MDedge ObGyn

Each week, Kim Puterbaugh, MD, sees several pregnant patients at a Cleveland hospital who are experiencing complications involving bleeding or infection. The ob.gyn. has to make quick decisions about how to treat them, including whether to remove the dead or dying fetus to protect the health and life of the mother. Leaving in place a fetus that has no chance of survival dramatically increases the chance of maternal infection and permanent injury.

But now her medical decisions are complicated by Ohio’s new abortion law, which generally prohibits abortions after 6 weeks of pregnancy if cardiac activity is detected in the embryo or fetus – which can persist for hours or days even if a pregnancy has no chance of progressing. Given the new law, University Hospitals Cleveland Medical Center has streamlined its system of having an administrator and legal team on call for Dr. Puterbaugh and other physicians if anyone questions whether the planned treatment is allowed under the law.

Since the Supreme Court erased the constitutional right to abortion in June, Dr. Puterbaugh said these cases put her and doctors like her in an impossible position – squeezing doctors between antiabortion laws in Ohio and other states and the federal Emergency Medical Treatment & Labor Act. That 1986 law requires hospitals and physicians to provide screening and stabilizing treatment – including abortion, if necessary – in emergency situations.

“It’s a challenge to balance both those two things,” said Dr. Puterbaugh, president of the Society of OB/GYN Hospitalists. “But it’s not really a challenge to me because, in my mind, the life and health of the mother always comes first.”

The Biden administration argues that EMTALA trumps state abortion bans in emergency situations. On Aug. 2, the Department of Justice filed a federal lawsuit challenging an Idaho law that bans abortion in nearly all circumstances. The suit claims the law would make it a criminal offense for medical providers to comply with EMTALA’s requirement to provide abortion, if needed, for women experiencing emergency pregnancy complications.

In a July policy guidance and letter, the Department of Health & Human Services reaffirmed that EMTALA requires hospitals and physicians to offer life- or health-saving medical services, including abortion, in emergency situations. The letter refers to situations such as ectopic pregnancies, severe blood pressure spikes known as preeclampsia, and premature ruptures of the membrane causing a woman’s water to break before her pregnancy is viable.

The guidance stressed that this federal requirement supersedes any state laws that bar abortion, and that hospitals and physicians who don’t comply with the federal mandate could face civil fines and termination from the Medicare and Medicaid programs.

There are no known reports so far of EMTALA investigations arising from denial of emergency care in pregnancy situations.

But elected officials in states that have sharply restricted abortion disagree with the federal judgment. Texas Attorney General Ken Paxton sued the Biden administration in July to prevent the federal government from using the EMTALA law to require abortions in emergency cases. The suit claims that EMTALA doesn’t specifically mandate particular medical procedures such as abortion.

Abortion foes argue that state antiabortion laws already include adequate exceptions when a pregnant woman’s life or health is in danger. John Seago, president of Texas Right to Life, said one of Texas’ laws specifies that treatment for ectopic pregnancies or miscarriages is not prohibited. In addition, the law defines a medical emergency allowing abortion as a condition in which a woman is at serious risk of a “substantial impairment of a major bodily function.”

Mr. Seago blamed the news media and medical associations for deliberately sowing confusion about the laws. “The law is very clear,” he said.

Legal wrangling aside, in practice, physicians and hospital lawyers say much depends on the interpretation of vaguely worded exceptions in state abortion bans, and that’s further complicated by the existence of contradictory laws, such as those banning abortion based on cardiac activity. And medical providers don’t want to risk criminal prosecution, fines, and loss of licensure if someone accuses them of violating these confusing laws.

Louise Joy, an attorney in Austin, Tex., who represents hospitals and other health care providers, said her clients perhaps are being overly cautious, but that’s not surprising. “I try to encourage them to do the right thing, but I can’t assure them they’ll be risk free.”

A lot hinges on when a pregnancy-ending complication is deemed an emergency, a moment that is hard to define. Some Missouri women have come to the hospital ED with mild cramping and bleeding and were found to have an ectopic pregnancy that hadn’t ruptured yet, colleagues have told Alison Haddock, MD, a Houston emergency physician who chairs the board of the American College of Emergency Physicians. The standard treatment is to provide the drug methotrexate, which can terminate a pregnancy.

“You’re stable until it ruptures, then it becomes unstable,” she said. “But how unstable do you need to be? The woman’s life is not clearly at risk yet. It’s not clear if EMTALA applies. There will be a lot of gray areas that make it really tough for emergency physicians who want to do what’s right for patients without violating any laws.”

Physicians and hospital attorneys are hoping for clearer federal guidance and guarantees of protection from state prosecutors who might oppose their medical judgment on political grounds.

“This is when we need the federal government to step up and say: ‘Doctors, you must provide the standard of care, and we will prevent the prosecution of anyone who is following appropriate medical practices and doing the right thing for patients,” Ms. Joy said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Each week, Kim Puterbaugh, MD, sees several pregnant patients at a Cleveland hospital who are experiencing complications involving bleeding or infection. The ob.gyn. has to make quick decisions about how to treat them, including whether to remove the dead or dying fetus to protect the health and life of the mother. Leaving in place a fetus that has no chance of survival dramatically increases the chance of maternal infection and permanent injury.

But now her medical decisions are complicated by Ohio’s new abortion law, which generally prohibits abortions after 6 weeks of pregnancy if cardiac activity is detected in the embryo or fetus – which can persist for hours or days even if a pregnancy has no chance of progressing. Given the new law, University Hospitals Cleveland Medical Center has streamlined its system of having an administrator and legal team on call for Dr. Puterbaugh and other physicians if anyone questions whether the planned treatment is allowed under the law.

Since the Supreme Court erased the constitutional right to abortion in June, Dr. Puterbaugh said these cases put her and doctors like her in an impossible position – squeezing doctors between antiabortion laws in Ohio and other states and the federal Emergency Medical Treatment & Labor Act. That 1986 law requires hospitals and physicians to provide screening and stabilizing treatment – including abortion, if necessary – in emergency situations.

“It’s a challenge to balance both those two things,” said Dr. Puterbaugh, president of the Society of OB/GYN Hospitalists. “But it’s not really a challenge to me because, in my mind, the life and health of the mother always comes first.”

The Biden administration argues that EMTALA trumps state abortion bans in emergency situations. On Aug. 2, the Department of Justice filed a federal lawsuit challenging an Idaho law that bans abortion in nearly all circumstances. The suit claims the law would make it a criminal offense for medical providers to comply with EMTALA’s requirement to provide abortion, if needed, for women experiencing emergency pregnancy complications.

In a July policy guidance and letter, the Department of Health & Human Services reaffirmed that EMTALA requires hospitals and physicians to offer life- or health-saving medical services, including abortion, in emergency situations. The letter refers to situations such as ectopic pregnancies, severe blood pressure spikes known as preeclampsia, and premature ruptures of the membrane causing a woman’s water to break before her pregnancy is viable.

The guidance stressed that this federal requirement supersedes any state laws that bar abortion, and that hospitals and physicians who don’t comply with the federal mandate could face civil fines and termination from the Medicare and Medicaid programs.

There are no known reports so far of EMTALA investigations arising from denial of emergency care in pregnancy situations.

But elected officials in states that have sharply restricted abortion disagree with the federal judgment. Texas Attorney General Ken Paxton sued the Biden administration in July to prevent the federal government from using the EMTALA law to require abortions in emergency cases. The suit claims that EMTALA doesn’t specifically mandate particular medical procedures such as abortion.

Abortion foes argue that state antiabortion laws already include adequate exceptions when a pregnant woman’s life or health is in danger. John Seago, president of Texas Right to Life, said one of Texas’ laws specifies that treatment for ectopic pregnancies or miscarriages is not prohibited. In addition, the law defines a medical emergency allowing abortion as a condition in which a woman is at serious risk of a “substantial impairment of a major bodily function.”

Mr. Seago blamed the news media and medical associations for deliberately sowing confusion about the laws. “The law is very clear,” he said.

Legal wrangling aside, in practice, physicians and hospital lawyers say much depends on the interpretation of vaguely worded exceptions in state abortion bans, and that’s further complicated by the existence of contradictory laws, such as those banning abortion based on cardiac activity. And medical providers don’t want to risk criminal prosecution, fines, and loss of licensure if someone accuses them of violating these confusing laws.

Louise Joy, an attorney in Austin, Tex., who represents hospitals and other health care providers, said her clients perhaps are being overly cautious, but that’s not surprising. “I try to encourage them to do the right thing, but I can’t assure them they’ll be risk free.”

A lot hinges on when a pregnancy-ending complication is deemed an emergency, a moment that is hard to define. Some Missouri women have come to the hospital ED with mild cramping and bleeding and were found to have an ectopic pregnancy that hadn’t ruptured yet, colleagues have told Alison Haddock, MD, a Houston emergency physician who chairs the board of the American College of Emergency Physicians. The standard treatment is to provide the drug methotrexate, which can terminate a pregnancy.

“You’re stable until it ruptures, then it becomes unstable,” she said. “But how unstable do you need to be? The woman’s life is not clearly at risk yet. It’s not clear if EMTALA applies. There will be a lot of gray areas that make it really tough for emergency physicians who want to do what’s right for patients without violating any laws.”

Physicians and hospital attorneys are hoping for clearer federal guidance and guarantees of protection from state prosecutors who might oppose their medical judgment on political grounds.

“This is when we need the federal government to step up and say: ‘Doctors, you must provide the standard of care, and we will prevent the prosecution of anyone who is following appropriate medical practices and doing the right thing for patients,” Ms. Joy said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Each week, Kim Puterbaugh, MD, sees several pregnant patients at a Cleveland hospital who are experiencing complications involving bleeding or infection. The ob.gyn. has to make quick decisions about how to treat them, including whether to remove the dead or dying fetus to protect the health and life of the mother. Leaving in place a fetus that has no chance of survival dramatically increases the chance of maternal infection and permanent injury.

But now her medical decisions are complicated by Ohio’s new abortion law, which generally prohibits abortions after 6 weeks of pregnancy if cardiac activity is detected in the embryo or fetus – which can persist for hours or days even if a pregnancy has no chance of progressing. Given the new law, University Hospitals Cleveland Medical Center has streamlined its system of having an administrator and legal team on call for Dr. Puterbaugh and other physicians if anyone questions whether the planned treatment is allowed under the law.

Since the Supreme Court erased the constitutional right to abortion in June, Dr. Puterbaugh said these cases put her and doctors like her in an impossible position – squeezing doctors between antiabortion laws in Ohio and other states and the federal Emergency Medical Treatment & Labor Act. That 1986 law requires hospitals and physicians to provide screening and stabilizing treatment – including abortion, if necessary – in emergency situations.

“It’s a challenge to balance both those two things,” said Dr. Puterbaugh, president of the Society of OB/GYN Hospitalists. “But it’s not really a challenge to me because, in my mind, the life and health of the mother always comes first.”

The Biden administration argues that EMTALA trumps state abortion bans in emergency situations. On Aug. 2, the Department of Justice filed a federal lawsuit challenging an Idaho law that bans abortion in nearly all circumstances. The suit claims the law would make it a criminal offense for medical providers to comply with EMTALA’s requirement to provide abortion, if needed, for women experiencing emergency pregnancy complications.

In a July policy guidance and letter, the Department of Health & Human Services reaffirmed that EMTALA requires hospitals and physicians to offer life- or health-saving medical services, including abortion, in emergency situations. The letter refers to situations such as ectopic pregnancies, severe blood pressure spikes known as preeclampsia, and premature ruptures of the membrane causing a woman’s water to break before her pregnancy is viable.

The guidance stressed that this federal requirement supersedes any state laws that bar abortion, and that hospitals and physicians who don’t comply with the federal mandate could face civil fines and termination from the Medicare and Medicaid programs.

There are no known reports so far of EMTALA investigations arising from denial of emergency care in pregnancy situations.

But elected officials in states that have sharply restricted abortion disagree with the federal judgment. Texas Attorney General Ken Paxton sued the Biden administration in July to prevent the federal government from using the EMTALA law to require abortions in emergency cases. The suit claims that EMTALA doesn’t specifically mandate particular medical procedures such as abortion.

Abortion foes argue that state antiabortion laws already include adequate exceptions when a pregnant woman’s life or health is in danger. John Seago, president of Texas Right to Life, said one of Texas’ laws specifies that treatment for ectopic pregnancies or miscarriages is not prohibited. In addition, the law defines a medical emergency allowing abortion as a condition in which a woman is at serious risk of a “substantial impairment of a major bodily function.”

Mr. Seago blamed the news media and medical associations for deliberately sowing confusion about the laws. “The law is very clear,” he said.

Legal wrangling aside, in practice, physicians and hospital lawyers say much depends on the interpretation of vaguely worded exceptions in state abortion bans, and that’s further complicated by the existence of contradictory laws, such as those banning abortion based on cardiac activity. And medical providers don’t want to risk criminal prosecution, fines, and loss of licensure if someone accuses them of violating these confusing laws.

Louise Joy, an attorney in Austin, Tex., who represents hospitals and other health care providers, said her clients perhaps are being overly cautious, but that’s not surprising. “I try to encourage them to do the right thing, but I can’t assure them they’ll be risk free.”

A lot hinges on when a pregnancy-ending complication is deemed an emergency, a moment that is hard to define. Some Missouri women have come to the hospital ED with mild cramping and bleeding and were found to have an ectopic pregnancy that hadn’t ruptured yet, colleagues have told Alison Haddock, MD, a Houston emergency physician who chairs the board of the American College of Emergency Physicians. The standard treatment is to provide the drug methotrexate, which can terminate a pregnancy.

“You’re stable until it ruptures, then it becomes unstable,” she said. “But how unstable do you need to be? The woman’s life is not clearly at risk yet. It’s not clear if EMTALA applies. There will be a lot of gray areas that make it really tough for emergency physicians who want to do what’s right for patients without violating any laws.”

Physicians and hospital attorneys are hoping for clearer federal guidance and guarantees of protection from state prosecutors who might oppose their medical judgment on political grounds.

“This is when we need the federal government to step up and say: ‘Doctors, you must provide the standard of care, and we will prevent the prosecution of anyone who is following appropriate medical practices and doing the right thing for patients,” Ms. Joy said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

People who are severely ill with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often too sick to leave home, but clinicians can still support them in many ways, experts say.

Approximately 250,000 people in the United Kingdom (0.2%-0.4%) have ME/CFS – where it’s called “ME.” As many as 2.5 million in the United States have it. Those numbers are expected to dramatically increase with the addition of people with long COVID. An estimated 25% of patients with the condition are so severely impaired that they are housebound or bedbound to the point where they’re unable to attend medical office visits. There are very few data about them because they’re typically unable to participate in studies.

Speaking at the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME), patient advocate Helen Baxter, of the U.K. charity 25% ME Group, presented a case series of five patients bedbound with ME/CFS who became severely malnourished because of delays in the placement of feeding tubes. The delays occurred because it was not recognized that the patients were unable to eat. The inability to eat may be due to a variety of factors, including gastrointestinal dysfunction, dysphagia, nausea, or lack of sufficient energy to eat or drink.

A report of those cases was included in a special issue of Healthcare, devoted to the topic of severe and very severe ME/CFS. The issue, which was published in April 2021, included 25 articles on the pathophysiology of severe ME/CFS, ways that clinicians can support patients who are too sick to make office visits, and psychosocial aspects of the condition that result from physical debilitation.

Two additional articles by specialist physicians aim to counter the skepticism about ME/CFS that has long persisted among some in the medical community.

“ME/CFS is under-researched and has historically received insufficient funding for research, particularly when compared to other chronic conditions, such as multiple sclerosis. And most of the research that has been done about it has focused on patients who are able to attend clinics. Patients with severe ME/CFS have largely been excluded from research due to the severity of their illness and are often described as ‘hard to reach.’ Consequently, research into severe ME is very limited,” Ms. Baxter said.

Asked to comment, Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, told this news organization, “It’s a big gap, even in the knowledgeable community. The research is totally skewed towards people who can get up and go participate in research. ... I don’t think most clinicians have any idea how sick people can get with ME/CFS.”

Cardiopulmonary exercise testing (CPET), which is commonly used in research, is intended to elicit objective biomarker responses. Such testing, which is considered the gold standard for determining disability, is impossible for the most severely ill patients with ME/CFS and is potentially harmful to these patients because of the hallmark postexertional malaise (PEM) phenomenon, Dr. Bateman noted.

“If we want to use CPET for research, we have to remember that it harms people to some degree and that we’re only studying the people who aren’t as sick. ... It’s one of the reasons I’ve been aggressively pursuing medical education about orthostatic testing, because it’s a clear objective marker, not as deleterious, and potentially leads to treatment options,” she said.

Misdiagnosis, treatment delays led to life-threatening malnutrition

The five patients that Ms. Baxter presented had become severely malnourished and dehydrated. There was evidence of clinical inertia for each of them.

“All were judged to have anorexia nervosa, and psychiatrists were involved, which was an added delay to starting tube feeding. ... In each case, the doctors resorted to making inappropriate psychological diagnoses without positive evidence of psychopathology, failing to recognize the significance of the malnutrition,” Ms. Baxter said. (Urgent tube feeding would have been warranted even had anorexia nervosa been the correct diagnosis, she pointed out.)

Once the problem was finally recognized, “all participants saw an improvement in their situation following the allocation of a home enteral nutrition dietician.”

At the IACFS/ME conference, Ms. Baxter described the painstaking methods used for gathering information, which were described in the same journal. These involved a combination of online, telephone, and text communications with patients or their caregivers. Efforts were made to avoid overtaxing the patients and triggering PEM.

“An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake, prompt action is taken, and tube feeding started, thereby avoiding undernutrition in patients with very severe ME,” Ms. Baxter and colleagues write.

Indeed, coauthor and semiretired pediatric ME/CFS specialist physician Nigel Speight, of Durham, United Kingdom, said in an interview, “In most of my patients, I used tube feeding early simply to avoid using unnecessary energy and causing stress to the patient.”

Dr. Speight added, “Patients can also die from sheer weakness leading to lack of respiratory drive. Also, and very understandably, some commit suicide.”
 

Caring for the patient with severe or very severe ME/CFS

Appearing in the special issue is an article entitled, “Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. It was authored by a multidisciplinary group led by Jose G. Montoya, MD, of the Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Calif.

In that article, four levels of severity are defined: mild, moderate, severe, and very severe. Included in the “severe” category are patients who are mostly homebound and whose activities of daily living are limited. They may have severe cognitive difficulties. Patients in the “very severe” caregory are bedbound and are unable to care for themselves.

Clinical features include more extreme versions of the core ME/CFS criteria: profound fatigue/weakness, PEM, unrefreshing sleep, orthostatic intolerance, and cognitive impairment. Additional symptoms in those with severe/very severe ME can include extreme hypersensitivity to light, sound, touch, and/or odors. Even small amounts of physical, mental, emotional, and orthostatic stressors can trigger PEM and increased weakness.

The authors recommend a “patient-centered, collaborative approach that is grounded in compassion and respect for the patient in all interactions,” and they provide lists of steps providers can take. These include seeing patients at home if possible and considerations regarding that care, such as partnering with the patient’s caregivers and other health care providers, who may include physical and occupational therapists, home health nurses, and social workers who understand the condition. Home visits by optometrists or ophthalmologists and dentists may be required.

Documenting limitations in activities of daily living is particularly important for helping patients to obtain homecare and disability benefits, Dr. Montoya and colleagues say.

Clinicians should investigate any medical problems that may be amenable to treatment, including orthostatic intolerance, pain, sleep difficulties, comorbidities, or gastrointestinal problems. For patients with pain, bloating, and diarrhea who are found on assessment to have mast cell activation disorder (MCAD), a trial of sodium cromoglicate may be tried, Ms. Baxter told this news organization.

Nonmedical problems that may be contributing to the patient’s morbidity should also be assessed, including a lack of caretaking, social services, transportation, food, and/or supportive devices, such as wheelchairs, bedpans, feeding tubes, and catheters.

The article provides additional detailed recommendations regarding pharmacologic treatments, follow-up visits – in-person or virtual – and hospitalization, as well as recommendations for energy conservation and management.

A section titled Practical Considerations for Busy Providers includes advice to be aware of any regulatory or insurance requirements for providing home visits and to maximize reimbursement by diagnosing any comorbidities, such as postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, or MCAD.

Dr. Speight, who authored an article in the special issue on the management of ME in children, called the article by Dr. Montoya and colleagues “absolutely excellent,” and added his own advice, which included not “overinvestigating to cover your back but at the expense of causing stress to the patient” and considering a trial of immunoglobulin.

Importantly, Dr. Speight stressed, “avoid referral to psychiatrists unless specifically indicated for additional psychiatric morbidity; in which case, make clear that the psychiatrist accepts [that the] basic illness is medical.”

He also advised that clinicians stop using the term “chronic fatigue syndrome” because it suggests the illness is mild and/or psychosomatic. “Maybe the United States should embrace the term ME once and for all,” he said.

Dr. Baxter, Dr. Speight, and Dr. Montoya have disclosed no relevant financial relationships. Dr. Bateman is conducting research for Terra Biological.

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

People who are severely ill with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often too sick to leave home, but clinicians can still support them in many ways, experts say.

Approximately 250,000 people in the United Kingdom (0.2%-0.4%) have ME/CFS – where it’s called “ME.” As many as 2.5 million in the United States have it. Those numbers are expected to dramatically increase with the addition of people with long COVID. An estimated 25% of patients with the condition are so severely impaired that they are housebound or bedbound to the point where they’re unable to attend medical office visits. There are very few data about them because they’re typically unable to participate in studies.

Speaking at the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME), patient advocate Helen Baxter, of the U.K. charity 25% ME Group, presented a case series of five patients bedbound with ME/CFS who became severely malnourished because of delays in the placement of feeding tubes. The delays occurred because it was not recognized that the patients were unable to eat. The inability to eat may be due to a variety of factors, including gastrointestinal dysfunction, dysphagia, nausea, or lack of sufficient energy to eat or drink.

A report of those cases was included in a special issue of Healthcare, devoted to the topic of severe and very severe ME/CFS. The issue, which was published in April 2021, included 25 articles on the pathophysiology of severe ME/CFS, ways that clinicians can support patients who are too sick to make office visits, and psychosocial aspects of the condition that result from physical debilitation.

Two additional articles by specialist physicians aim to counter the skepticism about ME/CFS that has long persisted among some in the medical community.

“ME/CFS is under-researched and has historically received insufficient funding for research, particularly when compared to other chronic conditions, such as multiple sclerosis. And most of the research that has been done about it has focused on patients who are able to attend clinics. Patients with severe ME/CFS have largely been excluded from research due to the severity of their illness and are often described as ‘hard to reach.’ Consequently, research into severe ME is very limited,” Ms. Baxter said.

Asked to comment, Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, told this news organization, “It’s a big gap, even in the knowledgeable community. The research is totally skewed towards people who can get up and go participate in research. ... I don’t think most clinicians have any idea how sick people can get with ME/CFS.”

Cardiopulmonary exercise testing (CPET), which is commonly used in research, is intended to elicit objective biomarker responses. Such testing, which is considered the gold standard for determining disability, is impossible for the most severely ill patients with ME/CFS and is potentially harmful to these patients because of the hallmark postexertional malaise (PEM) phenomenon, Dr. Bateman noted.

“If we want to use CPET for research, we have to remember that it harms people to some degree and that we’re only studying the people who aren’t as sick. ... It’s one of the reasons I’ve been aggressively pursuing medical education about orthostatic testing, because it’s a clear objective marker, not as deleterious, and potentially leads to treatment options,” she said.

Misdiagnosis, treatment delays led to life-threatening malnutrition

The five patients that Ms. Baxter presented had become severely malnourished and dehydrated. There was evidence of clinical inertia for each of them.

“All were judged to have anorexia nervosa, and psychiatrists were involved, which was an added delay to starting tube feeding. ... In each case, the doctors resorted to making inappropriate psychological diagnoses without positive evidence of psychopathology, failing to recognize the significance of the malnutrition,” Ms. Baxter said. (Urgent tube feeding would have been warranted even had anorexia nervosa been the correct diagnosis, she pointed out.)

Once the problem was finally recognized, “all participants saw an improvement in their situation following the allocation of a home enteral nutrition dietician.”

At the IACFS/ME conference, Ms. Baxter described the painstaking methods used for gathering information, which were described in the same journal. These involved a combination of online, telephone, and text communications with patients or their caregivers. Efforts were made to avoid overtaxing the patients and triggering PEM.

“An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake, prompt action is taken, and tube feeding started, thereby avoiding undernutrition in patients with very severe ME,” Ms. Baxter and colleagues write.

Indeed, coauthor and semiretired pediatric ME/CFS specialist physician Nigel Speight, of Durham, United Kingdom, said in an interview, “In most of my patients, I used tube feeding early simply to avoid using unnecessary energy and causing stress to the patient.”

Dr. Speight added, “Patients can also die from sheer weakness leading to lack of respiratory drive. Also, and very understandably, some commit suicide.”
 

Caring for the patient with severe or very severe ME/CFS

Appearing in the special issue is an article entitled, “Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. It was authored by a multidisciplinary group led by Jose G. Montoya, MD, of the Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Calif.

In that article, four levels of severity are defined: mild, moderate, severe, and very severe. Included in the “severe” category are patients who are mostly homebound and whose activities of daily living are limited. They may have severe cognitive difficulties. Patients in the “very severe” caregory are bedbound and are unable to care for themselves.

Clinical features include more extreme versions of the core ME/CFS criteria: profound fatigue/weakness, PEM, unrefreshing sleep, orthostatic intolerance, and cognitive impairment. Additional symptoms in those with severe/very severe ME can include extreme hypersensitivity to light, sound, touch, and/or odors. Even small amounts of physical, mental, emotional, and orthostatic stressors can trigger PEM and increased weakness.

The authors recommend a “patient-centered, collaborative approach that is grounded in compassion and respect for the patient in all interactions,” and they provide lists of steps providers can take. These include seeing patients at home if possible and considerations regarding that care, such as partnering with the patient’s caregivers and other health care providers, who may include physical and occupational therapists, home health nurses, and social workers who understand the condition. Home visits by optometrists or ophthalmologists and dentists may be required.

Documenting limitations in activities of daily living is particularly important for helping patients to obtain homecare and disability benefits, Dr. Montoya and colleagues say.

Clinicians should investigate any medical problems that may be amenable to treatment, including orthostatic intolerance, pain, sleep difficulties, comorbidities, or gastrointestinal problems. For patients with pain, bloating, and diarrhea who are found on assessment to have mast cell activation disorder (MCAD), a trial of sodium cromoglicate may be tried, Ms. Baxter told this news organization.

Nonmedical problems that may be contributing to the patient’s morbidity should also be assessed, including a lack of caretaking, social services, transportation, food, and/or supportive devices, such as wheelchairs, bedpans, feeding tubes, and catheters.

The article provides additional detailed recommendations regarding pharmacologic treatments, follow-up visits – in-person or virtual – and hospitalization, as well as recommendations for energy conservation and management.

A section titled Practical Considerations for Busy Providers includes advice to be aware of any regulatory or insurance requirements for providing home visits and to maximize reimbursement by diagnosing any comorbidities, such as postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, or MCAD.

Dr. Speight, who authored an article in the special issue on the management of ME in children, called the article by Dr. Montoya and colleagues “absolutely excellent,” and added his own advice, which included not “overinvestigating to cover your back but at the expense of causing stress to the patient” and considering a trial of immunoglobulin.

Importantly, Dr. Speight stressed, “avoid referral to psychiatrists unless specifically indicated for additional psychiatric morbidity; in which case, make clear that the psychiatrist accepts [that the] basic illness is medical.”

He also advised that clinicians stop using the term “chronic fatigue syndrome” because it suggests the illness is mild and/or psychosomatic. “Maybe the United States should embrace the term ME once and for all,” he said.

Dr. Baxter, Dr. Speight, and Dr. Montoya have disclosed no relevant financial relationships. Dr. Bateman is conducting research for Terra Biological.

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

People who are severely ill with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often too sick to leave home, but clinicians can still support them in many ways, experts say.

Approximately 250,000 people in the United Kingdom (0.2%-0.4%) have ME/CFS – where it’s called “ME.” As many as 2.5 million in the United States have it. Those numbers are expected to dramatically increase with the addition of people with long COVID. An estimated 25% of patients with the condition are so severely impaired that they are housebound or bedbound to the point where they’re unable to attend medical office visits. There are very few data about them because they’re typically unable to participate in studies.

Speaking at the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME), patient advocate Helen Baxter, of the U.K. charity 25% ME Group, presented a case series of five patients bedbound with ME/CFS who became severely malnourished because of delays in the placement of feeding tubes. The delays occurred because it was not recognized that the patients were unable to eat. The inability to eat may be due to a variety of factors, including gastrointestinal dysfunction, dysphagia, nausea, or lack of sufficient energy to eat or drink.

A report of those cases was included in a special issue of Healthcare, devoted to the topic of severe and very severe ME/CFS. The issue, which was published in April 2021, included 25 articles on the pathophysiology of severe ME/CFS, ways that clinicians can support patients who are too sick to make office visits, and psychosocial aspects of the condition that result from physical debilitation.

Two additional articles by specialist physicians aim to counter the skepticism about ME/CFS that has long persisted among some in the medical community.

“ME/CFS is under-researched and has historically received insufficient funding for research, particularly when compared to other chronic conditions, such as multiple sclerosis. And most of the research that has been done about it has focused on patients who are able to attend clinics. Patients with severe ME/CFS have largely been excluded from research due to the severity of their illness and are often described as ‘hard to reach.’ Consequently, research into severe ME is very limited,” Ms. Baxter said.

Asked to comment, Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, told this news organization, “It’s a big gap, even in the knowledgeable community. The research is totally skewed towards people who can get up and go participate in research. ... I don’t think most clinicians have any idea how sick people can get with ME/CFS.”

Cardiopulmonary exercise testing (CPET), which is commonly used in research, is intended to elicit objective biomarker responses. Such testing, which is considered the gold standard for determining disability, is impossible for the most severely ill patients with ME/CFS and is potentially harmful to these patients because of the hallmark postexertional malaise (PEM) phenomenon, Dr. Bateman noted.

“If we want to use CPET for research, we have to remember that it harms people to some degree and that we’re only studying the people who aren’t as sick. ... It’s one of the reasons I’ve been aggressively pursuing medical education about orthostatic testing, because it’s a clear objective marker, not as deleterious, and potentially leads to treatment options,” she said.

Misdiagnosis, treatment delays led to life-threatening malnutrition

The five patients that Ms. Baxter presented had become severely malnourished and dehydrated. There was evidence of clinical inertia for each of them.

“All were judged to have anorexia nervosa, and psychiatrists were involved, which was an added delay to starting tube feeding. ... In each case, the doctors resorted to making inappropriate psychological diagnoses without positive evidence of psychopathology, failing to recognize the significance of the malnutrition,” Ms. Baxter said. (Urgent tube feeding would have been warranted even had anorexia nervosa been the correct diagnosis, she pointed out.)

Once the problem was finally recognized, “all participants saw an improvement in their situation following the allocation of a home enteral nutrition dietician.”

At the IACFS/ME conference, Ms. Baxter described the painstaking methods used for gathering information, which were described in the same journal. These involved a combination of online, telephone, and text communications with patients or their caregivers. Efforts were made to avoid overtaxing the patients and triggering PEM.

“An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake, prompt action is taken, and tube feeding started, thereby avoiding undernutrition in patients with very severe ME,” Ms. Baxter and colleagues write.

Indeed, coauthor and semiretired pediatric ME/CFS specialist physician Nigel Speight, of Durham, United Kingdom, said in an interview, “In most of my patients, I used tube feeding early simply to avoid using unnecessary energy and causing stress to the patient.”

Dr. Speight added, “Patients can also die from sheer weakness leading to lack of respiratory drive. Also, and very understandably, some commit suicide.”
 

Caring for the patient with severe or very severe ME/CFS

Appearing in the special issue is an article entitled, “Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. It was authored by a multidisciplinary group led by Jose G. Montoya, MD, of the Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Calif.

In that article, four levels of severity are defined: mild, moderate, severe, and very severe. Included in the “severe” category are patients who are mostly homebound and whose activities of daily living are limited. They may have severe cognitive difficulties. Patients in the “very severe” caregory are bedbound and are unable to care for themselves.

Clinical features include more extreme versions of the core ME/CFS criteria: profound fatigue/weakness, PEM, unrefreshing sleep, orthostatic intolerance, and cognitive impairment. Additional symptoms in those with severe/very severe ME can include extreme hypersensitivity to light, sound, touch, and/or odors. Even small amounts of physical, mental, emotional, and orthostatic stressors can trigger PEM and increased weakness.

The authors recommend a “patient-centered, collaborative approach that is grounded in compassion and respect for the patient in all interactions,” and they provide lists of steps providers can take. These include seeing patients at home if possible and considerations regarding that care, such as partnering with the patient’s caregivers and other health care providers, who may include physical and occupational therapists, home health nurses, and social workers who understand the condition. Home visits by optometrists or ophthalmologists and dentists may be required.

Documenting limitations in activities of daily living is particularly important for helping patients to obtain homecare and disability benefits, Dr. Montoya and colleagues say.

Clinicians should investigate any medical problems that may be amenable to treatment, including orthostatic intolerance, pain, sleep difficulties, comorbidities, or gastrointestinal problems. For patients with pain, bloating, and diarrhea who are found on assessment to have mast cell activation disorder (MCAD), a trial of sodium cromoglicate may be tried, Ms. Baxter told this news organization.

Nonmedical problems that may be contributing to the patient’s morbidity should also be assessed, including a lack of caretaking, social services, transportation, food, and/or supportive devices, such as wheelchairs, bedpans, feeding tubes, and catheters.

The article provides additional detailed recommendations regarding pharmacologic treatments, follow-up visits – in-person or virtual – and hospitalization, as well as recommendations for energy conservation and management.

A section titled Practical Considerations for Busy Providers includes advice to be aware of any regulatory or insurance requirements for providing home visits and to maximize reimbursement by diagnosing any comorbidities, such as postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, or MCAD.

Dr. Speight, who authored an article in the special issue on the management of ME in children, called the article by Dr. Montoya and colleagues “absolutely excellent,” and added his own advice, which included not “overinvestigating to cover your back but at the expense of causing stress to the patient” and considering a trial of immunoglobulin.

Importantly, Dr. Speight stressed, “avoid referral to psychiatrists unless specifically indicated for additional psychiatric morbidity; in which case, make clear that the psychiatrist accepts [that the] basic illness is medical.”

He also advised that clinicians stop using the term “chronic fatigue syndrome” because it suggests the illness is mild and/or psychosomatic. “Maybe the United States should embrace the term ME once and for all,” he said.

Dr. Baxter, Dr. Speight, and Dr. Montoya have disclosed no relevant financial relationships. Dr. Bateman is conducting research for Terra Biological.

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

Pain is classified as chronic when it lasts or recurs for more than 3-6 months (“Classification of chronic pain” 2nd ed. Seattle: IASP Press, 1994). This universally accepted definition does not distinguish between physical and emotional pain. Categorically, pain is pain. Two prevalent chronic gynecologic diseases are closely related medically and emotionally. Forty percent to 50% of women with endometriosis have infertility; 30%-50% of women with infertility are found to have coexisting endometriosis. The approach to both is, typically, symptomatic treatment. In this month’s column, I examine the relationship between these ailments and how we can advise women on management.

Endometriosis is simply defined as the displacement of normal endometrial glands and stroma from their natural anatomical location to elsewhere in the body. With the recent identification of the disease in the spleen, endometriosis has been found in every organ system. Endometriosis is identified in 6%-10% of the general female population. The prevalence ranges from 2% to 11% among asymptomatic women and from 5% to 21% in women hospitalized for pelvic pain (Best Pract Res Clin Obstet Gynaecol. 2018;51:1-15). Compared with fertile women, infertile women are six to eight times more likely to have endometriosis (Fertil Steril. 2012;98:591-8).

Retrograde menstruation is the presumed theory for the origins of endometriosis, that is, the reflux of menstrual debris containing active endometrial cells through the fallopian tubes into the peritoneal cavity (Am J Obstet Gynecol. 1927;14:422-69). Because of the varied etiologies of the most common symptoms of endometriosis, dysmenorrhea, dyspareunia, dyschezia, and infertility, women visit, on average, seven physicians before being diagnosed (Fertil Steril. 2011;96:366). The delay in promptly identifying endometriosis is further impaired by the lack of specific biomarkers, awareness, and inadequate evaluation (N Engl J Med. 2020;382:1244-56).

The 2008 U.S. health care costs for endometriosis were approximately $4,000 per affected woman, analogous to the costs for other chronic conditions such as type 2 diabetes, Crohn’s disease, and rheumatoid arthritis (Hum Reprod. 2012;27:1292-9). The management of symptoms further increases the financial burden because of the effect of the disease on physical, mental, sexual, and social well-being, as well as productivity (Health Qual Life Outcomes. 2019;17:123).

We have known the paradoxical relationship between the stage of endometriosis and symptoms: Women with low-stage disease may present with severe pain and/or infertility but those with advanced-stage disease may be asymptomatic. Endometriotic cells and tissue elicit a localized immune and inflammatory response with the production of cytokines, chemokines, and prostaglandins. Given the usual intra-abdominal location and the small size of implants, endometriosis requires a surgical diagnosis, ideally with histopathology for confirmation. However, imaging – transvaginal ultrasound or MRI – has more than 90% sensitivity and specificity for identifying endometriomas (Cochrane Database Syst Rev. 2016;2[2]:CD009591).

The effect of endometriosis on fertility, particularly in women with minimal to mild stages, is not clear, and many studies have been retrospective. Tubal factor infertility can be a result of endometriosis. Per the 2020 Cochrane Database Systemic Reviews (2020 Oct;2020[10]:CD011031), “Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis; no data were reported on live birth. There is moderate-quality evidence that laparoscopic surgery increases viable intrauterine pregnancy rates confirmed by ultrasound compared to diagnostic laparoscopy only.” In women undergoing IVF, more advanced stages of endometriosis have reduced pregnancy outcomes as shown in recent meta-analyses (Obstet Gynecol. 2015;125:79-88).

The revised ASRM (rASRM) surgical staging classification of endometriosis has been widely used to describe the degree, although it poorly correlates with fertility potential (Fertil Steril. 2012;98:591-8). Women diagnosed with endometriosis may benefit from the Endometriosis Fertility Index (EFI), published in 2010 as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and intrauterine insemination) based on patient characteristics, rASRM staging and “least function” score of the adnexa (Fertil Steril. 2010;94:1609-15).

Compared with diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. “Further research is needed considering the management of different subtypes of endometriosis and comparing laparoscopic interventions with lifestyle and medical interventions (Cochrane Database Syst Rev. 2020 Oct;2020[10]:CD011031).”

The treatment of endometriosis is directly related to the desire for and timing of fertility since therapy is often contraceptive, as opposed to surgery. Because endometriosis is exacerbated by estradiol, the mainstay of medical therapy is initially combined hormonal or progestin-only contraception as a means of reducing pelvic pain by reducing estradiol production and action, respectively. GnRH-agonist suppression of follicle stimulation hormone and luteinizing hormone remains the standard for inactivating endogenous estradiol. In 2018, the U.S. Food and Drug Administration approved elagolix for the treatment of pain associated with endometriosis – the first pill specifically approved for endometriosis pain relief. An off-label approach for women is letrozole, the aromatase inhibitor, to reduce circulating estradiol levels. Unfortunately, estradiol suppression cannot be used solely long term without add-back therapy, because of the risk of bone loss and vasomotor symptoms.

Excision of endometriomas adversely affects ovarian follicular reserve (as indicated by lower levels of anti-müllerian hormone and reduced ovarian antral follicle counts on ultrasound). For women who want to preserve their fertility, the potential benefits of surgery should be weighed against these negative effects. Surgical treatment of endometriosis in women without other identifiable infertility factors may improve rates of spontaneous pregnancy. In women with moderate to severe endometriosis, intrauterine insemination with ovarian stimulation may be of value, particularly with preceding GnRH-agonist therapy (J Endometr Pelvic Pain Disord. 2018;10[3]:158-73).

Despite the reduction in IVF outcomes in women with moderate to severe endometriosis, it remains unclear whether surgery improves the likelihood of pregnancy with IVF as does the concurrent use of prolonged GnRH agonist during IVF stimulation. (Fertil Steril. 2012;98:591-8).

Summary

• Medical therapy alone does not appear to improve fertility in endometriosis.
• Surgical treatment of endometriosis improves natural fertility, particularly in lower-stage endometriosis.
• EFI is a useful tool to predict postoperative natural fertility and assess the need for IVF.
• Despite advanced endometriosis reducing IVF outcomes, surgery or medical pretreatment to increase IVF success remains unproven.

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.

Pain is classified as chronic when it lasts or recurs for more than 3-6 months (“Classification of chronic pain” 2nd ed. Seattle: IASP Press, 1994). This universally accepted definition does not distinguish between physical and emotional pain. Categorically, pain is pain. Two prevalent chronic gynecologic diseases are closely related medically and emotionally. Forty percent to 50% of women with endometriosis have infertility; 30%-50% of women with infertility are found to have coexisting endometriosis. The approach to both is, typically, symptomatic treatment. In this month’s column, I examine the relationship between these ailments and how we can advise women on management.

Endometriosis is simply defined as the displacement of normal endometrial glands and stroma from their natural anatomical location to elsewhere in the body. With the recent identification of the disease in the spleen, endometriosis has been found in every organ system. Endometriosis is identified in 6%-10% of the general female population. The prevalence ranges from 2% to 11% among asymptomatic women and from 5% to 21% in women hospitalized for pelvic pain (Best Pract Res Clin Obstet Gynaecol. 2018;51:1-15). Compared with fertile women, infertile women are six to eight times more likely to have endometriosis (Fertil Steril. 2012;98:591-8).

Retrograde menstruation is the presumed theory for the origins of endometriosis, that is, the reflux of menstrual debris containing active endometrial cells through the fallopian tubes into the peritoneal cavity (Am J Obstet Gynecol. 1927;14:422-69). Because of the varied etiologies of the most common symptoms of endometriosis, dysmenorrhea, dyspareunia, dyschezia, and infertility, women visit, on average, seven physicians before being diagnosed (Fertil Steril. 2011;96:366). The delay in promptly identifying endometriosis is further impaired by the lack of specific biomarkers, awareness, and inadequate evaluation (N Engl J Med. 2020;382:1244-56).

The 2008 U.S. health care costs for endometriosis were approximately $4,000 per affected woman, analogous to the costs for other chronic conditions such as type 2 diabetes, Crohn’s disease, and rheumatoid arthritis (Hum Reprod. 2012;27:1292-9). The management of symptoms further increases the financial burden because of the effect of the disease on physical, mental, sexual, and social well-being, as well as productivity (Health Qual Life Outcomes. 2019;17:123).

We have known the paradoxical relationship between the stage of endometriosis and symptoms: Women with low-stage disease may present with severe pain and/or infertility but those with advanced-stage disease may be asymptomatic. Endometriotic cells and tissue elicit a localized immune and inflammatory response with the production of cytokines, chemokines, and prostaglandins. Given the usual intra-abdominal location and the small size of implants, endometriosis requires a surgical diagnosis, ideally with histopathology for confirmation. However, imaging – transvaginal ultrasound or MRI – has more than 90% sensitivity and specificity for identifying endometriomas (Cochrane Database Syst Rev. 2016;2[2]:CD009591).

The effect of endometriosis on fertility, particularly in women with minimal to mild stages, is not clear, and many studies have been retrospective. Tubal factor infertility can be a result of endometriosis. Per the 2020 Cochrane Database Systemic Reviews (2020 Oct;2020[10]:CD011031), “Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis; no data were reported on live birth. There is moderate-quality evidence that laparoscopic surgery increases viable intrauterine pregnancy rates confirmed by ultrasound compared to diagnostic laparoscopy only.” In women undergoing IVF, more advanced stages of endometriosis have reduced pregnancy outcomes as shown in recent meta-analyses (Obstet Gynecol. 2015;125:79-88).

The revised ASRM (rASRM) surgical staging classification of endometriosis has been widely used to describe the degree, although it poorly correlates with fertility potential (Fertil Steril. 2012;98:591-8). Women diagnosed with endometriosis may benefit from the Endometriosis Fertility Index (EFI), published in 2010 as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and intrauterine insemination) based on patient characteristics, rASRM staging and “least function” score of the adnexa (Fertil Steril. 2010;94:1609-15).

Compared with diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. “Further research is needed considering the management of different subtypes of endometriosis and comparing laparoscopic interventions with lifestyle and medical interventions (Cochrane Database Syst Rev. 2020 Oct;2020[10]:CD011031).”

The treatment of endometriosis is directly related to the desire for and timing of fertility since therapy is often contraceptive, as opposed to surgery. Because endometriosis is exacerbated by estradiol, the mainstay of medical therapy is initially combined hormonal or progestin-only contraception as a means of reducing pelvic pain by reducing estradiol production and action, respectively. GnRH-agonist suppression of follicle stimulation hormone and luteinizing hormone remains the standard for inactivating endogenous estradiol. In 2018, the U.S. Food and Drug Administration approved elagolix for the treatment of pain associated with endometriosis – the first pill specifically approved for endometriosis pain relief. An off-label approach for women is letrozole, the aromatase inhibitor, to reduce circulating estradiol levels. Unfortunately, estradiol suppression cannot be used solely long term without add-back therapy, because of the risk of bone loss and vasomotor symptoms.

Excision of endometriomas adversely affects ovarian follicular reserve (as indicated by lower levels of anti-müllerian hormone and reduced ovarian antral follicle counts on ultrasound). For women who want to preserve their fertility, the potential benefits of surgery should be weighed against these negative effects. Surgical treatment of endometriosis in women without other identifiable infertility factors may improve rates of spontaneous pregnancy. In women with moderate to severe endometriosis, intrauterine insemination with ovarian stimulation may be of value, particularly with preceding GnRH-agonist therapy (J Endometr Pelvic Pain Disord. 2018;10[3]:158-73).

Despite the reduction in IVF outcomes in women with moderate to severe endometriosis, it remains unclear whether surgery improves the likelihood of pregnancy with IVF as does the concurrent use of prolonged GnRH agonist during IVF stimulation. (Fertil Steril. 2012;98:591-8).

Summary

• Medical therapy alone does not appear to improve fertility in endometriosis.
• Surgical treatment of endometriosis improves natural fertility, particularly in lower-stage endometriosis.
• EFI is a useful tool to predict postoperative natural fertility and assess the need for IVF.
• Despite advanced endometriosis reducing IVF outcomes, surgery or medical pretreatment to increase IVF success remains unproven.

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.

Pain is classified as chronic when it lasts or recurs for more than 3-6 months (“Classification of chronic pain” 2nd ed. Seattle: IASP Press, 1994). This universally accepted definition does not distinguish between physical and emotional pain. Categorically, pain is pain. Two prevalent chronic gynecologic diseases are closely related medically and emotionally. Forty percent to 50% of women with endometriosis have infertility; 30%-50% of women with infertility are found to have coexisting endometriosis. The approach to both is, typically, symptomatic treatment. In this month’s column, I examine the relationship between these ailments and how we can advise women on management.

Endometriosis is simply defined as the displacement of normal endometrial glands and stroma from their natural anatomical location to elsewhere in the body. With the recent identification of the disease in the spleen, endometriosis has been found in every organ system. Endometriosis is identified in 6%-10% of the general female population. The prevalence ranges from 2% to 11% among asymptomatic women and from 5% to 21% in women hospitalized for pelvic pain (Best Pract Res Clin Obstet Gynaecol. 2018;51:1-15). Compared with fertile women, infertile women are six to eight times more likely to have endometriosis (Fertil Steril. 2012;98:591-8).

Retrograde menstruation is the presumed theory for the origins of endometriosis, that is, the reflux of menstrual debris containing active endometrial cells through the fallopian tubes into the peritoneal cavity (Am J Obstet Gynecol. 1927;14:422-69). Because of the varied etiologies of the most common symptoms of endometriosis, dysmenorrhea, dyspareunia, dyschezia, and infertility, women visit, on average, seven physicians before being diagnosed (Fertil Steril. 2011;96:366). The delay in promptly identifying endometriosis is further impaired by the lack of specific biomarkers, awareness, and inadequate evaluation (N Engl J Med. 2020;382:1244-56).

The 2008 U.S. health care costs for endometriosis were approximately $4,000 per affected woman, analogous to the costs for other chronic conditions such as type 2 diabetes, Crohn’s disease, and rheumatoid arthritis (Hum Reprod. 2012;27:1292-9). The management of symptoms further increases the financial burden because of the effect of the disease on physical, mental, sexual, and social well-being, as well as productivity (Health Qual Life Outcomes. 2019;17:123).

We have known the paradoxical relationship between the stage of endometriosis and symptoms: Women with low-stage disease may present with severe pain and/or infertility but those with advanced-stage disease may be asymptomatic. Endometriotic cells and tissue elicit a localized immune and inflammatory response with the production of cytokines, chemokines, and prostaglandins. Given the usual intra-abdominal location and the small size of implants, endometriosis requires a surgical diagnosis, ideally with histopathology for confirmation. However, imaging – transvaginal ultrasound or MRI – has more than 90% sensitivity and specificity for identifying endometriomas (Cochrane Database Syst Rev. 2016;2[2]:CD009591).

The effect of endometriosis on fertility, particularly in women with minimal to mild stages, is not clear, and many studies have been retrospective. Tubal factor infertility can be a result of endometriosis. Per the 2020 Cochrane Database Systemic Reviews (2020 Oct;2020[10]:CD011031), “Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis; no data were reported on live birth. There is moderate-quality evidence that laparoscopic surgery increases viable intrauterine pregnancy rates confirmed by ultrasound compared to diagnostic laparoscopy only.” In women undergoing IVF, more advanced stages of endometriosis have reduced pregnancy outcomes as shown in recent meta-analyses (Obstet Gynecol. 2015;125:79-88).

The revised ASRM (rASRM) surgical staging classification of endometriosis has been widely used to describe the degree, although it poorly correlates with fertility potential (Fertil Steril. 2012;98:591-8). Women diagnosed with endometriosis may benefit from the Endometriosis Fertility Index (EFI), published in 2010 as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and intrauterine insemination) based on patient characteristics, rASRM staging and “least function” score of the adnexa (Fertil Steril. 2010;94:1609-15).

Compared with diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. “Further research is needed considering the management of different subtypes of endometriosis and comparing laparoscopic interventions with lifestyle and medical interventions (Cochrane Database Syst Rev. 2020 Oct;2020[10]:CD011031).”

The treatment of endometriosis is directly related to the desire for and timing of fertility since therapy is often contraceptive, as opposed to surgery. Because endometriosis is exacerbated by estradiol, the mainstay of medical therapy is initially combined hormonal or progestin-only contraception as a means of reducing pelvic pain by reducing estradiol production and action, respectively. GnRH-agonist suppression of follicle stimulation hormone and luteinizing hormone remains the standard for inactivating endogenous estradiol. In 2018, the U.S. Food and Drug Administration approved elagolix for the treatment of pain associated with endometriosis – the first pill specifically approved for endometriosis pain relief. An off-label approach for women is letrozole, the aromatase inhibitor, to reduce circulating estradiol levels. Unfortunately, estradiol suppression cannot be used solely long term without add-back therapy, because of the risk of bone loss and vasomotor symptoms.

Excision of endometriomas adversely affects ovarian follicular reserve (as indicated by lower levels of anti-müllerian hormone and reduced ovarian antral follicle counts on ultrasound). For women who want to preserve their fertility, the potential benefits of surgery should be weighed against these negative effects. Surgical treatment of endometriosis in women without other identifiable infertility factors may improve rates of spontaneous pregnancy. In women with moderate to severe endometriosis, intrauterine insemination with ovarian stimulation may be of value, particularly with preceding GnRH-agonist therapy (J Endometr Pelvic Pain Disord. 2018;10[3]:158-73).

Despite the reduction in IVF outcomes in women with moderate to severe endometriosis, it remains unclear whether surgery improves the likelihood of pregnancy with IVF as does the concurrent use of prolonged GnRH agonist during IVF stimulation. (Fertil Steril. 2012;98:591-8).

Summary

• Medical therapy alone does not appear to improve fertility in endometriosis.
• Surgical treatment of endometriosis improves natural fertility, particularly in lower-stage endometriosis.
• EFI is a useful tool to predict postoperative natural fertility and assess the need for IVF.
• Despite advanced endometriosis reducing IVF outcomes, surgery or medical pretreatment to increase IVF success remains unproven.

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

A variety of treatments, most already commercially available, are under investigation for treating the constellation of overlapping symptoms associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), “long COVID,” and dysautonomia.

At the virtual annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, speakers presented data for a variety of approaches to ease symptoms common across postviral conditions, such as extreme fatigue, postexertional malaise (“crash”), cognitive dysfunction (“brain fog”), orthostatic intolerance including postural orthostatic tachycardia syndrome (POTS), and chronic pain. Most of the modalities are already commercially available for other indications, although some are costly and not covered by payers for these conditions.

“Both post–acute COVID-19 syndrome and ME/CFS are forms of postinfectious viral syndromes and they have overlapping symptoms. ... In the past, patients were told ‘you have chronic fatigue syndrome but there’s nothing we can do for it.’ That certainly is not the case. There aren’t cures, but there are many management techniques to improve symptoms,” Charles W. Lapp, MD, medical director of the Hunter-Hopkins Center, Charlotte, N.C., said in an interview.

A current mainstay of treatment for ME/CFS – including that triggered by COVID-19 – is activity pacing, in which patients learn to stay within their “energy envelopes” in order to avoid postexertional malaise, a worsening of all symptoms with exertion. The use of “graded exercise” is no longer recommended, per U.K. and U.S. guidelines.

Data for the following approaches were presented at the IACFS/ME conference:
 

Pyridostigmine (mestinon, others)

Pyridostigmine, an acetylcholinesterase inhibitor, is approved for the treatment of muscle weakness resulting from myasthenia gravis and is available in generic form. It has previously been shown to produce significant improvement in both symptom burden and heart rate response in POTS.

At the IACFS/ME conference, David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital and director of the Massachusetts General Hospital Cardiopulmonary laboratory, both in Boston, summarized his group’s study in patients with ME/CFS using pyridostigmine as both a potential treatment for improving exercise capacity and a proof-of-concept that neurovascular dysregulation underlies exertional intolerance in the condition.

A total of 45 patients were randomized to 60 mg oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test, and a second test performed 50 minutes later. Peak VO₂ increased after pyridostigmine but decreased after placebo (+13.3 mL/min vs. –40.2 mL/min, P < .05). Cardiac output and right atrial pressure were also significantly improved with pyridostigmine and worse with placebo.

“We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS. ... Pyridostigmine may be a useful repurposed off-label treatment [for] a subset of patients with exercise intolerance,” Dr. Systrom said.

Asked to comment, Dr. Lapp said: “We’ve used Mestinon for years because it helps with POTS and also with neurally mediated hypotension. Systrom is taking it to a new level because he’s shown that it increases preload to the heart.” However, he noted that it’s unclear whether the drug will help patients who don’t have POTS specifically. On the other hand, patients rarely experience side effects from the drug.

Since the generic tablets come only in 60-mg doses, and the starting dose is 30 mg three times a day, he advised cutting the tablets in half during titration up to 60 mg three times a day.
 

Oxaloacetate (benaGene)

David Lyons Kaufman, MD, of the Center for Complex Diseases, Mountain View, Calif., summarized data from his group’s recently published open-label, nonrandomized, “proof-of-concept” study on use of the commercially available nutritional supplement anhydrous enol-oxaloacetate for treating mental and physical fatigue in 76 patients with longstanding ME/CFS and 43 with long-COVID fatigue.

Oxaloacetate is a major step in the Krebs cycle within the mitochondria that are depleted in patients with ME/CFS. It is also an energy metabolite that has multiple effects in cells and mitochondria, Dr. Kaufman explained.

Doses ranging from 500 mg twice daily up to 1,000 mg three times a day were given for 6 weeks. Up to 33% of the patients with ME/CFS and up to 46.8% of the long-COVID group achieved clinical efficacy as measured by physical and mental fatigue scores, compared with just 5.9% of historical ME/CFS controls. All doses showed highly significant improvements.

The only adverse effects were occasional dyspepsia, which was avoided by taking the supplement with food, and insomnia, resolved by having them dose at breakfast and lunch, Dr. Kaufman said.

Following those preliminary data, there is now an ongoing 90-day, randomized, placebo-controlled clinical trial of 80 patients with ME/CFS using 2,000 mg anhydrous enol-oxaloacetate per day. Endpoints include multiple objective measures.

“We have a health care crisis with long COVID, and we’ve had this smoldering crisis with ME/CFS for decades that’s never been addressed. ME/CFS and long COVID, if not identical, are certainly overlapping. ... We have to pursue these translational medicine pilot studies as rapidly as possible,” Dr. Kaufman remarked.

Dr. Lapp told this news organization that it makes sense to use constituents of the Krebs cycle to improve mitochondrial function, but the problem with oxaloacetate is its cost. Dr. Kaufman mentioned that based on the preliminary trial, the therapeutic “sweet spot” appeared to be 1,000 mg twice daily. The manufacturer’s website lists the price for a single bottle of 30 250-mg capsules at $49, or $42 if purchased via a monthly subscription.

“It’s a benign drug, and it’s over the counter. I would give it to any patient who’s got a big wallet,” Dr. Lapp quipped, adding: “If they’ve got the money, they can order it tonight.”
 

Inspiritol

Inspiritol is an investigational “nebulized, inhaled, multimechanism medication designed to treat the major symptoms of respiratory distress with antioxidant, anti-inflammatory, and broad-spectrum antiviral and antibacterial properties. Inspiritol is composed of both endogenously produced and naturally occurring, well-tolerated biochemicals,” according to the company website.

The hypothesis, Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, said at the meeting, is that “ME/CFS and long COVID-19 result from an aberrant response to an immunological trigger like infection, which results in a permanently dysregulated immune system as a result of overactivation of CD8 T cells and subsequent exhaustion.”

Inspiritol, containing five antioxidants, acts as an immune modulator to reverse the CD8 T cell exhaustion and improve symptoms. Administration by inhaler delivers it directly to the brain from the lung. It was originally designed for use in chronic obstructive pulmonary disease and asthma and has shown efficacy for acute COVID-19, Dr. Selin said.

In a preliminary study, four patients with ME/CFS and five with long COVID have been treated with Inspiritol for 2-15 months, and all have self-reported improved symptoms. Cough has been the only reported side effect.

The company is pursuing an Investigational New Drug Application for the product with the Food and Drug Administration and has several patents pending. Dr. Lapp called Inspiritol “very interesting,” and said that reversal of CD8 “exhaustion” also would appear to be a promising approach. However, he noted, “the problem is that we don’t know what’s in it.”
 

Stellate ganglion block

Injection of local anesthetic near the stellate ganglion to block activity of the entire cervical sympathetic chain has been used for nearly a century to treat a variety of sympathetically mediated conditions, including complex regional pain syndrome (CRPS), shingles, and phantom-limb pain. More recently, it has been used in a variety of other conditions, including PTSD, Raynaud’s disease, menopausal hot flashes, and hyperhidrosis.

Insurance companies typically cover it for CRPS, neuropathic upper-extremity pain, hyperhidrosis, and Raynaud’s, said Luke Liu, MD, an anesthesiologist who is founder and chief executive officer of Alaska-based pain management company Neuroversion.

Deborah Duricka, PhD, also with Neuroversion, presented results from a now-published case series of 11 patients with long COVID who underwent stellate ganglion block by a board-certified anesthesiologist, first on one side at the level of C6, then on the contralateral side the following day.

Clinically meaningful benefits were seen in at least five of the patients in fatigue, memory problems, problems concentrating, rapid heartbeat, orthostatic intolerance, sleep problems, postexertional malaise, anxiety, and depression.

The hypothetical mechanism, she said, is that “sympathetic block prevents sympathetically driven vasoconstriction in carotid and vertebral arteries.”

Dr. Liu presented another case series of five patients with ME/CFS who underwent the procedure with ultrasound guidance, again on one side and the other side the next day. All had upper-limb autonomic issues such as Raynaud’s and/or neuropathic pain that had been refractory to more conventional treatments.

All five patients reported improvements in symptoms of ME/CFS, including energy level, cognition, pain, and postexertional malaise. One patient reported “feeling well for the first time in decades.” However, that patient relapsed after a mild viral illness 3.5 months after treatment. Some of the patients have required further treatments.

Dr. Lapp commented that, although the procedure is generally safe when performed by an experienced clinician, “Any time you do an injection like that, there’s a high risk that you could nick an artery or a vein or hit an essential nerve in the neck. That’s why it has to be done under fluoroscopy or ultrasound.”

He said he’s had a few patients undergo the procedure, mostly for CRPS, and they seem to have benefited from it. “It might increase cerebral blood flow and preload to the heart, so it might decrease ME/CFS symptoms and help with POTS as well.”

Nonetheless, Dr. Lapp said he wouldn’t consider stellate ganglion block as first-line treatment for ME/CFS or long COVID. “I think it would be for the treatment-resistant patient, when you’ve gone through all the treatments that we know and addressed all the comorbidities and they’re still not getting better.”

But, he added, it is a standard procedure. “Any pain clinic can do a stellate block.”
 

Transcutaneous auricular vagus nerve stimulation

Nicola Clague-Baker, PhD, a physiotherapist at the University of Liverpool (England), presented findings from an international survey of people with ME/CFS regarding their experience with transcutaneous auricular vagus nerve stimulation (taVNS) to manage their autonomic symptoms. The technique involves stimulation of the autonomic nervous system via the vagus nerve using electrodes applied to part of the ear. The theory is that the technique stimulates the parasympathetic nervous system and improves autonomic balance.

Two small previous trials showing benefit of vagus nerve stimulation for people with ME/CFS used more invasive and less comfortable methods of applying the stimulation rather than to the ear, Dr. Clague-Baker and colleagues noted in a poster. It has also been used successfully in treating POTS, another conference speaker noted.

A total of 131 people with ME/CFS (called simply “ME” in the United Kingdom) responded to a survey advertised on social media and websites. The majority (60%) were from the United Kingdom while the rest were from Europe, Australia, and North America. Most were female, and slightly more than half had lived with ME for 10 or more years.

The majority (72%) were still using taVNS, while 28% had stopped using it. Only 9% had used the modality for longer than a year. Respondents identified more than 30 benefits in symptoms and activities, with improvements in postexertional malaise (39%) and brain fog (37%) being the most common. One reported significant reduction in constipation.

However, respondents also mentioned more than 20 short- and long-term negatives, including headaches (15%) and long-term irritation at the site (9%). One participant reported a “big improvement in neuropathic pain, but not so much for muscles and joints.”

Overall, 80% reported that they would continue using taVNS and 67% said they would recommend it to others with ME, and 56% said that the system was mildly to very beneficial.

Dr. Lapp noted that several types of transcutaneous electrical nerve stimulation units with ear clips are sold online, and he’s seen them work well for migraine treatment. However, he cautioned that some patients have had side effects from the treatment, such as headaches and dizziness. “It’s putting an electrical current through your brain. In my mind, it’s another last-ditch measure.”

Dr. Lapp reported no financial disclosures.

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

A variety of treatments, most already commercially available, are under investigation for treating the constellation of overlapping symptoms associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), “long COVID,” and dysautonomia.

At the virtual annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, speakers presented data for a variety of approaches to ease symptoms common across postviral conditions, such as extreme fatigue, postexertional malaise (“crash”), cognitive dysfunction (“brain fog”), orthostatic intolerance including postural orthostatic tachycardia syndrome (POTS), and chronic pain. Most of the modalities are already commercially available for other indications, although some are costly and not covered by payers for these conditions.

“Both post–acute COVID-19 syndrome and ME/CFS are forms of postinfectious viral syndromes and they have overlapping symptoms. ... In the past, patients were told ‘you have chronic fatigue syndrome but there’s nothing we can do for it.’ That certainly is not the case. There aren’t cures, but there are many management techniques to improve symptoms,” Charles W. Lapp, MD, medical director of the Hunter-Hopkins Center, Charlotte, N.C., said in an interview.

A current mainstay of treatment for ME/CFS – including that triggered by COVID-19 – is activity pacing, in which patients learn to stay within their “energy envelopes” in order to avoid postexertional malaise, a worsening of all symptoms with exertion. The use of “graded exercise” is no longer recommended, per U.K. and U.S. guidelines.

Data for the following approaches were presented at the IACFS/ME conference:
 

Pyridostigmine (mestinon, others)

Pyridostigmine, an acetylcholinesterase inhibitor, is approved for the treatment of muscle weakness resulting from myasthenia gravis and is available in generic form. It has previously been shown to produce significant improvement in both symptom burden and heart rate response in POTS.

At the IACFS/ME conference, David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital and director of the Massachusetts General Hospital Cardiopulmonary laboratory, both in Boston, summarized his group’s study in patients with ME/CFS using pyridostigmine as both a potential treatment for improving exercise capacity and a proof-of-concept that neurovascular dysregulation underlies exertional intolerance in the condition.

A total of 45 patients were randomized to 60 mg oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test, and a second test performed 50 minutes later. Peak VO₂ increased after pyridostigmine but decreased after placebo (+13.3 mL/min vs. –40.2 mL/min, P < .05). Cardiac output and right atrial pressure were also significantly improved with pyridostigmine and worse with placebo.

“We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS. ... Pyridostigmine may be a useful repurposed off-label treatment [for] a subset of patients with exercise intolerance,” Dr. Systrom said.

Asked to comment, Dr. Lapp said: “We’ve used Mestinon for years because it helps with POTS and also with neurally mediated hypotension. Systrom is taking it to a new level because he’s shown that it increases preload to the heart.” However, he noted that it’s unclear whether the drug will help patients who don’t have POTS specifically. On the other hand, patients rarely experience side effects from the drug.

Since the generic tablets come only in 60-mg doses, and the starting dose is 30 mg three times a day, he advised cutting the tablets in half during titration up to 60 mg three times a day.
 

Oxaloacetate (benaGene)

David Lyons Kaufman, MD, of the Center for Complex Diseases, Mountain View, Calif., summarized data from his group’s recently published open-label, nonrandomized, “proof-of-concept” study on use of the commercially available nutritional supplement anhydrous enol-oxaloacetate for treating mental and physical fatigue in 76 patients with longstanding ME/CFS and 43 with long-COVID fatigue.

Oxaloacetate is a major step in the Krebs cycle within the mitochondria that are depleted in patients with ME/CFS. It is also an energy metabolite that has multiple effects in cells and mitochondria, Dr. Kaufman explained.

Doses ranging from 500 mg twice daily up to 1,000 mg three times a day were given for 6 weeks. Up to 33% of the patients with ME/CFS and up to 46.8% of the long-COVID group achieved clinical efficacy as measured by physical and mental fatigue scores, compared with just 5.9% of historical ME/CFS controls. All doses showed highly significant improvements.

The only adverse effects were occasional dyspepsia, which was avoided by taking the supplement with food, and insomnia, resolved by having them dose at breakfast and lunch, Dr. Kaufman said.

Following those preliminary data, there is now an ongoing 90-day, randomized, placebo-controlled clinical trial of 80 patients with ME/CFS using 2,000 mg anhydrous enol-oxaloacetate per day. Endpoints include multiple objective measures.

“We have a health care crisis with long COVID, and we’ve had this smoldering crisis with ME/CFS for decades that’s never been addressed. ME/CFS and long COVID, if not identical, are certainly overlapping. ... We have to pursue these translational medicine pilot studies as rapidly as possible,” Dr. Kaufman remarked.

Dr. Lapp told this news organization that it makes sense to use constituents of the Krebs cycle to improve mitochondrial function, but the problem with oxaloacetate is its cost. Dr. Kaufman mentioned that based on the preliminary trial, the therapeutic “sweet spot” appeared to be 1,000 mg twice daily. The manufacturer’s website lists the price for a single bottle of 30 250-mg capsules at $49, or $42 if purchased via a monthly subscription.

“It’s a benign drug, and it’s over the counter. I would give it to any patient who’s got a big wallet,” Dr. Lapp quipped, adding: “If they’ve got the money, they can order it tonight.”
 

Inspiritol

Inspiritol is an investigational “nebulized, inhaled, multimechanism medication designed to treat the major symptoms of respiratory distress with antioxidant, anti-inflammatory, and broad-spectrum antiviral and antibacterial properties. Inspiritol is composed of both endogenously produced and naturally occurring, well-tolerated biochemicals,” according to the company website.

The hypothesis, Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, said at the meeting, is that “ME/CFS and long COVID-19 result from an aberrant response to an immunological trigger like infection, which results in a permanently dysregulated immune system as a result of overactivation of CD8 T cells and subsequent exhaustion.”

Inspiritol, containing five antioxidants, acts as an immune modulator to reverse the CD8 T cell exhaustion and improve symptoms. Administration by inhaler delivers it directly to the brain from the lung. It was originally designed for use in chronic obstructive pulmonary disease and asthma and has shown efficacy for acute COVID-19, Dr. Selin said.

In a preliminary study, four patients with ME/CFS and five with long COVID have been treated with Inspiritol for 2-15 months, and all have self-reported improved symptoms. Cough has been the only reported side effect.

The company is pursuing an Investigational New Drug Application for the product with the Food and Drug Administration and has several patents pending. Dr. Lapp called Inspiritol “very interesting,” and said that reversal of CD8 “exhaustion” also would appear to be a promising approach. However, he noted, “the problem is that we don’t know what’s in it.”
 

Stellate ganglion block

Injection of local anesthetic near the stellate ganglion to block activity of the entire cervical sympathetic chain has been used for nearly a century to treat a variety of sympathetically mediated conditions, including complex regional pain syndrome (CRPS), shingles, and phantom-limb pain. More recently, it has been used in a variety of other conditions, including PTSD, Raynaud’s disease, menopausal hot flashes, and hyperhidrosis.

Insurance companies typically cover it for CRPS, neuropathic upper-extremity pain, hyperhidrosis, and Raynaud’s, said Luke Liu, MD, an anesthesiologist who is founder and chief executive officer of Alaska-based pain management company Neuroversion.

Deborah Duricka, PhD, also with Neuroversion, presented results from a now-published case series of 11 patients with long COVID who underwent stellate ganglion block by a board-certified anesthesiologist, first on one side at the level of C6, then on the contralateral side the following day.

Clinically meaningful benefits were seen in at least five of the patients in fatigue, memory problems, problems concentrating, rapid heartbeat, orthostatic intolerance, sleep problems, postexertional malaise, anxiety, and depression.

The hypothetical mechanism, she said, is that “sympathetic block prevents sympathetically driven vasoconstriction in carotid and vertebral arteries.”

Dr. Liu presented another case series of five patients with ME/CFS who underwent the procedure with ultrasound guidance, again on one side and the other side the next day. All had upper-limb autonomic issues such as Raynaud’s and/or neuropathic pain that had been refractory to more conventional treatments.

All five patients reported improvements in symptoms of ME/CFS, including energy level, cognition, pain, and postexertional malaise. One patient reported “feeling well for the first time in decades.” However, that patient relapsed after a mild viral illness 3.5 months after treatment. Some of the patients have required further treatments.

Dr. Lapp commented that, although the procedure is generally safe when performed by an experienced clinician, “Any time you do an injection like that, there’s a high risk that you could nick an artery or a vein or hit an essential nerve in the neck. That’s why it has to be done under fluoroscopy or ultrasound.”

He said he’s had a few patients undergo the procedure, mostly for CRPS, and they seem to have benefited from it. “It might increase cerebral blood flow and preload to the heart, so it might decrease ME/CFS symptoms and help with POTS as well.”

Nonetheless, Dr. Lapp said he wouldn’t consider stellate ganglion block as first-line treatment for ME/CFS or long COVID. “I think it would be for the treatment-resistant patient, when you’ve gone through all the treatments that we know and addressed all the comorbidities and they’re still not getting better.”

But, he added, it is a standard procedure. “Any pain clinic can do a stellate block.”
 

Transcutaneous auricular vagus nerve stimulation

Nicola Clague-Baker, PhD, a physiotherapist at the University of Liverpool (England), presented findings from an international survey of people with ME/CFS regarding their experience with transcutaneous auricular vagus nerve stimulation (taVNS) to manage their autonomic symptoms. The technique involves stimulation of the autonomic nervous system via the vagus nerve using electrodes applied to part of the ear. The theory is that the technique stimulates the parasympathetic nervous system and improves autonomic balance.

Two small previous trials showing benefit of vagus nerve stimulation for people with ME/CFS used more invasive and less comfortable methods of applying the stimulation rather than to the ear, Dr. Clague-Baker and colleagues noted in a poster. It has also been used successfully in treating POTS, another conference speaker noted.

A total of 131 people with ME/CFS (called simply “ME” in the United Kingdom) responded to a survey advertised on social media and websites. The majority (60%) were from the United Kingdom while the rest were from Europe, Australia, and North America. Most were female, and slightly more than half had lived with ME for 10 or more years.

The majority (72%) were still using taVNS, while 28% had stopped using it. Only 9% had used the modality for longer than a year. Respondents identified more than 30 benefits in symptoms and activities, with improvements in postexertional malaise (39%) and brain fog (37%) being the most common. One reported significant reduction in constipation.

However, respondents also mentioned more than 20 short- and long-term negatives, including headaches (15%) and long-term irritation at the site (9%). One participant reported a “big improvement in neuropathic pain, but not so much for muscles and joints.”

Overall, 80% reported that they would continue using taVNS and 67% said they would recommend it to others with ME, and 56% said that the system was mildly to very beneficial.

Dr. Lapp noted that several types of transcutaneous electrical nerve stimulation units with ear clips are sold online, and he’s seen them work well for migraine treatment. However, he cautioned that some patients have had side effects from the treatment, such as headaches and dizziness. “It’s putting an electrical current through your brain. In my mind, it’s another last-ditch measure.”

Dr. Lapp reported no financial disclosures.

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

A variety of treatments, most already commercially available, are under investigation for treating the constellation of overlapping symptoms associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), “long COVID,” and dysautonomia.

At the virtual annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, speakers presented data for a variety of approaches to ease symptoms common across postviral conditions, such as extreme fatigue, postexertional malaise (“crash”), cognitive dysfunction (“brain fog”), orthostatic intolerance including postural orthostatic tachycardia syndrome (POTS), and chronic pain. Most of the modalities are already commercially available for other indications, although some are costly and not covered by payers for these conditions.

“Both post–acute COVID-19 syndrome and ME/CFS are forms of postinfectious viral syndromes and they have overlapping symptoms. ... In the past, patients were told ‘you have chronic fatigue syndrome but there’s nothing we can do for it.’ That certainly is not the case. There aren’t cures, but there are many management techniques to improve symptoms,” Charles W. Lapp, MD, medical director of the Hunter-Hopkins Center, Charlotte, N.C., said in an interview.

A current mainstay of treatment for ME/CFS – including that triggered by COVID-19 – is activity pacing, in which patients learn to stay within their “energy envelopes” in order to avoid postexertional malaise, a worsening of all symptoms with exertion. The use of “graded exercise” is no longer recommended, per U.K. and U.S. guidelines.

Data for the following approaches were presented at the IACFS/ME conference:
 

Pyridostigmine (mestinon, others)

Pyridostigmine, an acetylcholinesterase inhibitor, is approved for the treatment of muscle weakness resulting from myasthenia gravis and is available in generic form. It has previously been shown to produce significant improvement in both symptom burden and heart rate response in POTS.

At the IACFS/ME conference, David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital and director of the Massachusetts General Hospital Cardiopulmonary laboratory, both in Boston, summarized his group’s study in patients with ME/CFS using pyridostigmine as both a potential treatment for improving exercise capacity and a proof-of-concept that neurovascular dysregulation underlies exertional intolerance in the condition.

A total of 45 patients were randomized to 60 mg oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test, and a second test performed 50 minutes later. Peak VO₂ increased after pyridostigmine but decreased after placebo (+13.3 mL/min vs. –40.2 mL/min, P < .05). Cardiac output and right atrial pressure were also significantly improved with pyridostigmine and worse with placebo.

“We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS. ... Pyridostigmine may be a useful repurposed off-label treatment [for] a subset of patients with exercise intolerance,” Dr. Systrom said.

Asked to comment, Dr. Lapp said: “We’ve used Mestinon for years because it helps with POTS and also with neurally mediated hypotension. Systrom is taking it to a new level because he’s shown that it increases preload to the heart.” However, he noted that it’s unclear whether the drug will help patients who don’t have POTS specifically. On the other hand, patients rarely experience side effects from the drug.

Since the generic tablets come only in 60-mg doses, and the starting dose is 30 mg three times a day, he advised cutting the tablets in half during titration up to 60 mg three times a day.
 

Oxaloacetate (benaGene)

David Lyons Kaufman, MD, of the Center for Complex Diseases, Mountain View, Calif., summarized data from his group’s recently published open-label, nonrandomized, “proof-of-concept” study on use of the commercially available nutritional supplement anhydrous enol-oxaloacetate for treating mental and physical fatigue in 76 patients with longstanding ME/CFS and 43 with long-COVID fatigue.

Oxaloacetate is a major step in the Krebs cycle within the mitochondria that are depleted in patients with ME/CFS. It is also an energy metabolite that has multiple effects in cells and mitochondria, Dr. Kaufman explained.

Doses ranging from 500 mg twice daily up to 1,000 mg three times a day were given for 6 weeks. Up to 33% of the patients with ME/CFS and up to 46.8% of the long-COVID group achieved clinical efficacy as measured by physical and mental fatigue scores, compared with just 5.9% of historical ME/CFS controls. All doses showed highly significant improvements.

The only adverse effects were occasional dyspepsia, which was avoided by taking the supplement with food, and insomnia, resolved by having them dose at breakfast and lunch, Dr. Kaufman said.

Following those preliminary data, there is now an ongoing 90-day, randomized, placebo-controlled clinical trial of 80 patients with ME/CFS using 2,000 mg anhydrous enol-oxaloacetate per day. Endpoints include multiple objective measures.

“We have a health care crisis with long COVID, and we’ve had this smoldering crisis with ME/CFS for decades that’s never been addressed. ME/CFS and long COVID, if not identical, are certainly overlapping. ... We have to pursue these translational medicine pilot studies as rapidly as possible,” Dr. Kaufman remarked.

Dr. Lapp told this news organization that it makes sense to use constituents of the Krebs cycle to improve mitochondrial function, but the problem with oxaloacetate is its cost. Dr. Kaufman mentioned that based on the preliminary trial, the therapeutic “sweet spot” appeared to be 1,000 mg twice daily. The manufacturer’s website lists the price for a single bottle of 30 250-mg capsules at $49, or $42 if purchased via a monthly subscription.

“It’s a benign drug, and it’s over the counter. I would give it to any patient who’s got a big wallet,” Dr. Lapp quipped, adding: “If they’ve got the money, they can order it tonight.”
 

Inspiritol

Inspiritol is an investigational “nebulized, inhaled, multimechanism medication designed to treat the major symptoms of respiratory distress with antioxidant, anti-inflammatory, and broad-spectrum antiviral and antibacterial properties. Inspiritol is composed of both endogenously produced and naturally occurring, well-tolerated biochemicals,” according to the company website.

The hypothesis, Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, said at the meeting, is that “ME/CFS and long COVID-19 result from an aberrant response to an immunological trigger like infection, which results in a permanently dysregulated immune system as a result of overactivation of CD8 T cells and subsequent exhaustion.”

Inspiritol, containing five antioxidants, acts as an immune modulator to reverse the CD8 T cell exhaustion and improve symptoms. Administration by inhaler delivers it directly to the brain from the lung. It was originally designed for use in chronic obstructive pulmonary disease and asthma and has shown efficacy for acute COVID-19, Dr. Selin said.

In a preliminary study, four patients with ME/CFS and five with long COVID have been treated with Inspiritol for 2-15 months, and all have self-reported improved symptoms. Cough has been the only reported side effect.

The company is pursuing an Investigational New Drug Application for the product with the Food and Drug Administration and has several patents pending. Dr. Lapp called Inspiritol “very interesting,” and said that reversal of CD8 “exhaustion” also would appear to be a promising approach. However, he noted, “the problem is that we don’t know what’s in it.”
 

Stellate ganglion block

Injection of local anesthetic near the stellate ganglion to block activity of the entire cervical sympathetic chain has been used for nearly a century to treat a variety of sympathetically mediated conditions, including complex regional pain syndrome (CRPS), shingles, and phantom-limb pain. More recently, it has been used in a variety of other conditions, including PTSD, Raynaud’s disease, menopausal hot flashes, and hyperhidrosis.

Insurance companies typically cover it for CRPS, neuropathic upper-extremity pain, hyperhidrosis, and Raynaud’s, said Luke Liu, MD, an anesthesiologist who is founder and chief executive officer of Alaska-based pain management company Neuroversion.

Deborah Duricka, PhD, also with Neuroversion, presented results from a now-published case series of 11 patients with long COVID who underwent stellate ganglion block by a board-certified anesthesiologist, first on one side at the level of C6, then on the contralateral side the following day.

Clinically meaningful benefits were seen in at least five of the patients in fatigue, memory problems, problems concentrating, rapid heartbeat, orthostatic intolerance, sleep problems, postexertional malaise, anxiety, and depression.

The hypothetical mechanism, she said, is that “sympathetic block prevents sympathetically driven vasoconstriction in carotid and vertebral arteries.”

Dr. Liu presented another case series of five patients with ME/CFS who underwent the procedure with ultrasound guidance, again on one side and the other side the next day. All had upper-limb autonomic issues such as Raynaud’s and/or neuropathic pain that had been refractory to more conventional treatments.

All five patients reported improvements in symptoms of ME/CFS, including energy level, cognition, pain, and postexertional malaise. One patient reported “feeling well for the first time in decades.” However, that patient relapsed after a mild viral illness 3.5 months after treatment. Some of the patients have required further treatments.

Dr. Lapp commented that, although the procedure is generally safe when performed by an experienced clinician, “Any time you do an injection like that, there’s a high risk that you could nick an artery or a vein or hit an essential nerve in the neck. That’s why it has to be done under fluoroscopy or ultrasound.”

He said he’s had a few patients undergo the procedure, mostly for CRPS, and they seem to have benefited from it. “It might increase cerebral blood flow and preload to the heart, so it might decrease ME/CFS symptoms and help with POTS as well.”

Nonetheless, Dr. Lapp said he wouldn’t consider stellate ganglion block as first-line treatment for ME/CFS or long COVID. “I think it would be for the treatment-resistant patient, when you’ve gone through all the treatments that we know and addressed all the comorbidities and they’re still not getting better.”

But, he added, it is a standard procedure. “Any pain clinic can do a stellate block.”
 

Transcutaneous auricular vagus nerve stimulation

Nicola Clague-Baker, PhD, a physiotherapist at the University of Liverpool (England), presented findings from an international survey of people with ME/CFS regarding their experience with transcutaneous auricular vagus nerve stimulation (taVNS) to manage their autonomic symptoms. The technique involves stimulation of the autonomic nervous system via the vagus nerve using electrodes applied to part of the ear. The theory is that the technique stimulates the parasympathetic nervous system and improves autonomic balance.

Two small previous trials showing benefit of vagus nerve stimulation for people with ME/CFS used more invasive and less comfortable methods of applying the stimulation rather than to the ear, Dr. Clague-Baker and colleagues noted in a poster. It has also been used successfully in treating POTS, another conference speaker noted.

A total of 131 people with ME/CFS (called simply “ME” in the United Kingdom) responded to a survey advertised on social media and websites. The majority (60%) were from the United Kingdom while the rest were from Europe, Australia, and North America. Most were female, and slightly more than half had lived with ME for 10 or more years.

The majority (72%) were still using taVNS, while 28% had stopped using it. Only 9% had used the modality for longer than a year. Respondents identified more than 30 benefits in symptoms and activities, with improvements in postexertional malaise (39%) and brain fog (37%) being the most common. One reported significant reduction in constipation.

However, respondents also mentioned more than 20 short- and long-term negatives, including headaches (15%) and long-term irritation at the site (9%). One participant reported a “big improvement in neuropathic pain, but not so much for muscles and joints.”

Overall, 80% reported that they would continue using taVNS and 67% said they would recommend it to others with ME, and 56% said that the system was mildly to very beneficial.

Dr. Lapp noted that several types of transcutaneous electrical nerve stimulation units with ear clips are sold online, and he’s seen them work well for migraine treatment. However, he cautioned that some patients have had side effects from the treatment, such as headaches and dizziness. “It’s putting an electrical current through your brain. In my mind, it’s another last-ditch measure.”

Dr. Lapp reported no financial disclosures.

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

Doctors in states where abortion is legal are likely to be the next target for antiabortion activists who want to deter residents from seeking abortions across state lines, say legal experts.

Antiabortion legislators in several states are mounting efforts to clamp down on out-of-state abortions, which they view as a legal loophole.

Nineteen states have already banned the use of telemedicine to prescribe medication abortion by requiring the clinician to be physically present when the medication is administered. These states include Arizona, Louisiana, Tennessee, and Texas, which also recently criminalized sending abortion pills through the mail.

Some state legislators plan to introduce legislation based on a Texas abortion ban enacted last year in which private citizens can sue anyone who assists state residents in obtaining an out-of-state abortion.

Meanwhile, legislators in states including New York where abortion is legal have introduced bills to shield doctors involved in reproductive care from possible negative actions by medical malpractice companies and professional misconduct charges.

This news organization asked legal experts for advice on how doctors can protect themselves and still provide appropriate medical care in this rapidly changing legal landscape. Here’s what they had to say.
 

1. What if patients from states where abortion is banned want to come to my practice in a legal state? What should I be aware of?

“Doctors should do what they think is medically necessary, but they should be aware of potential criminal and/or civil consequences in a patient’s home state, especially if those states have staked out more extreme positions on abortion such as Texas, Oklahoma, and Louisiana,” says Katherine Florey, JD, a professor at the University of California, Davis, School of Law.

The patient’s home state would need to have criminal laws in place that would explicitly ban residents from obtaining out-of-state abortions. “Probably the greater risk on the criminal front is that many states have existing laws that don’t specify their geographical reach but that could be construed to allow for criminal jurisdiction over out-of-state providers who help residents in obtaining an abortion,” she says.

However, criminal laws would be harder to enforce because of constitutional obstacles that would require the U.S. Supreme Court to resolve in a court case. Another barrier is that criminal law typically requires that a significant element of the offense take place in the prosecuting state, says Ms. Florey.
 

2. Am I likely to be sued by a patient from a state with an abortion ban?

“It’s more likely that states with abortion bans will pursue civil liability cases, particularly in states such as Texas and Oklahoma that allow private individuals to pursue lawsuits against individuals providing or assisting with abortions.”

Such liability is particularly appealing to antiabortion states because it allows them to target abortion care providers rather than the women seeking abortions, an approach that might be both more politically palatable and more effective in achieving abortion-restriction goals, says Ms. Florey.

“It’s not just the threat of jail time that can deter physicians from providing abortions. They can face significant career consequences from civil liability, including being reported to their medical licensing boards and having their malpractice insurance premiums increase,” says Ms. Florey.
 

3. What if I provide ‘abortion pill’ prescriptions by telemedicine to a patient in another state?

Doctors need to know what the rules are in the patient’s home state because states generally regard where the patient is located as where telemedicine is legally conducted, says Ms. Florey. “It’s more problematic to conduct telemedicine in states where it’s illegal. It could be viewed legally as if the doctor were prescribing a medication abortion in the patient’s state.”

Ms. Florey also advises doctors to find out whether the patient’s home state bans medication abortions. “The courts or states could decide that the physician is practicing in the jurisdiction where the patient is located even if care is provided remotely. In that case, the doctor would have to comply with all the laws of that state.”

She recommends that doctors counsel patients seeking medication abortions to come to the state where abortion is legal and get on their computers there.

“It’s not a perfect solution, but it provides more legal protection than providing medication abortion across state lines,” says Ms. Florey.
 

4. Can doctors be sued by patients for not informing them of the full range of treatment options, including abortion, when their health is at risk?

If the doctor is in a state that has banned abortion and the procedure is illegal, they can’t recommend something that the law doesn’t allow, says Ms. Florey.

It’s a tough call for doctors in states where abortion is illegal because they could get into legal trouble if they counsel a woman to get an abortion and the court later deems it was not medically necessary, says Ms. Florey.

But doctors could also get into legal trouble if they don’t counsel a woman to get an abortion if her life is in danger and she meets the exception in the abortion ban.

“Ultimately, I think doctors have to follow their conscience and best medical judgment but recognize the legal hazards that exist. If a physician is seeing a lot of out-of-state patients from a single jurisdiction (such as a neighboring state), it would be best to consult with an attorney from that state,” advises Ms. Florey.
 

5. If a patient from another state comes to me (in a legal state) for abortion care, am I required to provide them with any warnings, information, and so on?

Doctors may be required by some antiabortion states to mention certain risks, especially to the mother’s mental health, that could arise from abortions even if they are not well-supported by evidence, says Ms. Florey.

If a warning is required in a patient’s home state and there were complications from the procedure or the patient became depressed, it could be grounds for a civil lawsuit, says Ms. Florey.

“There is a Montana case, for example, where the plaintiff sued for malpractice after having an abortion. She alleged that she was given medically inaccurate information about the fetus’s HIV status, but she also claimed that she wasn’t informed that she might become depressed as a result of the abortion,” says Ms. Florey. (The case was ultimately decided on a different ground.)
 

6. What about complications from abortion care that I provided to a patient from another state? What are my responsibilities and risks? Can I be sued for malpractice when the patient returns to her home state?

If physicians can’t monitor the patients after their visit and something goes wrong, the doctors are at greater risk of negligence and being sued for malpractice in the patient’s home state, says Ms. Florey.

She recommends that doctors ask patients to stay for monitoring after the procedure. “I realize that may not be possible for all patients, but it’s a much safer alternative,” says Ms. Florey.

Otherwise, if the doctor communicates with the patient about the complications in her antiabortion state, the state’s courts could view the doctor as having ties to the state and claim they have jurisdiction in the case and apply the state’s laws, says Ms. Florey.

“Criminal jurisdiction would be more of stretch because the central conduct happened out of state, but states could still try to prosecute a case,” she says.
 

7. If a patient comes to me from another state, are there any residency requirements, or does the person need to find residence in my state for a period of time? Am I responsible for knowing their arrangements?

Generally, as a constitutional principle, a person can go to another state and have the services that a resident is entitled to, says Ms. Florey. 

“States can’t normally discriminate against patients from out of state, so it’s not a residency requirement unless a state imposes one. If a state did that, it would probably be unconstitutional,” she says. 

It would be less risky legally, though, if a patient remains in the state where she received abortion care for a significant period of time, says Ms. Florey.
 

8. How can I protect the privacy of patients’ medical records if they received an abortion or other reproductive care in the state?

To some extent, HIPAA accommodates state laws that mandate reporting of patient information, says Lisa C. Ikemoto, JD, also a professor at the UC Davis School of Law.

The Privacy Rule doesn’t require doctors to disclose protected health information about a patient when state laws require reporting. But the rule allows them to disclose private health information when there’s a court order such as a warrant or subpoena, says Ms. Ikemoto.

“Providers should make sure that patient information remains in records that are HIPAA protected. Some states, including California, have enacted privacy laws that are more protective of patient information,” she says.

The Department of Health & Human Services issued new guidance in June for health care professionals to clarify what the Privacy Rule requires them to report in light of the restrictive abortion laws.
 

9. I practice in a state where abortion is legal. Can I be extradited to another state if I’m prosecuted for crimes relating to reproductive health services?

Yes, generally, if your state allows it, says Ms. Florey. States have a constitutional obligation to extradite citizens of a different state if that person’s home state asks for that, but states do not have to extradite their own citizens.

However, traditionally, states have cooperated with extradition requests and most states have laws in place providing for extradition in those circumstances, which they could change to exempt abortion providers.

A handful of states – Connecticut, New York, Delaware, and New Jersey – have passed laws specifically shielding medical providers from being prosecuted under abortion restrictions passed in other states.

Governors in Massachusetts, Minnesota, New Mexico, and Nevada have issued executive orders saying they will not extradite abortion providers to states that have banned abortion provision, and that state employees will generally not comply with those out-of-state investigations.
 

10. Should I increase my malpractice insurance in anticipation of more potential legal problems from patients coming to me from antiabortion states?

Yes, I would recommend that doctors increase their malpractice coverage because of the increased legal risks they could face.

“It’s possible that a state might file a lawsuit against out-of-state abortion providers. Criminal prosecution is also a possibility, but the obstacles to prosecuting a case against an out-of-state provider would be considerable, especially if their home state has passed laws shielding abortion providers,” says Ms. Florey.

Individual malpractice claims or some sort of private enforcement action in a state that has established one would be more likely, she adds.

Ms. Florey advises doctors to monitor this rapidly evolving area of law. “Everything I am saying today could change with a single Supreme Court case. There will also be this kind of push/pull as antiabortion states try to crack down on out-of-state residents who provide or assist in abortion and physicians’ home states that try to protect them from legal consequences.”

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

Doctors in states where abortion is legal are likely to be the next target for antiabortion activists who want to deter residents from seeking abortions across state lines, say legal experts.

Antiabortion legislators in several states are mounting efforts to clamp down on out-of-state abortions, which they view as a legal loophole.

Nineteen states have already banned the use of telemedicine to prescribe medication abortion by requiring the clinician to be physically present when the medication is administered. These states include Arizona, Louisiana, Tennessee, and Texas, which also recently criminalized sending abortion pills through the mail.

Some state legislators plan to introduce legislation based on a Texas abortion ban enacted last year in which private citizens can sue anyone who assists state residents in obtaining an out-of-state abortion.

Meanwhile, legislators in states including New York where abortion is legal have introduced bills to shield doctors involved in reproductive care from possible negative actions by medical malpractice companies and professional misconduct charges.

This news organization asked legal experts for advice on how doctors can protect themselves and still provide appropriate medical care in this rapidly changing legal landscape. Here’s what they had to say.
 

1. What if patients from states where abortion is banned want to come to my practice in a legal state? What should I be aware of?

“Doctors should do what they think is medically necessary, but they should be aware of potential criminal and/or civil consequences in a patient’s home state, especially if those states have staked out more extreme positions on abortion such as Texas, Oklahoma, and Louisiana,” says Katherine Florey, JD, a professor at the University of California, Davis, School of Law.

The patient’s home state would need to have criminal laws in place that would explicitly ban residents from obtaining out-of-state abortions. “Probably the greater risk on the criminal front is that many states have existing laws that don’t specify their geographical reach but that could be construed to allow for criminal jurisdiction over out-of-state providers who help residents in obtaining an abortion,” she says.

However, criminal laws would be harder to enforce because of constitutional obstacles that would require the U.S. Supreme Court to resolve in a court case. Another barrier is that criminal law typically requires that a significant element of the offense take place in the prosecuting state, says Ms. Florey.
 

2. Am I likely to be sued by a patient from a state with an abortion ban?

“It’s more likely that states with abortion bans will pursue civil liability cases, particularly in states such as Texas and Oklahoma that allow private individuals to pursue lawsuits against individuals providing or assisting with abortions.”

Such liability is particularly appealing to antiabortion states because it allows them to target abortion care providers rather than the women seeking abortions, an approach that might be both more politically palatable and more effective in achieving abortion-restriction goals, says Ms. Florey.

“It’s not just the threat of jail time that can deter physicians from providing abortions. They can face significant career consequences from civil liability, including being reported to their medical licensing boards and having their malpractice insurance premiums increase,” says Ms. Florey.
 

3. What if I provide ‘abortion pill’ prescriptions by telemedicine to a patient in another state?

Doctors need to know what the rules are in the patient’s home state because states generally regard where the patient is located as where telemedicine is legally conducted, says Ms. Florey. “It’s more problematic to conduct telemedicine in states where it’s illegal. It could be viewed legally as if the doctor were prescribing a medication abortion in the patient’s state.”

Ms. Florey also advises doctors to find out whether the patient’s home state bans medication abortions. “The courts or states could decide that the physician is practicing in the jurisdiction where the patient is located even if care is provided remotely. In that case, the doctor would have to comply with all the laws of that state.”

She recommends that doctors counsel patients seeking medication abortions to come to the state where abortion is legal and get on their computers there.

“It’s not a perfect solution, but it provides more legal protection than providing medication abortion across state lines,” says Ms. Florey.
 

4. Can doctors be sued by patients for not informing them of the full range of treatment options, including abortion, when their health is at risk?

If the doctor is in a state that has banned abortion and the procedure is illegal, they can’t recommend something that the law doesn’t allow, says Ms. Florey.

It’s a tough call for doctors in states where abortion is illegal because they could get into legal trouble if they counsel a woman to get an abortion and the court later deems it was not medically necessary, says Ms. Florey.

But doctors could also get into legal trouble if they don’t counsel a woman to get an abortion if her life is in danger and she meets the exception in the abortion ban.

“Ultimately, I think doctors have to follow their conscience and best medical judgment but recognize the legal hazards that exist. If a physician is seeing a lot of out-of-state patients from a single jurisdiction (such as a neighboring state), it would be best to consult with an attorney from that state,” advises Ms. Florey.
 

5. If a patient from another state comes to me (in a legal state) for abortion care, am I required to provide them with any warnings, information, and so on?

Doctors may be required by some antiabortion states to mention certain risks, especially to the mother’s mental health, that could arise from abortions even if they are not well-supported by evidence, says Ms. Florey.

If a warning is required in a patient’s home state and there were complications from the procedure or the patient became depressed, it could be grounds for a civil lawsuit, says Ms. Florey.

“There is a Montana case, for example, where the plaintiff sued for malpractice after having an abortion. She alleged that she was given medically inaccurate information about the fetus’s HIV status, but she also claimed that she wasn’t informed that she might become depressed as a result of the abortion,” says Ms. Florey. (The case was ultimately decided on a different ground.)
 

6. What about complications from abortion care that I provided to a patient from another state? What are my responsibilities and risks? Can I be sued for malpractice when the patient returns to her home state?

If physicians can’t monitor the patients after their visit and something goes wrong, the doctors are at greater risk of negligence and being sued for malpractice in the patient’s home state, says Ms. Florey.

She recommends that doctors ask patients to stay for monitoring after the procedure. “I realize that may not be possible for all patients, but it’s a much safer alternative,” says Ms. Florey.

Otherwise, if the doctor communicates with the patient about the complications in her antiabortion state, the state’s courts could view the doctor as having ties to the state and claim they have jurisdiction in the case and apply the state’s laws, says Ms. Florey.

“Criminal jurisdiction would be more of stretch because the central conduct happened out of state, but states could still try to prosecute a case,” she says.
 

7. If a patient comes to me from another state, are there any residency requirements, or does the person need to find residence in my state for a period of time? Am I responsible for knowing their arrangements?

Generally, as a constitutional principle, a person can go to another state and have the services that a resident is entitled to, says Ms. Florey. 

“States can’t normally discriminate against patients from out of state, so it’s not a residency requirement unless a state imposes one. If a state did that, it would probably be unconstitutional,” she says. 

It would be less risky legally, though, if a patient remains in the state where she received abortion care for a significant period of time, says Ms. Florey.
 

8. How can I protect the privacy of patients’ medical records if they received an abortion or other reproductive care in the state?

To some extent, HIPAA accommodates state laws that mandate reporting of patient information, says Lisa C. Ikemoto, JD, also a professor at the UC Davis School of Law.

The Privacy Rule doesn’t require doctors to disclose protected health information about a patient when state laws require reporting. But the rule allows them to disclose private health information when there’s a court order such as a warrant or subpoena, says Ms. Ikemoto.

“Providers should make sure that patient information remains in records that are HIPAA protected. Some states, including California, have enacted privacy laws that are more protective of patient information,” she says.

The Department of Health & Human Services issued new guidance in June for health care professionals to clarify what the Privacy Rule requires them to report in light of the restrictive abortion laws.
 

9. I practice in a state where abortion is legal. Can I be extradited to another state if I’m prosecuted for crimes relating to reproductive health services?

Yes, generally, if your state allows it, says Ms. Florey. States have a constitutional obligation to extradite citizens of a different state if that person’s home state asks for that, but states do not have to extradite their own citizens.

However, traditionally, states have cooperated with extradition requests and most states have laws in place providing for extradition in those circumstances, which they could change to exempt abortion providers.

A handful of states – Connecticut, New York, Delaware, and New Jersey – have passed laws specifically shielding medical providers from being prosecuted under abortion restrictions passed in other states.

Governors in Massachusetts, Minnesota, New Mexico, and Nevada have issued executive orders saying they will not extradite abortion providers to states that have banned abortion provision, and that state employees will generally not comply with those out-of-state investigations.
 

10. Should I increase my malpractice insurance in anticipation of more potential legal problems from patients coming to me from antiabortion states?

Yes, I would recommend that doctors increase their malpractice coverage because of the increased legal risks they could face.

“It’s possible that a state might file a lawsuit against out-of-state abortion providers. Criminal prosecution is also a possibility, but the obstacles to prosecuting a case against an out-of-state provider would be considerable, especially if their home state has passed laws shielding abortion providers,” says Ms. Florey.

Individual malpractice claims or some sort of private enforcement action in a state that has established one would be more likely, she adds.

Ms. Florey advises doctors to monitor this rapidly evolving area of law. “Everything I am saying today could change with a single Supreme Court case. There will also be this kind of push/pull as antiabortion states try to crack down on out-of-state residents who provide or assist in abortion and physicians’ home states that try to protect them from legal consequences.”

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

Doctors in states where abortion is legal are likely to be the next target for antiabortion activists who want to deter residents from seeking abortions across state lines, say legal experts.

Antiabortion legislators in several states are mounting efforts to clamp down on out-of-state abortions, which they view as a legal loophole.

Nineteen states have already banned the use of telemedicine to prescribe medication abortion by requiring the clinician to be physically present when the medication is administered. These states include Arizona, Louisiana, Tennessee, and Texas, which also recently criminalized sending abortion pills through the mail.

Some state legislators plan to introduce legislation based on a Texas abortion ban enacted last year in which private citizens can sue anyone who assists state residents in obtaining an out-of-state abortion.

Meanwhile, legislators in states including New York where abortion is legal have introduced bills to shield doctors involved in reproductive care from possible negative actions by medical malpractice companies and professional misconduct charges.

This news organization asked legal experts for advice on how doctors can protect themselves and still provide appropriate medical care in this rapidly changing legal landscape. Here’s what they had to say.
 

1. What if patients from states where abortion is banned want to come to my practice in a legal state? What should I be aware of?

“Doctors should do what they think is medically necessary, but they should be aware of potential criminal and/or civil consequences in a patient’s home state, especially if those states have staked out more extreme positions on abortion such as Texas, Oklahoma, and Louisiana,” says Katherine Florey, JD, a professor at the University of California, Davis, School of Law.

The patient’s home state would need to have criminal laws in place that would explicitly ban residents from obtaining out-of-state abortions. “Probably the greater risk on the criminal front is that many states have existing laws that don’t specify their geographical reach but that could be construed to allow for criminal jurisdiction over out-of-state providers who help residents in obtaining an abortion,” she says.

However, criminal laws would be harder to enforce because of constitutional obstacles that would require the U.S. Supreme Court to resolve in a court case. Another barrier is that criminal law typically requires that a significant element of the offense take place in the prosecuting state, says Ms. Florey.
 

2. Am I likely to be sued by a patient from a state with an abortion ban?

“It’s more likely that states with abortion bans will pursue civil liability cases, particularly in states such as Texas and Oklahoma that allow private individuals to pursue lawsuits against individuals providing or assisting with abortions.”

Such liability is particularly appealing to antiabortion states because it allows them to target abortion care providers rather than the women seeking abortions, an approach that might be both more politically palatable and more effective in achieving abortion-restriction goals, says Ms. Florey.

“It’s not just the threat of jail time that can deter physicians from providing abortions. They can face significant career consequences from civil liability, including being reported to their medical licensing boards and having their malpractice insurance premiums increase,” says Ms. Florey.
 

3. What if I provide ‘abortion pill’ prescriptions by telemedicine to a patient in another state?

Doctors need to know what the rules are in the patient’s home state because states generally regard where the patient is located as where telemedicine is legally conducted, says Ms. Florey. “It’s more problematic to conduct telemedicine in states where it’s illegal. It could be viewed legally as if the doctor were prescribing a medication abortion in the patient’s state.”

Ms. Florey also advises doctors to find out whether the patient’s home state bans medication abortions. “The courts or states could decide that the physician is practicing in the jurisdiction where the patient is located even if care is provided remotely. In that case, the doctor would have to comply with all the laws of that state.”

She recommends that doctors counsel patients seeking medication abortions to come to the state where abortion is legal and get on their computers there.

“It’s not a perfect solution, but it provides more legal protection than providing medication abortion across state lines,” says Ms. Florey.
 

4. Can doctors be sued by patients for not informing them of the full range of treatment options, including abortion, when their health is at risk?

If the doctor is in a state that has banned abortion and the procedure is illegal, they can’t recommend something that the law doesn’t allow, says Ms. Florey.

It’s a tough call for doctors in states where abortion is illegal because they could get into legal trouble if they counsel a woman to get an abortion and the court later deems it was not medically necessary, says Ms. Florey.

But doctors could also get into legal trouble if they don’t counsel a woman to get an abortion if her life is in danger and she meets the exception in the abortion ban.

“Ultimately, I think doctors have to follow their conscience and best medical judgment but recognize the legal hazards that exist. If a physician is seeing a lot of out-of-state patients from a single jurisdiction (such as a neighboring state), it would be best to consult with an attorney from that state,” advises Ms. Florey.
 

5. If a patient from another state comes to me (in a legal state) for abortion care, am I required to provide them with any warnings, information, and so on?

Doctors may be required by some antiabortion states to mention certain risks, especially to the mother’s mental health, that could arise from abortions even if they are not well-supported by evidence, says Ms. Florey.

If a warning is required in a patient’s home state and there were complications from the procedure or the patient became depressed, it could be grounds for a civil lawsuit, says Ms. Florey.

“There is a Montana case, for example, where the plaintiff sued for malpractice after having an abortion. She alleged that she was given medically inaccurate information about the fetus’s HIV status, but she also claimed that she wasn’t informed that she might become depressed as a result of the abortion,” says Ms. Florey. (The case was ultimately decided on a different ground.)
 

6. What about complications from abortion care that I provided to a patient from another state? What are my responsibilities and risks? Can I be sued for malpractice when the patient returns to her home state?

If physicians can’t monitor the patients after their visit and something goes wrong, the doctors are at greater risk of negligence and being sued for malpractice in the patient’s home state, says Ms. Florey.

She recommends that doctors ask patients to stay for monitoring after the procedure. “I realize that may not be possible for all patients, but it’s a much safer alternative,” says Ms. Florey.

Otherwise, if the doctor communicates with the patient about the complications in her antiabortion state, the state’s courts could view the doctor as having ties to the state and claim they have jurisdiction in the case and apply the state’s laws, says Ms. Florey.

“Criminal jurisdiction would be more of stretch because the central conduct happened out of state, but states could still try to prosecute a case,” she says.
 

7. If a patient comes to me from another state, are there any residency requirements, or does the person need to find residence in my state for a period of time? Am I responsible for knowing their arrangements?

Generally, as a constitutional principle, a person can go to another state and have the services that a resident is entitled to, says Ms. Florey. 

“States can’t normally discriminate against patients from out of state, so it’s not a residency requirement unless a state imposes one. If a state did that, it would probably be unconstitutional,” she says. 

It would be less risky legally, though, if a patient remains in the state where she received abortion care for a significant period of time, says Ms. Florey.
 

8. How can I protect the privacy of patients’ medical records if they received an abortion or other reproductive care in the state?

To some extent, HIPAA accommodates state laws that mandate reporting of patient information, says Lisa C. Ikemoto, JD, also a professor at the UC Davis School of Law.

The Privacy Rule doesn’t require doctors to disclose protected health information about a patient when state laws require reporting. But the rule allows them to disclose private health information when there’s a court order such as a warrant or subpoena, says Ms. Ikemoto.

“Providers should make sure that patient information remains in records that are HIPAA protected. Some states, including California, have enacted privacy laws that are more protective of patient information,” she says.

The Department of Health & Human Services issued new guidance in June for health care professionals to clarify what the Privacy Rule requires them to report in light of the restrictive abortion laws.
 

9. I practice in a state where abortion is legal. Can I be extradited to another state if I’m prosecuted for crimes relating to reproductive health services?

Yes, generally, if your state allows it, says Ms. Florey. States have a constitutional obligation to extradite citizens of a different state if that person’s home state asks for that, but states do not have to extradite their own citizens.

However, traditionally, states have cooperated with extradition requests and most states have laws in place providing for extradition in those circumstances, which they could change to exempt abortion providers.

A handful of states – Connecticut, New York, Delaware, and New Jersey – have passed laws specifically shielding medical providers from being prosecuted under abortion restrictions passed in other states.

Governors in Massachusetts, Minnesota, New Mexico, and Nevada have issued executive orders saying they will not extradite abortion providers to states that have banned abortion provision, and that state employees will generally not comply with those out-of-state investigations.
 

10. Should I increase my malpractice insurance in anticipation of more potential legal problems from patients coming to me from antiabortion states?

Yes, I would recommend that doctors increase their malpractice coverage because of the increased legal risks they could face.

“It’s possible that a state might file a lawsuit against out-of-state abortion providers. Criminal prosecution is also a possibility, but the obstacles to prosecuting a case against an out-of-state provider would be considerable, especially if their home state has passed laws shielding abortion providers,” says Ms. Florey.

Individual malpractice claims or some sort of private enforcement action in a state that has established one would be more likely, she adds.

Ms. Florey advises doctors to monitor this rapidly evolving area of law. “Everything I am saying today could change with a single Supreme Court case. There will also be this kind of push/pull as antiabortion states try to crack down on out-of-state residents who provide or assist in abortion and physicians’ home states that try to protect them from legal consequences.”

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

SACRAMENTO, CALIF. – Californians will decide in November whether to lock the right to abortion into the state constitution.

If they vote “yes” on Proposition 1, they will also lock in a right that has gotten less attention: The right to birth control.

Should the measure succeed, California would become one of the first states – if not the first – to create explicit constitutional rights to both abortion and contraception.

The lawmakers and activists behind the constitutional amendment said they hope to score a one-two punch: Protect abortion in California after the U.S. Supreme Court ended the federal constitutional right to abortion under Roe v. Wade, and get ahead of what they see as the next front in the reproductive rights fight: Birth control.

“The United States Supreme Court said that the privacy and liberty protections in the United States Constitution did not extend to abortion,” said UCLA law professor Cary Franklin, an expert in constitutional law and reproductive rights who has testified before the California legislature in support of the amendment. “If they said ‘no’ on abortion, they’re probably going to say ‘no’ on birth control because that has a similar history.”

In June, the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization ended the federal right to abortion and left states to regulate the service. In his concurring opinion, Justice Clarence Thomas said the court should revisit other cases that have created protections for Americans based on an implicit right to privacy in the U.S. Constitution, such as the 1965 case Griswold v. Connecticut, which established a federal right to contraception for married people, and which was later extended to unmarried people.

Some congressional Democrats are now trying to codify the right to contraception in federal law. In July, the U.S. House of Representatives passed the Right to Contraception Act, which would give patients the right to access and use contraception and providers the right to furnish it. But the bill has little chance of success in the U.S. Senate, where Republicans have already blocked it once.

Protecting access to contraception is popular with voters. A national poll from Morning Consult and Politico conducted in late July found that 75% of registered voters support a federal law that protects a right to birth control access.

California isn’t the only state where voters are considering reproductive rights in their constitutions.

On Aug. 2, Kansas voters decisively rejected a constitutional amendment that would have allowed state lawmakers to ban or dramatically restrict abortion. It failed by nearly 18 percentage points.

Kentucky voters will face a similar decision in November with a proposed constitutional amendment that would declare that the state’s constitutional right to privacy does not cover abortion.

Vermont is going in the opposite direction. Voters there will weigh a ballot measure in November that would add a right to “personal reproductive autonomy” to the state constitution, though it does not explicitly mention abortion or contraception. In Michigan, a proposed constitutional amendment that would guarantee a right to both abortion and contraception is expected to qualify for the November ballot.

In California, Proposition 1 would prevent the state from denying or interfering with “an individual’s reproductive freedom in their most intimate decisions, which includes their fundamental right to choose to have an abortion and their fundamental right to choose or refuse contraceptives.”

The proposed constitutional amendment doesn’t go into detail about what enshrining the right to contraception in the state constitution would mean.

California already has some of the strongest contraceptive-access laws in the country – and lawmakers are considering more proposals this year. For instance, state-regulated health plans must cover all Food and Drug Administration–approved contraception; pharmacists must dispense emergency contraception to anyone with a prescription, regardless of age; and pharmacists can prescribe birth control pills on the spot. State courts have also interpreted California’s constitution to include a right to privacy that covers reproductive health decisions.

The amendment, if adopted, could provide a new legal pathway for people to sue when they’re denied contraceptives, said Michele Goodwin, chancellor’s professor of law at the University of California, Irvine.

If a pharmacist refused to fill a birth control prescription or a cashier declined to ring up condoms, she said, customers could make a case that their rights had been violated.

Making the rights to abortion and contraception explicit in the state constitution – instead of relying on a right to privacy – would also protect against shifting political winds, said state Senate leader Toni Atkins (D–San Diego), who was the director of a women’s health clinic in the 1980s. Although California’s lawmakers and executive officers are solid supporters of abortion rights, she said, the composition of the legislature and courts’ interpretation of laws could change.

“I want to know for sure that that right is protected,” Ms. Atkins said at a legislative hearing in June. “We are protecting ourselves from future courts and future politicians.”

The amendment would solidify California’s role as a reproductive rights sanctuary as much of the country chips away at birth control availability, Ms. Goodwin added.

Experts said two forms of birth control that are vulnerable to restrictions in other states are intrauterine devices, or IUDs, and emergency contraception such as Plan B. These methods are often incorrectly conflated with abortion pills, which end a pregnancy instead of preventing it.

Nine states have laws that restrict emergency contraception – for example, by allowing pharmacies to refuse to dispense it or excluding it from state family planning programs – according to the Guttmacher Institute, a research organization that supports abortion rights. In Alabama and Louisiana this year, abortion opponents introduced legislation that would restrict or ban abortion, and would also apply to emergency contraception.

“We’re seeing an erosion of abortion access that is playing out in statehouses across the country that have and will continue to target contraceptive care as well,” said Audrey Sandusky, senior director of policy and communications for the National Family Planning and Reproductive Health Association.

Susan Arnall, vice president of California’s Right to Life League, said the proposed amendment is symbolic and merely echoes current laws. Ms. Arnall said the campaign is mostly about Democratic politicians trying to score political points.

“It just allows the pro-abort legislators to trumpet and give them talking points about how they’re doing something about the overturn of Roe v. Wade,” she said. “It is political virtue signaling. I don’t think it does much of anything else.”

Ms. Goodwin argues that the measure’s symbolism is significant and overdue. She pointed to the Civil War era, when enslaved people in Southern states could look to free states for spiritual hope and material help. “Symbolically, what that meant is a kind of beacon of hope, that those places did exist, where one’s humanity could be regarded,” Ms. Goodwin said.

But California’s reputation as a haven for contraceptive availability may not be fully warranted, said Dima Qato, PharmD, PhD, an associate professor at the University of Southern California School of Pharmacy. In her 2020 study of contraceptive access in Los Angeles County, which has some of the highest rates of teen and unintended pregnancy in the country, Dr. Qato found that only 10% of pharmacies surveyed offered pharmacist-prescribed birth control. Pharmacies in low-income and minority communities were the least likely to offer the service, Dr. Qato said, worsening disparities instead of solving them.

Dr. Qato supports the constitutional amendment but said California should focus on improving and enforcing the laws it already has.

“We don’t need more laws when we don’t address the root cause of a lack of effectiveness of these laws in these communities,” she said. “Lack of enforcement and accountability disproportionately impacts communities of color.”

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Rachel Bluth is a correspondent for California Healthline. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

SACRAMENTO, CALIF. – Californians will decide in November whether to lock the right to abortion into the state constitution.

If they vote “yes” on Proposition 1, they will also lock in a right that has gotten less attention: The right to birth control.

Should the measure succeed, California would become one of the first states – if not the first – to create explicit constitutional rights to both abortion and contraception.

The lawmakers and activists behind the constitutional amendment said they hope to score a one-two punch: Protect abortion in California after the U.S. Supreme Court ended the federal constitutional right to abortion under Roe v. Wade, and get ahead of what they see as the next front in the reproductive rights fight: Birth control.

“The United States Supreme Court said that the privacy and liberty protections in the United States Constitution did not extend to abortion,” said UCLA law professor Cary Franklin, an expert in constitutional law and reproductive rights who has testified before the California legislature in support of the amendment. “If they said ‘no’ on abortion, they’re probably going to say ‘no’ on birth control because that has a similar history.”

In June, the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization ended the federal right to abortion and left states to regulate the service. In his concurring opinion, Justice Clarence Thomas said the court should revisit other cases that have created protections for Americans based on an implicit right to privacy in the U.S. Constitution, such as the 1965 case Griswold v. Connecticut, which established a federal right to contraception for married people, and which was later extended to unmarried people.

Some congressional Democrats are now trying to codify the right to contraception in federal law. In July, the U.S. House of Representatives passed the Right to Contraception Act, which would give patients the right to access and use contraception and providers the right to furnish it. But the bill has little chance of success in the U.S. Senate, where Republicans have already blocked it once.

Protecting access to contraception is popular with voters. A national poll from Morning Consult and Politico conducted in late July found that 75% of registered voters support a federal law that protects a right to birth control access.

California isn’t the only state where voters are considering reproductive rights in their constitutions.

On Aug. 2, Kansas voters decisively rejected a constitutional amendment that would have allowed state lawmakers to ban or dramatically restrict abortion. It failed by nearly 18 percentage points.

Kentucky voters will face a similar decision in November with a proposed constitutional amendment that would declare that the state’s constitutional right to privacy does not cover abortion.

Vermont is going in the opposite direction. Voters there will weigh a ballot measure in November that would add a right to “personal reproductive autonomy” to the state constitution, though it does not explicitly mention abortion or contraception. In Michigan, a proposed constitutional amendment that would guarantee a right to both abortion and contraception is expected to qualify for the November ballot.

In California, Proposition 1 would prevent the state from denying or interfering with “an individual’s reproductive freedom in their most intimate decisions, which includes their fundamental right to choose to have an abortion and their fundamental right to choose or refuse contraceptives.”

The proposed constitutional amendment doesn’t go into detail about what enshrining the right to contraception in the state constitution would mean.

California already has some of the strongest contraceptive-access laws in the country – and lawmakers are considering more proposals this year. For instance, state-regulated health plans must cover all Food and Drug Administration–approved contraception; pharmacists must dispense emergency contraception to anyone with a prescription, regardless of age; and pharmacists can prescribe birth control pills on the spot. State courts have also interpreted California’s constitution to include a right to privacy that covers reproductive health decisions.

The amendment, if adopted, could provide a new legal pathway for people to sue when they’re denied contraceptives, said Michele Goodwin, chancellor’s professor of law at the University of California, Irvine.

If a pharmacist refused to fill a birth control prescription or a cashier declined to ring up condoms, she said, customers could make a case that their rights had been violated.

Making the rights to abortion and contraception explicit in the state constitution – instead of relying on a right to privacy – would also protect against shifting political winds, said state Senate leader Toni Atkins (D–San Diego), who was the director of a women’s health clinic in the 1980s. Although California’s lawmakers and executive officers are solid supporters of abortion rights, she said, the composition of the legislature and courts’ interpretation of laws could change.

“I want to know for sure that that right is protected,” Ms. Atkins said at a legislative hearing in June. “We are protecting ourselves from future courts and future politicians.”

The amendment would solidify California’s role as a reproductive rights sanctuary as much of the country chips away at birth control availability, Ms. Goodwin added.

Experts said two forms of birth control that are vulnerable to restrictions in other states are intrauterine devices, or IUDs, and emergency contraception such as Plan B. These methods are often incorrectly conflated with abortion pills, which end a pregnancy instead of preventing it.

Nine states have laws that restrict emergency contraception – for example, by allowing pharmacies to refuse to dispense it or excluding it from state family planning programs – according to the Guttmacher Institute, a research organization that supports abortion rights. In Alabama and Louisiana this year, abortion opponents introduced legislation that would restrict or ban abortion, and would also apply to emergency contraception.

“We’re seeing an erosion of abortion access that is playing out in statehouses across the country that have and will continue to target contraceptive care as well,” said Audrey Sandusky, senior director of policy and communications for the National Family Planning and Reproductive Health Association.

Susan Arnall, vice president of California’s Right to Life League, said the proposed amendment is symbolic and merely echoes current laws. Ms. Arnall said the campaign is mostly about Democratic politicians trying to score political points.

“It just allows the pro-abort legislators to trumpet and give them talking points about how they’re doing something about the overturn of Roe v. Wade,” she said. “It is political virtue signaling. I don’t think it does much of anything else.”

Ms. Goodwin argues that the measure’s symbolism is significant and overdue. She pointed to the Civil War era, when enslaved people in Southern states could look to free states for spiritual hope and material help. “Symbolically, what that meant is a kind of beacon of hope, that those places did exist, where one’s humanity could be regarded,” Ms. Goodwin said.

But California’s reputation as a haven for contraceptive availability may not be fully warranted, said Dima Qato, PharmD, PhD, an associate professor at the University of Southern California School of Pharmacy. In her 2020 study of contraceptive access in Los Angeles County, which has some of the highest rates of teen and unintended pregnancy in the country, Dr. Qato found that only 10% of pharmacies surveyed offered pharmacist-prescribed birth control. Pharmacies in low-income and minority communities were the least likely to offer the service, Dr. Qato said, worsening disparities instead of solving them.

Dr. Qato supports the constitutional amendment but said California should focus on improving and enforcing the laws it already has.

“We don’t need more laws when we don’t address the root cause of a lack of effectiveness of these laws in these communities,” she said. “Lack of enforcement and accountability disproportionately impacts communities of color.”

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Rachel Bluth is a correspondent for California Healthline. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

SACRAMENTO, CALIF. – Californians will decide in November whether to lock the right to abortion into the state constitution.

If they vote “yes” on Proposition 1, they will also lock in a right that has gotten less attention: The right to birth control.

Should the measure succeed, California would become one of the first states – if not the first – to create explicit constitutional rights to both abortion and contraception.

The lawmakers and activists behind the constitutional amendment said they hope to score a one-two punch: Protect abortion in California after the U.S. Supreme Court ended the federal constitutional right to abortion under Roe v. Wade, and get ahead of what they see as the next front in the reproductive rights fight: Birth control.

“The United States Supreme Court said that the privacy and liberty protections in the United States Constitution did not extend to abortion,” said UCLA law professor Cary Franklin, an expert in constitutional law and reproductive rights who has testified before the California legislature in support of the amendment. “If they said ‘no’ on abortion, they’re probably going to say ‘no’ on birth control because that has a similar history.”

In June, the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization ended the federal right to abortion and left states to regulate the service. In his concurring opinion, Justice Clarence Thomas said the court should revisit other cases that have created protections for Americans based on an implicit right to privacy in the U.S. Constitution, such as the 1965 case Griswold v. Connecticut, which established a federal right to contraception for married people, and which was later extended to unmarried people.

Some congressional Democrats are now trying to codify the right to contraception in federal law. In July, the U.S. House of Representatives passed the Right to Contraception Act, which would give patients the right to access and use contraception and providers the right to furnish it. But the bill has little chance of success in the U.S. Senate, where Republicans have already blocked it once.

Protecting access to contraception is popular with voters. A national poll from Morning Consult and Politico conducted in late July found that 75% of registered voters support a federal law that protects a right to birth control access.

California isn’t the only state where voters are considering reproductive rights in their constitutions.

On Aug. 2, Kansas voters decisively rejected a constitutional amendment that would have allowed state lawmakers to ban or dramatically restrict abortion. It failed by nearly 18 percentage points.

Kentucky voters will face a similar decision in November with a proposed constitutional amendment that would declare that the state’s constitutional right to privacy does not cover abortion.

Vermont is going in the opposite direction. Voters there will weigh a ballot measure in November that would add a right to “personal reproductive autonomy” to the state constitution, though it does not explicitly mention abortion or contraception. In Michigan, a proposed constitutional amendment that would guarantee a right to both abortion and contraception is expected to qualify for the November ballot.

In California, Proposition 1 would prevent the state from denying or interfering with “an individual’s reproductive freedom in their most intimate decisions, which includes their fundamental right to choose to have an abortion and their fundamental right to choose or refuse contraceptives.”

The proposed constitutional amendment doesn’t go into detail about what enshrining the right to contraception in the state constitution would mean.

California already has some of the strongest contraceptive-access laws in the country – and lawmakers are considering more proposals this year. For instance, state-regulated health plans must cover all Food and Drug Administration–approved contraception; pharmacists must dispense emergency contraception to anyone with a prescription, regardless of age; and pharmacists can prescribe birth control pills on the spot. State courts have also interpreted California’s constitution to include a right to privacy that covers reproductive health decisions.

The amendment, if adopted, could provide a new legal pathway for people to sue when they’re denied contraceptives, said Michele Goodwin, chancellor’s professor of law at the University of California, Irvine.

If a pharmacist refused to fill a birth control prescription or a cashier declined to ring up condoms, she said, customers could make a case that their rights had been violated.

Making the rights to abortion and contraception explicit in the state constitution – instead of relying on a right to privacy – would also protect against shifting political winds, said state Senate leader Toni Atkins (D–San Diego), who was the director of a women’s health clinic in the 1980s. Although California’s lawmakers and executive officers are solid supporters of abortion rights, she said, the composition of the legislature and courts’ interpretation of laws could change.

“I want to know for sure that that right is protected,” Ms. Atkins said at a legislative hearing in June. “We are protecting ourselves from future courts and future politicians.”

The amendment would solidify California’s role as a reproductive rights sanctuary as much of the country chips away at birth control availability, Ms. Goodwin added.

Experts said two forms of birth control that are vulnerable to restrictions in other states are intrauterine devices, or IUDs, and emergency contraception such as Plan B. These methods are often incorrectly conflated with abortion pills, which end a pregnancy instead of preventing it.

Nine states have laws that restrict emergency contraception – for example, by allowing pharmacies to refuse to dispense it or excluding it from state family planning programs – according to the Guttmacher Institute, a research organization that supports abortion rights. In Alabama and Louisiana this year, abortion opponents introduced legislation that would restrict or ban abortion, and would also apply to emergency contraception.

“We’re seeing an erosion of abortion access that is playing out in statehouses across the country that have and will continue to target contraceptive care as well,” said Audrey Sandusky, senior director of policy and communications for the National Family Planning and Reproductive Health Association.

Susan Arnall, vice president of California’s Right to Life League, said the proposed amendment is symbolic and merely echoes current laws. Ms. Arnall said the campaign is mostly about Democratic politicians trying to score political points.

“It just allows the pro-abort legislators to trumpet and give them talking points about how they’re doing something about the overturn of Roe v. Wade,” she said. “It is political virtue signaling. I don’t think it does much of anything else.”

Ms. Goodwin argues that the measure’s symbolism is significant and overdue. She pointed to the Civil War era, when enslaved people in Southern states could look to free states for spiritual hope and material help. “Symbolically, what that meant is a kind of beacon of hope, that those places did exist, where one’s humanity could be regarded,” Ms. Goodwin said.

But California’s reputation as a haven for contraceptive availability may not be fully warranted, said Dima Qato, PharmD, PhD, an associate professor at the University of Southern California School of Pharmacy. In her 2020 study of contraceptive access in Los Angeles County, which has some of the highest rates of teen and unintended pregnancy in the country, Dr. Qato found that only 10% of pharmacies surveyed offered pharmacist-prescribed birth control. Pharmacies in low-income and minority communities were the least likely to offer the service, Dr. Qato said, worsening disparities instead of solving them.

Dr. Qato supports the constitutional amendment but said California should focus on improving and enforcing the laws it already has.

“We don’t need more laws when we don’t address the root cause of a lack of effectiveness of these laws in these communities,” she said. “Lack of enforcement and accountability disproportionately impacts communities of color.”

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Rachel Bluth is a correspondent for California Healthline. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

A new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.

CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.

Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.

But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”

CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.

The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).

Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”

Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”

This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”

Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”

This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.

But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.

Ms. Bulens and Dr. Price reported no relevant financial relationships.

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

A new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.

CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.

Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.

But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”

CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.

The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).

Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”

Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”

This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”

Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”

This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.

But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.

Ms. Bulens and Dr. Price reported no relevant financial relationships.

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

A new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.

CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.

Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.

But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”

CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.

The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).

Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”

Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”

This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”

Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”

This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.

But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.

Ms. Bulens and Dr. Price reported no relevant financial relationships.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

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

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

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

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

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