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Patient Navigators for Serious Illnesses Can Now Bill Under New Medicare Codes
In a move that acknowledges the gauntlet the US health system poses for people facing serious and fatal illnesses, Medicare will pay for a new class of workers to help patients manage treatments for conditions like cancer and heart failure.
The 2024 Medicare physician fee schedule includes new billing codes, including G0023, to pay for 60 minutes a month of care coordination by certified or trained auxiliary personnel working under the direction of a clinician.
A diagnosis of cancer or another serious illness takes a toll beyond the physical effects of the disease. Patients often scramble to make adjustments in family and work schedules to manage treatment, said Samyukta Mullangi, MD, MBA, medical director of oncology at Thyme Care, a Nashville, Tennessee–based firm that provides navigation and coordination services to oncology practices and insurers.
“It just really does create a bit of a pressure cooker for patients,” Dr. Mullangi told this news organization.
Medicare has for many years paid for medical professionals to help patients cope with the complexities of disease, such as chronic care management (CCM) provided by physicians, nurses, and physician assistants.
The new principal illness navigation (PIN) payments are intended to pay for work that to date typically has been done by people without medical degrees, including those involved in peer support networks and community health programs. The US Centers for Medicare and Medicaid Services(CMS) expects these navigators will undergo training and work under the supervision of clinicians.
The new navigators may coordinate care transitions between medical settings, follow up with patients after emergency department (ED) visits, or communicate with skilled nursing facilities regarding the psychosocial needs and functional deficits of a patient, among other functions.
CMS expects the new navigators may:
- Conduct assessments to understand a patient’s life story, strengths, needs, goals, preferences, and desired outcomes, including understanding cultural and linguistic factors.
- Provide support to accomplish the clinician’s treatment plan.
- Coordinate the receipt of needed services from healthcare facilities, home- and community-based service providers, and caregivers.
Peers as Navigators
The new navigators can be former patients who have undergone similar treatments for serious diseases, CMS said. This approach sets the new program apart from other care management services Medicare already covers, program officials wrote in the 2024 physician fee schedule.
“For some conditions, patients are best able to engage with the healthcare system and access care if they have assistance from a single, dedicated individual who has ‘lived experience,’ ” according to the rule.
The agency has taken a broad initial approach in defining what kinds of illnesses a patient may have to qualify for services. Patients must have a serious condition that is expected to last at least 3 months, such as cancer, heart failure, or substance use disorder.
But those without a definitive diagnosis may also qualify to receive navigator services.
In the rule, CMS cited a case in which a CT scan identified a suspicious mass in a patient’s colon. A clinician might decide this person would benefit from navigation services due to the potential risks for an undiagnosed illness.
“Regardless of the definitive diagnosis of the mass, presence of a colonic mass for that patient may be a serious high-risk condition that could, for example, cause obstruction and lead the patient to present to the emergency department, as well as be potentially indicative of an underlying life-threatening illness such as colon cancer,” CMS wrote in the rule.
Navigators often start their work when cancer patients are screened and guide them through initial diagnosis, potential surgery, radiation, or chemotherapy, said Sharon Gentry, MSN, RN, a former nurse navigator who is now the editor in chief of the Journal of the Academy of Oncology Nurse & Patient Navigators.
The navigators are meant to be a trusted and continual presence for patients, who otherwise might be left to start anew in finding help at each phase of care.
The navigators “see the whole picture. They see the whole journey the patient takes, from pre-diagnosis all the way through diagnosis care out through survival,” Ms. Gentry said.
Gaining a special Medicare payment for these kinds of services will elevate this work, she said.
Many newer drugs can target specific mechanisms and proteins of cancer. Often, oncology treatment involves testing to find out if mutations are allowing the cancer cells to evade a patient’s immune system.
Checking these biomarkers takes time, however. Patients sometimes become frustrated because they are anxious to begin treatment. Patients may receive inaccurate information from friends or family who went through treatment previously. Navigators can provide knowledge on the current state of care for a patient’s disease, helping them better manage anxieties.
“You have to explain to them that things have changed since the guy you drink coffee with was diagnosed with cancer, and there may be a drug that could target that,” Ms. Gentry said.
Potential Challenges
Initial uptake of the new PIN codes may be slow going, however, as clinicians and health systems may already use well-established codes. These include CCM and principal care management services, which may pay higher rates, Mullangi said.
“There might be sensitivity around not wanting to cannibalize existing programs with a new program,” Dr. Mullangi said.
In addition, many patients will have a copay for the services of principal illness navigators, Dr. Mullangi said.
While many patients have additional insurance that would cover the service, not all do. People with traditional Medicare coverage can sometimes pay 20% of the cost of some medical services.
“I think that may give patients pause, particularly if they’re already feeling the financial burden of a cancer treatment journey,” Dr. Mullangi said.
Pay rates for PIN services involve calculations of regional price differences, which are posted publicly by CMS, and potential added fees for services provided by hospital-affiliated organizations.
Consider payments for code G0023, covering 60 minutes of principal navigation services provided in a single month.
A set reimbursement for patients cared for in independent medical practices exists, with variation for local costs. Medicare’s non-facility price for G0023 would be $102.41 in some parts of Silicon Valley in California, including San Jose. In Arkansas, where costs are lower, reimbursement would be $73.14 for this same service.
Patients who get services covered by code G0023 in independent medical practices would have monthly copays of about $15-$20, depending on where they live.
The tab for patients tends to be higher for these same services if delivered through a medical practice owned by a hospital, as this would trigger the addition of facility fees to the payments made to cover the services. Facility fees are difficult for the public to ascertain before getting a treatment or service.
Dr. Mullangi and Ms. Gentry reported no relevant financial disclosures outside of their employers.
A version of this article first appeared on Medscape.com.
In a move that acknowledges the gauntlet the US health system poses for people facing serious and fatal illnesses, Medicare will pay for a new class of workers to help patients manage treatments for conditions like cancer and heart failure.
The 2024 Medicare physician fee schedule includes new billing codes, including G0023, to pay for 60 minutes a month of care coordination by certified or trained auxiliary personnel working under the direction of a clinician.
A diagnosis of cancer or another serious illness takes a toll beyond the physical effects of the disease. Patients often scramble to make adjustments in family and work schedules to manage treatment, said Samyukta Mullangi, MD, MBA, medical director of oncology at Thyme Care, a Nashville, Tennessee–based firm that provides navigation and coordination services to oncology practices and insurers.
“It just really does create a bit of a pressure cooker for patients,” Dr. Mullangi told this news organization.
Medicare has for many years paid for medical professionals to help patients cope with the complexities of disease, such as chronic care management (CCM) provided by physicians, nurses, and physician assistants.
The new principal illness navigation (PIN) payments are intended to pay for work that to date typically has been done by people without medical degrees, including those involved in peer support networks and community health programs. The US Centers for Medicare and Medicaid Services(CMS) expects these navigators will undergo training and work under the supervision of clinicians.
The new navigators may coordinate care transitions between medical settings, follow up with patients after emergency department (ED) visits, or communicate with skilled nursing facilities regarding the psychosocial needs and functional deficits of a patient, among other functions.
CMS expects the new navigators may:
- Conduct assessments to understand a patient’s life story, strengths, needs, goals, preferences, and desired outcomes, including understanding cultural and linguistic factors.
- Provide support to accomplish the clinician’s treatment plan.
- Coordinate the receipt of needed services from healthcare facilities, home- and community-based service providers, and caregivers.
Peers as Navigators
The new navigators can be former patients who have undergone similar treatments for serious diseases, CMS said. This approach sets the new program apart from other care management services Medicare already covers, program officials wrote in the 2024 physician fee schedule.
“For some conditions, patients are best able to engage with the healthcare system and access care if they have assistance from a single, dedicated individual who has ‘lived experience,’ ” according to the rule.
The agency has taken a broad initial approach in defining what kinds of illnesses a patient may have to qualify for services. Patients must have a serious condition that is expected to last at least 3 months, such as cancer, heart failure, or substance use disorder.
But those without a definitive diagnosis may also qualify to receive navigator services.
In the rule, CMS cited a case in which a CT scan identified a suspicious mass in a patient’s colon. A clinician might decide this person would benefit from navigation services due to the potential risks for an undiagnosed illness.
“Regardless of the definitive diagnosis of the mass, presence of a colonic mass for that patient may be a serious high-risk condition that could, for example, cause obstruction and lead the patient to present to the emergency department, as well as be potentially indicative of an underlying life-threatening illness such as colon cancer,” CMS wrote in the rule.
Navigators often start their work when cancer patients are screened and guide them through initial diagnosis, potential surgery, radiation, or chemotherapy, said Sharon Gentry, MSN, RN, a former nurse navigator who is now the editor in chief of the Journal of the Academy of Oncology Nurse & Patient Navigators.
The navigators are meant to be a trusted and continual presence for patients, who otherwise might be left to start anew in finding help at each phase of care.
The navigators “see the whole picture. They see the whole journey the patient takes, from pre-diagnosis all the way through diagnosis care out through survival,” Ms. Gentry said.
Gaining a special Medicare payment for these kinds of services will elevate this work, she said.
Many newer drugs can target specific mechanisms and proteins of cancer. Often, oncology treatment involves testing to find out if mutations are allowing the cancer cells to evade a patient’s immune system.
Checking these biomarkers takes time, however. Patients sometimes become frustrated because they are anxious to begin treatment. Patients may receive inaccurate information from friends or family who went through treatment previously. Navigators can provide knowledge on the current state of care for a patient’s disease, helping them better manage anxieties.
“You have to explain to them that things have changed since the guy you drink coffee with was diagnosed with cancer, and there may be a drug that could target that,” Ms. Gentry said.
Potential Challenges
Initial uptake of the new PIN codes may be slow going, however, as clinicians and health systems may already use well-established codes. These include CCM and principal care management services, which may pay higher rates, Mullangi said.
“There might be sensitivity around not wanting to cannibalize existing programs with a new program,” Dr. Mullangi said.
In addition, many patients will have a copay for the services of principal illness navigators, Dr. Mullangi said.
While many patients have additional insurance that would cover the service, not all do. People with traditional Medicare coverage can sometimes pay 20% of the cost of some medical services.
“I think that may give patients pause, particularly if they’re already feeling the financial burden of a cancer treatment journey,” Dr. Mullangi said.
Pay rates for PIN services involve calculations of regional price differences, which are posted publicly by CMS, and potential added fees for services provided by hospital-affiliated organizations.
Consider payments for code G0023, covering 60 minutes of principal navigation services provided in a single month.
A set reimbursement for patients cared for in independent medical practices exists, with variation for local costs. Medicare’s non-facility price for G0023 would be $102.41 in some parts of Silicon Valley in California, including San Jose. In Arkansas, where costs are lower, reimbursement would be $73.14 for this same service.
Patients who get services covered by code G0023 in independent medical practices would have monthly copays of about $15-$20, depending on where they live.
The tab for patients tends to be higher for these same services if delivered through a medical practice owned by a hospital, as this would trigger the addition of facility fees to the payments made to cover the services. Facility fees are difficult for the public to ascertain before getting a treatment or service.
Dr. Mullangi and Ms. Gentry reported no relevant financial disclosures outside of their employers.
A version of this article first appeared on Medscape.com.
In a move that acknowledges the gauntlet the US health system poses for people facing serious and fatal illnesses, Medicare will pay for a new class of workers to help patients manage treatments for conditions like cancer and heart failure.
The 2024 Medicare physician fee schedule includes new billing codes, including G0023, to pay for 60 minutes a month of care coordination by certified or trained auxiliary personnel working under the direction of a clinician.
A diagnosis of cancer or another serious illness takes a toll beyond the physical effects of the disease. Patients often scramble to make adjustments in family and work schedules to manage treatment, said Samyukta Mullangi, MD, MBA, medical director of oncology at Thyme Care, a Nashville, Tennessee–based firm that provides navigation and coordination services to oncology practices and insurers.
“It just really does create a bit of a pressure cooker for patients,” Dr. Mullangi told this news organization.
Medicare has for many years paid for medical professionals to help patients cope with the complexities of disease, such as chronic care management (CCM) provided by physicians, nurses, and physician assistants.
The new principal illness navigation (PIN) payments are intended to pay for work that to date typically has been done by people without medical degrees, including those involved in peer support networks and community health programs. The US Centers for Medicare and Medicaid Services(CMS) expects these navigators will undergo training and work under the supervision of clinicians.
The new navigators may coordinate care transitions between medical settings, follow up with patients after emergency department (ED) visits, or communicate with skilled nursing facilities regarding the psychosocial needs and functional deficits of a patient, among other functions.
CMS expects the new navigators may:
- Conduct assessments to understand a patient’s life story, strengths, needs, goals, preferences, and desired outcomes, including understanding cultural and linguistic factors.
- Provide support to accomplish the clinician’s treatment plan.
- Coordinate the receipt of needed services from healthcare facilities, home- and community-based service providers, and caregivers.
Peers as Navigators
The new navigators can be former patients who have undergone similar treatments for serious diseases, CMS said. This approach sets the new program apart from other care management services Medicare already covers, program officials wrote in the 2024 physician fee schedule.
“For some conditions, patients are best able to engage with the healthcare system and access care if they have assistance from a single, dedicated individual who has ‘lived experience,’ ” according to the rule.
The agency has taken a broad initial approach in defining what kinds of illnesses a patient may have to qualify for services. Patients must have a serious condition that is expected to last at least 3 months, such as cancer, heart failure, or substance use disorder.
But those without a definitive diagnosis may also qualify to receive navigator services.
In the rule, CMS cited a case in which a CT scan identified a suspicious mass in a patient’s colon. A clinician might decide this person would benefit from navigation services due to the potential risks for an undiagnosed illness.
“Regardless of the definitive diagnosis of the mass, presence of a colonic mass for that patient may be a serious high-risk condition that could, for example, cause obstruction and lead the patient to present to the emergency department, as well as be potentially indicative of an underlying life-threatening illness such as colon cancer,” CMS wrote in the rule.
Navigators often start their work when cancer patients are screened and guide them through initial diagnosis, potential surgery, radiation, or chemotherapy, said Sharon Gentry, MSN, RN, a former nurse navigator who is now the editor in chief of the Journal of the Academy of Oncology Nurse & Patient Navigators.
The navigators are meant to be a trusted and continual presence for patients, who otherwise might be left to start anew in finding help at each phase of care.
The navigators “see the whole picture. They see the whole journey the patient takes, from pre-diagnosis all the way through diagnosis care out through survival,” Ms. Gentry said.
Gaining a special Medicare payment for these kinds of services will elevate this work, she said.
Many newer drugs can target specific mechanisms and proteins of cancer. Often, oncology treatment involves testing to find out if mutations are allowing the cancer cells to evade a patient’s immune system.
Checking these biomarkers takes time, however. Patients sometimes become frustrated because they are anxious to begin treatment. Patients may receive inaccurate information from friends or family who went through treatment previously. Navigators can provide knowledge on the current state of care for a patient’s disease, helping them better manage anxieties.
“You have to explain to them that things have changed since the guy you drink coffee with was diagnosed with cancer, and there may be a drug that could target that,” Ms. Gentry said.
Potential Challenges
Initial uptake of the new PIN codes may be slow going, however, as clinicians and health systems may already use well-established codes. These include CCM and principal care management services, which may pay higher rates, Mullangi said.
“There might be sensitivity around not wanting to cannibalize existing programs with a new program,” Dr. Mullangi said.
In addition, many patients will have a copay for the services of principal illness navigators, Dr. Mullangi said.
While many patients have additional insurance that would cover the service, not all do. People with traditional Medicare coverage can sometimes pay 20% of the cost of some medical services.
“I think that may give patients pause, particularly if they’re already feeling the financial burden of a cancer treatment journey,” Dr. Mullangi said.
Pay rates for PIN services involve calculations of regional price differences, which are posted publicly by CMS, and potential added fees for services provided by hospital-affiliated organizations.
Consider payments for code G0023, covering 60 minutes of principal navigation services provided in a single month.
A set reimbursement for patients cared for in independent medical practices exists, with variation for local costs. Medicare’s non-facility price for G0023 would be $102.41 in some parts of Silicon Valley in California, including San Jose. In Arkansas, where costs are lower, reimbursement would be $73.14 for this same service.
Patients who get services covered by code G0023 in independent medical practices would have monthly copays of about $15-$20, depending on where they live.
The tab for patients tends to be higher for these same services if delivered through a medical practice owned by a hospital, as this would trigger the addition of facility fees to the payments made to cover the services. Facility fees are difficult for the public to ascertain before getting a treatment or service.
Dr. Mullangi and Ms. Gentry reported no relevant financial disclosures outside of their employers.
A version of this article first appeared on Medscape.com.
Lessons Learned: What Docs Wish Med Students Knew
Despite 4 years of med school and 3-7 years in residency, when you enter the workforce as a doctor, you still have much to learn. There is only so much your professors and attending physicians can pack in. Going forward, you’ll continue to learn on the job and via continuing education.
Some of that lifelong learning will involve soft skills — how to compassionately work with your patients and their families, for instance. Other lessons will get down to the business of medicine — the paperwork, the work/life balance, and the moral dilemmas you never saw coming. And still others will involve learning how to take care of yourself in the middle of seemingly endless hours on the job.
“We all have things we wish we had known upon starting our careers,” said Daniel Opris, MD, a primary care physician at Ohio-based Executive Medical Centers.
We tapped several veteran physicians and an educator to learn what they wish med students knew as they enter the workforce. We’ve compiled them here to give you a head start on the lessons ahead.
You Won’t Know Everything, and That’s Okay
When you go through your medical training, it can feel overwhelming to absorb all the knowledge your professors and attendings impart. The bottom line, said Shoshana Ungerleider, MD, an internal medicine specialist, is that you shouldn’t worry about it.
David Lenihan, PhD, CEO at Ponce Health Sciences University, agrees. “What we’ve lost in recent years, is the ability to apply your skill set and say, ‘let me take a day and get back to you,’” he said. “Doctors love it when you do that because it shows you can pitch in and work as part of a team.”
Medicine is a collaborative field, said Ungerleider, and learning from others, whether peers, nurses, or specialists, is “not a weakness.” She recommends embracing uncertainty and getting comfortable with the unknown.
You’ll Take Your Work Home With You
Doctors enter the field because they care about their patients and want to help. Successful outcomes are never guaranteed, however, no matter how much you try. The result? Some days you’ll bring home those upsetting and haunting cases, said Lenihan.
“We often believe that we should leave our work at the office, but sometimes you need to bring it home and think it through,” he said. “It can’t overwhelm you, but you should digest what happened.”
When you do, said Lenihan, you’ll come out the other end more empathetic and that helps the healthcare system in the long run. “The more you reflect on your day, the better you’ll get at reading the room and treating your patients.”
Drew Remignanti, MD, a retired emergency medicine physician from New Hampshire, agrees, but puts a different spin on bringing work home.
“We revisit the patient care decisions we made, second-guess ourselves, and worry about our patients’ welfare and outcomes,” he said. “I think it can only lead to better outcomes down the road, however, if you learn from that bad decision, preventing you from committing a similar mistake.”
Burnout Is Real — Make Self-Care a Priority
As a retired physician who spent 40 years practicing medicine, Remignanti experienced the evolution of healthcare as it has become what he calls a “consumer-provider” model. “Productivity didn’t use to be part of the equation, but now it’s the focus,” he said.
The result is burnout, a very real threat to incoming physicians. Remignanti holds that if you are aware of the risk, you can resist it. Part of avoiding burnout is self-care, according to Ungerleider. “The sooner you prioritize your mental, emotional, and physical well-being, the better,” she said. “Balancing work and life may feel impossible at times but taking care of yourself is essential to being a better physician in the long run.”
That means carving out time for exercise, hobbies, and connections outside of the medical field. It also means making sleep and nutrition a priority, even when that feels hard to accomplish. “If you don’t take care of yourself, you can’t take care of others,” added Opris. “It’s so common to lose yourself in your career, but you need to hold onto your physical, emotional, and spiritual self.”
Avoid Relying Too Heavily on Tech
Technology is invading every aspect of our lives — often for the greater good — but in medicine, it’s important to always return to your core knowledge above all else. Case in point, said Opris, the UpToDate app. While it can be a useful tool, it’s important not to become too reliant on it. “UpToDate is expert opinion-based guidance, and it’s a fantastic resource,” he said. “But you need to use your references and knowledge in every case.”
It’s key to remember that every patient is different, and their case may not line up perfectly with the guidance presented in UpToDate or other technology source. Piggybacking on that, Ungerleider added that it’s important to remember medicine is about people, not just conditions.
“It’s easy to focus on mastering the science, but the real art of medicine comes from seeing the whole person in front of you,” she said. “Your patients are more than their diagnoses — they come with complex emotions, life stories, and needs.” Being compassionate, listening carefully, and building trust should match up to your clinical skills.
Partner With Your Patients, Even When It’s Difficult
Perhaps the most difficult lesson of all is remembering that your patients may not always agree with your recommendations and choose to ignore them. After all your years spent learning, there may be times when it feels your education is going to waste.
“Remember that the landscape today is so varied, and that bleeds into medicine,” said Opris. “We go into cases with our own biases, and it’s important to take a step back to reset, every time.”
Opris reminds himself of Sir William Osler’s famous essay, “Aequanimitas,” in which he tells graduating medical students to practice with “coolness and presence of mind under all circumstances.”
Remignanti offers this advice: “Physicians need to be able to partner with their patients and jointly decide which courses of action are most effective,” he said. “Cling to the idea that you are forming a partnership with your patients — what can we together determine is the best course?”
At the same time, the path the patient chooses may not be what’s best for them — potentially even leading to a poor outcome.
“You may not always understand their choices,” said Opris. “But they do have a choice. Think of yourself almost like a consultant.”
A version of this article first appeared on Medscape.com.
Despite 4 years of med school and 3-7 years in residency, when you enter the workforce as a doctor, you still have much to learn. There is only so much your professors and attending physicians can pack in. Going forward, you’ll continue to learn on the job and via continuing education.
Some of that lifelong learning will involve soft skills — how to compassionately work with your patients and their families, for instance. Other lessons will get down to the business of medicine — the paperwork, the work/life balance, and the moral dilemmas you never saw coming. And still others will involve learning how to take care of yourself in the middle of seemingly endless hours on the job.
“We all have things we wish we had known upon starting our careers,” said Daniel Opris, MD, a primary care physician at Ohio-based Executive Medical Centers.
We tapped several veteran physicians and an educator to learn what they wish med students knew as they enter the workforce. We’ve compiled them here to give you a head start on the lessons ahead.
You Won’t Know Everything, and That’s Okay
When you go through your medical training, it can feel overwhelming to absorb all the knowledge your professors and attendings impart. The bottom line, said Shoshana Ungerleider, MD, an internal medicine specialist, is that you shouldn’t worry about it.
David Lenihan, PhD, CEO at Ponce Health Sciences University, agrees. “What we’ve lost in recent years, is the ability to apply your skill set and say, ‘let me take a day and get back to you,’” he said. “Doctors love it when you do that because it shows you can pitch in and work as part of a team.”
Medicine is a collaborative field, said Ungerleider, and learning from others, whether peers, nurses, or specialists, is “not a weakness.” She recommends embracing uncertainty and getting comfortable with the unknown.
You’ll Take Your Work Home With You
Doctors enter the field because they care about their patients and want to help. Successful outcomes are never guaranteed, however, no matter how much you try. The result? Some days you’ll bring home those upsetting and haunting cases, said Lenihan.
“We often believe that we should leave our work at the office, but sometimes you need to bring it home and think it through,” he said. “It can’t overwhelm you, but you should digest what happened.”
When you do, said Lenihan, you’ll come out the other end more empathetic and that helps the healthcare system in the long run. “The more you reflect on your day, the better you’ll get at reading the room and treating your patients.”
Drew Remignanti, MD, a retired emergency medicine physician from New Hampshire, agrees, but puts a different spin on bringing work home.
“We revisit the patient care decisions we made, second-guess ourselves, and worry about our patients’ welfare and outcomes,” he said. “I think it can only lead to better outcomes down the road, however, if you learn from that bad decision, preventing you from committing a similar mistake.”
Burnout Is Real — Make Self-Care a Priority
As a retired physician who spent 40 years practicing medicine, Remignanti experienced the evolution of healthcare as it has become what he calls a “consumer-provider” model. “Productivity didn’t use to be part of the equation, but now it’s the focus,” he said.
The result is burnout, a very real threat to incoming physicians. Remignanti holds that if you are aware of the risk, you can resist it. Part of avoiding burnout is self-care, according to Ungerleider. “The sooner you prioritize your mental, emotional, and physical well-being, the better,” she said. “Balancing work and life may feel impossible at times but taking care of yourself is essential to being a better physician in the long run.”
That means carving out time for exercise, hobbies, and connections outside of the medical field. It also means making sleep and nutrition a priority, even when that feels hard to accomplish. “If you don’t take care of yourself, you can’t take care of others,” added Opris. “It’s so common to lose yourself in your career, but you need to hold onto your physical, emotional, and spiritual self.”
Avoid Relying Too Heavily on Tech
Technology is invading every aspect of our lives — often for the greater good — but in medicine, it’s important to always return to your core knowledge above all else. Case in point, said Opris, the UpToDate app. While it can be a useful tool, it’s important not to become too reliant on it. “UpToDate is expert opinion-based guidance, and it’s a fantastic resource,” he said. “But you need to use your references and knowledge in every case.”
It’s key to remember that every patient is different, and their case may not line up perfectly with the guidance presented in UpToDate or other technology source. Piggybacking on that, Ungerleider added that it’s important to remember medicine is about people, not just conditions.
“It’s easy to focus on mastering the science, but the real art of medicine comes from seeing the whole person in front of you,” she said. “Your patients are more than their diagnoses — they come with complex emotions, life stories, and needs.” Being compassionate, listening carefully, and building trust should match up to your clinical skills.
Partner With Your Patients, Even When It’s Difficult
Perhaps the most difficult lesson of all is remembering that your patients may not always agree with your recommendations and choose to ignore them. After all your years spent learning, there may be times when it feels your education is going to waste.
“Remember that the landscape today is so varied, and that bleeds into medicine,” said Opris. “We go into cases with our own biases, and it’s important to take a step back to reset, every time.”
Opris reminds himself of Sir William Osler’s famous essay, “Aequanimitas,” in which he tells graduating medical students to practice with “coolness and presence of mind under all circumstances.”
Remignanti offers this advice: “Physicians need to be able to partner with their patients and jointly decide which courses of action are most effective,” he said. “Cling to the idea that you are forming a partnership with your patients — what can we together determine is the best course?”
At the same time, the path the patient chooses may not be what’s best for them — potentially even leading to a poor outcome.
“You may not always understand their choices,” said Opris. “But they do have a choice. Think of yourself almost like a consultant.”
A version of this article first appeared on Medscape.com.
Despite 4 years of med school and 3-7 years in residency, when you enter the workforce as a doctor, you still have much to learn. There is only so much your professors and attending physicians can pack in. Going forward, you’ll continue to learn on the job and via continuing education.
Some of that lifelong learning will involve soft skills — how to compassionately work with your patients and their families, for instance. Other lessons will get down to the business of medicine — the paperwork, the work/life balance, and the moral dilemmas you never saw coming. And still others will involve learning how to take care of yourself in the middle of seemingly endless hours on the job.
“We all have things we wish we had known upon starting our careers,” said Daniel Opris, MD, a primary care physician at Ohio-based Executive Medical Centers.
We tapped several veteran physicians and an educator to learn what they wish med students knew as they enter the workforce. We’ve compiled them here to give you a head start on the lessons ahead.
You Won’t Know Everything, and That’s Okay
When you go through your medical training, it can feel overwhelming to absorb all the knowledge your professors and attendings impart. The bottom line, said Shoshana Ungerleider, MD, an internal medicine specialist, is that you shouldn’t worry about it.
David Lenihan, PhD, CEO at Ponce Health Sciences University, agrees. “What we’ve lost in recent years, is the ability to apply your skill set and say, ‘let me take a day and get back to you,’” he said. “Doctors love it when you do that because it shows you can pitch in and work as part of a team.”
Medicine is a collaborative field, said Ungerleider, and learning from others, whether peers, nurses, or specialists, is “not a weakness.” She recommends embracing uncertainty and getting comfortable with the unknown.
You’ll Take Your Work Home With You
Doctors enter the field because they care about their patients and want to help. Successful outcomes are never guaranteed, however, no matter how much you try. The result? Some days you’ll bring home those upsetting and haunting cases, said Lenihan.
“We often believe that we should leave our work at the office, but sometimes you need to bring it home and think it through,” he said. “It can’t overwhelm you, but you should digest what happened.”
When you do, said Lenihan, you’ll come out the other end more empathetic and that helps the healthcare system in the long run. “The more you reflect on your day, the better you’ll get at reading the room and treating your patients.”
Drew Remignanti, MD, a retired emergency medicine physician from New Hampshire, agrees, but puts a different spin on bringing work home.
“We revisit the patient care decisions we made, second-guess ourselves, and worry about our patients’ welfare and outcomes,” he said. “I think it can only lead to better outcomes down the road, however, if you learn from that bad decision, preventing you from committing a similar mistake.”
Burnout Is Real — Make Self-Care a Priority
As a retired physician who spent 40 years practicing medicine, Remignanti experienced the evolution of healthcare as it has become what he calls a “consumer-provider” model. “Productivity didn’t use to be part of the equation, but now it’s the focus,” he said.
The result is burnout, a very real threat to incoming physicians. Remignanti holds that if you are aware of the risk, you can resist it. Part of avoiding burnout is self-care, according to Ungerleider. “The sooner you prioritize your mental, emotional, and physical well-being, the better,” she said. “Balancing work and life may feel impossible at times but taking care of yourself is essential to being a better physician in the long run.”
That means carving out time for exercise, hobbies, and connections outside of the medical field. It also means making sleep and nutrition a priority, even when that feels hard to accomplish. “If you don’t take care of yourself, you can’t take care of others,” added Opris. “It’s so common to lose yourself in your career, but you need to hold onto your physical, emotional, and spiritual self.”
Avoid Relying Too Heavily on Tech
Technology is invading every aspect of our lives — often for the greater good — but in medicine, it’s important to always return to your core knowledge above all else. Case in point, said Opris, the UpToDate app. While it can be a useful tool, it’s important not to become too reliant on it. “UpToDate is expert opinion-based guidance, and it’s a fantastic resource,” he said. “But you need to use your references and knowledge in every case.”
It’s key to remember that every patient is different, and their case may not line up perfectly with the guidance presented in UpToDate or other technology source. Piggybacking on that, Ungerleider added that it’s important to remember medicine is about people, not just conditions.
“It’s easy to focus on mastering the science, but the real art of medicine comes from seeing the whole person in front of you,” she said. “Your patients are more than their diagnoses — they come with complex emotions, life stories, and needs.” Being compassionate, listening carefully, and building trust should match up to your clinical skills.
Partner With Your Patients, Even When It’s Difficult
Perhaps the most difficult lesson of all is remembering that your patients may not always agree with your recommendations and choose to ignore them. After all your years spent learning, there may be times when it feels your education is going to waste.
“Remember that the landscape today is so varied, and that bleeds into medicine,” said Opris. “We go into cases with our own biases, and it’s important to take a step back to reset, every time.”
Opris reminds himself of Sir William Osler’s famous essay, “Aequanimitas,” in which he tells graduating medical students to practice with “coolness and presence of mind under all circumstances.”
Remignanti offers this advice: “Physicians need to be able to partner with their patients and jointly decide which courses of action are most effective,” he said. “Cling to the idea that you are forming a partnership with your patients — what can we together determine is the best course?”
At the same time, the path the patient chooses may not be what’s best for them — potentially even leading to a poor outcome.
“You may not always understand their choices,” said Opris. “But they do have a choice. Think of yourself almost like a consultant.”
A version of this article first appeared on Medscape.com.
Building an AI Army of Digital Twins to Fight Cancer
A patient has cancer. It’s decision time.
Clinician and patient alike face, really, the ultimate challenge when making those decisions. They have to consider the patient’s individual circumstances, available treatment options, potential side effects, relevant clinical data such as the patient’s genetic profile and cancer specifics, and more.
“That’s a lot of information to hold,” said Uzma Asghar, PhD, MRCP, a British consultant medical oncologist at The Royal Marsden Hospital and a chief scientific officer at Concr LTD.
What if there were a way to test — quickly and accurately — all the potential paths forward?
That’s the goal of digital twins.
“What the [digital twin] model can do for the clinician is to hold all that information and process it really quickly, within a couple of minutes,” Asghar noted.
A digital twin is more than just a computer model or simulation because it copies a real-world person and relies on real-world data. Some digital twin programs also integrate new information as it becomes available. This technology holds promise for personalized medicine, drug discovery, developing screening strategies, and better understanding diseases.
How to Deliver a Twin
To create a digital twin, experts develop a computer model with data to hone its expertise in an area of medicine, such as cancer types and treatments. Then “you train the model on information it’s seen, and then introduce a patient and patient’s information,” said Asghar.
Asghar is currently working with colleagues to develop digital twins that could eventually help solve the aforementioned cancer scenario — a doctor and patient decide the best course of cancer treatment. But their applications are manifold, particularly in clinical research.
Digital twins often include a machine learning component, which would fall under the umbrella term of AI, said Asghar, but it’s not like ChatGPT or other generative AI modules many people are now familiar with.
“The difference here is the model is not there to replace the clinician or to replace clinical trials,” Asghar noted. Instead, digital twins help make decisions faster in a way that can be more affordable.
Digital Twins to Predict Cancer Outcomes
Asghar is currently involved in UK clinical trials enrolling patients with cancer to test the accuracy of digital twin programs.
At this point, these studies do not yet use digital twins to guide the course of treatment, which is something they hope to do eventually. For now, they are still at the validation phase — the digital twin program makes predictions about the treatments and then the researchers later evaluate how accurate the predictions turned out to be based on real information from the enrolled patients.
Their current model gives predictions for RECIST (response evaluation criteria in solid tumor), treatment response, and survival. In addition to collecting data from ongoing clinical trials, they’ve used retrospective data, such as from the Cancer Tumor Atlas, to test the model.
“We’ve clinically validated it now in over 9000 patients,” said Asghar, who noted that they are constantly testing it on new patients. Their data include 30 chemotherapies and 23 cancer types, but they are focusing on four: Triple-negative breast cancer, cancer of unknown primary, pancreatic cancer, and colorectal cancer.
“The reason for choosing those four cancer types is that they are aggressive, their response to chemotherapy isn’t as great, and the outcome for those patient populations, there’s significant room for improvement,” Asghar explained.
Currently, Asghar said, the model is around 80%-90% correct in predicting what the actual clinical outcomes turn out to be.
The final stage of their work, before it becomes widely available to clinicians, will be to integrate it into a clinical trial in which some clinicians use the model to make decisions about treatment vs some who don’t use the model. By studying patient outcomes in both groups, they will be able to determine the value of the digital twin program they created.
What Else Can a Twin Do? A Lot
While a model that helps clinicians make decisions about cancer treatments may be among the first digital twin programs that become widely available, there are many other kinds of digital twins in the works.
For example, a digital twin could be used as a benchmark for a patient to determine how their cancer might have progressed without treatment. Say a patient’s tumor grew during treatment, it might seem like the treatment failed, but a digital twin might show that if left untreated, the tumor would have grown five times as fast, said Paul Macklin, PhD, professor in the Department of Intelligent Systems Engineering at Indiana University Bloomington.
Alternatively, if the virtual patient’s tumor is around the same size as the real patient’s tumor, “that means that treatment has lost its efficacy. It’s time to do something new,” said Macklin. And a digital twin could help with not only choosing a therapy but also choosing a dosing schedule, he noted.
The models can also be updated as new treatments come out, which could help clinicians virtually explore how they might affect a patient before having that patient switch treatments.
Digital twins could also assist in decision-making based on a patient’s priorities and real-life circumstances. “Maybe your priority is not necessarily to shrink this [tumor] at all costs ... maybe your priority is some mix of that and also quality of life,” Macklin said, referring to potential side effects. Or if someone lives 3 hours from the nearest cancer center, a digital twin could help determine whether less frequent treatments could still be effective.
And while much of the activity around digital twins in biomedical research has been focused on cancer, Asghar said the technology has the potential to be applied to other diseases as well. A digital twin for cardiovascular disease could help doctors choose the best treatment. It could also integrate new information from a smartwatch or glucose monitor to make better predictions and help doctors adjust the treatment plan.
Faster, More Effective Research With Twins
Because digital twin programs can quickly analyze large datasets, they can also make real-world studies more effective and efficient.
Though digital twins would not fully replace real clinical trials, they could help run through preliminary scenarios before starting a full clinical trial, which would “save everybody some money, time and pain and risk,” said Macklin.
It’s also possible to use digital twins to design better screening strategies for early cancer detection and monitoring, said Ioannis Zervantonakis, PhD, a bioengineering professor at the University of Pittsburgh.
Zervantonakis is tapping digital twin technology for research that homes in on understanding tumors. In this case, the digital twin is a virtual representation of a real tumor, complete with its complex network of cells and the surrounding tissue.
Zervantonakis’ lab is using the technology to study cell-cell interactions in the tumor microenvironment, with a focus on human epidermal growth factor receptor 2–targeted therapy resistance in breast cancer. The digital twin they developed will simulate tumor growth, predict drug response, analyze cellular interactions, and optimize treatment strategies.
The Long Push Forward
One big hurdle to making digital twins more widely available is that regulation for the technology is still in progress.
“We’re developing the technology, and what’s also happening is the regulatory framework is being developed in parallel. So we’re almost developing things blindly on the basis that we think this is what the regulators would want,” explained Asghar.
“It’s really important that these technologies are regulated properly, just like drugs, and that’s what we’re pushing and advocating for,” said Asghar, noting that people need to know that like drugs, a digital twin has strengths and limitations.
And while a digital twin can be a cost-saving approach in the long run, it does require funding to get a program built, and finding funds can be difficult because not everyone knows about the technology. More funding means more trials.
With more data, Asghar is hopeful that within a few years, a digital twin model could be available for clinicians to use to help inform treatment decisions. This could lead to more effective treatments and, ultimately, better patient outcomes.
A version of this article appeared on Medscape.com.
A patient has cancer. It’s decision time.
Clinician and patient alike face, really, the ultimate challenge when making those decisions. They have to consider the patient’s individual circumstances, available treatment options, potential side effects, relevant clinical data such as the patient’s genetic profile and cancer specifics, and more.
“That’s a lot of information to hold,” said Uzma Asghar, PhD, MRCP, a British consultant medical oncologist at The Royal Marsden Hospital and a chief scientific officer at Concr LTD.
What if there were a way to test — quickly and accurately — all the potential paths forward?
That’s the goal of digital twins.
“What the [digital twin] model can do for the clinician is to hold all that information and process it really quickly, within a couple of minutes,” Asghar noted.
A digital twin is more than just a computer model or simulation because it copies a real-world person and relies on real-world data. Some digital twin programs also integrate new information as it becomes available. This technology holds promise for personalized medicine, drug discovery, developing screening strategies, and better understanding diseases.
How to Deliver a Twin
To create a digital twin, experts develop a computer model with data to hone its expertise in an area of medicine, such as cancer types and treatments. Then “you train the model on information it’s seen, and then introduce a patient and patient’s information,” said Asghar.
Asghar is currently working with colleagues to develop digital twins that could eventually help solve the aforementioned cancer scenario — a doctor and patient decide the best course of cancer treatment. But their applications are manifold, particularly in clinical research.
Digital twins often include a machine learning component, which would fall under the umbrella term of AI, said Asghar, but it’s not like ChatGPT or other generative AI modules many people are now familiar with.
“The difference here is the model is not there to replace the clinician or to replace clinical trials,” Asghar noted. Instead, digital twins help make decisions faster in a way that can be more affordable.
Digital Twins to Predict Cancer Outcomes
Asghar is currently involved in UK clinical trials enrolling patients with cancer to test the accuracy of digital twin programs.
At this point, these studies do not yet use digital twins to guide the course of treatment, which is something they hope to do eventually. For now, they are still at the validation phase — the digital twin program makes predictions about the treatments and then the researchers later evaluate how accurate the predictions turned out to be based on real information from the enrolled patients.
Their current model gives predictions for RECIST (response evaluation criteria in solid tumor), treatment response, and survival. In addition to collecting data from ongoing clinical trials, they’ve used retrospective data, such as from the Cancer Tumor Atlas, to test the model.
“We’ve clinically validated it now in over 9000 patients,” said Asghar, who noted that they are constantly testing it on new patients. Their data include 30 chemotherapies and 23 cancer types, but they are focusing on four: Triple-negative breast cancer, cancer of unknown primary, pancreatic cancer, and colorectal cancer.
“The reason for choosing those four cancer types is that they are aggressive, their response to chemotherapy isn’t as great, and the outcome for those patient populations, there’s significant room for improvement,” Asghar explained.
Currently, Asghar said, the model is around 80%-90% correct in predicting what the actual clinical outcomes turn out to be.
The final stage of their work, before it becomes widely available to clinicians, will be to integrate it into a clinical trial in which some clinicians use the model to make decisions about treatment vs some who don’t use the model. By studying patient outcomes in both groups, they will be able to determine the value of the digital twin program they created.
What Else Can a Twin Do? A Lot
While a model that helps clinicians make decisions about cancer treatments may be among the first digital twin programs that become widely available, there are many other kinds of digital twins in the works.
For example, a digital twin could be used as a benchmark for a patient to determine how their cancer might have progressed without treatment. Say a patient’s tumor grew during treatment, it might seem like the treatment failed, but a digital twin might show that if left untreated, the tumor would have grown five times as fast, said Paul Macklin, PhD, professor in the Department of Intelligent Systems Engineering at Indiana University Bloomington.
Alternatively, if the virtual patient’s tumor is around the same size as the real patient’s tumor, “that means that treatment has lost its efficacy. It’s time to do something new,” said Macklin. And a digital twin could help with not only choosing a therapy but also choosing a dosing schedule, he noted.
The models can also be updated as new treatments come out, which could help clinicians virtually explore how they might affect a patient before having that patient switch treatments.
Digital twins could also assist in decision-making based on a patient’s priorities and real-life circumstances. “Maybe your priority is not necessarily to shrink this [tumor] at all costs ... maybe your priority is some mix of that and also quality of life,” Macklin said, referring to potential side effects. Or if someone lives 3 hours from the nearest cancer center, a digital twin could help determine whether less frequent treatments could still be effective.
And while much of the activity around digital twins in biomedical research has been focused on cancer, Asghar said the technology has the potential to be applied to other diseases as well. A digital twin for cardiovascular disease could help doctors choose the best treatment. It could also integrate new information from a smartwatch or glucose monitor to make better predictions and help doctors adjust the treatment plan.
Faster, More Effective Research With Twins
Because digital twin programs can quickly analyze large datasets, they can also make real-world studies more effective and efficient.
Though digital twins would not fully replace real clinical trials, they could help run through preliminary scenarios before starting a full clinical trial, which would “save everybody some money, time and pain and risk,” said Macklin.
It’s also possible to use digital twins to design better screening strategies for early cancer detection and monitoring, said Ioannis Zervantonakis, PhD, a bioengineering professor at the University of Pittsburgh.
Zervantonakis is tapping digital twin technology for research that homes in on understanding tumors. In this case, the digital twin is a virtual representation of a real tumor, complete with its complex network of cells and the surrounding tissue.
Zervantonakis’ lab is using the technology to study cell-cell interactions in the tumor microenvironment, with a focus on human epidermal growth factor receptor 2–targeted therapy resistance in breast cancer. The digital twin they developed will simulate tumor growth, predict drug response, analyze cellular interactions, and optimize treatment strategies.
The Long Push Forward
One big hurdle to making digital twins more widely available is that regulation for the technology is still in progress.
“We’re developing the technology, and what’s also happening is the regulatory framework is being developed in parallel. So we’re almost developing things blindly on the basis that we think this is what the regulators would want,” explained Asghar.
“It’s really important that these technologies are regulated properly, just like drugs, and that’s what we’re pushing and advocating for,” said Asghar, noting that people need to know that like drugs, a digital twin has strengths and limitations.
And while a digital twin can be a cost-saving approach in the long run, it does require funding to get a program built, and finding funds can be difficult because not everyone knows about the technology. More funding means more trials.
With more data, Asghar is hopeful that within a few years, a digital twin model could be available for clinicians to use to help inform treatment decisions. This could lead to more effective treatments and, ultimately, better patient outcomes.
A version of this article appeared on Medscape.com.
A patient has cancer. It’s decision time.
Clinician and patient alike face, really, the ultimate challenge when making those decisions. They have to consider the patient’s individual circumstances, available treatment options, potential side effects, relevant clinical data such as the patient’s genetic profile and cancer specifics, and more.
“That’s a lot of information to hold,” said Uzma Asghar, PhD, MRCP, a British consultant medical oncologist at The Royal Marsden Hospital and a chief scientific officer at Concr LTD.
What if there were a way to test — quickly and accurately — all the potential paths forward?
That’s the goal of digital twins.
“What the [digital twin] model can do for the clinician is to hold all that information and process it really quickly, within a couple of minutes,” Asghar noted.
A digital twin is more than just a computer model or simulation because it copies a real-world person and relies on real-world data. Some digital twin programs also integrate new information as it becomes available. This technology holds promise for personalized medicine, drug discovery, developing screening strategies, and better understanding diseases.
How to Deliver a Twin
To create a digital twin, experts develop a computer model with data to hone its expertise in an area of medicine, such as cancer types and treatments. Then “you train the model on information it’s seen, and then introduce a patient and patient’s information,” said Asghar.
Asghar is currently working with colleagues to develop digital twins that could eventually help solve the aforementioned cancer scenario — a doctor and patient decide the best course of cancer treatment. But their applications are manifold, particularly in clinical research.
Digital twins often include a machine learning component, which would fall under the umbrella term of AI, said Asghar, but it’s not like ChatGPT or other generative AI modules many people are now familiar with.
“The difference here is the model is not there to replace the clinician or to replace clinical trials,” Asghar noted. Instead, digital twins help make decisions faster in a way that can be more affordable.
Digital Twins to Predict Cancer Outcomes
Asghar is currently involved in UK clinical trials enrolling patients with cancer to test the accuracy of digital twin programs.
At this point, these studies do not yet use digital twins to guide the course of treatment, which is something they hope to do eventually. For now, they are still at the validation phase — the digital twin program makes predictions about the treatments and then the researchers later evaluate how accurate the predictions turned out to be based on real information from the enrolled patients.
Their current model gives predictions for RECIST (response evaluation criteria in solid tumor), treatment response, and survival. In addition to collecting data from ongoing clinical trials, they’ve used retrospective data, such as from the Cancer Tumor Atlas, to test the model.
“We’ve clinically validated it now in over 9000 patients,” said Asghar, who noted that they are constantly testing it on new patients. Their data include 30 chemotherapies and 23 cancer types, but they are focusing on four: Triple-negative breast cancer, cancer of unknown primary, pancreatic cancer, and colorectal cancer.
“The reason for choosing those four cancer types is that they are aggressive, their response to chemotherapy isn’t as great, and the outcome for those patient populations, there’s significant room for improvement,” Asghar explained.
Currently, Asghar said, the model is around 80%-90% correct in predicting what the actual clinical outcomes turn out to be.
The final stage of their work, before it becomes widely available to clinicians, will be to integrate it into a clinical trial in which some clinicians use the model to make decisions about treatment vs some who don’t use the model. By studying patient outcomes in both groups, they will be able to determine the value of the digital twin program they created.
What Else Can a Twin Do? A Lot
While a model that helps clinicians make decisions about cancer treatments may be among the first digital twin programs that become widely available, there are many other kinds of digital twins in the works.
For example, a digital twin could be used as a benchmark for a patient to determine how their cancer might have progressed without treatment. Say a patient’s tumor grew during treatment, it might seem like the treatment failed, but a digital twin might show that if left untreated, the tumor would have grown five times as fast, said Paul Macklin, PhD, professor in the Department of Intelligent Systems Engineering at Indiana University Bloomington.
Alternatively, if the virtual patient’s tumor is around the same size as the real patient’s tumor, “that means that treatment has lost its efficacy. It’s time to do something new,” said Macklin. And a digital twin could help with not only choosing a therapy but also choosing a dosing schedule, he noted.
The models can also be updated as new treatments come out, which could help clinicians virtually explore how they might affect a patient before having that patient switch treatments.
Digital twins could also assist in decision-making based on a patient’s priorities and real-life circumstances. “Maybe your priority is not necessarily to shrink this [tumor] at all costs ... maybe your priority is some mix of that and also quality of life,” Macklin said, referring to potential side effects. Or if someone lives 3 hours from the nearest cancer center, a digital twin could help determine whether less frequent treatments could still be effective.
And while much of the activity around digital twins in biomedical research has been focused on cancer, Asghar said the technology has the potential to be applied to other diseases as well. A digital twin for cardiovascular disease could help doctors choose the best treatment. It could also integrate new information from a smartwatch or glucose monitor to make better predictions and help doctors adjust the treatment plan.
Faster, More Effective Research With Twins
Because digital twin programs can quickly analyze large datasets, they can also make real-world studies more effective and efficient.
Though digital twins would not fully replace real clinical trials, they could help run through preliminary scenarios before starting a full clinical trial, which would “save everybody some money, time and pain and risk,” said Macklin.
It’s also possible to use digital twins to design better screening strategies for early cancer detection and monitoring, said Ioannis Zervantonakis, PhD, a bioengineering professor at the University of Pittsburgh.
Zervantonakis is tapping digital twin technology for research that homes in on understanding tumors. In this case, the digital twin is a virtual representation of a real tumor, complete with its complex network of cells and the surrounding tissue.
Zervantonakis’ lab is using the technology to study cell-cell interactions in the tumor microenvironment, with a focus on human epidermal growth factor receptor 2–targeted therapy resistance in breast cancer. The digital twin they developed will simulate tumor growth, predict drug response, analyze cellular interactions, and optimize treatment strategies.
The Long Push Forward
One big hurdle to making digital twins more widely available is that regulation for the technology is still in progress.
“We’re developing the technology, and what’s also happening is the regulatory framework is being developed in parallel. So we’re almost developing things blindly on the basis that we think this is what the regulators would want,” explained Asghar.
“It’s really important that these technologies are regulated properly, just like drugs, and that’s what we’re pushing and advocating for,” said Asghar, noting that people need to know that like drugs, a digital twin has strengths and limitations.
And while a digital twin can be a cost-saving approach in the long run, it does require funding to get a program built, and finding funds can be difficult because not everyone knows about the technology. More funding means more trials.
With more data, Asghar is hopeful that within a few years, a digital twin model could be available for clinicians to use to help inform treatment decisions. This could lead to more effective treatments and, ultimately, better patient outcomes.
A version of this article appeared on Medscape.com.
Endometriosis Raises Rates of Postpartum Depression, Other Disorders
Women with endometriosis have a much higher risk of being diagnosed with several psychiatric disorders during the postpartum period according to an oral abstract presented at the American Society for Reproductive Medicine’s 2024 Scientific Congress and Expo in Denver, Colorado.
Researchers compared rates of postpartum depression, anxiety, mood disturbance (temporary low or anxious mood requiring no treatment), and obsessive-compulsive disorder (OCD) diagnoses among over 200 million adult women from 67 healthcare organizations who had a child between 2005 and 2023.
Within a year after giving birth, women with prepregnancy endometriosis were 25% more likely to be diagnosed with postpartum depression, 85% more likely to be diagnosed with postpartum mood disturbance, 44% more likely to be diagnosed with anxiety, and 1.26 times more likely to be diagnosed with OCD.
About 75% of women studied had no preexisting depression. This population had a 17% higher risk of receiving a postpartum depression diagnosis, a 95% higher risk of receiving an OCD diagnosis, a 72% higher risk of receiving a postpartum mood disturbance diagnosis, and a 38% risk of receiving an anxiety diagnosis.
Among women without preexisting depression, the risk increased by 64% for OCD, 42% for postpartum mood disturbance, and 25% for anxiety, while the risk for postpartum depression was negligible, indicating that women already experiencing depression likely have a higher baseline risk for worsening symptoms postpartum, said the study’s lead author Tina Yi-Jin Hsieh, MD, MPH, biomedical researcher at Harvard Medical School in Boston, Massachusetts.
“We think that because preexisting depression is the more dominant risk factor, it doesn’t really matter if you have another additional risk factor like endometriosis to really change the risk of postpartum depression,” said Hsieh.
Endometriosis is a debilitating condition in which tissue similar to uterine lining grows on the outside of the uterus, causing chronic pain and infertility. It affects between 6% and 10% of women worldwide and takes an average of between 4 and 11 years to be diagnosed. It has been linked to depression and anxiety disorders, yet the study authors say there’s little research examining its impact on women in the year after giving birth.
“Endometriosis is a complex condition that can affect both physical and mental health over much of a person’s life,” said Anna Modest, PhD, assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and a study author. “Perinatal and maternal mental health can have a huge impact on children and their family — we need to better understand who is at risk for challenges in the postpartum period.”
“Most chronic medical illnesses, particularly those causing pain, have been shown to increase the risk of mood disorders,” said Ripal Shah, MD, MPH, clinical associate professor of Psychiatry and Behavioral Sciences at Stanford Medicine in California. Shah specializes in reproductive psychiatry and was not associated with the study.
“What’s interesting about endometriosis though is that genome-wide association studies have shown that there may be a genetic predisposition for some women to develop both endometriosis and a mood disorder,” said Shah.
A 2023 study suggested that endometriosis, anxiety, and depression may be connected through a shared genetic basis.
But the experience patients with endometriosis go through also lends itself to the development of mood disorders, said Daniel Ginn, DO, assistant clinical professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles. Ginn specializes in the treatment of endometriosis and was not a part of the study.
Beyond postpartum depression, Ginn wasn’t surprised by the association of endometriosis with anxiety or OCD because what he hears from patients “on a daily basis is the telling of a history that has been hallmarked by not being listened to, not being believed, and not having symptoms managed well.”
As a result, he said many patients focus heavily on learning about their condition, coming into office visits with binders full of test results and information in an effort to understand and manage it themselves. This “does lead to a certain sense of a need to grasp for control because no one else is helping them [treat their condition effectively].”
He added: “I find it hard to believe that anxiety and OCD were preexisting of the conditions rather than the consequence of a long-term suboptimally managed disease.”
The authors reported no disclosures or sources of funding.
A version of this article first appeared on Medscape.com.
Women with endometriosis have a much higher risk of being diagnosed with several psychiatric disorders during the postpartum period according to an oral abstract presented at the American Society for Reproductive Medicine’s 2024 Scientific Congress and Expo in Denver, Colorado.
Researchers compared rates of postpartum depression, anxiety, mood disturbance (temporary low or anxious mood requiring no treatment), and obsessive-compulsive disorder (OCD) diagnoses among over 200 million adult women from 67 healthcare organizations who had a child between 2005 and 2023.
Within a year after giving birth, women with prepregnancy endometriosis were 25% more likely to be diagnosed with postpartum depression, 85% more likely to be diagnosed with postpartum mood disturbance, 44% more likely to be diagnosed with anxiety, and 1.26 times more likely to be diagnosed with OCD.
About 75% of women studied had no preexisting depression. This population had a 17% higher risk of receiving a postpartum depression diagnosis, a 95% higher risk of receiving an OCD diagnosis, a 72% higher risk of receiving a postpartum mood disturbance diagnosis, and a 38% risk of receiving an anxiety diagnosis.
Among women without preexisting depression, the risk increased by 64% for OCD, 42% for postpartum mood disturbance, and 25% for anxiety, while the risk for postpartum depression was negligible, indicating that women already experiencing depression likely have a higher baseline risk for worsening symptoms postpartum, said the study’s lead author Tina Yi-Jin Hsieh, MD, MPH, biomedical researcher at Harvard Medical School in Boston, Massachusetts.
“We think that because preexisting depression is the more dominant risk factor, it doesn’t really matter if you have another additional risk factor like endometriosis to really change the risk of postpartum depression,” said Hsieh.
Endometriosis is a debilitating condition in which tissue similar to uterine lining grows on the outside of the uterus, causing chronic pain and infertility. It affects between 6% and 10% of women worldwide and takes an average of between 4 and 11 years to be diagnosed. It has been linked to depression and anxiety disorders, yet the study authors say there’s little research examining its impact on women in the year after giving birth.
“Endometriosis is a complex condition that can affect both physical and mental health over much of a person’s life,” said Anna Modest, PhD, assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and a study author. “Perinatal and maternal mental health can have a huge impact on children and their family — we need to better understand who is at risk for challenges in the postpartum period.”
“Most chronic medical illnesses, particularly those causing pain, have been shown to increase the risk of mood disorders,” said Ripal Shah, MD, MPH, clinical associate professor of Psychiatry and Behavioral Sciences at Stanford Medicine in California. Shah specializes in reproductive psychiatry and was not associated with the study.
“What’s interesting about endometriosis though is that genome-wide association studies have shown that there may be a genetic predisposition for some women to develop both endometriosis and a mood disorder,” said Shah.
A 2023 study suggested that endometriosis, anxiety, and depression may be connected through a shared genetic basis.
But the experience patients with endometriosis go through also lends itself to the development of mood disorders, said Daniel Ginn, DO, assistant clinical professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles. Ginn specializes in the treatment of endometriosis and was not a part of the study.
Beyond postpartum depression, Ginn wasn’t surprised by the association of endometriosis with anxiety or OCD because what he hears from patients “on a daily basis is the telling of a history that has been hallmarked by not being listened to, not being believed, and not having symptoms managed well.”
As a result, he said many patients focus heavily on learning about their condition, coming into office visits with binders full of test results and information in an effort to understand and manage it themselves. This “does lead to a certain sense of a need to grasp for control because no one else is helping them [treat their condition effectively].”
He added: “I find it hard to believe that anxiety and OCD were preexisting of the conditions rather than the consequence of a long-term suboptimally managed disease.”
The authors reported no disclosures or sources of funding.
A version of this article first appeared on Medscape.com.
Women with endometriosis have a much higher risk of being diagnosed with several psychiatric disorders during the postpartum period according to an oral abstract presented at the American Society for Reproductive Medicine’s 2024 Scientific Congress and Expo in Denver, Colorado.
Researchers compared rates of postpartum depression, anxiety, mood disturbance (temporary low or anxious mood requiring no treatment), and obsessive-compulsive disorder (OCD) diagnoses among over 200 million adult women from 67 healthcare organizations who had a child between 2005 and 2023.
Within a year after giving birth, women with prepregnancy endometriosis were 25% more likely to be diagnosed with postpartum depression, 85% more likely to be diagnosed with postpartum mood disturbance, 44% more likely to be diagnosed with anxiety, and 1.26 times more likely to be diagnosed with OCD.
About 75% of women studied had no preexisting depression. This population had a 17% higher risk of receiving a postpartum depression diagnosis, a 95% higher risk of receiving an OCD diagnosis, a 72% higher risk of receiving a postpartum mood disturbance diagnosis, and a 38% risk of receiving an anxiety diagnosis.
Among women without preexisting depression, the risk increased by 64% for OCD, 42% for postpartum mood disturbance, and 25% for anxiety, while the risk for postpartum depression was negligible, indicating that women already experiencing depression likely have a higher baseline risk for worsening symptoms postpartum, said the study’s lead author Tina Yi-Jin Hsieh, MD, MPH, biomedical researcher at Harvard Medical School in Boston, Massachusetts.
“We think that because preexisting depression is the more dominant risk factor, it doesn’t really matter if you have another additional risk factor like endometriosis to really change the risk of postpartum depression,” said Hsieh.
Endometriosis is a debilitating condition in which tissue similar to uterine lining grows on the outside of the uterus, causing chronic pain and infertility. It affects between 6% and 10% of women worldwide and takes an average of between 4 and 11 years to be diagnosed. It has been linked to depression and anxiety disorders, yet the study authors say there’s little research examining its impact on women in the year after giving birth.
“Endometriosis is a complex condition that can affect both physical and mental health over much of a person’s life,” said Anna Modest, PhD, assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and a study author. “Perinatal and maternal mental health can have a huge impact on children and their family — we need to better understand who is at risk for challenges in the postpartum period.”
“Most chronic medical illnesses, particularly those causing pain, have been shown to increase the risk of mood disorders,” said Ripal Shah, MD, MPH, clinical associate professor of Psychiatry and Behavioral Sciences at Stanford Medicine in California. Shah specializes in reproductive psychiatry and was not associated with the study.
“What’s interesting about endometriosis though is that genome-wide association studies have shown that there may be a genetic predisposition for some women to develop both endometriosis and a mood disorder,” said Shah.
A 2023 study suggested that endometriosis, anxiety, and depression may be connected through a shared genetic basis.
But the experience patients with endometriosis go through also lends itself to the development of mood disorders, said Daniel Ginn, DO, assistant clinical professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles. Ginn specializes in the treatment of endometriosis and was not a part of the study.
Beyond postpartum depression, Ginn wasn’t surprised by the association of endometriosis with anxiety or OCD because what he hears from patients “on a daily basis is the telling of a history that has been hallmarked by not being listened to, not being believed, and not having symptoms managed well.”
As a result, he said many patients focus heavily on learning about their condition, coming into office visits with binders full of test results and information in an effort to understand and manage it themselves. This “does lead to a certain sense of a need to grasp for control because no one else is helping them [treat their condition effectively].”
He added: “I find it hard to believe that anxiety and OCD were preexisting of the conditions rather than the consequence of a long-term suboptimally managed disease.”
The authors reported no disclosures or sources of funding.
A version of this article first appeared on Medscape.com.
FROM ASRM 2024
Fibroids: Medical Therapy Not Hysterectomy Should Be First Treatment Choice Interventional Options Case Study
Although hysterectomy remains the most common procedure for treating fibroids and fibroids are the leading indication for hysterectomy, its long-term sequelae make less invasive alternatives the better choice for managing most of these myometrial masses, an invited clinical practice paper in the New England Journal of Medicine (NEJM) asserts.
The practice summary also calls for earlier identification and treatment of fibroid disease and may raise awareness among general gynecologists and primary care physicians less familiar with newer treatments.
Based on a review of evidence and existing formal guidelines, the paper urges wider use of uterus-sparing approaches such as hormone therapy, uterine-artery embolization, focused ultrasound ablation, and radiofrequency ablation. Authored by ob.gyns. Elizabeth A. Stewart, MD, and Shannon K. Laughlin-Tommaso, MD, MPH, of the Mayo Clinic in Rochester, Minnesota, the document also features textbook-style diagrams illustrating procedures.
“To clarify, this is not a new guidance but an invited clinical practice paper,” Laughlin-Tommaso told this news organization. “I believe NEJM recognized the gap in knowledge among all providers, for early diagnosis of uterine fibroids, especially in young patients and those presenting with anemia.”
The less invasive treatments highlighted in the paper can help women recover faster and resume their normal activities more quickly, said Laughlin-Tommaso. “Additionally, many studies have now shown that there are health benefits to keeping the uterus and the ovaries.”
Despite multiple uterine-sparing options, however, a recent study in a commercially insured population found nearly 60% of fibroid patients undergoing hysterectomy had never received a prior conservative treatment.
Why hysterectomy for a benign condition? Hysterectomy, which is universally available in ob.gyn. practices, makes decision-making easier for medical providers and patients, Laughlin-Tommaso explained. “It’s the only treatment that is definitive in that patients will not have bleeding or fibroids in the future and providers don’t have to determine which fibroids to treat or remove.”
More common in Black women, fibroids affect up to 80% of persons with a uterus during their lifetime and up to 50% have symptoms such as heavy and prolonged menstrual bleeding, anemia-associated fatigue, pelvic pressure, and menstrual and nonmenstrual pain, the authors noted. These lesions can also compress nearby structures causing painful intercourse, constipation, and urinary frequency, urgency, or retention.
In 2021 the American College of Obstetricians and Gynecologists issued a practice bulletin on the management of symptomatic uterine leiomyomas, similarly endorsing individualized care that accounts for the desire to preserve fertility or the uterus, increase quality of life, and reduce symptoms. It, too, recommended medical management as first-line treatment for symptomatic fibroids.
“This paper will be helpful for clinicians by covering some of the newer options such as gonadotropin-releasing hormone antagonists introduced in the past 5 years and tailoring treatment to patients depending on whether they still want to conceive,” Sandra M. Hurtado, MD, an ob.gyn. and an assistant professor at UTHealth Houston Medical Center and McGovern Medical School in Houston, Texas, said in an interview. “And the illustrations will be useful to doctors who are not gynecologists and will help to explain the interventional options to patients,” added Hurtado, who was not involved in the paper.
Offering another outside perspective on the paper, Charles J. Ascher-Walsh, MD, senior system vice chair for gynecology and division director of urogynecology in the Raquel and Jaime Gilinski Department of Obstetrics, Gynecology and Reproductive Science at Mount Sinai in New York City, called it a useful though not new summary. Reaching the wider audience of NEJM may raise awareness of newer fibroid therapies among general, nonspecialist ob.gyns., whose practices may concentrate largely on obstetrics, he added, “and the excellent illustrations clarify the treatment options.” In his view, broader awareness may increase much-needed funding for this neglected area of research.
Among the paper’s recommendations:
Diagnosis
Pelvic ultrasonography is the most cost-effective imaging method, providing information on size, location, and number of fibroids and ruling out adnexal masses. It is limited, however, by less-accurate resolution if the uterine volume is greater than 375 mL or if fibroids number more than four.
Medical Alternatives to Hysterectomy
Early diagnosis and first-line medical therapies are recommended.
Contraceptive hormones to control heavy menstrual bleeding are the first step in most algorithms for treating fibroid-related bleeding, despite low-quality evidence.
Nonsteroidal anti-inflammatory agents and tranexamic acid during menstruation also limit heavy menses but have more evidence of efficacy for idiopathic heavy menses.
Gonadotropin-releasing hormone (GnRH) agonists in depot form are approved for short-term preoperative therapy. While they cause amenorrhea in nearly 90% of patients and reduce uterine volume by 30%-60%, they have a high incidence of hypogonadal symptoms, including bone loss and hot flushes. They also cause a “steroidal flare” when the stored gonadotropins are released and cause subsequent heavy menstrual bleeding with the rapid decrease in estrogen levels.
Oral GnRH antagonist combinations are a major therapeutic advance, pairing a GnRH antagonist (such as elagolix or relugolix, which rapidly inhibit ovarian steroidogenesis) with estradiol and progestin at doses equivalent to systemic levels in the early follicular phase of the menstrual cycle.
In clinical trials these combinations decreased heavy menstrual bleeding by 50%-75%, pain by 40%-50%, and bulk-related symptoms through a 10% decrease in uterine volume. Side effects are few, with hot flushes, headaches, and nausea occurring in fewer than 20% of participants.
Smaller fibroids in the submucosal to intramural spaces can be treated transcervically, while larger lesions of any type or smaller subserosa fibroids are treated abdominally.
Uterine-artery embolization uses minimally invasive radiologically guided catheterization to release embolic particles directly into both uterine arteries. This process causes ischemic infarction of the fibroids and decreases bleeding, pain, and bulk-related symptoms.
Other procedures shrink individual fibroids with energy that creates coagulative necrosis. These include focused ultrasound ablation (with MRI or ultrasound guidance) and radiofrequency ablation (with laparoscopic or transcervical ultrasound guidance).
Unlike uterine-artery embolization, which treats all fibroids concurrently, these therapies require individual targeting of fibroids.
Radiofrequency ablation can be done concurrently with other surgical therapies, such as laparoscopic excision of endometriosis or hysteroscopic myomectomy.
Myomectomy, or the surgical removal of fibroids, is most often used in persons actively seeking pregnancy or having very large fibroids in whom shrinkage would be inadequate. Most guidelines recommend surgical excision rather than shrinking procedures to optimize fertility. However, myomectomy often commits patients to future cesarean section, which increases pregnancy-related morbidity.
Although myomectomy is seen as superior to uterine-artery embolization for improving quality of life, both approaches provide substantial symptom relief.
Recurrence
Incidence of recurring fibroids is high, with, for example, new fibroids developing in approximately 50% of persons within 5 years of myomectomy.
Earlier this year, a large cohort study reported that myomectomy was best for avoiding reintervention after surgical leiomyoma management.
Reintervention rates vary according to procedure, patient age, disease extent, and symptoms and can be as high as 33% up to 5 years after treatment, with lower percentages seen among persons older than 45 years of age.
Hysterectomy
Minimally invasive hysterectomy is recommended. Drawbacks to hysterectomy include perioperative risk and concomitant oophorectomy, which was common until the early 2000s when large cohort studies showed elevated risks of death, cardiovascular disease, dementia, and other illnesses compared with hysterectomy plus ovarian conservation. Oophorectomy but not hysterectomy rates have since decreased.
Still needing study, according to Laughlin-Tommaso are the underlying reasons for health disparities in fibroids, especially among Black and Latina individuals. “Some studies have found associations with vitamin D deficiency and with stress and racism,” she said.
Looking ahead, the authors stressed the need for a fibroid risk-prediction model, a staging system, and large randomized trials of treatment effectiveness. Also needed are methods for primary and secondary prevention. “Earlier screening and medical treatment in primary care settings could potentially minimize morbidity and the incidence of unnecessary hysterectomies, and primary care–based screening trials are warranted,” they wrote.
In addition to procedural illustrations the practice document includes a vignette of a 33-year-old never-pregnant Black woman (but desiring motherhood) with heavy menstrual bleeding, abdominal bloating, and non–iron deficiency anemia. Evaluation for thalassemia and sickle cell anemia is negative, but ultrasonography reveals an enlarged uterus with multiple fibroids and normal ovaries.
In line with the clinical review, the authors prescribe oral GnRH agonist combination therapy, plus iron and multivitamin supplementation, and recommend annual reassessment — earlier if pregnancy is desired or if symptoms escalate. Since the patient prioritizes fertility, hysterectomy would be appropriate only if she had biopsy-proven cancer.
The authors received no external funding for this practice paper, but both have funding from the National Institutes of Health for fibroid research. Laughlin-Tommaso reported royalties from UpToDate. Stewart reported research support from the Agency for Healthcare Research and Quality, and speaking, data-monitoring, and consulting fees for various private companies, including AbbVie, Anylam Pharmaceuticals, ASKA Pharma, and Myovant Sciences. She holds a patent on treatment for abnormal uterine bleeding and has been involved in CME for various medical educational agencies. Hurtado and Ascher-Walsh had no relevant conflicts of interest to declare.
A version of this article first appeared on Medscape.com.
Although hysterectomy remains the most common procedure for treating fibroids and fibroids are the leading indication for hysterectomy, its long-term sequelae make less invasive alternatives the better choice for managing most of these myometrial masses, an invited clinical practice paper in the New England Journal of Medicine (NEJM) asserts.
The practice summary also calls for earlier identification and treatment of fibroid disease and may raise awareness among general gynecologists and primary care physicians less familiar with newer treatments.
Based on a review of evidence and existing formal guidelines, the paper urges wider use of uterus-sparing approaches such as hormone therapy, uterine-artery embolization, focused ultrasound ablation, and radiofrequency ablation. Authored by ob.gyns. Elizabeth A. Stewart, MD, and Shannon K. Laughlin-Tommaso, MD, MPH, of the Mayo Clinic in Rochester, Minnesota, the document also features textbook-style diagrams illustrating procedures.
“To clarify, this is not a new guidance but an invited clinical practice paper,” Laughlin-Tommaso told this news organization. “I believe NEJM recognized the gap in knowledge among all providers, for early diagnosis of uterine fibroids, especially in young patients and those presenting with anemia.”
The less invasive treatments highlighted in the paper can help women recover faster and resume their normal activities more quickly, said Laughlin-Tommaso. “Additionally, many studies have now shown that there are health benefits to keeping the uterus and the ovaries.”
Despite multiple uterine-sparing options, however, a recent study in a commercially insured population found nearly 60% of fibroid patients undergoing hysterectomy had never received a prior conservative treatment.
Why hysterectomy for a benign condition? Hysterectomy, which is universally available in ob.gyn. practices, makes decision-making easier for medical providers and patients, Laughlin-Tommaso explained. “It’s the only treatment that is definitive in that patients will not have bleeding or fibroids in the future and providers don’t have to determine which fibroids to treat or remove.”
More common in Black women, fibroids affect up to 80% of persons with a uterus during their lifetime and up to 50% have symptoms such as heavy and prolonged menstrual bleeding, anemia-associated fatigue, pelvic pressure, and menstrual and nonmenstrual pain, the authors noted. These lesions can also compress nearby structures causing painful intercourse, constipation, and urinary frequency, urgency, or retention.
In 2021 the American College of Obstetricians and Gynecologists issued a practice bulletin on the management of symptomatic uterine leiomyomas, similarly endorsing individualized care that accounts for the desire to preserve fertility or the uterus, increase quality of life, and reduce symptoms. It, too, recommended medical management as first-line treatment for symptomatic fibroids.
“This paper will be helpful for clinicians by covering some of the newer options such as gonadotropin-releasing hormone antagonists introduced in the past 5 years and tailoring treatment to patients depending on whether they still want to conceive,” Sandra M. Hurtado, MD, an ob.gyn. and an assistant professor at UTHealth Houston Medical Center and McGovern Medical School in Houston, Texas, said in an interview. “And the illustrations will be useful to doctors who are not gynecologists and will help to explain the interventional options to patients,” added Hurtado, who was not involved in the paper.
Offering another outside perspective on the paper, Charles J. Ascher-Walsh, MD, senior system vice chair for gynecology and division director of urogynecology in the Raquel and Jaime Gilinski Department of Obstetrics, Gynecology and Reproductive Science at Mount Sinai in New York City, called it a useful though not new summary. Reaching the wider audience of NEJM may raise awareness of newer fibroid therapies among general, nonspecialist ob.gyns., whose practices may concentrate largely on obstetrics, he added, “and the excellent illustrations clarify the treatment options.” In his view, broader awareness may increase much-needed funding for this neglected area of research.
Among the paper’s recommendations:
Diagnosis
Pelvic ultrasonography is the most cost-effective imaging method, providing information on size, location, and number of fibroids and ruling out adnexal masses. It is limited, however, by less-accurate resolution if the uterine volume is greater than 375 mL or if fibroids number more than four.
Medical Alternatives to Hysterectomy
Early diagnosis and first-line medical therapies are recommended.
Contraceptive hormones to control heavy menstrual bleeding are the first step in most algorithms for treating fibroid-related bleeding, despite low-quality evidence.
Nonsteroidal anti-inflammatory agents and tranexamic acid during menstruation also limit heavy menses but have more evidence of efficacy for idiopathic heavy menses.
Gonadotropin-releasing hormone (GnRH) agonists in depot form are approved for short-term preoperative therapy. While they cause amenorrhea in nearly 90% of patients and reduce uterine volume by 30%-60%, they have a high incidence of hypogonadal symptoms, including bone loss and hot flushes. They also cause a “steroidal flare” when the stored gonadotropins are released and cause subsequent heavy menstrual bleeding with the rapid decrease in estrogen levels.
Oral GnRH antagonist combinations are a major therapeutic advance, pairing a GnRH antagonist (such as elagolix or relugolix, which rapidly inhibit ovarian steroidogenesis) with estradiol and progestin at doses equivalent to systemic levels in the early follicular phase of the menstrual cycle.
In clinical trials these combinations decreased heavy menstrual bleeding by 50%-75%, pain by 40%-50%, and bulk-related symptoms through a 10% decrease in uterine volume. Side effects are few, with hot flushes, headaches, and nausea occurring in fewer than 20% of participants.
Smaller fibroids in the submucosal to intramural spaces can be treated transcervically, while larger lesions of any type or smaller subserosa fibroids are treated abdominally.
Uterine-artery embolization uses minimally invasive radiologically guided catheterization to release embolic particles directly into both uterine arteries. This process causes ischemic infarction of the fibroids and decreases bleeding, pain, and bulk-related symptoms.
Other procedures shrink individual fibroids with energy that creates coagulative necrosis. These include focused ultrasound ablation (with MRI or ultrasound guidance) and radiofrequency ablation (with laparoscopic or transcervical ultrasound guidance).
Unlike uterine-artery embolization, which treats all fibroids concurrently, these therapies require individual targeting of fibroids.
Radiofrequency ablation can be done concurrently with other surgical therapies, such as laparoscopic excision of endometriosis or hysteroscopic myomectomy.
Myomectomy, or the surgical removal of fibroids, is most often used in persons actively seeking pregnancy or having very large fibroids in whom shrinkage would be inadequate. Most guidelines recommend surgical excision rather than shrinking procedures to optimize fertility. However, myomectomy often commits patients to future cesarean section, which increases pregnancy-related morbidity.
Although myomectomy is seen as superior to uterine-artery embolization for improving quality of life, both approaches provide substantial symptom relief.
Recurrence
Incidence of recurring fibroids is high, with, for example, new fibroids developing in approximately 50% of persons within 5 years of myomectomy.
Earlier this year, a large cohort study reported that myomectomy was best for avoiding reintervention after surgical leiomyoma management.
Reintervention rates vary according to procedure, patient age, disease extent, and symptoms and can be as high as 33% up to 5 years after treatment, with lower percentages seen among persons older than 45 years of age.
Hysterectomy
Minimally invasive hysterectomy is recommended. Drawbacks to hysterectomy include perioperative risk and concomitant oophorectomy, which was common until the early 2000s when large cohort studies showed elevated risks of death, cardiovascular disease, dementia, and other illnesses compared with hysterectomy plus ovarian conservation. Oophorectomy but not hysterectomy rates have since decreased.
Still needing study, according to Laughlin-Tommaso are the underlying reasons for health disparities in fibroids, especially among Black and Latina individuals. “Some studies have found associations with vitamin D deficiency and with stress and racism,” she said.
Looking ahead, the authors stressed the need for a fibroid risk-prediction model, a staging system, and large randomized trials of treatment effectiveness. Also needed are methods for primary and secondary prevention. “Earlier screening and medical treatment in primary care settings could potentially minimize morbidity and the incidence of unnecessary hysterectomies, and primary care–based screening trials are warranted,” they wrote.
In addition to procedural illustrations the practice document includes a vignette of a 33-year-old never-pregnant Black woman (but desiring motherhood) with heavy menstrual bleeding, abdominal bloating, and non–iron deficiency anemia. Evaluation for thalassemia and sickle cell anemia is negative, but ultrasonography reveals an enlarged uterus with multiple fibroids and normal ovaries.
In line with the clinical review, the authors prescribe oral GnRH agonist combination therapy, plus iron and multivitamin supplementation, and recommend annual reassessment — earlier if pregnancy is desired or if symptoms escalate. Since the patient prioritizes fertility, hysterectomy would be appropriate only if she had biopsy-proven cancer.
The authors received no external funding for this practice paper, but both have funding from the National Institutes of Health for fibroid research. Laughlin-Tommaso reported royalties from UpToDate. Stewart reported research support from the Agency for Healthcare Research and Quality, and speaking, data-monitoring, and consulting fees for various private companies, including AbbVie, Anylam Pharmaceuticals, ASKA Pharma, and Myovant Sciences. She holds a patent on treatment for abnormal uterine bleeding and has been involved in CME for various medical educational agencies. Hurtado and Ascher-Walsh had no relevant conflicts of interest to declare.
A version of this article first appeared on Medscape.com.
Although hysterectomy remains the most common procedure for treating fibroids and fibroids are the leading indication for hysterectomy, its long-term sequelae make less invasive alternatives the better choice for managing most of these myometrial masses, an invited clinical practice paper in the New England Journal of Medicine (NEJM) asserts.
The practice summary also calls for earlier identification and treatment of fibroid disease and may raise awareness among general gynecologists and primary care physicians less familiar with newer treatments.
Based on a review of evidence and existing formal guidelines, the paper urges wider use of uterus-sparing approaches such as hormone therapy, uterine-artery embolization, focused ultrasound ablation, and radiofrequency ablation. Authored by ob.gyns. Elizabeth A. Stewart, MD, and Shannon K. Laughlin-Tommaso, MD, MPH, of the Mayo Clinic in Rochester, Minnesota, the document also features textbook-style diagrams illustrating procedures.
“To clarify, this is not a new guidance but an invited clinical practice paper,” Laughlin-Tommaso told this news organization. “I believe NEJM recognized the gap in knowledge among all providers, for early diagnosis of uterine fibroids, especially in young patients and those presenting with anemia.”
The less invasive treatments highlighted in the paper can help women recover faster and resume their normal activities more quickly, said Laughlin-Tommaso. “Additionally, many studies have now shown that there are health benefits to keeping the uterus and the ovaries.”
Despite multiple uterine-sparing options, however, a recent study in a commercially insured population found nearly 60% of fibroid patients undergoing hysterectomy had never received a prior conservative treatment.
Why hysterectomy for a benign condition? Hysterectomy, which is universally available in ob.gyn. practices, makes decision-making easier for medical providers and patients, Laughlin-Tommaso explained. “It’s the only treatment that is definitive in that patients will not have bleeding or fibroids in the future and providers don’t have to determine which fibroids to treat or remove.”
More common in Black women, fibroids affect up to 80% of persons with a uterus during their lifetime and up to 50% have symptoms such as heavy and prolonged menstrual bleeding, anemia-associated fatigue, pelvic pressure, and menstrual and nonmenstrual pain, the authors noted. These lesions can also compress nearby structures causing painful intercourse, constipation, and urinary frequency, urgency, or retention.
In 2021 the American College of Obstetricians and Gynecologists issued a practice bulletin on the management of symptomatic uterine leiomyomas, similarly endorsing individualized care that accounts for the desire to preserve fertility or the uterus, increase quality of life, and reduce symptoms. It, too, recommended medical management as first-line treatment for symptomatic fibroids.
“This paper will be helpful for clinicians by covering some of the newer options such as gonadotropin-releasing hormone antagonists introduced in the past 5 years and tailoring treatment to patients depending on whether they still want to conceive,” Sandra M. Hurtado, MD, an ob.gyn. and an assistant professor at UTHealth Houston Medical Center and McGovern Medical School in Houston, Texas, said in an interview. “And the illustrations will be useful to doctors who are not gynecologists and will help to explain the interventional options to patients,” added Hurtado, who was not involved in the paper.
Offering another outside perspective on the paper, Charles J. Ascher-Walsh, MD, senior system vice chair for gynecology and division director of urogynecology in the Raquel and Jaime Gilinski Department of Obstetrics, Gynecology and Reproductive Science at Mount Sinai in New York City, called it a useful though not new summary. Reaching the wider audience of NEJM may raise awareness of newer fibroid therapies among general, nonspecialist ob.gyns., whose practices may concentrate largely on obstetrics, he added, “and the excellent illustrations clarify the treatment options.” In his view, broader awareness may increase much-needed funding for this neglected area of research.
Among the paper’s recommendations:
Diagnosis
Pelvic ultrasonography is the most cost-effective imaging method, providing information on size, location, and number of fibroids and ruling out adnexal masses. It is limited, however, by less-accurate resolution if the uterine volume is greater than 375 mL or if fibroids number more than four.
Medical Alternatives to Hysterectomy
Early diagnosis and first-line medical therapies are recommended.
Contraceptive hormones to control heavy menstrual bleeding are the first step in most algorithms for treating fibroid-related bleeding, despite low-quality evidence.
Nonsteroidal anti-inflammatory agents and tranexamic acid during menstruation also limit heavy menses but have more evidence of efficacy for idiopathic heavy menses.
Gonadotropin-releasing hormone (GnRH) agonists in depot form are approved for short-term preoperative therapy. While they cause amenorrhea in nearly 90% of patients and reduce uterine volume by 30%-60%, they have a high incidence of hypogonadal symptoms, including bone loss and hot flushes. They also cause a “steroidal flare” when the stored gonadotropins are released and cause subsequent heavy menstrual bleeding with the rapid decrease in estrogen levels.
Oral GnRH antagonist combinations are a major therapeutic advance, pairing a GnRH antagonist (such as elagolix or relugolix, which rapidly inhibit ovarian steroidogenesis) with estradiol and progestin at doses equivalent to systemic levels in the early follicular phase of the menstrual cycle.
In clinical trials these combinations decreased heavy menstrual bleeding by 50%-75%, pain by 40%-50%, and bulk-related symptoms through a 10% decrease in uterine volume. Side effects are few, with hot flushes, headaches, and nausea occurring in fewer than 20% of participants.
Smaller fibroids in the submucosal to intramural spaces can be treated transcervically, while larger lesions of any type or smaller subserosa fibroids are treated abdominally.
Uterine-artery embolization uses minimally invasive radiologically guided catheterization to release embolic particles directly into both uterine arteries. This process causes ischemic infarction of the fibroids and decreases bleeding, pain, and bulk-related symptoms.
Other procedures shrink individual fibroids with energy that creates coagulative necrosis. These include focused ultrasound ablation (with MRI or ultrasound guidance) and radiofrequency ablation (with laparoscopic or transcervical ultrasound guidance).
Unlike uterine-artery embolization, which treats all fibroids concurrently, these therapies require individual targeting of fibroids.
Radiofrequency ablation can be done concurrently with other surgical therapies, such as laparoscopic excision of endometriosis or hysteroscopic myomectomy.
Myomectomy, or the surgical removal of fibroids, is most often used in persons actively seeking pregnancy or having very large fibroids in whom shrinkage would be inadequate. Most guidelines recommend surgical excision rather than shrinking procedures to optimize fertility. However, myomectomy often commits patients to future cesarean section, which increases pregnancy-related morbidity.
Although myomectomy is seen as superior to uterine-artery embolization for improving quality of life, both approaches provide substantial symptom relief.
Recurrence
Incidence of recurring fibroids is high, with, for example, new fibroids developing in approximately 50% of persons within 5 years of myomectomy.
Earlier this year, a large cohort study reported that myomectomy was best for avoiding reintervention after surgical leiomyoma management.
Reintervention rates vary according to procedure, patient age, disease extent, and symptoms and can be as high as 33% up to 5 years after treatment, with lower percentages seen among persons older than 45 years of age.
Hysterectomy
Minimally invasive hysterectomy is recommended. Drawbacks to hysterectomy include perioperative risk and concomitant oophorectomy, which was common until the early 2000s when large cohort studies showed elevated risks of death, cardiovascular disease, dementia, and other illnesses compared with hysterectomy plus ovarian conservation. Oophorectomy but not hysterectomy rates have since decreased.
Still needing study, according to Laughlin-Tommaso are the underlying reasons for health disparities in fibroids, especially among Black and Latina individuals. “Some studies have found associations with vitamin D deficiency and with stress and racism,” she said.
Looking ahead, the authors stressed the need for a fibroid risk-prediction model, a staging system, and large randomized trials of treatment effectiveness. Also needed are methods for primary and secondary prevention. “Earlier screening and medical treatment in primary care settings could potentially minimize morbidity and the incidence of unnecessary hysterectomies, and primary care–based screening trials are warranted,” they wrote.
In addition to procedural illustrations the practice document includes a vignette of a 33-year-old never-pregnant Black woman (but desiring motherhood) with heavy menstrual bleeding, abdominal bloating, and non–iron deficiency anemia. Evaluation for thalassemia and sickle cell anemia is negative, but ultrasonography reveals an enlarged uterus with multiple fibroids and normal ovaries.
In line with the clinical review, the authors prescribe oral GnRH agonist combination therapy, plus iron and multivitamin supplementation, and recommend annual reassessment — earlier if pregnancy is desired or if symptoms escalate. Since the patient prioritizes fertility, hysterectomy would be appropriate only if she had biopsy-proven cancer.
The authors received no external funding for this practice paper, but both have funding from the National Institutes of Health for fibroid research. Laughlin-Tommaso reported royalties from UpToDate. Stewart reported research support from the Agency for Healthcare Research and Quality, and speaking, data-monitoring, and consulting fees for various private companies, including AbbVie, Anylam Pharmaceuticals, ASKA Pharma, and Myovant Sciences. She holds a patent on treatment for abnormal uterine bleeding and has been involved in CME for various medical educational agencies. Hurtado and Ascher-Walsh had no relevant conflicts of interest to declare.
A version of this article first appeared on Medscape.com.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Update Coming for Thyroid Disease in Pregnancy Guidelines
CHICAGO — A preview of much-anticipated updates to guidelines on managing thyroid disease in pregnancy shows key changes to recommendations in the evolving field, ranging from consideration of the chance of spontaneous normalization of thyroid levels during pregnancy to a heightened emphasis on shared decision-making and the nuances can factor into personalized treatment.
The guidelines, expected to be published in early 2025, have not been updated since 2017, and with substantial advances and evidence from countless studies since then, the new guidelines were developed with a goal to start afresh, said ATA Thyroid and Pregnancy Guidelines Task Force cochair Tim IM Korevaar, MD, PhD, in presenting the final draft guidelines at the American Thyroid Association (ATA) 2024 Meeting.
“Obviously, we’re not going to ignore the 2017 guidelines, which have been a very good resource for us so far, but we really wanted to start from scratch and follow a ‘blank canvas’ approach in optimizing the evidence,” said Korevaar, an endocrinologist and obstetric internist with the Division of Pharmacology and Vascular Medicine & Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
The guidelines, developed through a collaborative effort involving a wide variety of related medical societies, involved 14 systematic literature reviews. While the pregnancy issues covered by the guidelines is extensive, key highlights include:
Management in Preconception
Beginning with preconception, a key change in the guidelines will be that patients with euthyroid thyroid peroxidase (TPO) antibodies, which can be indicative of thyroid dysfunction, routine treatment with levothyroxine is not recommended, based on new evidence from randomized trials of high-risk patients showing no clear benefit from the treatment.
“In these trials, and across analyses, there was absolutely no beneficial effect of levothyroxine in these patients [with euthyroid TPO antibody positivity],” he said.
With evidence showing, however, that TPO antibody positivity can lead to subclinical or overt hypothyroidism within 1 or 2 years, the guidelines will recommend that TPO antibody–positive patients do have thyroid stimulating hormone (TSH) levels tested every 3-6 months until pregnancy, and existing recommendations to test during pregnancy among those patients remain in place, Korevaar reported.
In terms of preconception subclinical hypothyroidism, the guidelines will emphasize the existing recommendation “to always strive to reassess” thyroid levels, and if subclinical hypothyroidism does persist, to treat with low-dose levothyroxine.
During Pregnancy
During pregnancy, the new proposed recommendations will reflect the important change that three key risk factors, including age over 30 years, having at least two prior pregnancies, and morbid obesity (body mass index [BMI] at least 40 kg/m2), previously considered a risk for thyroid dysfunction in pregnancy, should not, on their own, suggest the need for thyroid testing, based on low evidence of an increased risk in pregnancy.
Research on the issue includes a recent study from Korevaar’s team showing these factors to in fact have low predictability of thyroid dysfunction.
“We deemed that these risk differences weren’t really clinically meaningful (in predicting risk), and so we have removed to maternal age, BMI, and parity as risk factors for thyroid testing indications in pregnancy,” Korevaar said.
Factors considered a risk, resulting in recommended testing at presentation include a history of subclinical or clinical hypo- or hyperthyroidism, postpartum thyroiditis, known thyroid antibody positivity, symptoms of thyroid dysfunction or goiter, and other factors.
Treatment for Subclinical Hypothyroidism in Pregnancy
Whereas current guidelines recommend TPO antibody status in determining when to consider treatment for subclinical hypothyroidism, the new proposed guideline will instead recommend treatment based on the timing of the diagnosis of the subclinical hypothyroidism, with consideration of treatment during the first trimester, but not in the second or third trimester, based on newer evidence of the absolute risk for pregnancy complications and randomized trial data.
“The recommendations are now to no longer based on TPO antibody status, but instead according to the timing of the diagnosis of subclinical hypothyroidism,” Korevaar said.
Based on the collective data, “due to the low risk, we do not recommend for routine levothyroxine treatment in the second or third trimester groups with TSH levels under 10 mU/L now.”
“However, for subclinical hypothyroidism diagnosed in the first trimester, the recommendation would be that you can consider levothyroxine treatment,” he said.
While a clear indication for treatment in any trimester is the presence of overt hypothyroidism, or TSH levels over 10 mU/L, Korevaar underscored the importance of considering nuances of the recommendations that may warrant flexibility, for instance among patients with borderline TSH levels.
Spontaneous Normalization of Thyroid Levels in Pregnancy
Another new recommendation addresses the issue of spontaneous normalization of abnormal thyroid function during pregnancy, with several large studies showing a large proportion of subclinical hypothyroidism cases spontaneously revert to euthyroidism by the third trimester — despite no treatment having been provided.
Under the important proposed recommendation, retesting of subclinical hypothyroidism is suggested within 3 weeks.
“The data shows that a large proportion of patients spontaneously revert to euthyroidism,” Korevaar said.
“Upon identifying subclinical hypothyroidism in the first trimester, there will be essentially two options that clinicians can discuss with their patient — one would be to consider confirmatory tests in 3 weeks or to discuss the starting the lower dose levothyroxine in the first trimester,” he said.
In terms of overt hypothyroidism, likewise, if patients have a TSH levels below 6 mU/L in pregnancy, “you can either consider doing confirmatory testing within 3 weeks, or discussing with the patient starting levothyroxine treatment,” Korevaar added.
Overt Hyperthyroidism
For overt hyperthyroidism, no significant changes from current guidelines are being proposed, with the key exception of a heightened emphasis on the need for shared decision-making with patients, Korevaar said.
“We want to emphasize shared decision-making especially for women who have Graves’ disease prior to pregnancy, because the antithyroid treatment modalities, primarily methimazole (MMI) and propylthiouracil (PTU), have different advantages and disadvantages for an upcoming pregnancy,” he said.
“If you help a patient become involved in the decision-making process, that can also be very helpful in managing the disease and following-up on the pregnancy.”
Under the recommendations, PTU remains the preferred drug in overt hyperthyroidism, due to a more favorable profile in terms of potential birth defects vs MMI, with research showing a higher absolute risk of 3% vs 5%.
The guidelines further suggest the option of stopping the antithyroid medications upon a positive pregnancy test, with the exception of high-risk patients.
Korevaar noted that, if the treatment is stopped early in pregnancy, relapse is not likely to occur until after approximately 3 months, or 12 weeks, at which time, the high-risk teratogenic period, which is between week 5 and week 15, will have passed.
Current guidelines regarding whether to stop treatment in higher-risk hyperthyroid patients are recommended to remain unchanged.
Thyroid Nodules and Cancer
Recommendations regarding thyroid nodules and cancer during pregnancy are also expected to remain largely similar to those in the 2017 guidelines, with the exception of an emphasis on simply considering how the patient would normally be managed outside of pregnancy.
For instance, regarding the question of whether treatment can be withheld for 9 months during pregnancy. “A lot of times, the answer is yes,” Korevaar said.
Other topics that will be largely unchanged include issues of universal screening, definitions of normal and abnormal TSH and free T4 reference ranges and isolated hypothyroxinemia.
Steps Forward in Improving Updates, Readability
In addition to recommendation updates, the new guidelines are being revised to better reflect more recent evidence-based developments and user-friendliness.
“We have now made the step to a more systematic and replicable methodology to ensure for easier updates with a shorter interval,” Korevaar told this news organization.
“Furthermore, since 2006, the ATA guideline documents have followed a question-and-answer format, lacked recommendation tables and had none or only a few graphic illustrations,” he added.
“We are now further developing the typical outline of the guidelines to improve the readability and dissemination of the guideline document.”
Korevaar’s disclosures include lectureship fees from IBSA, Merck, and Berlin Chemie.
A version of this article first appeared on Medscape.com.
CHICAGO — A preview of much-anticipated updates to guidelines on managing thyroid disease in pregnancy shows key changes to recommendations in the evolving field, ranging from consideration of the chance of spontaneous normalization of thyroid levels during pregnancy to a heightened emphasis on shared decision-making and the nuances can factor into personalized treatment.
The guidelines, expected to be published in early 2025, have not been updated since 2017, and with substantial advances and evidence from countless studies since then, the new guidelines were developed with a goal to start afresh, said ATA Thyroid and Pregnancy Guidelines Task Force cochair Tim IM Korevaar, MD, PhD, in presenting the final draft guidelines at the American Thyroid Association (ATA) 2024 Meeting.
“Obviously, we’re not going to ignore the 2017 guidelines, which have been a very good resource for us so far, but we really wanted to start from scratch and follow a ‘blank canvas’ approach in optimizing the evidence,” said Korevaar, an endocrinologist and obstetric internist with the Division of Pharmacology and Vascular Medicine & Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
The guidelines, developed through a collaborative effort involving a wide variety of related medical societies, involved 14 systematic literature reviews. While the pregnancy issues covered by the guidelines is extensive, key highlights include:
Management in Preconception
Beginning with preconception, a key change in the guidelines will be that patients with euthyroid thyroid peroxidase (TPO) antibodies, which can be indicative of thyroid dysfunction, routine treatment with levothyroxine is not recommended, based on new evidence from randomized trials of high-risk patients showing no clear benefit from the treatment.
“In these trials, and across analyses, there was absolutely no beneficial effect of levothyroxine in these patients [with euthyroid TPO antibody positivity],” he said.
With evidence showing, however, that TPO antibody positivity can lead to subclinical or overt hypothyroidism within 1 or 2 years, the guidelines will recommend that TPO antibody–positive patients do have thyroid stimulating hormone (TSH) levels tested every 3-6 months until pregnancy, and existing recommendations to test during pregnancy among those patients remain in place, Korevaar reported.
In terms of preconception subclinical hypothyroidism, the guidelines will emphasize the existing recommendation “to always strive to reassess” thyroid levels, and if subclinical hypothyroidism does persist, to treat with low-dose levothyroxine.
During Pregnancy
During pregnancy, the new proposed recommendations will reflect the important change that three key risk factors, including age over 30 years, having at least two prior pregnancies, and morbid obesity (body mass index [BMI] at least 40 kg/m2), previously considered a risk for thyroid dysfunction in pregnancy, should not, on their own, suggest the need for thyroid testing, based on low evidence of an increased risk in pregnancy.
Research on the issue includes a recent study from Korevaar’s team showing these factors to in fact have low predictability of thyroid dysfunction.
“We deemed that these risk differences weren’t really clinically meaningful (in predicting risk), and so we have removed to maternal age, BMI, and parity as risk factors for thyroid testing indications in pregnancy,” Korevaar said.
Factors considered a risk, resulting in recommended testing at presentation include a history of subclinical or clinical hypo- or hyperthyroidism, postpartum thyroiditis, known thyroid antibody positivity, symptoms of thyroid dysfunction or goiter, and other factors.
Treatment for Subclinical Hypothyroidism in Pregnancy
Whereas current guidelines recommend TPO antibody status in determining when to consider treatment for subclinical hypothyroidism, the new proposed guideline will instead recommend treatment based on the timing of the diagnosis of the subclinical hypothyroidism, with consideration of treatment during the first trimester, but not in the second or third trimester, based on newer evidence of the absolute risk for pregnancy complications and randomized trial data.
“The recommendations are now to no longer based on TPO antibody status, but instead according to the timing of the diagnosis of subclinical hypothyroidism,” Korevaar said.
Based on the collective data, “due to the low risk, we do not recommend for routine levothyroxine treatment in the second or third trimester groups with TSH levels under 10 mU/L now.”
“However, for subclinical hypothyroidism diagnosed in the first trimester, the recommendation would be that you can consider levothyroxine treatment,” he said.
While a clear indication for treatment in any trimester is the presence of overt hypothyroidism, or TSH levels over 10 mU/L, Korevaar underscored the importance of considering nuances of the recommendations that may warrant flexibility, for instance among patients with borderline TSH levels.
Spontaneous Normalization of Thyroid Levels in Pregnancy
Another new recommendation addresses the issue of spontaneous normalization of abnormal thyroid function during pregnancy, with several large studies showing a large proportion of subclinical hypothyroidism cases spontaneously revert to euthyroidism by the third trimester — despite no treatment having been provided.
Under the important proposed recommendation, retesting of subclinical hypothyroidism is suggested within 3 weeks.
“The data shows that a large proportion of patients spontaneously revert to euthyroidism,” Korevaar said.
“Upon identifying subclinical hypothyroidism in the first trimester, there will be essentially two options that clinicians can discuss with their patient — one would be to consider confirmatory tests in 3 weeks or to discuss the starting the lower dose levothyroxine in the first trimester,” he said.
In terms of overt hypothyroidism, likewise, if patients have a TSH levels below 6 mU/L in pregnancy, “you can either consider doing confirmatory testing within 3 weeks, or discussing with the patient starting levothyroxine treatment,” Korevaar added.
Overt Hyperthyroidism
For overt hyperthyroidism, no significant changes from current guidelines are being proposed, with the key exception of a heightened emphasis on the need for shared decision-making with patients, Korevaar said.
“We want to emphasize shared decision-making especially for women who have Graves’ disease prior to pregnancy, because the antithyroid treatment modalities, primarily methimazole (MMI) and propylthiouracil (PTU), have different advantages and disadvantages for an upcoming pregnancy,” he said.
“If you help a patient become involved in the decision-making process, that can also be very helpful in managing the disease and following-up on the pregnancy.”
Under the recommendations, PTU remains the preferred drug in overt hyperthyroidism, due to a more favorable profile in terms of potential birth defects vs MMI, with research showing a higher absolute risk of 3% vs 5%.
The guidelines further suggest the option of stopping the antithyroid medications upon a positive pregnancy test, with the exception of high-risk patients.
Korevaar noted that, if the treatment is stopped early in pregnancy, relapse is not likely to occur until after approximately 3 months, or 12 weeks, at which time, the high-risk teratogenic period, which is between week 5 and week 15, will have passed.
Current guidelines regarding whether to stop treatment in higher-risk hyperthyroid patients are recommended to remain unchanged.
Thyroid Nodules and Cancer
Recommendations regarding thyroid nodules and cancer during pregnancy are also expected to remain largely similar to those in the 2017 guidelines, with the exception of an emphasis on simply considering how the patient would normally be managed outside of pregnancy.
For instance, regarding the question of whether treatment can be withheld for 9 months during pregnancy. “A lot of times, the answer is yes,” Korevaar said.
Other topics that will be largely unchanged include issues of universal screening, definitions of normal and abnormal TSH and free T4 reference ranges and isolated hypothyroxinemia.
Steps Forward in Improving Updates, Readability
In addition to recommendation updates, the new guidelines are being revised to better reflect more recent evidence-based developments and user-friendliness.
“We have now made the step to a more systematic and replicable methodology to ensure for easier updates with a shorter interval,” Korevaar told this news organization.
“Furthermore, since 2006, the ATA guideline documents have followed a question-and-answer format, lacked recommendation tables and had none or only a few graphic illustrations,” he added.
“We are now further developing the typical outline of the guidelines to improve the readability and dissemination of the guideline document.”
Korevaar’s disclosures include lectureship fees from IBSA, Merck, and Berlin Chemie.
A version of this article first appeared on Medscape.com.
CHICAGO — A preview of much-anticipated updates to guidelines on managing thyroid disease in pregnancy shows key changes to recommendations in the evolving field, ranging from consideration of the chance of spontaneous normalization of thyroid levels during pregnancy to a heightened emphasis on shared decision-making and the nuances can factor into personalized treatment.
The guidelines, expected to be published in early 2025, have not been updated since 2017, and with substantial advances and evidence from countless studies since then, the new guidelines were developed with a goal to start afresh, said ATA Thyroid and Pregnancy Guidelines Task Force cochair Tim IM Korevaar, MD, PhD, in presenting the final draft guidelines at the American Thyroid Association (ATA) 2024 Meeting.
“Obviously, we’re not going to ignore the 2017 guidelines, which have been a very good resource for us so far, but we really wanted to start from scratch and follow a ‘blank canvas’ approach in optimizing the evidence,” said Korevaar, an endocrinologist and obstetric internist with the Division of Pharmacology and Vascular Medicine & Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
The guidelines, developed through a collaborative effort involving a wide variety of related medical societies, involved 14 systematic literature reviews. While the pregnancy issues covered by the guidelines is extensive, key highlights include:
Management in Preconception
Beginning with preconception, a key change in the guidelines will be that patients with euthyroid thyroid peroxidase (TPO) antibodies, which can be indicative of thyroid dysfunction, routine treatment with levothyroxine is not recommended, based on new evidence from randomized trials of high-risk patients showing no clear benefit from the treatment.
“In these trials, and across analyses, there was absolutely no beneficial effect of levothyroxine in these patients [with euthyroid TPO antibody positivity],” he said.
With evidence showing, however, that TPO antibody positivity can lead to subclinical or overt hypothyroidism within 1 or 2 years, the guidelines will recommend that TPO antibody–positive patients do have thyroid stimulating hormone (TSH) levels tested every 3-6 months until pregnancy, and existing recommendations to test during pregnancy among those patients remain in place, Korevaar reported.
In terms of preconception subclinical hypothyroidism, the guidelines will emphasize the existing recommendation “to always strive to reassess” thyroid levels, and if subclinical hypothyroidism does persist, to treat with low-dose levothyroxine.
During Pregnancy
During pregnancy, the new proposed recommendations will reflect the important change that three key risk factors, including age over 30 years, having at least two prior pregnancies, and morbid obesity (body mass index [BMI] at least 40 kg/m2), previously considered a risk for thyroid dysfunction in pregnancy, should not, on their own, suggest the need for thyroid testing, based on low evidence of an increased risk in pregnancy.
Research on the issue includes a recent study from Korevaar’s team showing these factors to in fact have low predictability of thyroid dysfunction.
“We deemed that these risk differences weren’t really clinically meaningful (in predicting risk), and so we have removed to maternal age, BMI, and parity as risk factors for thyroid testing indications in pregnancy,” Korevaar said.
Factors considered a risk, resulting in recommended testing at presentation include a history of subclinical or clinical hypo- or hyperthyroidism, postpartum thyroiditis, known thyroid antibody positivity, symptoms of thyroid dysfunction or goiter, and other factors.
Treatment for Subclinical Hypothyroidism in Pregnancy
Whereas current guidelines recommend TPO antibody status in determining when to consider treatment for subclinical hypothyroidism, the new proposed guideline will instead recommend treatment based on the timing of the diagnosis of the subclinical hypothyroidism, with consideration of treatment during the first trimester, but not in the second or third trimester, based on newer evidence of the absolute risk for pregnancy complications and randomized trial data.
“The recommendations are now to no longer based on TPO antibody status, but instead according to the timing of the diagnosis of subclinical hypothyroidism,” Korevaar said.
Based on the collective data, “due to the low risk, we do not recommend for routine levothyroxine treatment in the second or third trimester groups with TSH levels under 10 mU/L now.”
“However, for subclinical hypothyroidism diagnosed in the first trimester, the recommendation would be that you can consider levothyroxine treatment,” he said.
While a clear indication for treatment in any trimester is the presence of overt hypothyroidism, or TSH levels over 10 mU/L, Korevaar underscored the importance of considering nuances of the recommendations that may warrant flexibility, for instance among patients with borderline TSH levels.
Spontaneous Normalization of Thyroid Levels in Pregnancy
Another new recommendation addresses the issue of spontaneous normalization of abnormal thyroid function during pregnancy, with several large studies showing a large proportion of subclinical hypothyroidism cases spontaneously revert to euthyroidism by the third trimester — despite no treatment having been provided.
Under the important proposed recommendation, retesting of subclinical hypothyroidism is suggested within 3 weeks.
“The data shows that a large proportion of patients spontaneously revert to euthyroidism,” Korevaar said.
“Upon identifying subclinical hypothyroidism in the first trimester, there will be essentially two options that clinicians can discuss with their patient — one would be to consider confirmatory tests in 3 weeks or to discuss the starting the lower dose levothyroxine in the first trimester,” he said.
In terms of overt hypothyroidism, likewise, if patients have a TSH levels below 6 mU/L in pregnancy, “you can either consider doing confirmatory testing within 3 weeks, or discussing with the patient starting levothyroxine treatment,” Korevaar added.
Overt Hyperthyroidism
For overt hyperthyroidism, no significant changes from current guidelines are being proposed, with the key exception of a heightened emphasis on the need for shared decision-making with patients, Korevaar said.
“We want to emphasize shared decision-making especially for women who have Graves’ disease prior to pregnancy, because the antithyroid treatment modalities, primarily methimazole (MMI) and propylthiouracil (PTU), have different advantages and disadvantages for an upcoming pregnancy,” he said.
“If you help a patient become involved in the decision-making process, that can also be very helpful in managing the disease and following-up on the pregnancy.”
Under the recommendations, PTU remains the preferred drug in overt hyperthyroidism, due to a more favorable profile in terms of potential birth defects vs MMI, with research showing a higher absolute risk of 3% vs 5%.
The guidelines further suggest the option of stopping the antithyroid medications upon a positive pregnancy test, with the exception of high-risk patients.
Korevaar noted that, if the treatment is stopped early in pregnancy, relapse is not likely to occur until after approximately 3 months, or 12 weeks, at which time, the high-risk teratogenic period, which is between week 5 and week 15, will have passed.
Current guidelines regarding whether to stop treatment in higher-risk hyperthyroid patients are recommended to remain unchanged.
Thyroid Nodules and Cancer
Recommendations regarding thyroid nodules and cancer during pregnancy are also expected to remain largely similar to those in the 2017 guidelines, with the exception of an emphasis on simply considering how the patient would normally be managed outside of pregnancy.
For instance, regarding the question of whether treatment can be withheld for 9 months during pregnancy. “A lot of times, the answer is yes,” Korevaar said.
Other topics that will be largely unchanged include issues of universal screening, definitions of normal and abnormal TSH and free T4 reference ranges and isolated hypothyroxinemia.
Steps Forward in Improving Updates, Readability
In addition to recommendation updates, the new guidelines are being revised to better reflect more recent evidence-based developments and user-friendliness.
“We have now made the step to a more systematic and replicable methodology to ensure for easier updates with a shorter interval,” Korevaar told this news organization.
“Furthermore, since 2006, the ATA guideline documents have followed a question-and-answer format, lacked recommendation tables and had none or only a few graphic illustrations,” he added.
“We are now further developing the typical outline of the guidelines to improve the readability and dissemination of the guideline document.”
Korevaar’s disclosures include lectureship fees from IBSA, Merck, and Berlin Chemie.
A version of this article first appeared on Medscape.com.
FROM ATA 2024
Postpartum Exercise Reduces Depression and Anxiety Symptoms
TOPLINE:
Postpartum exercise reduces the severity of depressive and anxiety symptoms. Initiating exercise within 12 weeks post partum is linked to greater reductions in depressive symptoms.
METHODOLOGY:
- Researchers conducted a systematic review and meta-analysis including 35 studies with a total of 4072 participants.
- The review included randomized controlled trials and nonrandomized interventions examining the impact of postpartum exercise on depression and anxiety.
- Participants were postpartum individuals within the first year after childbirth, with interventions including various types of exercise.
- Data sources included online databases with data up to January 2024, reference lists, and hand searches.
- The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess the certainty of evidence.
TAKEAWAY:
- Postpartum exercise-only interventions resulted in a moderate reduction in the severity of depressive symptoms (standardized mean difference [SMD], –0.52; 95% CI, –0.80 to –0.24).
- Exercise-only interventions were associated with a small reduction in the severity of anxiety symptoms (SMD, –0.25; 95% CI, –0.43 to –0.08).
- Initiating exercise within 12 weeks post partum was associated with a greater reduction in depressive symptoms, compared with starting later.
- Postpartum exercise was associated with a 45% reduction in the odds of developing depression (odds ratio, 0.55; 95% CI, 0.32-0.95).
IN PRACTICE:
“Further investigation should aim to investigate the effects of postpartum exercise in individuals who experienced perinatal complications and in those who had limitations to exercise during pregnancy. Additionally, more investigation is required to address the possible lasting effects of postpartum exercise on maternal mental health as there were very limited studies reporting on this outcome,” the authors of the study wrote.
SOURCE:
This study was led by Margie H. Davenport, University of Alberta in Edmonton, Canada. It was published online in British Journal of Sports Medicine.
LIMITATIONS:
This study’s limitations included high heterogeneity among included studies, small sample sizes in some studies, and the combination of exercise with other interventions in some cases. These factors may have affected the generalizability and precision of the findings.
DISCLOSURES:
This study was funded by the Christenson Professorship in Active Healthy Living. Davenport is funded by a Christenson Professorship in Active Healthy Living. One coauthor is funded by the Université du Québec à Trois-Rivières research chair in physical activity and maternal and neonatal health. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Postpartum exercise reduces the severity of depressive and anxiety symptoms. Initiating exercise within 12 weeks post partum is linked to greater reductions in depressive symptoms.
METHODOLOGY:
- Researchers conducted a systematic review and meta-analysis including 35 studies with a total of 4072 participants.
- The review included randomized controlled trials and nonrandomized interventions examining the impact of postpartum exercise on depression and anxiety.
- Participants were postpartum individuals within the first year after childbirth, with interventions including various types of exercise.
- Data sources included online databases with data up to January 2024, reference lists, and hand searches.
- The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess the certainty of evidence.
TAKEAWAY:
- Postpartum exercise-only interventions resulted in a moderate reduction in the severity of depressive symptoms (standardized mean difference [SMD], –0.52; 95% CI, –0.80 to –0.24).
- Exercise-only interventions were associated with a small reduction in the severity of anxiety symptoms (SMD, –0.25; 95% CI, –0.43 to –0.08).
- Initiating exercise within 12 weeks post partum was associated with a greater reduction in depressive symptoms, compared with starting later.
- Postpartum exercise was associated with a 45% reduction in the odds of developing depression (odds ratio, 0.55; 95% CI, 0.32-0.95).
IN PRACTICE:
“Further investigation should aim to investigate the effects of postpartum exercise in individuals who experienced perinatal complications and in those who had limitations to exercise during pregnancy. Additionally, more investigation is required to address the possible lasting effects of postpartum exercise on maternal mental health as there were very limited studies reporting on this outcome,” the authors of the study wrote.
SOURCE:
This study was led by Margie H. Davenport, University of Alberta in Edmonton, Canada. It was published online in British Journal of Sports Medicine.
LIMITATIONS:
This study’s limitations included high heterogeneity among included studies, small sample sizes in some studies, and the combination of exercise with other interventions in some cases. These factors may have affected the generalizability and precision of the findings.
DISCLOSURES:
This study was funded by the Christenson Professorship in Active Healthy Living. Davenport is funded by a Christenson Professorship in Active Healthy Living. One coauthor is funded by the Université du Québec à Trois-Rivières research chair in physical activity and maternal and neonatal health. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Postpartum exercise reduces the severity of depressive and anxiety symptoms. Initiating exercise within 12 weeks post partum is linked to greater reductions in depressive symptoms.
METHODOLOGY:
- Researchers conducted a systematic review and meta-analysis including 35 studies with a total of 4072 participants.
- The review included randomized controlled trials and nonrandomized interventions examining the impact of postpartum exercise on depression and anxiety.
- Participants were postpartum individuals within the first year after childbirth, with interventions including various types of exercise.
- Data sources included online databases with data up to January 2024, reference lists, and hand searches.
- The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess the certainty of evidence.
TAKEAWAY:
- Postpartum exercise-only interventions resulted in a moderate reduction in the severity of depressive symptoms (standardized mean difference [SMD], –0.52; 95% CI, –0.80 to –0.24).
- Exercise-only interventions were associated with a small reduction in the severity of anxiety symptoms (SMD, –0.25; 95% CI, –0.43 to –0.08).
- Initiating exercise within 12 weeks post partum was associated with a greater reduction in depressive symptoms, compared with starting later.
- Postpartum exercise was associated with a 45% reduction in the odds of developing depression (odds ratio, 0.55; 95% CI, 0.32-0.95).
IN PRACTICE:
“Further investigation should aim to investigate the effects of postpartum exercise in individuals who experienced perinatal complications and in those who had limitations to exercise during pregnancy. Additionally, more investigation is required to address the possible lasting effects of postpartum exercise on maternal mental health as there were very limited studies reporting on this outcome,” the authors of the study wrote.
SOURCE:
This study was led by Margie H. Davenport, University of Alberta in Edmonton, Canada. It was published online in British Journal of Sports Medicine.
LIMITATIONS:
This study’s limitations included high heterogeneity among included studies, small sample sizes in some studies, and the combination of exercise with other interventions in some cases. These factors may have affected the generalizability and precision of the findings.
DISCLOSURES:
This study was funded by the Christenson Professorship in Active Healthy Living. Davenport is funded by a Christenson Professorship in Active Healthy Living. One coauthor is funded by the Université du Québec à Trois-Rivières research chair in physical activity and maternal and neonatal health. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Many Patients With Cancer Visit EDs Before Diagnosis
Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.
Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.
“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”
The findings were published online on November 4 in CMAJ).
Neurologic Cancers Prominent
In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.
Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.
Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.
Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).
The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.
“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.
The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.
The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
‘Unpacking the Data’
The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.
“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.
“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”
All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.
“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.
This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.
Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.
“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”
The findings were published online on November 4 in CMAJ).
Neurologic Cancers Prominent
In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.
Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.
Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.
Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).
The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.
“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.
The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.
The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
‘Unpacking the Data’
The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.
“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.
“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”
All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.
“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.
This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.
Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.
“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”
The findings were published online on November 4 in CMAJ).
Neurologic Cancers Prominent
In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.
Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.
Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.
Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).
The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.
“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.
The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.
The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
‘Unpacking the Data’
The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.
“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.
“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”
All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.
“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.
This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM CMAJ
Are GLP-1s the Newest Fertility Treatment?
First, there were “Ozempic babies.” Now, there is also Ozempic-before-baby.
Unplanned pregnancies are still regularly being reported among people using glucagon-like peptide 1 receptor agonist (GLP-1 RA) drugs, and now fertility specialists are increasingly incorporating the medicines into preconception care plans.
The specialists say their colleagues in other areas of medicine may have an opportunity, too, to talk about weight loss using these new drugs in terms of reproductive health. Motivation and compliance can transform when the goal isn’t simply weight loss but having children.
“We have this really special moment to help patients be healthier, in order to be healthier for their kids,” said Christina Boots, MD, MSci, an associate professor of reproductive endocrinology and infertility at Northwestern University’s Feinberg School of Medicine, Chicago. “And I think that’s also a very motivating moment. It may be hard to get up and go for a run to make my jeans fit better, but when I think about it in terms of, ‘this might someday help my future daughter,’ that is a whole different level of motivation.”
Here’s why, what to know about the current lengthy list of unknowns and risks, and some options for approaching the topic with patients.
What Fertility Docs Are Doing
While overweight and obesity are consistently linked to fertility and pregnancy outcomes, Boots predicts the biggest impact of GLP-1 weight loss for fertility among women will be a specific subset: Those who are not cycling regularly, such as those with polycystic ovary syndrome (PCOS).
“The women who are cycling regularly who have very unexplained infertility and no other comorbidities like high blood pressure or something else going on, I don’t think it’s going to help their fertility very much at all,” she said “It might, but I think there’s probably something else going on in her tubes or with her eggs or his sperm, but it has nothing to do with her metabolic health.
Women who aren’t cycling regularly will benefit, but those with truly unexplained fertility probably won’t, she said.
In their recent narrative review on treating obesity and fertility with GLP-1 RAs that appeared in Fertility and Sterility, Boots and co-author Alyse S. Goldberg, MD, an endocrinologist with the University of Toronto, Ontario, Canada, advocate for the use of GLP-1s as a go-to treatment for obesity as part of preconception care by reproductive endocrinologists, calling the drugs “the most effective, least invasive means of weight loss.”
The paper is timely and necessary because use of GLP-1s is only going to increase, Patricia Jimenez, MD, an associate professor of obstetrics and gynecology at Washington University School of Medicine in St. Louis, Missouri, said in an email to this news organization.
“GLP-1 RAs are becoming a larger part of my practice. More patients are either using them already or interested in using them,” said Jimenez, who is board certified in reproductive endocrinology, obstetrics and gynecology, and obesity medicine. “I specifically see patients to discuss this and do prescribe antiobesity medications, not only GLP-1 RAs. Often this is with people with PCOS who are not planning to conceive soon or patients willing to delay fertility treatment [by] 3-6 months.”
Treating obesity is also important for women who are seeking in vitro fertilization, Boots said, because many IVF clinics have a body mass index cutoff of 40 kg/m2.
Like Jimenez’s approach, Boots and Goldberg call for comprehensive obesity care beyond the use of medication, including nutritional counseling and mental health support. Those supports are important during the transition off of GLP-1 medications, which poses a risk for rapid weight regain. That’s even with the potential support of taking metformin, which Boots often prescribes as a bridge.
Semaglutide should be stopped at least 2 months prior to conception, and tirzepatide should be stopped 1 month prior to conception, according to the manufacturers. (Boots and Goldberg listed the Canadian label recommendation for stopping tirzepatide, noting there is no suggested timeline for stopping prior to conception on the US label.)
Numerous studies have shown rapid weight regain is common when stopping GLP-1s, which presents a unique set of risks for pregnant women including early pregnancy loss, gestational diabetes, preeclampsia, and nonelective cesarean delivery.
Weighing Risks, Benefits, and Unknowns
Early looks at small human data sets, mostly involving semaglutide and earlier short-acting GLP-1s, and their impact on the risk for birth defects are “reassuring,” Boots said.
“But birth defects are just one small aspect. There’s also metabolic health and things like that long-term. Understanding what it does to the growing baby and the proximity of that medication to that growing baby is really important to see, and can’t be answered with animal studies, not perfectly anyway,” Boots said.
There are no published reports, from clinical trials nor case collections, examining the use of tirzepatide among pregnant people.
“One of the most important questions we need to answer is the preconception safety of these medications, and that includes safety for men,” Joshua Halpern, MD, MS, an adjunct assistant professor of urology at Northwestern University’s Feinberg School of Medicine, and chief scientific officer for Posterity Health, said in an email to this news organization.
“For example, a recent study found that men who were taking metformin, another popular medication for diabetes, were more likely to have children with birth defects, compared with those who were not taking the medication,” Halpern said. “Further studies are needed to determine whether a similar effect might hold true for the GLP-1 agonists.”
Small early studies on sperm are encouraging, Halpern said, suggesting that GLP-1 use may be beneficial, but a better understanding of direct effects is needed.
Among women, there may be cases where continuing use of a GLP-1 during pregnancy may offer benefits that outweigh risks, Boots suggested. Manufacturers have also created pregnancy exposure registries to measure the safety of their therapies during pregnancy.
“I have a group of patients whose sugars are so well controlled on these medications, but as soon as they come off, they get weight regain and their glucose is just so poorly controlled,” she said. “There may be a group of women where the benefits of glucose control outweigh the risks of being on the medication the whole pregnancy.”
The list of important unknowns also includes a need to examine how rapid weight loss may impact ovulation rates and spontaneous conception, as well as miscarriage rates, birth weight, and metabolic health of the child.
More detailed rebound weight gain data is coming next year, with additional analysis expected as well on birth weight and pregnancy outcomes, said Jacqueline Maya, MD, first author of the research abstract presented at this year’s American Diabetes Association conference that examined gestational weight gain among people with preexisting type 2 diabetes who were exposed to GLP-1s during pregnancy. The study included 47 exposed pregnancies (based on prescription records and electronic chart information) and compared gestational weight gain to 141 unexposed matched pregnancies. Among the exposed group, 62% exceeded recommended weight gain, compared with 41% in the unexposed group. On average, gestational weight gain in exposed pregnancies exceeded that among matched unexposed pregnancies by about 6 pounds.
The team is now working with an additional data set to examine exposed pregnancies among people with obesity, said Maya, an instructor of pediatrics at Mass General Hospital and Harvard School of Medicine. She is particularly interested in examining weight trajectories during pregnancy to see how they may affect fetal outcomes. Her team’s current project also will likely include analysis to examine other variables like postpartum weight gain and adiposity characteristics of the baby.
Maya said the team hopes to have more to report at the American Diabetes Association conference in June next year.
Offer the Conversation
Using a GLP-1 for weight loss takes time, usually around 1 year to reach a plateau. Boots encouraged nonfertility providers to ask patients of reproductive age about their family plans as an opening.
“I hope for all primary care doctors and gynecologists, that with any patient of reproductive age, you should be bringing this up, asking, ‘Have you thought about having kids? Are you thinking about it soon?’ And if they say they are sometime in the near future, then you can say, ‘Is it OK if I bring up your weight?’ And you should ask permission.”
If the patient declines, it’s OK to bring it up again at a future visit.
“People with obesity have often experienced negative weight bias that impacts their care,” Jimenez said. “Treat obesity as a disease, not a personal failing. Ask permission to discuss weight with the patient beforehand. If they say no, respect that answer. This goes a long way in developing a positive relationship, so they return for care and may be willing to discuss later.”
When patients are open to the conversation, Boots suggests not focusing on the potential for poor outcomes, and instead perhaps saying, “If you’re thinking about having a baby in 5 years, optimizing your health now will not only make your pregnancy healthier, but your child healthier long-term.”
Discussing contraception plans remains important. People starting semaglutide or tirzepatide should use contraception other than oral birth control for 4 weeks while starting the medicine and for 4 weeks after each dose increase.
Boots said that the contraception conversation is particularly important because many people have come to deeply believe that they are infertile and, thus, may perhaps think contraception advice doesn’t apply to them. Maya hypothesized that behavioral changes following weight loss may also be a pathway toward pregnancy.
“Pregnancy while on GLP-1 RAs does happen. I always have a discussion about this possibility and contraception. This can sometimes be challenging for people with infertility to consider,” Jimenez said. “Explaining the risks, benefits, and unknowns can help. As the [Fertility and Sterility] paper describes, the limited data available has not shown increased fetal or maternal complications. We need more high quality data to better understand the impact of exposure or use around the time of conception and during pregnancy.”
It’s also important to introduce the idea to patients that they may someday need to come off the medications, such as when they are ready to have children, and how important lifestyle and behavioral changes will be at that time, Maya said.
“We do know what the alternative is, and we do know what the risks of obesity are,” she said. “So, it’s a tug and pull. We’re not starting off with healthy. We’re starting off with a disease that is physically and emotionally very difficult for the patient, especially when it starts in childhood.”
A version of this article appeared on Medscape.com.
First, there were “Ozempic babies.” Now, there is also Ozempic-before-baby.
Unplanned pregnancies are still regularly being reported among people using glucagon-like peptide 1 receptor agonist (GLP-1 RA) drugs, and now fertility specialists are increasingly incorporating the medicines into preconception care plans.
The specialists say their colleagues in other areas of medicine may have an opportunity, too, to talk about weight loss using these new drugs in terms of reproductive health. Motivation and compliance can transform when the goal isn’t simply weight loss but having children.
“We have this really special moment to help patients be healthier, in order to be healthier for their kids,” said Christina Boots, MD, MSci, an associate professor of reproductive endocrinology and infertility at Northwestern University’s Feinberg School of Medicine, Chicago. “And I think that’s also a very motivating moment. It may be hard to get up and go for a run to make my jeans fit better, but when I think about it in terms of, ‘this might someday help my future daughter,’ that is a whole different level of motivation.”
Here’s why, what to know about the current lengthy list of unknowns and risks, and some options for approaching the topic with patients.
What Fertility Docs Are Doing
While overweight and obesity are consistently linked to fertility and pregnancy outcomes, Boots predicts the biggest impact of GLP-1 weight loss for fertility among women will be a specific subset: Those who are not cycling regularly, such as those with polycystic ovary syndrome (PCOS).
“The women who are cycling regularly who have very unexplained infertility and no other comorbidities like high blood pressure or something else going on, I don’t think it’s going to help their fertility very much at all,” she said “It might, but I think there’s probably something else going on in her tubes or with her eggs or his sperm, but it has nothing to do with her metabolic health.
Women who aren’t cycling regularly will benefit, but those with truly unexplained fertility probably won’t, she said.
In their recent narrative review on treating obesity and fertility with GLP-1 RAs that appeared in Fertility and Sterility, Boots and co-author Alyse S. Goldberg, MD, an endocrinologist with the University of Toronto, Ontario, Canada, advocate for the use of GLP-1s as a go-to treatment for obesity as part of preconception care by reproductive endocrinologists, calling the drugs “the most effective, least invasive means of weight loss.”
The paper is timely and necessary because use of GLP-1s is only going to increase, Patricia Jimenez, MD, an associate professor of obstetrics and gynecology at Washington University School of Medicine in St. Louis, Missouri, said in an email to this news organization.
“GLP-1 RAs are becoming a larger part of my practice. More patients are either using them already or interested in using them,” said Jimenez, who is board certified in reproductive endocrinology, obstetrics and gynecology, and obesity medicine. “I specifically see patients to discuss this and do prescribe antiobesity medications, not only GLP-1 RAs. Often this is with people with PCOS who are not planning to conceive soon or patients willing to delay fertility treatment [by] 3-6 months.”
Treating obesity is also important for women who are seeking in vitro fertilization, Boots said, because many IVF clinics have a body mass index cutoff of 40 kg/m2.
Like Jimenez’s approach, Boots and Goldberg call for comprehensive obesity care beyond the use of medication, including nutritional counseling and mental health support. Those supports are important during the transition off of GLP-1 medications, which poses a risk for rapid weight regain. That’s even with the potential support of taking metformin, which Boots often prescribes as a bridge.
Semaglutide should be stopped at least 2 months prior to conception, and tirzepatide should be stopped 1 month prior to conception, according to the manufacturers. (Boots and Goldberg listed the Canadian label recommendation for stopping tirzepatide, noting there is no suggested timeline for stopping prior to conception on the US label.)
Numerous studies have shown rapid weight regain is common when stopping GLP-1s, which presents a unique set of risks for pregnant women including early pregnancy loss, gestational diabetes, preeclampsia, and nonelective cesarean delivery.
Weighing Risks, Benefits, and Unknowns
Early looks at small human data sets, mostly involving semaglutide and earlier short-acting GLP-1s, and their impact on the risk for birth defects are “reassuring,” Boots said.
“But birth defects are just one small aspect. There’s also metabolic health and things like that long-term. Understanding what it does to the growing baby and the proximity of that medication to that growing baby is really important to see, and can’t be answered with animal studies, not perfectly anyway,” Boots said.
There are no published reports, from clinical trials nor case collections, examining the use of tirzepatide among pregnant people.
“One of the most important questions we need to answer is the preconception safety of these medications, and that includes safety for men,” Joshua Halpern, MD, MS, an adjunct assistant professor of urology at Northwestern University’s Feinberg School of Medicine, and chief scientific officer for Posterity Health, said in an email to this news organization.
“For example, a recent study found that men who were taking metformin, another popular medication for diabetes, were more likely to have children with birth defects, compared with those who were not taking the medication,” Halpern said. “Further studies are needed to determine whether a similar effect might hold true for the GLP-1 agonists.”
Small early studies on sperm are encouraging, Halpern said, suggesting that GLP-1 use may be beneficial, but a better understanding of direct effects is needed.
Among women, there may be cases where continuing use of a GLP-1 during pregnancy may offer benefits that outweigh risks, Boots suggested. Manufacturers have also created pregnancy exposure registries to measure the safety of their therapies during pregnancy.
“I have a group of patients whose sugars are so well controlled on these medications, but as soon as they come off, they get weight regain and their glucose is just so poorly controlled,” she said. “There may be a group of women where the benefits of glucose control outweigh the risks of being on the medication the whole pregnancy.”
The list of important unknowns also includes a need to examine how rapid weight loss may impact ovulation rates and spontaneous conception, as well as miscarriage rates, birth weight, and metabolic health of the child.
More detailed rebound weight gain data is coming next year, with additional analysis expected as well on birth weight and pregnancy outcomes, said Jacqueline Maya, MD, first author of the research abstract presented at this year’s American Diabetes Association conference that examined gestational weight gain among people with preexisting type 2 diabetes who were exposed to GLP-1s during pregnancy. The study included 47 exposed pregnancies (based on prescription records and electronic chart information) and compared gestational weight gain to 141 unexposed matched pregnancies. Among the exposed group, 62% exceeded recommended weight gain, compared with 41% in the unexposed group. On average, gestational weight gain in exposed pregnancies exceeded that among matched unexposed pregnancies by about 6 pounds.
The team is now working with an additional data set to examine exposed pregnancies among people with obesity, said Maya, an instructor of pediatrics at Mass General Hospital and Harvard School of Medicine. She is particularly interested in examining weight trajectories during pregnancy to see how they may affect fetal outcomes. Her team’s current project also will likely include analysis to examine other variables like postpartum weight gain and adiposity characteristics of the baby.
Maya said the team hopes to have more to report at the American Diabetes Association conference in June next year.
Offer the Conversation
Using a GLP-1 for weight loss takes time, usually around 1 year to reach a plateau. Boots encouraged nonfertility providers to ask patients of reproductive age about their family plans as an opening.
“I hope for all primary care doctors and gynecologists, that with any patient of reproductive age, you should be bringing this up, asking, ‘Have you thought about having kids? Are you thinking about it soon?’ And if they say they are sometime in the near future, then you can say, ‘Is it OK if I bring up your weight?’ And you should ask permission.”
If the patient declines, it’s OK to bring it up again at a future visit.
“People with obesity have often experienced negative weight bias that impacts their care,” Jimenez said. “Treat obesity as a disease, not a personal failing. Ask permission to discuss weight with the patient beforehand. If they say no, respect that answer. This goes a long way in developing a positive relationship, so they return for care and may be willing to discuss later.”
When patients are open to the conversation, Boots suggests not focusing on the potential for poor outcomes, and instead perhaps saying, “If you’re thinking about having a baby in 5 years, optimizing your health now will not only make your pregnancy healthier, but your child healthier long-term.”
Discussing contraception plans remains important. People starting semaglutide or tirzepatide should use contraception other than oral birth control for 4 weeks while starting the medicine and for 4 weeks after each dose increase.
Boots said that the contraception conversation is particularly important because many people have come to deeply believe that they are infertile and, thus, may perhaps think contraception advice doesn’t apply to them. Maya hypothesized that behavioral changes following weight loss may also be a pathway toward pregnancy.
“Pregnancy while on GLP-1 RAs does happen. I always have a discussion about this possibility and contraception. This can sometimes be challenging for people with infertility to consider,” Jimenez said. “Explaining the risks, benefits, and unknowns can help. As the [Fertility and Sterility] paper describes, the limited data available has not shown increased fetal or maternal complications. We need more high quality data to better understand the impact of exposure or use around the time of conception and during pregnancy.”
It’s also important to introduce the idea to patients that they may someday need to come off the medications, such as when they are ready to have children, and how important lifestyle and behavioral changes will be at that time, Maya said.
“We do know what the alternative is, and we do know what the risks of obesity are,” she said. “So, it’s a tug and pull. We’re not starting off with healthy. We’re starting off with a disease that is physically and emotionally very difficult for the patient, especially when it starts in childhood.”
A version of this article appeared on Medscape.com.
First, there were “Ozempic babies.” Now, there is also Ozempic-before-baby.
Unplanned pregnancies are still regularly being reported among people using glucagon-like peptide 1 receptor agonist (GLP-1 RA) drugs, and now fertility specialists are increasingly incorporating the medicines into preconception care plans.
The specialists say their colleagues in other areas of medicine may have an opportunity, too, to talk about weight loss using these new drugs in terms of reproductive health. Motivation and compliance can transform when the goal isn’t simply weight loss but having children.
“We have this really special moment to help patients be healthier, in order to be healthier for their kids,” said Christina Boots, MD, MSci, an associate professor of reproductive endocrinology and infertility at Northwestern University’s Feinberg School of Medicine, Chicago. “And I think that’s also a very motivating moment. It may be hard to get up and go for a run to make my jeans fit better, but when I think about it in terms of, ‘this might someday help my future daughter,’ that is a whole different level of motivation.”
Here’s why, what to know about the current lengthy list of unknowns and risks, and some options for approaching the topic with patients.
What Fertility Docs Are Doing
While overweight and obesity are consistently linked to fertility and pregnancy outcomes, Boots predicts the biggest impact of GLP-1 weight loss for fertility among women will be a specific subset: Those who are not cycling regularly, such as those with polycystic ovary syndrome (PCOS).
“The women who are cycling regularly who have very unexplained infertility and no other comorbidities like high blood pressure or something else going on, I don’t think it’s going to help their fertility very much at all,” she said “It might, but I think there’s probably something else going on in her tubes or with her eggs or his sperm, but it has nothing to do with her metabolic health.
Women who aren’t cycling regularly will benefit, but those with truly unexplained fertility probably won’t, she said.
In their recent narrative review on treating obesity and fertility with GLP-1 RAs that appeared in Fertility and Sterility, Boots and co-author Alyse S. Goldberg, MD, an endocrinologist with the University of Toronto, Ontario, Canada, advocate for the use of GLP-1s as a go-to treatment for obesity as part of preconception care by reproductive endocrinologists, calling the drugs “the most effective, least invasive means of weight loss.”
The paper is timely and necessary because use of GLP-1s is only going to increase, Patricia Jimenez, MD, an associate professor of obstetrics and gynecology at Washington University School of Medicine in St. Louis, Missouri, said in an email to this news organization.
“GLP-1 RAs are becoming a larger part of my practice. More patients are either using them already or interested in using them,” said Jimenez, who is board certified in reproductive endocrinology, obstetrics and gynecology, and obesity medicine. “I specifically see patients to discuss this and do prescribe antiobesity medications, not only GLP-1 RAs. Often this is with people with PCOS who are not planning to conceive soon or patients willing to delay fertility treatment [by] 3-6 months.”
Treating obesity is also important for women who are seeking in vitro fertilization, Boots said, because many IVF clinics have a body mass index cutoff of 40 kg/m2.
Like Jimenez’s approach, Boots and Goldberg call for comprehensive obesity care beyond the use of medication, including nutritional counseling and mental health support. Those supports are important during the transition off of GLP-1 medications, which poses a risk for rapid weight regain. That’s even with the potential support of taking metformin, which Boots often prescribes as a bridge.
Semaglutide should be stopped at least 2 months prior to conception, and tirzepatide should be stopped 1 month prior to conception, according to the manufacturers. (Boots and Goldberg listed the Canadian label recommendation for stopping tirzepatide, noting there is no suggested timeline for stopping prior to conception on the US label.)
Numerous studies have shown rapid weight regain is common when stopping GLP-1s, which presents a unique set of risks for pregnant women including early pregnancy loss, gestational diabetes, preeclampsia, and nonelective cesarean delivery.
Weighing Risks, Benefits, and Unknowns
Early looks at small human data sets, mostly involving semaglutide and earlier short-acting GLP-1s, and their impact on the risk for birth defects are “reassuring,” Boots said.
“But birth defects are just one small aspect. There’s also metabolic health and things like that long-term. Understanding what it does to the growing baby and the proximity of that medication to that growing baby is really important to see, and can’t be answered with animal studies, not perfectly anyway,” Boots said.
There are no published reports, from clinical trials nor case collections, examining the use of tirzepatide among pregnant people.
“One of the most important questions we need to answer is the preconception safety of these medications, and that includes safety for men,” Joshua Halpern, MD, MS, an adjunct assistant professor of urology at Northwestern University’s Feinberg School of Medicine, and chief scientific officer for Posterity Health, said in an email to this news organization.
“For example, a recent study found that men who were taking metformin, another popular medication for diabetes, were more likely to have children with birth defects, compared with those who were not taking the medication,” Halpern said. “Further studies are needed to determine whether a similar effect might hold true for the GLP-1 agonists.”
Small early studies on sperm are encouraging, Halpern said, suggesting that GLP-1 use may be beneficial, but a better understanding of direct effects is needed.
Among women, there may be cases where continuing use of a GLP-1 during pregnancy may offer benefits that outweigh risks, Boots suggested. Manufacturers have also created pregnancy exposure registries to measure the safety of their therapies during pregnancy.
“I have a group of patients whose sugars are so well controlled on these medications, but as soon as they come off, they get weight regain and their glucose is just so poorly controlled,” she said. “There may be a group of women where the benefits of glucose control outweigh the risks of being on the medication the whole pregnancy.”
The list of important unknowns also includes a need to examine how rapid weight loss may impact ovulation rates and spontaneous conception, as well as miscarriage rates, birth weight, and metabolic health of the child.
More detailed rebound weight gain data is coming next year, with additional analysis expected as well on birth weight and pregnancy outcomes, said Jacqueline Maya, MD, first author of the research abstract presented at this year’s American Diabetes Association conference that examined gestational weight gain among people with preexisting type 2 diabetes who were exposed to GLP-1s during pregnancy. The study included 47 exposed pregnancies (based on prescription records and electronic chart information) and compared gestational weight gain to 141 unexposed matched pregnancies. Among the exposed group, 62% exceeded recommended weight gain, compared with 41% in the unexposed group. On average, gestational weight gain in exposed pregnancies exceeded that among matched unexposed pregnancies by about 6 pounds.
The team is now working with an additional data set to examine exposed pregnancies among people with obesity, said Maya, an instructor of pediatrics at Mass General Hospital and Harvard School of Medicine. She is particularly interested in examining weight trajectories during pregnancy to see how they may affect fetal outcomes. Her team’s current project also will likely include analysis to examine other variables like postpartum weight gain and adiposity characteristics of the baby.
Maya said the team hopes to have more to report at the American Diabetes Association conference in June next year.
Offer the Conversation
Using a GLP-1 for weight loss takes time, usually around 1 year to reach a plateau. Boots encouraged nonfertility providers to ask patients of reproductive age about their family plans as an opening.
“I hope for all primary care doctors and gynecologists, that with any patient of reproductive age, you should be bringing this up, asking, ‘Have you thought about having kids? Are you thinking about it soon?’ And if they say they are sometime in the near future, then you can say, ‘Is it OK if I bring up your weight?’ And you should ask permission.”
If the patient declines, it’s OK to bring it up again at a future visit.
“People with obesity have often experienced negative weight bias that impacts their care,” Jimenez said. “Treat obesity as a disease, not a personal failing. Ask permission to discuss weight with the patient beforehand. If they say no, respect that answer. This goes a long way in developing a positive relationship, so they return for care and may be willing to discuss later.”
When patients are open to the conversation, Boots suggests not focusing on the potential for poor outcomes, and instead perhaps saying, “If you’re thinking about having a baby in 5 years, optimizing your health now will not only make your pregnancy healthier, but your child healthier long-term.”
Discussing contraception plans remains important. People starting semaglutide or tirzepatide should use contraception other than oral birth control for 4 weeks while starting the medicine and for 4 weeks after each dose increase.
Boots said that the contraception conversation is particularly important because many people have come to deeply believe that they are infertile and, thus, may perhaps think contraception advice doesn’t apply to them. Maya hypothesized that behavioral changes following weight loss may also be a pathway toward pregnancy.
“Pregnancy while on GLP-1 RAs does happen. I always have a discussion about this possibility and contraception. This can sometimes be challenging for people with infertility to consider,” Jimenez said. “Explaining the risks, benefits, and unknowns can help. As the [Fertility and Sterility] paper describes, the limited data available has not shown increased fetal or maternal complications. We need more high quality data to better understand the impact of exposure or use around the time of conception and during pregnancy.”
It’s also important to introduce the idea to patients that they may someday need to come off the medications, such as when they are ready to have children, and how important lifestyle and behavioral changes will be at that time, Maya said.
“We do know what the alternative is, and we do know what the risks of obesity are,” she said. “So, it’s a tug and pull. We’re not starting off with healthy. We’re starting off with a disease that is physically and emotionally very difficult for the patient, especially when it starts in childhood.”
A version of this article appeared on Medscape.com.
Plasma Omega-6 and Omega-3 Fatty Acids Inversely Associated With Cancer
TOPLINE:
Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.
METHODOLOGY:
- Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
- They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
- Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
- Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
- The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.
TAKEAWAY:
- Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
- Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
- Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
- A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.
IN PRACTICE:
“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.
SOURCE:
The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.
LIMITATIONS:
The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants.
DISCLOSURES:
This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.
METHODOLOGY:
- Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
- They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
- Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
- Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
- The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.
TAKEAWAY:
- Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
- Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
- Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
- A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.
IN PRACTICE:
“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.
SOURCE:
The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.
LIMITATIONS:
The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants.
DISCLOSURES:
This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.
METHODOLOGY:
- Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
- They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
- Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
- Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
- The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.
TAKEAWAY:
- Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
- Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
- Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
- A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.
IN PRACTICE:
“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.
SOURCE:
The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.
LIMITATIONS:
The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants.
DISCLOSURES:
This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.