are multiple ways to correct a CSD; however, there is no gold standard that has been identified in the literature.
Details about the study
The study by He and colleagues is a meta-analysis aimed at comparing the treatment of CSDs via laparoscopy, hysteroscopy, combined hysteroscopy and laparoscopy, and vaginal repair. The primary outcome measures were reduction in abnormal uterine bleeding and scar defect depth. A total of 10 studies (n = 858) were reviewed: 4 randomized controlled trials (RCTs) and 6 observational studies. The studies analyzed varied in terms of which techniques were compared.
Patients who underwent uterine scar resection by combined laparoscopy and hysteroscopy had a shorter duration of abnormal uterine bleeding when compared with hysteroscopy alone (standardized mean difference [SMD] = 1.36; 95% confidence interval [CI], 0.37−2.36; P = .007) and vaginal repair (SMD = 1.58; 95% CI, 0.97−2.19; P<.0001). Combined laparoscopic and hysteroscopic technique also was found to reduce the diverticulum depth more than in vaginal repair (SMD = 1.57; 95% CI, 0.54−2.61; P = .003).
Continue to: Study strengths and weaknesses...
Study strengths and weaknesses
This is the first meta-analysis to compare the different surgical techniques to correct a CSD. The authors were able to compare many of the characteristics regarding the routes of repair, including hysteroscopy, laparoscopy, and vaginal. The authors were able to analyze the combined laparoscopic and hysteroscopic approach, which facilitates evaluation of the location and satisfaction of defect repair during the procedure.
Some weaknesses of this study include the limited amount of RCTs available for review. All studies were also from China, where the rate of CSDs is higher. Therefore, the results may not be generalizable to all populations. Given that the included studies were done at different sites, it is difficult to determine surgical expertise and surgical technique. Additionally, the studies analyzed varied by which techniques were compared; therefore, indirect analyses were conducted to compare certain techniques. There was limited follow-up for these patients (anywhere from 3 to 6 months), so long-term data and future pregnancy data are needed to determine the efficacy of these procedures.
CSDs are a rising concern due to the increasing cesarean delivery rate. It is critical to be able to identify as well as correct these defects. This is the first systematic review to compare 4 techniques of managing CSDs. Based on this article, there may be some additional benefit from combined hysteroscopic and laparoscopic repair of these defects in terms of decreasing bleeding and decreasing the scar defect depth. However, how these results translate into long-term outcomes for patients and their future pregnancies is still unknown, and further research must be done.
STEPHANIE DELGADO, MD, AND XIAOMING GUAN, MD, PHD
- Woźniak A, Pyra K, Tinto HR, et al. Ultrasonographic criteria of cesarean scar defect evaluation. J Ultrason. 2018;18: 162-165.
- Antila-Långsjö RM, Mäenpää JU, Huhtala HS, et al. Cesarean scar defect: a prospective study on risk factors. Am J Obstet Gynecol. 2018:219:458e1-e8.
- Di Spiezio Sardo A, Saccone G, McCurdy R, et al. Risk of cesarean scar defect following single- vs double-layer uterine closure: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017;50:578-583.
- Roberge S, Demers S, Berghella V, et al. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and meta-analysis. Am J Obstet Gynecol. 2014;211:453-460.
He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: a systematic review and network meta-analysis. J Minim Invasive Gynecol. 2020;27:593-602.
EXPERT COMMENTARY
With the increase in cesarean deliveries performed over the decades, the sequelae of the surgery are now arising. Cesarean scar defects (CSDs) are a complication seen when the endometrium and muscular layers from a prior uterine scar are damaged. This damage in the uterine scar can lead to abnormal uterine bleeding and the implantation of an ectopic pregnancy, which can be life-threatening. Ultrasonography can be used to diagnose this defect, which can appear as a hypoechoic space filled with postmenstrual blood, representing a myometrial tear at the wound site.1 There are several risk factors for CSD, including multiple cesarean deliveries, cesarean delivery during advanced stages of labor, and uterine incisions near the cervix. Elevated body mass index as well as gestational diabetes also have been found to be associated with inadequate healing of the prior cesarean incision.2 Studies have shown that both single- and double-layer closure of the hysterotomy during a cesarean delivery have similar incidences of CSDs.3,4 There are multiple ways to correct a CSD; however, there is no gold standard that has been identified in the literature.
Details about the study
The study by He and colleagues is a meta-analysis aimed at comparing the treatment of CSDs via laparoscopy, hysteroscopy, combined hysteroscopy and laparoscopy, and vaginal repair. The primary outcome measures were reduction in abnormal uterine bleeding and scar defect depth. A total of 10 studies (n = 858) were reviewed: 4 randomized controlled trials (RCTs) and 6 observational studies. The studies analyzed varied in terms of which techniques were compared.
Patients who underwent uterine scar resection by combined laparoscopy and hysteroscopy had a shorter duration of abnormal uterine bleeding when compared with hysteroscopy alone (standardized mean difference [SMD] = 1.36; 95% confidence interval [CI], 0.37−2.36; P = .007) and vaginal repair (SMD = 1.58; 95% CI, 0.97−2.19; P<.0001). Combined laparoscopic and hysteroscopic technique also was found to reduce the diverticulum depth more than in vaginal repair (SMD = 1.57; 95% CI, 0.54−2.61; P = .003).
Continue to: Study strengths and weaknesses...
Study strengths and weaknesses
This is the first meta-analysis to compare the different surgical techniques to correct a CSD. The authors were able to compare many of the characteristics regarding the routes of repair, including hysteroscopy, laparoscopy, and vaginal. The authors were able to analyze the combined laparoscopic and hysteroscopic approach, which facilitates evaluation of the location and satisfaction of defect repair during the procedure.
Some weaknesses of this study include the limited amount of RCTs available for review. All studies were also from China, where the rate of CSDs is higher. Therefore, the results may not be generalizable to all populations. Given that the included studies were done at different sites, it is difficult to determine surgical expertise and surgical technique. Additionally, the studies analyzed varied by which techniques were compared; therefore, indirect analyses were conducted to compare certain techniques. There was limited follow-up for these patients (anywhere from 3 to 6 months), so long-term data and future pregnancy data are needed to determine the efficacy of these procedures.
CSDs are a rising concern due to the increasing cesarean delivery rate. It is critical to be able to identify as well as correct these defects. This is the first systematic review to compare 4 techniques of managing CSDs. Based on this article, there may be some additional benefit from combined hysteroscopic and laparoscopic repair of these defects in terms of decreasing bleeding and decreasing the scar defect depth. However, how these results translate into long-term outcomes for patients and their future pregnancies is still unknown, and further research must be done.
STEPHANIE DELGADO, MD, AND XIAOMING GUAN, MD, PHD
He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: a systematic review and network meta-analysis. J Minim Invasive Gynecol. 2020;27:593-602.
EXPERT COMMENTARY
With the increase in cesarean deliveries performed over the decades, the sequelae of the surgery are now arising. Cesarean scar defects (CSDs) are a complication seen when the endometrium and muscular layers from a prior uterine scar are damaged. This damage in the uterine scar can lead to abnormal uterine bleeding and the implantation of an ectopic pregnancy, which can be life-threatening. Ultrasonography can be used to diagnose this defect, which can appear as a hypoechoic space filled with postmenstrual blood, representing a myometrial tear at the wound site.1 There are several risk factors for CSD, including multiple cesarean deliveries, cesarean delivery during advanced stages of labor, and uterine incisions near the cervix. Elevated body mass index as well as gestational diabetes also have been found to be associated with inadequate healing of the prior cesarean incision.2 Studies have shown that both single- and double-layer closure of the hysterotomy during a cesarean delivery have similar incidences of CSDs.3,4 There are multiple ways to correct a CSD; however, there is no gold standard that has been identified in the literature.
Details about the study
The study by He and colleagues is a meta-analysis aimed at comparing the treatment of CSDs via laparoscopy, hysteroscopy, combined hysteroscopy and laparoscopy, and vaginal repair. The primary outcome measures were reduction in abnormal uterine bleeding and scar defect depth. A total of 10 studies (n = 858) were reviewed: 4 randomized controlled trials (RCTs) and 6 observational studies. The studies analyzed varied in terms of which techniques were compared.
Patients who underwent uterine scar resection by combined laparoscopy and hysteroscopy had a shorter duration of abnormal uterine bleeding when compared with hysteroscopy alone (standardized mean difference [SMD] = 1.36; 95% confidence interval [CI], 0.37−2.36; P = .007) and vaginal repair (SMD = 1.58; 95% CI, 0.97−2.19; P<.0001). Combined laparoscopic and hysteroscopic technique also was found to reduce the diverticulum depth more than in vaginal repair (SMD = 1.57; 95% CI, 0.54−2.61; P = .003).
Continue to: Study strengths and weaknesses...
Study strengths and weaknesses
This is the first meta-analysis to compare the different surgical techniques to correct a CSD. The authors were able to compare many of the characteristics regarding the routes of repair, including hysteroscopy, laparoscopy, and vaginal. The authors were able to analyze the combined laparoscopic and hysteroscopic approach, which facilitates evaluation of the location and satisfaction of defect repair during the procedure.
Some weaknesses of this study include the limited amount of RCTs available for review. All studies were also from China, where the rate of CSDs is higher. Therefore, the results may not be generalizable to all populations. Given that the included studies were done at different sites, it is difficult to determine surgical expertise and surgical technique. Additionally, the studies analyzed varied by which techniques were compared; therefore, indirect analyses were conducted to compare certain techniques. There was limited follow-up for these patients (anywhere from 3 to 6 months), so long-term data and future pregnancy data are needed to determine the efficacy of these procedures.
CSDs are a rising concern due to the increasing cesarean delivery rate. It is critical to be able to identify as well as correct these defects. This is the first systematic review to compare 4 techniques of managing CSDs. Based on this article, there may be some additional benefit from combined hysteroscopic and laparoscopic repair of these defects in terms of decreasing bleeding and decreasing the scar defect depth. However, how these results translate into long-term outcomes for patients and their future pregnancies is still unknown, and further research must be done.
STEPHANIE DELGADO, MD, AND XIAOMING GUAN, MD, PHD
- Woźniak A, Pyra K, Tinto HR, et al. Ultrasonographic criteria of cesarean scar defect evaluation. J Ultrason. 2018;18: 162-165.
- Antila-Långsjö RM, Mäenpää JU, Huhtala HS, et al. Cesarean scar defect: a prospective study on risk factors. Am J Obstet Gynecol. 2018:219:458e1-e8.
- Di Spiezio Sardo A, Saccone G, McCurdy R, et al. Risk of cesarean scar defect following single- vs double-layer uterine closure: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017;50:578-583.
- Roberge S, Demers S, Berghella V, et al. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and meta-analysis. Am J Obstet Gynecol. 2014;211:453-460.
- Woźniak A, Pyra K, Tinto HR, et al. Ultrasonographic criteria of cesarean scar defect evaluation. J Ultrason. 2018;18: 162-165.
- Antila-Långsjö RM, Mäenpää JU, Huhtala HS, et al. Cesarean scar defect: a prospective study on risk factors. Am J Obstet Gynecol. 2018:219:458e1-e8.
- Di Spiezio Sardo A, Saccone G, McCurdy R, et al. Risk of cesarean scar defect following single- vs double-layer uterine closure: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017;50:578-583.
- Roberge S, Demers S, Berghella V, et al. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and meta-analysis. Am J Obstet Gynecol. 2014;211:453-460.
High BMI does not complicate postpartum tubal ligation
GRAPEVINE, TEXAS – Higher body mass index is not associated with increased morbidity in women undergoing postpartum tubal ligation, according to a study of more than 1,000 patients.
John J. Byrne, MD, said at the Pregnancy Meeting. Dr. Byrne is affiliated with the department of obstetrics and gynecology at University of Texas Southwestern Medical Center in Dallas.
Physicians may recommend contraception within 6 weeks of delivery, but many patients do not attend postpartum visits. “One option for women who have completed childbearing is bilateral midsegment salpingectomy via minilaparotomy,” Dr. Byrne said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine. “Offering this procedure immediately after delivery makes it available to women who face obstacles to follow-up care.”
The procedure entails the risk of anesthetic complications, bowel injury, and vascular injury. Subsequent pregnancy or ectopic pregnancy also may occur. Some centers will not perform the procedure if a patient’s size affects the surgeon’s ability to feel the relevant anatomy, Dr. Byrne said. “Although operative complications are presumed to be higher among obese women,” prior studies have not examined whether BMI affects rates of procedure completion, complication, or subsequent pregnancy, the researchers said.
To study this question, Dr. Byrne and colleagues examined data from women who requested postpartum sterilization following vaginal delivery at their center in 2018. The center uses the Parkland tubal ligation technique. The researchers assessed complication rates using a composite measure that included surgical complications (that is, blood transfusion, aborted procedure, or extension of incision), anesthetic complications, readmission, superficial or deep wound infection, venous thromboembolism, ileus or small bowel obstruction, incomplete transection, and subsequent pregnancy. The investigators used statistical tests to assess the relationship between BMI and morbidity.
In all, 1,014 patients underwent a postpartum tubal ligation; 17% had undergone prior abdominal surgery. The researchers classified patients’ BMI as normal (7% of the population), overweight (28%), class I obesity (38%), class II obesity (18%), or class III obesity (9%). A composite morbidity event occurred in 2%, and the proportion of patients with a complication did not significantly differ across BMI categories. No morbid events occurred in patients with normal BMI, which indicates “minimal risk” in this population, Dr. Byrne said. One incomplete transection occurred in a patient with class I obesity, and one subsequent pregnancy occurred in a patient with class II obesity. Estimated blood loss ranged from 9 mL in patients with normal BMI to 13 mL in patients with class III obesity, and length of surgery ranged from 32 minutes to 40 minutes. Neither difference is clinically significant, Dr. Byrne said.
“For the woman who desires permanent contraception, BMI should not impede her access to the procedure,” he noted.
The researchers had no relevant disclosures.
SOURCE: Byrne JJ et al. Am J Obstet Gynecol. 2020 Jan;222(1):S290, Abstract 442.
GRAPEVINE, TEXAS – Higher body mass index is not associated with increased morbidity in women undergoing postpartum tubal ligation, according to a study of more than 1,000 patients.
John J. Byrne, MD, said at the Pregnancy Meeting. Dr. Byrne is affiliated with the department of obstetrics and gynecology at University of Texas Southwestern Medical Center in Dallas.
Physicians may recommend contraception within 6 weeks of delivery, but many patients do not attend postpartum visits. “One option for women who have completed childbearing is bilateral midsegment salpingectomy via minilaparotomy,” Dr. Byrne said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine. “Offering this procedure immediately after delivery makes it available to women who face obstacles to follow-up care.”
The procedure entails the risk of anesthetic complications, bowel injury, and vascular injury. Subsequent pregnancy or ectopic pregnancy also may occur. Some centers will not perform the procedure if a patient’s size affects the surgeon’s ability to feel the relevant anatomy, Dr. Byrne said. “Although operative complications are presumed to be higher among obese women,” prior studies have not examined whether BMI affects rates of procedure completion, complication, or subsequent pregnancy, the researchers said.
To study this question, Dr. Byrne and colleagues examined data from women who requested postpartum sterilization following vaginal delivery at their center in 2018. The center uses the Parkland tubal ligation technique. The researchers assessed complication rates using a composite measure that included surgical complications (that is, blood transfusion, aborted procedure, or extension of incision), anesthetic complications, readmission, superficial or deep wound infection, venous thromboembolism, ileus or small bowel obstruction, incomplete transection, and subsequent pregnancy. The investigators used statistical tests to assess the relationship between BMI and morbidity.
In all, 1,014 patients underwent a postpartum tubal ligation; 17% had undergone prior abdominal surgery. The researchers classified patients’ BMI as normal (7% of the population), overweight (28%), class I obesity (38%), class II obesity (18%), or class III obesity (9%). A composite morbidity event occurred in 2%, and the proportion of patients with a complication did not significantly differ across BMI categories. No morbid events occurred in patients with normal BMI, which indicates “minimal risk” in this population, Dr. Byrne said. One incomplete transection occurred in a patient with class I obesity, and one subsequent pregnancy occurred in a patient with class II obesity. Estimated blood loss ranged from 9 mL in patients with normal BMI to 13 mL in patients with class III obesity, and length of surgery ranged from 32 minutes to 40 minutes. Neither difference is clinically significant, Dr. Byrne said.
“For the woman who desires permanent contraception, BMI should not impede her access to the procedure,” he noted.
The researchers had no relevant disclosures.
SOURCE: Byrne JJ et al. Am J Obstet Gynecol. 2020 Jan;222(1):S290, Abstract 442.
GRAPEVINE, TEXAS – Higher body mass index is not associated with increased morbidity in women undergoing postpartum tubal ligation, according to a study of more than 1,000 patients.
John J. Byrne, MD, said at the Pregnancy Meeting. Dr. Byrne is affiliated with the department of obstetrics and gynecology at University of Texas Southwestern Medical Center in Dallas.
Physicians may recommend contraception within 6 weeks of delivery, but many patients do not attend postpartum visits. “One option for women who have completed childbearing is bilateral midsegment salpingectomy via minilaparotomy,” Dr. Byrne said at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine. “Offering this procedure immediately after delivery makes it available to women who face obstacles to follow-up care.”
The procedure entails the risk of anesthetic complications, bowel injury, and vascular injury. Subsequent pregnancy or ectopic pregnancy also may occur. Some centers will not perform the procedure if a patient’s size affects the surgeon’s ability to feel the relevant anatomy, Dr. Byrne said. “Although operative complications are presumed to be higher among obese women,” prior studies have not examined whether BMI affects rates of procedure completion, complication, or subsequent pregnancy, the researchers said.
To study this question, Dr. Byrne and colleagues examined data from women who requested postpartum sterilization following vaginal delivery at their center in 2018. The center uses the Parkland tubal ligation technique. The researchers assessed complication rates using a composite measure that included surgical complications (that is, blood transfusion, aborted procedure, or extension of incision), anesthetic complications, readmission, superficial or deep wound infection, venous thromboembolism, ileus or small bowel obstruction, incomplete transection, and subsequent pregnancy. The investigators used statistical tests to assess the relationship between BMI and morbidity.
In all, 1,014 patients underwent a postpartum tubal ligation; 17% had undergone prior abdominal surgery. The researchers classified patients’ BMI as normal (7% of the population), overweight (28%), class I obesity (38%), class II obesity (18%), or class III obesity (9%). A composite morbidity event occurred in 2%, and the proportion of patients with a complication did not significantly differ across BMI categories. No morbid events occurred in patients with normal BMI, which indicates “minimal risk” in this population, Dr. Byrne said. One incomplete transection occurred in a patient with class I obesity, and one subsequent pregnancy occurred in a patient with class II obesity. Estimated blood loss ranged from 9 mL in patients with normal BMI to 13 mL in patients with class III obesity, and length of surgery ranged from 32 minutes to 40 minutes. Neither difference is clinically significant, Dr. Byrne said.
“For the woman who desires permanent contraception, BMI should not impede her access to the procedure,” he noted.
The researchers had no relevant disclosures.
SOURCE: Byrne JJ et al. Am J Obstet Gynecol. 2020 Jan;222(1):S290, Abstract 442.
REPORTING FROM THE PREGNANCY MEETING
What is the role of the ObGyn in preventing and treating obesity?
Obesity is a disease causing a public health crisis. In the United States, tobacco use and obesity are the two most important causes of preventable premature death. They result in an estimated 480,0001 and 300,0002 premature deaths per year, respectively. Obesity is a major contributor to diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease. Obesity is also associated with increased rates of colon, breast, and endometrial cancer. Experts predict that in 2030, 50% of adults in the United States will have a body mass index (BMI) ≥ 30 kg/m2, and 25% will have a BMI ≥ 35 kg/m2.3 More women than men are predicted to be severely obese (FIGURE).3
As clinicians we need to increase our efforts to reduce the epidemic of obesity. ObGyns can play an important role in preventing and managing obesity, by recommending primary-care weight management practices, prescribing medications that influence central metabolism, and referring appropriate patients to bariatric surgery centers of excellence.
Primary-care weight management
Measuring BMI and recommending interventions to prevent and treat obesity are important components of a health maintenance encounter. For women who are overweight or obese, dietary changes and exercise are important recommendations. The American Heart Association recommends the following lifestyle interventions4:
- Eat a high-quality diet that includes vegetables, fruit, whole grains, beans, legumes, nuts, plant-based protein, lean animal protein, and fish.
- Limit intake of sugary drinks and foods, fatty or processed meats, full-fat dairy products, eggs, highly processed foods, and tropical oils.
- Exercise at least 150 minutes weekly at a moderate activity level, including muscle-strengthening activity.
- Reduce prolonged intervals of sitting.
- Consider using an activity tracker to monitor activity level.
Clinicians should consider referring overweight and obese patients to a nutritionist for a consultation to plan how to consume a high-quality, low-calorie diet. A nutritionist can spend time with patients explaining options for implementing a calorie-restricted diet. In addition, some health insurers will require patients to participate in a supervised calorie-restricted diet plan for at least 6 months before authorizing coverage of expensive weight loss medications or bariatric surgery. In addition to recommending diet and exercise, ObGyns may consider prescribing metformin for their obese patients.
Continue to: Metformin...
Metformin
Metformin is approved for the treatment of type 2 diabetes mellitus. Unlike insulin therapy, which is associated with weight gain, metformin is associated with modest weight loss. The Diabetes Prevention Program (DPP) randomly assigned 3,234 nondiabetic participants with a fasting glucose level between 95 and 125 mg/dL and impaired glucose tolerance (140 to 199 mg/dL) after a 75-g oral glucose load to intensive lifestyle changes (calorie-restricted diet to achieve 7% weight loss plus 150 minutes of exercise weekly), metformin (850 mg twice daily), or placebo.5,6 The mean age of the participants was 51 years, with a mean BMI of 34 kg/m2. Most (68%) of the participants were women.
After 12 months of follow-up, mean weight loss in the intensive lifestyle change, metformin, and placebo groups was 6.5%, 2.7%, and 0.4%, respectively. After 2 years of treatment, weight loss among those who reliably took their metformin pills was approximately 4%, while participants in the placebo group had a 1% weight gain. Among those who continued to reliably take their metformin pills, the weight loss persisted through 9 years of follow up.
The mechanisms by which metformin causes weight loss are not clear. Metformin stimulates phosphorylation of adenosine monophosphate (AMP)-activated protein kinase, which regulates mitochondrial function, hepatic and muscle fatty acid oxidation, glucose transport, insulin secretion, and lipogenesis.7
Many ObGyns have experience in using metformin for the treatment of polycystic ovary syndrome or gestational diabetes. Hence, the dosing and adverse effects of metformin are familiar to many obstetricians-gynecologists. Metformin is contraindicated in individuals with creatinine clearance less than 30 mL/min. Rarely, metformin can cause lactic acidosis. According to Lexicomp,8 the most common adverse effects of metformin extended release (metformin ER) are diarrhea (17%), nausea and vomiting (7%), and decreased vitamin B12 concentration (7%) due to malabsorption in the terminal ileum. Of note, in the DPP study, hemoglobin concentration was slightly lower over time in the metformin compared with the placebo group (13.6 mg/dL vs 13.8 mg/dL, respectively; P<.001).6 Some experts recommend annual vitamin B12 measurement in individuals taking metformin.
In my practice, I only prescribe metformin ER. I usually start metformin treatment with one 750 mg ER tablet with dinner. If the patient tolerates that dose, I increase the dose to two 750 mg ER tablets with dinner. Metformin-induced adverse effects include diarrhea (17%) and nausea and vomiting (7%). Metformin ER is inexpensive. A one-month supply of metformin (sixty 750 mg tablets) costs between $4 and $21 at major pharmacies.9 Health insurance companies generally do not require preauthorization to cover metformin prescriptions.
Weight loss medications
US Food and Drug Administration (FDA)-approved weight loss medications include: liraglutide (Victoza), orlistat (Xenical, Alli), combination phentermine-extended release topiramate (Qsymia), and combination extended release naltrexone-bupropion (Contrave). All FDA-approved weight loss medications result in mean weight loss in the range of 6% to 10%. Many of these medications are very expensive (more than $200 per month).10 Insurance preauthorization is commonly required for these medications. For ObGyns, it may be best to refer patients who would like to use a weight loss medication to a specialist or specialty center with expertise in using these medications.
Sustainable weight loss is very difficult to achieve through dieting alone. A multitude of dietary interventions have been presented as “revolutionary approaches” to the challenging problem of sustainable weight loss, including the Paleo diet, the Vegan diet, the low-carb diet, the Dukan diet, the ultra-lowfat diet, the Atkins diet, the HCG diet, the Zone diet, the South Beach diet, the plant-based diet, the Mediterranean diet, the Asian diet, and intermittent fasting. Recently, intermittent fasting has been presented as the latest and greatest approach to dieting, with the dual goals of achieving weight loss and improved health.1 In some animal models, intermittent dieting has been shown to increase life-span, a finding that has attracted great interest. A major goal of intermittent fasting is to promote “metabolic switching” with increased reliance on ketones to fuel cellular energy needs.
Two approaches to “prescribing” an intermittent fasting diet are to limit food intake to a period of 6 to 10 hours each day or to markedly reduce caloric intake one or two days per week, for example to 750 calories in a 24-hour period. There are no long-term studies of the health outcomes associated with intermittent fasting. In head-to-head clinical trials of intermittent fasting and daily calorie restriction (classic dieting), both diets result in similar weight loss. For example, in one clinical trial 100 obese participants, with a mean body mass index (BMI) of 34 kg/m2 , including 86 women, were randomly assigned to2:
1. intermittent fasting (25% of energy needs every other day)
2. daily calorie restriction (75% of energy needs every day), or
3. no intervention.
After 12 months of follow up, the participants in the no intervention group had gained 0.5% of their starting weight. The intermittent fasting and the daily calorie restriction groups had similar amounts of weight loss, approximately 5% of their starting weight. More individuals dropped out of the study from the intermittent fasting group than the daily calorie restriction group (38% vs 29%, respectively).
In another clinical trial, 107 overweight or obese premenopausal women, average age 40 years and mean BMI 31 kg/m2 , were randomly assigned to intermittent fasting (25% of energy needs 2 days per week) or daily calorie restriction (75% of energy needs daily) for 6 months. The mean weight of the participants at baseline was 83 kg. Weight loss was similar in the intermittent fasting and daily calorie restriction groups, 6.4 kg (-7.7%) and 5.6 kg (-6.7%), respectively (P=.4).3
The investigators concluded that intermittent fasting and daily calorie restriction could both be offered as effective approaches to weight loss. My conclusion is that intermittent fasting is not a miracle dietary intervention, but it is another important option in the armamentarium of weight loss interventions.
References
1. de Cabo R, Mattson MP. Effects of intermittent fasting on health, aging and disease. N Engl J Med. 2019;381:2541-2551.
2. Trepanowski JF, Kroeger CM, Barnosky A, et al. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. JAMA Intern Med. 2017;177:930-938.
3. Harvie MN, Pegington M, Mattson MP, et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disc disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond). 2011;35:714-727.
Sleeve gastrectomy
Two children are playing in a school yard. One child proudly states, “My mother is an endocrinologist. She treats diabetes.” Not to be outdone, the other child replies, “My mother is a bariatric surgeon. She cures diabetes.”
The dialogue reflects the reality that bariatric surgery results in more reliable and significant weight loss than diet, exercise, or weight loss medications. Diet, exercise, and weight loss medications often result in a 5% to 10% decrease in weight, but bariatric surgery typically results in a 25% decrease in weight. Until recently, 3 bariatric surgical procedures were commonly performed: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding (AGB). AGB is now seldom performed because it is less effective than RYGB and SG. Two recently published randomized trials compared the long-term outcomes associated with RYGB and SG. The studies found that SG and RYGB result in a similar degree of weight loss. RYGB resulted in slightly more weight loss than SG, but SG was associated with a lower rate of major complications, such as internal hernias. SG takes much less time to perform than RYGB. SG has become the most commonly performed bariatric surgery in premenopausal women considering pregnancy because of the low risk of internal hernias.
In the Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), 217 participants with a mean BMI of 44 kg/m2 and mean age of 45.5 years were randomly assigned to RYGB or SG and followed for 5 years.11 The majority (72%) of the participants were women. At 5 years of follow-up, in the RYGB and SG groups, mean weight loss was 37 kg and 33 kg, respectively (P=.19). In both groups, weight loss nadir was reached 12 to 24 months after surgery. Expressed as a percentage of original weight, weight loss in the RYGB and SG groups was -29% and -25%, respectively (P=.02). Gastric reflux worsened in both the RYGB and SG groups (6% vs 32%, respectively). The number of reoperations in the RYGB and SG groups was 22% and 16%. Of note, among individuals with prevalent diabetes, RYGB and SG resulted in remission of the diabetes in 68% and 62% of participants, respectively.
In the Sleeve vs Bypass study (SLEEVEPASS), 240 participants, with mean BMI of 46 kg/m2 and mean age of 48 years, were randomly assigned to RYGB or SG and followed for 5 years.12 Most (70%) of the participants were women. Following bariatric surgery, BMI decreased significantly in both groups. In the RYGB group, BMI decreased from 48 kg/m2 preoperatively to 35.4 kg/m2 at 5 years of follow up. In the SG group, BMI decreased from 47 kg/m2 preoperatively to 36.5 kg/m2 at 5 years of follow up. Late major complications (defined as complications occurring from 30 days to 5 years postoperatively) occurred more frequently in the RYGB group (15%) versus the SG group (8%). All the late major complications required reoperation. In the SG group, 7 of 10 reoperations were for severe gastric reflux disease. In the RYGB group 17 of 18 reoperations were for suspected internal hernia, requiring closure of a mesenteric defect at reoperation. There was no treatment-related mortality during the 5-year follow up.
Guidelines for bariatric surgery are BMI ≥ 40 kg/m2 without a comorbid illness or BMI ≥ 35 kg/m2 with at least one serious comorbid disease, such as diabetes.13 ObGyns can build a synergistic relationship with bariatric surgeons by referring eligible patients for surgical consultation and, in return, accepting referrals. A paradox and challenge is that many health insurers require patients to complete a supervised medical weight loss management program prior to being approved for bariatric surgery. However, the medical weight loss program might result in the patient no longer being eligible for insurance coverage of their surgery. For example, a patient who had a BMI of 42 kg/m2 prior to a medical weight loss management program who then lost enough weight to achieve a BMI of 38 kg/m2 might no longer be eligible for insurance coverage of a bariatric operation.14
Continue to: ObGyns need to prioritize treatment for obesity...
ObGyns need to prioritize treatment for obesity
Between 1959 and 2014, US life expectancy increased from 69.9 years to 79.1 years. However, in 2015 and 2016 life expectancy in the United States decreased slightly to 78.9 years, while continuing to improve in other countries.15 What could cause such an unexpected trend? Some experts believe that excess overweight and obesity in the US population, resulting in increased rates of diabetes, hypertension, and heart disease, accounts for a significant proportion of the life expectancy gap between US citizens and those who reside in Australia, Finland, Japan, and Sweden.16,17 All frontline clinicians play an important role in reversing the decades-long trend of increasing rates of overweight and obesity. Interventions that ObGyns could prioritize in their practices for treating overweight and obese patients include: a calorie-restricted diet, exercise, metformin, and SG.
- U.S. Department of Health and Human Services. The Health Consequences of Smoking—50 Years of Progress. A Report of the Surgeon General. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2014.
- Allison DB, Fontaine KR, Manson JE, et al. Annual deaths attributable to obesity in the United States. JAMA. 1999;282:1530-1538.
- Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. state-level prevalence of adult obesity and severe obesity. N Engl J Med. 2019;381:2440-2450.
- American Heart Association. My life check | Life’s simple 7. https://www.heart.org/en/healthyliving/healthy-lifestyle/my-life-check--lifessimple-7. Reviewed May 2, 2018. Accessed February 10, 2020.
- Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
- Diabetes Prevention Program Research Group. Long-term safety, tolerability and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 2012;35:731-737.
- Winder WW, Hardie DG. Inactivation of acetylCoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol. 1996;270(2 pt 1):E299-E304.
- Lexicomp. https://online.lexi.com/lco/action/ home. Accessed February 13, 2020.
- Metformin ER (Glucophage XR). GoodRX website. https://www.goodrx.com/metformin-erglucophage-xr?dosage=750mg&form=tablet&la bel_override=metformin+ER+%28Glucophage+X R%29&quantity=60. Accessed February 13, 2020.
- GoodRX website. www.goodrx.com. Accessed February 10, 2020.
- Peterli R, Wolnerhanssen BK, Peters T, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss in patients with morbid obesity: the SM-BOSS randomized clinical trial. JAMA. 2018;319:255-265.
- Salminen P, Helmiö M, Ovaska J, et al. Effect of laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass on weight loss at 5 years among patients with morbid obesity: The SLEEVEPASS randomized clinical trial. JAMA. 2018;319:241-254.
- Rubino F, Nathan DM, Eckel RH, et al; Delegates of the 2nd Diabetes Surgery Summit. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Obes Surg. 2017;27:2-21.
- Gebran SG, Knighton B, Ngaage LM, et al. Insurance coverage criteria for bariatric surgery: a survey of policies. Obes Surg. 2020;30:707-713.
- Woolf SH, Schoomaker H. Life expectancy and mortality rates in the United States, 1959-2017. JAMA. 2019;322:1996-2016.
- Preston SH, Vierboom YC, Stokes A. The role of obesity in exceptionally slow US mortality improvement. Proc Natl Acad Sci U S A. 2019;115:957-961.
- Xu H, Cupples LA, Stokes A, et al. Association of obesity with mortality over 24 years of weight history: findings from the Framingham Heart Study. JAMA Network Open. 2018;1:e184587.
Robert L. Barbieri, MD
Editor in Chief, OBG Management
Chair, Obstetrics and Gynecology
Brigham and Women’s Hospital
Boston, Massachusetts
Kate Macy Ladd Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Dr. Barbieri reports no financial relationships relevant to this article.
Robert L. Barbieri, MD
Editor in Chief, OBG Management
Chair, Obstetrics and Gynecology
Brigham and Women’s Hospital
Boston, Massachusetts
Kate Macy Ladd Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Dr. Barbieri reports no financial relationships relevant to this article.
Robert L. Barbieri, MD
Editor in Chief, OBG Management
Chair, Obstetrics and Gynecology
Brigham and Women’s Hospital
Boston, Massachusetts
Kate Macy Ladd Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School
Dr. Barbieri reports no financial relationships relevant to this article.
Obesity is a disease causing a public health crisis. In the United States, tobacco use and obesity are the two most important causes of preventable premature death. They result in an estimated 480,0001 and 300,0002 premature deaths per year, respectively. Obesity is a major contributor to diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease. Obesity is also associated with increased rates of colon, breast, and endometrial cancer. Experts predict that in 2030, 50% of adults in the United States will have a body mass index (BMI) ≥ 30 kg/m2, and 25% will have a BMI ≥ 35 kg/m2.3 More women than men are predicted to be severely obese (FIGURE).3
As clinicians we need to increase our efforts to reduce the epidemic of obesity. ObGyns can play an important role in preventing and managing obesity, by recommending primary-care weight management practices, prescribing medications that influence central metabolism, and referring appropriate patients to bariatric surgery centers of excellence.
Primary-care weight management
Measuring BMI and recommending interventions to prevent and treat obesity are important components of a health maintenance encounter. For women who are overweight or obese, dietary changes and exercise are important recommendations. The American Heart Association recommends the following lifestyle interventions4:
- Eat a high-quality diet that includes vegetables, fruit, whole grains, beans, legumes, nuts, plant-based protein, lean animal protein, and fish.
- Limit intake of sugary drinks and foods, fatty or processed meats, full-fat dairy products, eggs, highly processed foods, and tropical oils.
- Exercise at least 150 minutes weekly at a moderate activity level, including muscle-strengthening activity.
- Reduce prolonged intervals of sitting.
- Consider using an activity tracker to monitor activity level.
Clinicians should consider referring overweight and obese patients to a nutritionist for a consultation to plan how to consume a high-quality, low-calorie diet. A nutritionist can spend time with patients explaining options for implementing a calorie-restricted diet. In addition, some health insurers will require patients to participate in a supervised calorie-restricted diet plan for at least 6 months before authorizing coverage of expensive weight loss medications or bariatric surgery. In addition to recommending diet and exercise, ObGyns may consider prescribing metformin for their obese patients.
Continue to: Metformin...
Metformin
Metformin is approved for the treatment of type 2 diabetes mellitus. Unlike insulin therapy, which is associated with weight gain, metformin is associated with modest weight loss. The Diabetes Prevention Program (DPP) randomly assigned 3,234 nondiabetic participants with a fasting glucose level between 95 and 125 mg/dL and impaired glucose tolerance (140 to 199 mg/dL) after a 75-g oral glucose load to intensive lifestyle changes (calorie-restricted diet to achieve 7% weight loss plus 150 minutes of exercise weekly), metformin (850 mg twice daily), or placebo.5,6 The mean age of the participants was 51 years, with a mean BMI of 34 kg/m2. Most (68%) of the participants were women.
After 12 months of follow-up, mean weight loss in the intensive lifestyle change, metformin, and placebo groups was 6.5%, 2.7%, and 0.4%, respectively. After 2 years of treatment, weight loss among those who reliably took their metformin pills was approximately 4%, while participants in the placebo group had a 1% weight gain. Among those who continued to reliably take their metformin pills, the weight loss persisted through 9 years of follow up.
The mechanisms by which metformin causes weight loss are not clear. Metformin stimulates phosphorylation of adenosine monophosphate (AMP)-activated protein kinase, which regulates mitochondrial function, hepatic and muscle fatty acid oxidation, glucose transport, insulin secretion, and lipogenesis.7
Many ObGyns have experience in using metformin for the treatment of polycystic ovary syndrome or gestational diabetes. Hence, the dosing and adverse effects of metformin are familiar to many obstetricians-gynecologists. Metformin is contraindicated in individuals with creatinine clearance less than 30 mL/min. Rarely, metformin can cause lactic acidosis. According to Lexicomp,8 the most common adverse effects of metformin extended release (metformin ER) are diarrhea (17%), nausea and vomiting (7%), and decreased vitamin B12 concentration (7%) due to malabsorption in the terminal ileum. Of note, in the DPP study, hemoglobin concentration was slightly lower over time in the metformin compared with the placebo group (13.6 mg/dL vs 13.8 mg/dL, respectively; P<.001).6 Some experts recommend annual vitamin B12 measurement in individuals taking metformin.
In my practice, I only prescribe metformin ER. I usually start metformin treatment with one 750 mg ER tablet with dinner. If the patient tolerates that dose, I increase the dose to two 750 mg ER tablets with dinner. Metformin-induced adverse effects include diarrhea (17%) and nausea and vomiting (7%). Metformin ER is inexpensive. A one-month supply of metformin (sixty 750 mg tablets) costs between $4 and $21 at major pharmacies.9 Health insurance companies generally do not require preauthorization to cover metformin prescriptions.
Weight loss medications
US Food and Drug Administration (FDA)-approved weight loss medications include: liraglutide (Victoza), orlistat (Xenical, Alli), combination phentermine-extended release topiramate (Qsymia), and combination extended release naltrexone-bupropion (Contrave). All FDA-approved weight loss medications result in mean weight loss in the range of 6% to 10%. Many of these medications are very expensive (more than $200 per month).10 Insurance preauthorization is commonly required for these medications. For ObGyns, it may be best to refer patients who would like to use a weight loss medication to a specialist or specialty center with expertise in using these medications.
Sustainable weight loss is very difficult to achieve through dieting alone. A multitude of dietary interventions have been presented as “revolutionary approaches” to the challenging problem of sustainable weight loss, including the Paleo diet, the Vegan diet, the low-carb diet, the Dukan diet, the ultra-lowfat diet, the Atkins diet, the HCG diet, the Zone diet, the South Beach diet, the plant-based diet, the Mediterranean diet, the Asian diet, and intermittent fasting. Recently, intermittent fasting has been presented as the latest and greatest approach to dieting, with the dual goals of achieving weight loss and improved health.1 In some animal models, intermittent dieting has been shown to increase life-span, a finding that has attracted great interest. A major goal of intermittent fasting is to promote “metabolic switching” with increased reliance on ketones to fuel cellular energy needs.
Two approaches to “prescribing” an intermittent fasting diet are to limit food intake to a period of 6 to 10 hours each day or to markedly reduce caloric intake one or two days per week, for example to 750 calories in a 24-hour period. There are no long-term studies of the health outcomes associated with intermittent fasting. In head-to-head clinical trials of intermittent fasting and daily calorie restriction (classic dieting), both diets result in similar weight loss. For example, in one clinical trial 100 obese participants, with a mean body mass index (BMI) of 34 kg/m2 , including 86 women, were randomly assigned to2:
1. intermittent fasting (25% of energy needs every other day)
2. daily calorie restriction (75% of energy needs every day), or
3. no intervention.
After 12 months of follow up, the participants in the no intervention group had gained 0.5% of their starting weight. The intermittent fasting and the daily calorie restriction groups had similar amounts of weight loss, approximately 5% of their starting weight. More individuals dropped out of the study from the intermittent fasting group than the daily calorie restriction group (38% vs 29%, respectively).
In another clinical trial, 107 overweight or obese premenopausal women, average age 40 years and mean BMI 31 kg/m2 , were randomly assigned to intermittent fasting (25% of energy needs 2 days per week) or daily calorie restriction (75% of energy needs daily) for 6 months. The mean weight of the participants at baseline was 83 kg. Weight loss was similar in the intermittent fasting and daily calorie restriction groups, 6.4 kg (-7.7%) and 5.6 kg (-6.7%), respectively (P=.4).3
The investigators concluded that intermittent fasting and daily calorie restriction could both be offered as effective approaches to weight loss. My conclusion is that intermittent fasting is not a miracle dietary intervention, but it is another important option in the armamentarium of weight loss interventions.
References
1. de Cabo R, Mattson MP. Effects of intermittent fasting on health, aging and disease. N Engl J Med. 2019;381:2541-2551.
2. Trepanowski JF, Kroeger CM, Barnosky A, et al. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. JAMA Intern Med. 2017;177:930-938.
3. Harvie MN, Pegington M, Mattson MP, et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disc disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond). 2011;35:714-727.
Sleeve gastrectomy
Two children are playing in a school yard. One child proudly states, “My mother is an endocrinologist. She treats diabetes.” Not to be outdone, the other child replies, “My mother is a bariatric surgeon. She cures diabetes.”
The dialogue reflects the reality that bariatric surgery results in more reliable and significant weight loss than diet, exercise, or weight loss medications. Diet, exercise, and weight loss medications often result in a 5% to 10% decrease in weight, but bariatric surgery typically results in a 25% decrease in weight. Until recently, 3 bariatric surgical procedures were commonly performed: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding (AGB). AGB is now seldom performed because it is less effective than RYGB and SG. Two recently published randomized trials compared the long-term outcomes associated with RYGB and SG. The studies found that SG and RYGB result in a similar degree of weight loss. RYGB resulted in slightly more weight loss than SG, but SG was associated with a lower rate of major complications, such as internal hernias. SG takes much less time to perform than RYGB. SG has become the most commonly performed bariatric surgery in premenopausal women considering pregnancy because of the low risk of internal hernias.
In the Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), 217 participants with a mean BMI of 44 kg/m2 and mean age of 45.5 years were randomly assigned to RYGB or SG and followed for 5 years.11 The majority (72%) of the participants were women. At 5 years of follow-up, in the RYGB and SG groups, mean weight loss was 37 kg and 33 kg, respectively (P=.19). In both groups, weight loss nadir was reached 12 to 24 months after surgery. Expressed as a percentage of original weight, weight loss in the RYGB and SG groups was -29% and -25%, respectively (P=.02). Gastric reflux worsened in both the RYGB and SG groups (6% vs 32%, respectively). The number of reoperations in the RYGB and SG groups was 22% and 16%. Of note, among individuals with prevalent diabetes, RYGB and SG resulted in remission of the diabetes in 68% and 62% of participants, respectively.
In the Sleeve vs Bypass study (SLEEVEPASS), 240 participants, with mean BMI of 46 kg/m2 and mean age of 48 years, were randomly assigned to RYGB or SG and followed for 5 years.12 Most (70%) of the participants were women. Following bariatric surgery, BMI decreased significantly in both groups. In the RYGB group, BMI decreased from 48 kg/m2 preoperatively to 35.4 kg/m2 at 5 years of follow up. In the SG group, BMI decreased from 47 kg/m2 preoperatively to 36.5 kg/m2 at 5 years of follow up. Late major complications (defined as complications occurring from 30 days to 5 years postoperatively) occurred more frequently in the RYGB group (15%) versus the SG group (8%). All the late major complications required reoperation. In the SG group, 7 of 10 reoperations were for severe gastric reflux disease. In the RYGB group 17 of 18 reoperations were for suspected internal hernia, requiring closure of a mesenteric defect at reoperation. There was no treatment-related mortality during the 5-year follow up.
Guidelines for bariatric surgery are BMI ≥ 40 kg/m2 without a comorbid illness or BMI ≥ 35 kg/m2 with at least one serious comorbid disease, such as diabetes.13 ObGyns can build a synergistic relationship with bariatric surgeons by referring eligible patients for surgical consultation and, in return, accepting referrals. A paradox and challenge is that many health insurers require patients to complete a supervised medical weight loss management program prior to being approved for bariatric surgery. However, the medical weight loss program might result in the patient no longer being eligible for insurance coverage of their surgery. For example, a patient who had a BMI of 42 kg/m2 prior to a medical weight loss management program who then lost enough weight to achieve a BMI of 38 kg/m2 might no longer be eligible for insurance coverage of a bariatric operation.14
Continue to: ObGyns need to prioritize treatment for obesity...
ObGyns need to prioritize treatment for obesity
Between 1959 and 2014, US life expectancy increased from 69.9 years to 79.1 years. However, in 2015 and 2016 life expectancy in the United States decreased slightly to 78.9 years, while continuing to improve in other countries.15 What could cause such an unexpected trend? Some experts believe that excess overweight and obesity in the US population, resulting in increased rates of diabetes, hypertension, and heart disease, accounts for a significant proportion of the life expectancy gap between US citizens and those who reside in Australia, Finland, Japan, and Sweden.16,17 All frontline clinicians play an important role in reversing the decades-long trend of increasing rates of overweight and obesity. Interventions that ObGyns could prioritize in their practices for treating overweight and obese patients include: a calorie-restricted diet, exercise, metformin, and SG.
Obesity is a disease causing a public health crisis. In the United States, tobacco use and obesity are the two most important causes of preventable premature death. They result in an estimated 480,0001 and 300,0002 premature deaths per year, respectively. Obesity is a major contributor to diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease. Obesity is also associated with increased rates of colon, breast, and endometrial cancer. Experts predict that in 2030, 50% of adults in the United States will have a body mass index (BMI) ≥ 30 kg/m2, and 25% will have a BMI ≥ 35 kg/m2.3 More women than men are predicted to be severely obese (FIGURE).3
As clinicians we need to increase our efforts to reduce the epidemic of obesity. ObGyns can play an important role in preventing and managing obesity, by recommending primary-care weight management practices, prescribing medications that influence central metabolism, and referring appropriate patients to bariatric surgery centers of excellence.
Primary-care weight management
Measuring BMI and recommending interventions to prevent and treat obesity are important components of a health maintenance encounter. For women who are overweight or obese, dietary changes and exercise are important recommendations. The American Heart Association recommends the following lifestyle interventions4:
- Eat a high-quality diet that includes vegetables, fruit, whole grains, beans, legumes, nuts, plant-based protein, lean animal protein, and fish.
- Limit intake of sugary drinks and foods, fatty or processed meats, full-fat dairy products, eggs, highly processed foods, and tropical oils.
- Exercise at least 150 minutes weekly at a moderate activity level, including muscle-strengthening activity.
- Reduce prolonged intervals of sitting.
- Consider using an activity tracker to monitor activity level.
Clinicians should consider referring overweight and obese patients to a nutritionist for a consultation to plan how to consume a high-quality, low-calorie diet. A nutritionist can spend time with patients explaining options for implementing a calorie-restricted diet. In addition, some health insurers will require patients to participate in a supervised calorie-restricted diet plan for at least 6 months before authorizing coverage of expensive weight loss medications or bariatric surgery. In addition to recommending diet and exercise, ObGyns may consider prescribing metformin for their obese patients.
Continue to: Metformin...
Metformin
Metformin is approved for the treatment of type 2 diabetes mellitus. Unlike insulin therapy, which is associated with weight gain, metformin is associated with modest weight loss. The Diabetes Prevention Program (DPP) randomly assigned 3,234 nondiabetic participants with a fasting glucose level between 95 and 125 mg/dL and impaired glucose tolerance (140 to 199 mg/dL) after a 75-g oral glucose load to intensive lifestyle changes (calorie-restricted diet to achieve 7% weight loss plus 150 minutes of exercise weekly), metformin (850 mg twice daily), or placebo.5,6 The mean age of the participants was 51 years, with a mean BMI of 34 kg/m2. Most (68%) of the participants were women.
After 12 months of follow-up, mean weight loss in the intensive lifestyle change, metformin, and placebo groups was 6.5%, 2.7%, and 0.4%, respectively. After 2 years of treatment, weight loss among those who reliably took their metformin pills was approximately 4%, while participants in the placebo group had a 1% weight gain. Among those who continued to reliably take their metformin pills, the weight loss persisted through 9 years of follow up.
The mechanisms by which metformin causes weight loss are not clear. Metformin stimulates phosphorylation of adenosine monophosphate (AMP)-activated protein kinase, which regulates mitochondrial function, hepatic and muscle fatty acid oxidation, glucose transport, insulin secretion, and lipogenesis.7
Many ObGyns have experience in using metformin for the treatment of polycystic ovary syndrome or gestational diabetes. Hence, the dosing and adverse effects of metformin are familiar to many obstetricians-gynecologists. Metformin is contraindicated in individuals with creatinine clearance less than 30 mL/min. Rarely, metformin can cause lactic acidosis. According to Lexicomp,8 the most common adverse effects of metformin extended release (metformin ER) are diarrhea (17%), nausea and vomiting (7%), and decreased vitamin B12 concentration (7%) due to malabsorption in the terminal ileum. Of note, in the DPP study, hemoglobin concentration was slightly lower over time in the metformin compared with the placebo group (13.6 mg/dL vs 13.8 mg/dL, respectively; P<.001).6 Some experts recommend annual vitamin B12 measurement in individuals taking metformin.
In my practice, I only prescribe metformin ER. I usually start metformin treatment with one 750 mg ER tablet with dinner. If the patient tolerates that dose, I increase the dose to two 750 mg ER tablets with dinner. Metformin-induced adverse effects include diarrhea (17%) and nausea and vomiting (7%). Metformin ER is inexpensive. A one-month supply of metformin (sixty 750 mg tablets) costs between $4 and $21 at major pharmacies.9 Health insurance companies generally do not require preauthorization to cover metformin prescriptions.
Weight loss medications
US Food and Drug Administration (FDA)-approved weight loss medications include: liraglutide (Victoza), orlistat (Xenical, Alli), combination phentermine-extended release topiramate (Qsymia), and combination extended release naltrexone-bupropion (Contrave). All FDA-approved weight loss medications result in mean weight loss in the range of 6% to 10%. Many of these medications are very expensive (more than $200 per month).10 Insurance preauthorization is commonly required for these medications. For ObGyns, it may be best to refer patients who would like to use a weight loss medication to a specialist or specialty center with expertise in using these medications.
Sustainable weight loss is very difficult to achieve through dieting alone. A multitude of dietary interventions have been presented as “revolutionary approaches” to the challenging problem of sustainable weight loss, including the Paleo diet, the Vegan diet, the low-carb diet, the Dukan diet, the ultra-lowfat diet, the Atkins diet, the HCG diet, the Zone diet, the South Beach diet, the plant-based diet, the Mediterranean diet, the Asian diet, and intermittent fasting. Recently, intermittent fasting has been presented as the latest and greatest approach to dieting, with the dual goals of achieving weight loss and improved health.1 In some animal models, intermittent dieting has been shown to increase life-span, a finding that has attracted great interest. A major goal of intermittent fasting is to promote “metabolic switching” with increased reliance on ketones to fuel cellular energy needs.
Two approaches to “prescribing” an intermittent fasting diet are to limit food intake to a period of 6 to 10 hours each day or to markedly reduce caloric intake one or two days per week, for example to 750 calories in a 24-hour period. There are no long-term studies of the health outcomes associated with intermittent fasting. In head-to-head clinical trials of intermittent fasting and daily calorie restriction (classic dieting), both diets result in similar weight loss. For example, in one clinical trial 100 obese participants, with a mean body mass index (BMI) of 34 kg/m2 , including 86 women, were randomly assigned to2:
1. intermittent fasting (25% of energy needs every other day)
2. daily calorie restriction (75% of energy needs every day), or
3. no intervention.
After 12 months of follow up, the participants in the no intervention group had gained 0.5% of their starting weight. The intermittent fasting and the daily calorie restriction groups had similar amounts of weight loss, approximately 5% of their starting weight. More individuals dropped out of the study from the intermittent fasting group than the daily calorie restriction group (38% vs 29%, respectively).
In another clinical trial, 107 overweight or obese premenopausal women, average age 40 years and mean BMI 31 kg/m2 , were randomly assigned to intermittent fasting (25% of energy needs 2 days per week) or daily calorie restriction (75% of energy needs daily) for 6 months. The mean weight of the participants at baseline was 83 kg. Weight loss was similar in the intermittent fasting and daily calorie restriction groups, 6.4 kg (-7.7%) and 5.6 kg (-6.7%), respectively (P=.4).3
The investigators concluded that intermittent fasting and daily calorie restriction could both be offered as effective approaches to weight loss. My conclusion is that intermittent fasting is not a miracle dietary intervention, but it is another important option in the armamentarium of weight loss interventions.
References
1. de Cabo R, Mattson MP. Effects of intermittent fasting on health, aging and disease. N Engl J Med. 2019;381:2541-2551.
2. Trepanowski JF, Kroeger CM, Barnosky A, et al. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. JAMA Intern Med. 2017;177:930-938.
3. Harvie MN, Pegington M, Mattson MP, et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disc disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond). 2011;35:714-727.
Sleeve gastrectomy
Two children are playing in a school yard. One child proudly states, “My mother is an endocrinologist. She treats diabetes.” Not to be outdone, the other child replies, “My mother is a bariatric surgeon. She cures diabetes.”
The dialogue reflects the reality that bariatric surgery results in more reliable and significant weight loss than diet, exercise, or weight loss medications. Diet, exercise, and weight loss medications often result in a 5% to 10% decrease in weight, but bariatric surgery typically results in a 25% decrease in weight. Until recently, 3 bariatric surgical procedures were commonly performed: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding (AGB). AGB is now seldom performed because it is less effective than RYGB and SG. Two recently published randomized trials compared the long-term outcomes associated with RYGB and SG. The studies found that SG and RYGB result in a similar degree of weight loss. RYGB resulted in slightly more weight loss than SG, but SG was associated with a lower rate of major complications, such as internal hernias. SG takes much less time to perform than RYGB. SG has become the most commonly performed bariatric surgery in premenopausal women considering pregnancy because of the low risk of internal hernias.
In the Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), 217 participants with a mean BMI of 44 kg/m2 and mean age of 45.5 years were randomly assigned to RYGB or SG and followed for 5 years.11 The majority (72%) of the participants were women. At 5 years of follow-up, in the RYGB and SG groups, mean weight loss was 37 kg and 33 kg, respectively (P=.19). In both groups, weight loss nadir was reached 12 to 24 months after surgery. Expressed as a percentage of original weight, weight loss in the RYGB and SG groups was -29% and -25%, respectively (P=.02). Gastric reflux worsened in both the RYGB and SG groups (6% vs 32%, respectively). The number of reoperations in the RYGB and SG groups was 22% and 16%. Of note, among individuals with prevalent diabetes, RYGB and SG resulted in remission of the diabetes in 68% and 62% of participants, respectively.
In the Sleeve vs Bypass study (SLEEVEPASS), 240 participants, with mean BMI of 46 kg/m2 and mean age of 48 years, were randomly assigned to RYGB or SG and followed for 5 years.12 Most (70%) of the participants were women. Following bariatric surgery, BMI decreased significantly in both groups. In the RYGB group, BMI decreased from 48 kg/m2 preoperatively to 35.4 kg/m2 at 5 years of follow up. In the SG group, BMI decreased from 47 kg/m2 preoperatively to 36.5 kg/m2 at 5 years of follow up. Late major complications (defined as complications occurring from 30 days to 5 years postoperatively) occurred more frequently in the RYGB group (15%) versus the SG group (8%). All the late major complications required reoperation. In the SG group, 7 of 10 reoperations were for severe gastric reflux disease. In the RYGB group 17 of 18 reoperations were for suspected internal hernia, requiring closure of a mesenteric defect at reoperation. There was no treatment-related mortality during the 5-year follow up.
Guidelines for bariatric surgery are BMI ≥ 40 kg/m2 without a comorbid illness or BMI ≥ 35 kg/m2 with at least one serious comorbid disease, such as diabetes.13 ObGyns can build a synergistic relationship with bariatric surgeons by referring eligible patients for surgical consultation and, in return, accepting referrals. A paradox and challenge is that many health insurers require patients to complete a supervised medical weight loss management program prior to being approved for bariatric surgery. However, the medical weight loss program might result in the patient no longer being eligible for insurance coverage of their surgery. For example, a patient who had a BMI of 42 kg/m2 prior to a medical weight loss management program who then lost enough weight to achieve a BMI of 38 kg/m2 might no longer be eligible for insurance coverage of a bariatric operation.14
Continue to: ObGyns need to prioritize treatment for obesity...
ObGyns need to prioritize treatment for obesity
Between 1959 and 2014, US life expectancy increased from 69.9 years to 79.1 years. However, in 2015 and 2016 life expectancy in the United States decreased slightly to 78.9 years, while continuing to improve in other countries.15 What could cause such an unexpected trend? Some experts believe that excess overweight and obesity in the US population, resulting in increased rates of diabetes, hypertension, and heart disease, accounts for a significant proportion of the life expectancy gap between US citizens and those who reside in Australia, Finland, Japan, and Sweden.16,17 All frontline clinicians play an important role in reversing the decades-long trend of increasing rates of overweight and obesity. Interventions that ObGyns could prioritize in their practices for treating overweight and obese patients include: a calorie-restricted diet, exercise, metformin, and SG.
- U.S. Department of Health and Human Services. The Health Consequences of Smoking—50 Years of Progress. A Report of the Surgeon General. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2014.
- Allison DB, Fontaine KR, Manson JE, et al. Annual deaths attributable to obesity in the United States. JAMA. 1999;282:1530-1538.
- Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. state-level prevalence of adult obesity and severe obesity. N Engl J Med. 2019;381:2440-2450.
- American Heart Association. My life check | Life’s simple 7. https://www.heart.org/en/healthyliving/healthy-lifestyle/my-life-check--lifessimple-7. Reviewed May 2, 2018. Accessed February 10, 2020.
- Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
- Diabetes Prevention Program Research Group. Long-term safety, tolerability and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 2012;35:731-737.
- Winder WW, Hardie DG. Inactivation of acetylCoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol. 1996;270(2 pt 1):E299-E304.
- Lexicomp. https://online.lexi.com/lco/action/ home. Accessed February 13, 2020.
- Metformin ER (Glucophage XR). GoodRX website. https://www.goodrx.com/metformin-erglucophage-xr?dosage=750mg&form=tablet&la bel_override=metformin+ER+%28Glucophage+X R%29&quantity=60. Accessed February 13, 2020.
- GoodRX website. www.goodrx.com. Accessed February 10, 2020.
- Peterli R, Wolnerhanssen BK, Peters T, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss in patients with morbid obesity: the SM-BOSS randomized clinical trial. JAMA. 2018;319:255-265.
- Salminen P, Helmiö M, Ovaska J, et al. Effect of laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass on weight loss at 5 years among patients with morbid obesity: The SLEEVEPASS randomized clinical trial. JAMA. 2018;319:241-254.
- Rubino F, Nathan DM, Eckel RH, et al; Delegates of the 2nd Diabetes Surgery Summit. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Obes Surg. 2017;27:2-21.
- Gebran SG, Knighton B, Ngaage LM, et al. Insurance coverage criteria for bariatric surgery: a survey of policies. Obes Surg. 2020;30:707-713.
- Woolf SH, Schoomaker H. Life expectancy and mortality rates in the United States, 1959-2017. JAMA. 2019;322:1996-2016.
- Preston SH, Vierboom YC, Stokes A. The role of obesity in exceptionally slow US mortality improvement. Proc Natl Acad Sci U S A. 2019;115:957-961.
- Xu H, Cupples LA, Stokes A, et al. Association of obesity with mortality over 24 years of weight history: findings from the Framingham Heart Study. JAMA Network Open. 2018;1:e184587.
- U.S. Department of Health and Human Services. The Health Consequences of Smoking—50 Years of Progress. A Report of the Surgeon General. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2014.
- Allison DB, Fontaine KR, Manson JE, et al. Annual deaths attributable to obesity in the United States. JAMA. 1999;282:1530-1538.
- Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. state-level prevalence of adult obesity and severe obesity. N Engl J Med. 2019;381:2440-2450.
- American Heart Association. My life check | Life’s simple 7. https://www.heart.org/en/healthyliving/healthy-lifestyle/my-life-check--lifessimple-7. Reviewed May 2, 2018. Accessed February 10, 2020.
- Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
- Diabetes Prevention Program Research Group. Long-term safety, tolerability and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 2012;35:731-737.
- Winder WW, Hardie DG. Inactivation of acetylCoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol. 1996;270(2 pt 1):E299-E304.
- Lexicomp. https://online.lexi.com/lco/action/ home. Accessed February 13, 2020.
- Metformin ER (Glucophage XR). GoodRX website. https://www.goodrx.com/metformin-erglucophage-xr?dosage=750mg&form=tablet&la bel_override=metformin+ER+%28Glucophage+X R%29&quantity=60. Accessed February 13, 2020.
- GoodRX website. www.goodrx.com. Accessed February 10, 2020.
- Peterli R, Wolnerhanssen BK, Peters T, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss in patients with morbid obesity: the SM-BOSS randomized clinical trial. JAMA. 2018;319:255-265.
- Salminen P, Helmiö M, Ovaska J, et al. Effect of laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass on weight loss at 5 years among patients with morbid obesity: The SLEEVEPASS randomized clinical trial. JAMA. 2018;319:241-254.
- Rubino F, Nathan DM, Eckel RH, et al; Delegates of the 2nd Diabetes Surgery Summit. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Obes Surg. 2017;27:2-21.
- Gebran SG, Knighton B, Ngaage LM, et al. Insurance coverage criteria for bariatric surgery: a survey of policies. Obes Surg. 2020;30:707-713.
- Woolf SH, Schoomaker H. Life expectancy and mortality rates in the United States, 1959-2017. JAMA. 2019;322:1996-2016.
- Preston SH, Vierboom YC, Stokes A. The role of obesity in exceptionally slow US mortality improvement. Proc Natl Acad Sci U S A. 2019;115:957-961.
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Abbreviated MRI bests digital breast tomosynthesis in finding cancer in dense breasts
For women with dense breasts, abbreviated magnetic resonance imaging was more effective than was digital breast tomosynthesis for detecting invasive breast cancer in a cross-sectional study of 1,444 women who underwent both procedures.
Dense breasts are a common reason for failed early diagnosis of breast cancer, wrote Christopher E. Comstock, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Digital breast tomosynthesis (DBT) and abbreviated breast magnetic resonance imaging (MRI) are becoming more popular as safe and cost-effective breast cancer screening options, but their effectiveness in women with dense breasts and average breast cancer risk has not been compared.
The researchers reviewed data from 1,444 women aged 40-75 years at 47 institutions in the United States and 1 in Germany. The women underwent both DBT and MRI. The primary endpoint was the detection of invasive cancers, of which 17 were identified at baseline screening. Abbreviated breast MRI detected all 17 cases of invasive cancer, compared with 7 detected by DBT. In addition, MRI detected six of seven women with ductal carcinoma in situ, while DBT identified two of the seven cases, according to the study, which was published in JAMA.
Overall, the invasive cancer detection rate was 11.8 per 1,000 women for MRI compared with 4.8 per 1,000 women for DBT. Sensitivity for MRI and DBT was 96% vs. 39%, and specificity was 87% vs. 97%.
The rate of recommendation for further screening was not significantly different between the procedures (8% for MRI and 10% for DBT). The most common adverse events were three cases of mild allergic reactions and two cases of anxiety.
The study findings were limited by several factors including the inability to show an association between abbreviated breast MRI and breast cancer mortality and the lack of cost-effectiveness comparisons for the two procedures. Because eligibility criteria required a prior breast mammogram to see if the breasts were dense, the study compared an incidence DBT screen to a prevalence abbreviated MRI screen, Dr. Comstock and associates noted.
However, the results show a significantly increased breast cancer detection rate with abbreviated MRI, which merits additional research to examine the relationship between screening strategies and clinical outcomes for women with dense breasts, they said.
The study was supported in part by the National Cancer Institute of the National Institutes of Health, and by Bracco Diagnostics through funding to the ECOG-ACRIN Cancer Research Group. Dr. Comstock disclosed financial relationships with Bracco Diagnostics and Bayer, and three coauthors disclosed financial relationships with other imaging companies. The remaining coauthors had no relevant financial disclosures.
SOURCE: Comstock CK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0572.
For women with dense breasts, abbreviated magnetic resonance imaging was more effective than was digital breast tomosynthesis for detecting invasive breast cancer in a cross-sectional study of 1,444 women who underwent both procedures.
Dense breasts are a common reason for failed early diagnosis of breast cancer, wrote Christopher E. Comstock, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Digital breast tomosynthesis (DBT) and abbreviated breast magnetic resonance imaging (MRI) are becoming more popular as safe and cost-effective breast cancer screening options, but their effectiveness in women with dense breasts and average breast cancer risk has not been compared.
The researchers reviewed data from 1,444 women aged 40-75 years at 47 institutions in the United States and 1 in Germany. The women underwent both DBT and MRI. The primary endpoint was the detection of invasive cancers, of which 17 were identified at baseline screening. Abbreviated breast MRI detected all 17 cases of invasive cancer, compared with 7 detected by DBT. In addition, MRI detected six of seven women with ductal carcinoma in situ, while DBT identified two of the seven cases, according to the study, which was published in JAMA.
Overall, the invasive cancer detection rate was 11.8 per 1,000 women for MRI compared with 4.8 per 1,000 women for DBT. Sensitivity for MRI and DBT was 96% vs. 39%, and specificity was 87% vs. 97%.
The rate of recommendation for further screening was not significantly different between the procedures (8% for MRI and 10% for DBT). The most common adverse events were three cases of mild allergic reactions and two cases of anxiety.
The study findings were limited by several factors including the inability to show an association between abbreviated breast MRI and breast cancer mortality and the lack of cost-effectiveness comparisons for the two procedures. Because eligibility criteria required a prior breast mammogram to see if the breasts were dense, the study compared an incidence DBT screen to a prevalence abbreviated MRI screen, Dr. Comstock and associates noted.
However, the results show a significantly increased breast cancer detection rate with abbreviated MRI, which merits additional research to examine the relationship between screening strategies and clinical outcomes for women with dense breasts, they said.
The study was supported in part by the National Cancer Institute of the National Institutes of Health, and by Bracco Diagnostics through funding to the ECOG-ACRIN Cancer Research Group. Dr. Comstock disclosed financial relationships with Bracco Diagnostics and Bayer, and three coauthors disclosed financial relationships with other imaging companies. The remaining coauthors had no relevant financial disclosures.
SOURCE: Comstock CK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0572.
For women with dense breasts, abbreviated magnetic resonance imaging was more effective than was digital breast tomosynthesis for detecting invasive breast cancer in a cross-sectional study of 1,444 women who underwent both procedures.
Dense breasts are a common reason for failed early diagnosis of breast cancer, wrote Christopher E. Comstock, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Digital breast tomosynthesis (DBT) and abbreviated breast magnetic resonance imaging (MRI) are becoming more popular as safe and cost-effective breast cancer screening options, but their effectiveness in women with dense breasts and average breast cancer risk has not been compared.
The researchers reviewed data from 1,444 women aged 40-75 years at 47 institutions in the United States and 1 in Germany. The women underwent both DBT and MRI. The primary endpoint was the detection of invasive cancers, of which 17 were identified at baseline screening. Abbreviated breast MRI detected all 17 cases of invasive cancer, compared with 7 detected by DBT. In addition, MRI detected six of seven women with ductal carcinoma in situ, while DBT identified two of the seven cases, according to the study, which was published in JAMA.
Overall, the invasive cancer detection rate was 11.8 per 1,000 women for MRI compared with 4.8 per 1,000 women for DBT. Sensitivity for MRI and DBT was 96% vs. 39%, and specificity was 87% vs. 97%.
The rate of recommendation for further screening was not significantly different between the procedures (8% for MRI and 10% for DBT). The most common adverse events were three cases of mild allergic reactions and two cases of anxiety.
The study findings were limited by several factors including the inability to show an association between abbreviated breast MRI and breast cancer mortality and the lack of cost-effectiveness comparisons for the two procedures. Because eligibility criteria required a prior breast mammogram to see if the breasts were dense, the study compared an incidence DBT screen to a prevalence abbreviated MRI screen, Dr. Comstock and associates noted.
However, the results show a significantly increased breast cancer detection rate with abbreviated MRI, which merits additional research to examine the relationship between screening strategies and clinical outcomes for women with dense breasts, they said.
The study was supported in part by the National Cancer Institute of the National Institutes of Health, and by Bracco Diagnostics through funding to the ECOG-ACRIN Cancer Research Group. Dr. Comstock disclosed financial relationships with Bracco Diagnostics and Bayer, and three coauthors disclosed financial relationships with other imaging companies. The remaining coauthors had no relevant financial disclosures.
SOURCE: Comstock CK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0572.
FROM JAMA