Feature

When the world needed a COVID vaccine, leading HIV investigators answered the call to intervene in the coronavirus pandemic. Now, efforts to discover the world’s first HIV vaccine are revitalized.

“The body is capable of making antibodies to protect us from HIV,” says Yunda Huang, PhD, from the Fred Hutchinson Cancer Center in Seattle, Washington, who sat down with me before her talk today at the Conference on Retroviruses & Opportunistic Infections.

Dr. Huang spoke about the path forward for neutralizing antibody protection after the last attempt in a generation of HIV vaccine development ended in disappointment.

The past two decades marked the rise in HIV broadly neutralizing antibodies, with vaccine strategies to induce them. Promising advances include germline approaches, mRNA, and nanoparticle technologies.

The PrEP vaccine trial testing two experimental prevention regimens in Africa was stopped after investigators reported there is “little to no chance” the trial will show the vaccines are effective.
 

A Shape-Shifting Virus

HIV has been called the shape-shifting virus because it disguises itself so that even when people are able to make antibodies to it, the virus changes to escape.

But Dr. Huang and others are optimistic that an effective vaccine is still possible.

“We cannot and will not lose hope that the world will have an effective HIV vaccine that is accessible by all who need it, anywhere,” International AIDS Society (IAS) Executive Director Birgit Poniatowski said in a statement in December, when the trial was stopped.

HIV is a still persistent problem in the United States, according to the Centers for Disease Control and Prevention that reports it has affected an estimated 1.2 million people.

With new people infected every day around the globe, Dr. Huang says she feels a sense of urgency to help. “I think about all the people around the globe and the large number of young girls being hurt and I know our big pool of talent can intervene to change what we see happening.” 

Dr. Huang says the clinical trial failures we’ve seen so far will help guide next steps in HIV research as much as successes typically do.
 

Advances in the Field

With significant advances in protein nanoparticle science, mRNA technology, adjuvant development, and B-cell and antibody analyses, a new wave of clinical trials are on the way.

And with so many new approaches in the works, the HIV Vaccine Trials Network is retooling how it operates to navigate a burgeoning field and identify the most promising regimens.

A new Discovery Medicine Program will help the network assess new vaccine candidates. It will also aim to rule out others earlier on.

For COVID-19 and the flu, multimeric nanoparticles are an important alternative under investigation that could also be adapted for HIV.

Dr. Huang says she is particularly excited to watch the progress in cocktails of combination monoclonals. “I’ve been working in this field for 20 years now and there is a misconception that with pre-exposure prophylaxis, our job is done, but HIV is so far from away from being solved.”

But you just never know, Dr. Huang says. With new research, “we could bump on something at any point that changes everything.”

A version of this article appeared on Medscape.com.

When the world needed a COVID vaccine, leading HIV investigators answered the call to intervene in the coronavirus pandemic. Now, efforts to discover the world’s first HIV vaccine are revitalized.

“The body is capable of making antibodies to protect us from HIV,” says Yunda Huang, PhD, from the Fred Hutchinson Cancer Center in Seattle, Washington, who sat down with me before her talk today at the Conference on Retroviruses & Opportunistic Infections.

Dr. Huang spoke about the path forward for neutralizing antibody protection after the last attempt in a generation of HIV vaccine development ended in disappointment.

The past two decades marked the rise in HIV broadly neutralizing antibodies, with vaccine strategies to induce them. Promising advances include germline approaches, mRNA, and nanoparticle technologies.

The PrEP vaccine trial testing two experimental prevention regimens in Africa was stopped after investigators reported there is “little to no chance” the trial will show the vaccines are effective.
 

A Shape-Shifting Virus

HIV has been called the shape-shifting virus because it disguises itself so that even when people are able to make antibodies to it, the virus changes to escape.

But Dr. Huang and others are optimistic that an effective vaccine is still possible.

“We cannot and will not lose hope that the world will have an effective HIV vaccine that is accessible by all who need it, anywhere,” International AIDS Society (IAS) Executive Director Birgit Poniatowski said in a statement in December, when the trial was stopped.

HIV is a still persistent problem in the United States, according to the Centers for Disease Control and Prevention that reports it has affected an estimated 1.2 million people.

With new people infected every day around the globe, Dr. Huang says she feels a sense of urgency to help. “I think about all the people around the globe and the large number of young girls being hurt and I know our big pool of talent can intervene to change what we see happening.” 

Dr. Huang says the clinical trial failures we’ve seen so far will help guide next steps in HIV research as much as successes typically do.
 

Advances in the Field

With significant advances in protein nanoparticle science, mRNA technology, adjuvant development, and B-cell and antibody analyses, a new wave of clinical trials are on the way.

And with so many new approaches in the works, the HIV Vaccine Trials Network is retooling how it operates to navigate a burgeoning field and identify the most promising regimens.

A new Discovery Medicine Program will help the network assess new vaccine candidates. It will also aim to rule out others earlier on.

For COVID-19 and the flu, multimeric nanoparticles are an important alternative under investigation that could also be adapted for HIV.

Dr. Huang says she is particularly excited to watch the progress in cocktails of combination monoclonals. “I’ve been working in this field for 20 years now and there is a misconception that with pre-exposure prophylaxis, our job is done, but HIV is so far from away from being solved.”

But you just never know, Dr. Huang says. With new research, “we could bump on something at any point that changes everything.”

A version of this article appeared on Medscape.com.

When the world needed a COVID vaccine, leading HIV investigators answered the call to intervene in the coronavirus pandemic. Now, efforts to discover the world’s first HIV vaccine are revitalized.

“The body is capable of making antibodies to protect us from HIV,” says Yunda Huang, PhD, from the Fred Hutchinson Cancer Center in Seattle, Washington, who sat down with me before her talk today at the Conference on Retroviruses & Opportunistic Infections.

Dr. Huang spoke about the path forward for neutralizing antibody protection after the last attempt in a generation of HIV vaccine development ended in disappointment.

The past two decades marked the rise in HIV broadly neutralizing antibodies, with vaccine strategies to induce them. Promising advances include germline approaches, mRNA, and nanoparticle technologies.

The PrEP vaccine trial testing two experimental prevention regimens in Africa was stopped after investigators reported there is “little to no chance” the trial will show the vaccines are effective.
 

A Shape-Shifting Virus

HIV has been called the shape-shifting virus because it disguises itself so that even when people are able to make antibodies to it, the virus changes to escape.

But Dr. Huang and others are optimistic that an effective vaccine is still possible.

“We cannot and will not lose hope that the world will have an effective HIV vaccine that is accessible by all who need it, anywhere,” International AIDS Society (IAS) Executive Director Birgit Poniatowski said in a statement in December, when the trial was stopped.

HIV is a still persistent problem in the United States, according to the Centers for Disease Control and Prevention that reports it has affected an estimated 1.2 million people.

With new people infected every day around the globe, Dr. Huang says she feels a sense of urgency to help. “I think about all the people around the globe and the large number of young girls being hurt and I know our big pool of talent can intervene to change what we see happening.” 

Dr. Huang says the clinical trial failures we’ve seen so far will help guide next steps in HIV research as much as successes typically do.
 

Advances in the Field

With significant advances in protein nanoparticle science, mRNA technology, adjuvant development, and B-cell and antibody analyses, a new wave of clinical trials are on the way.

And with so many new approaches in the works, the HIV Vaccine Trials Network is retooling how it operates to navigate a burgeoning field and identify the most promising regimens.

A new Discovery Medicine Program will help the network assess new vaccine candidates. It will also aim to rule out others earlier on.

For COVID-19 and the flu, multimeric nanoparticles are an important alternative under investigation that could also be adapted for HIV.

Dr. Huang says she is particularly excited to watch the progress in cocktails of combination monoclonals. “I’ve been working in this field for 20 years now and there is a misconception that with pre-exposure prophylaxis, our job is done, but HIV is so far from away from being solved.”

But you just never know, Dr. Huang says. With new research, “we could bump on something at any point that changes everything.”

A version of this article appeared on Medscape.com.

Breast cancer-specific mortality risk in men with hormone receptor–positive breast cancer persists for at least 20 years, but patterns of breast cancer–specific mortality (BCSM) are distinct from those in women, a new study finds.

Previous studies in women with hormone receptor–positive (HR+) breast cancer have shown a risk of distant recurrence and death for at least 20 years after diagnosis, but data for men are limited, wrote Julieta Leone, MD, of the Dana Farber Cancer Institute, Boston, and colleagues.
 

What is Known About Hormone Receptor–Positive Breast Cancer Mortality in Men vs. Women?

Invasive breast cancer in men is rare and consequently understudied, the researchers wrote. Previous studies of BCSM in men with more than 5 years’ follow-up consist mainly of case series at single institutions, the researchers wrote in JAMA Oncology (2024 Feb 29. doi: 10.1001/jamaoncol.2023.7194).

“We believed it would be important to study this issue to help inform the management of men with breast cancer,” corresponding author, José P. Leone, MD, said in an interview.

In 2021, Dr. J.P. Leone and colleagues published a study in Breast Cancer Research and Treatment that examined the 20-year risk of BCSM in women that included more than 36,000 individuals who had survived for 5 years, with a median of 14 years’ follow-up.

In that study of women, the BCSM risk at 20 years was significantly higher for those with HR-negative tumors, but the risk was still elevated for both types. Patients with stage IIIC HR-positive disease had four times the risk of BCSM over 20 years and those with stage IIIC HR-negative disease had seven times the risk of BCSM over 20 years compared with the risk of death not related to breast cancer, the researchers wrote.

Another study of nearly 2,400 men with breast cancer (mainly HR+) by Dr. J.P. Leone and colleagues showed that cancer stage, tumor subtype, and race were associated with overall survival and breast cancer-specific survival.
 

What Does the New Study Add?

The current study included 2,836 men diagnosed with stage I to stage III HR+ breast cancer between 1990 and 2008, using data from the Surveillance, Epidemiology, and End Results (SEER) database.

“We found that in men with breast cancer, the risk of breast cancer mortality persists for at least 20 years and that [the risk] depends on traditional clinicopathologic factors, such as age, tumor size, nodal status and tumor grade,” Dr. J.P. Leone said in an interview.

“The prolonged risk [of breast-cancer specific mortality] over 20 years that we observed in our study is similar to that previously reported in women; however, the kinetics of the risk over the 20-year period appears different in men,” he emphasized.

The men in the study, especially those with a higher stage of disease, appeared to have a bimodal distribution of the BRCA mortality risk, he said.

Two peaks were identified, he explained; an early peak in mortality risk at approximately 4 years from diagnosis and another at approximately 11 years after diagnosis.

Although women with breast cancer had a prolonged risk of breast cancer mortality, “the kinetics of the risk does not include 2 peaks, even in women with higher stage of disease.” In women with higher stage breast cancer, the peak mortality risk occurs approximately 5 years after diagnosis, he said.

The reasons for the later peak in men remain unclear, the researchers wrote in the study, but possible explanations include nonadherence to endocrine therapy, differences in tumor biologic factors, and differences in the tumor microenvironment between men and women, they noted, in the discussion section.
 

What Drives the Risk?

Key factors for breast cancer-specific mortality were age, tumor stage, and tumor grade.

The cumulative 20-year risk of BCSM in the current study was 12.4%, 26.2%, and 46.0% for stage I, II, and III, respectively. The adjusted BCSM risk was increased in patients younger than 50 years, those with grade II or III/IV tumors, and those with stage II or III disease.
 

What Are the Limitations?

The current study by Leone and colleagues was limited by the relatively small subgroup sample of men with stage III and N3 disease, lack of data on the use of systemic therapies, and lack of data on human epidermal growth factor receptor 2 gene (ERBB2), the researchers wrote. However, the long-term follow-up strengthened the results, and the study is the first known to assess 20-year BCSM risk in men with nonmetastatic HR+ breast cancer.

What Do Oncologists Need to Know About the Study?

The study findings indicate that the risk of breast cancer mortality persists for 20 years in men with hormone receptor–positive breast cancer, Dr. J.P. Leone said in an interview. As in women, the risk depends on traditional clinicopathologic factors, he noted.

“However, the kinetics of that risk appears to be different between men and women. In order to reduce the breast cancer mortality risk in men with hormone receptor–positive breast cancer, it will be important for men to consider the benefits of the treatment options that may be indicated for their specific situation,” he said.

“I think early detection is also very important,” he emphasized. To that end, increased awareness of the possibility for breast cancer in men, as well as prompt intervention when breast cancer is suspected, will help to improve early detection when the risk of breast cancer mortality is lower, he added.
 

What Are the Next Steps for Research?

“I think our study underscores the need for additional research to improve our adjuvant therapy options in both men and women with hormone receptor-positive breast cancer, to reduce the risk of long-term mortality,” he said.

The study received no outside funding. Lead author Julieta Leone had no financial conflicts to disclose. Dr. José P. Leone disclosed receiving institutional grants from Kazia Therapeutics and Seagen unrelated to the current study.

Breast cancer-specific mortality risk in men with hormone receptor–positive breast cancer persists for at least 20 years, but patterns of breast cancer–specific mortality (BCSM) are distinct from those in women, a new study finds.

Previous studies in women with hormone receptor–positive (HR+) breast cancer have shown a risk of distant recurrence and death for at least 20 years after diagnosis, but data for men are limited, wrote Julieta Leone, MD, of the Dana Farber Cancer Institute, Boston, and colleagues.
 

What is Known About Hormone Receptor–Positive Breast Cancer Mortality in Men vs. Women?

Invasive breast cancer in men is rare and consequently understudied, the researchers wrote. Previous studies of BCSM in men with more than 5 years’ follow-up consist mainly of case series at single institutions, the researchers wrote in JAMA Oncology (2024 Feb 29. doi: 10.1001/jamaoncol.2023.7194).

“We believed it would be important to study this issue to help inform the management of men with breast cancer,” corresponding author, José P. Leone, MD, said in an interview.

In 2021, Dr. J.P. Leone and colleagues published a study in Breast Cancer Research and Treatment that examined the 20-year risk of BCSM in women that included more than 36,000 individuals who had survived for 5 years, with a median of 14 years’ follow-up.

In that study of women, the BCSM risk at 20 years was significantly higher for those with HR-negative tumors, but the risk was still elevated for both types. Patients with stage IIIC HR-positive disease had four times the risk of BCSM over 20 years and those with stage IIIC HR-negative disease had seven times the risk of BCSM over 20 years compared with the risk of death not related to breast cancer, the researchers wrote.

Another study of nearly 2,400 men with breast cancer (mainly HR+) by Dr. J.P. Leone and colleagues showed that cancer stage, tumor subtype, and race were associated with overall survival and breast cancer-specific survival.
 

What Does the New Study Add?

The current study included 2,836 men diagnosed with stage I to stage III HR+ breast cancer between 1990 and 2008, using data from the Surveillance, Epidemiology, and End Results (SEER) database.

“We found that in men with breast cancer, the risk of breast cancer mortality persists for at least 20 years and that [the risk] depends on traditional clinicopathologic factors, such as age, tumor size, nodal status and tumor grade,” Dr. J.P. Leone said in an interview.

“The prolonged risk [of breast-cancer specific mortality] over 20 years that we observed in our study is similar to that previously reported in women; however, the kinetics of the risk over the 20-year period appears different in men,” he emphasized.

The men in the study, especially those with a higher stage of disease, appeared to have a bimodal distribution of the BRCA mortality risk, he said.

Two peaks were identified, he explained; an early peak in mortality risk at approximately 4 years from diagnosis and another at approximately 11 years after diagnosis.

Although women with breast cancer had a prolonged risk of breast cancer mortality, “the kinetics of the risk does not include 2 peaks, even in women with higher stage of disease.” In women with higher stage breast cancer, the peak mortality risk occurs approximately 5 years after diagnosis, he said.

The reasons for the later peak in men remain unclear, the researchers wrote in the study, but possible explanations include nonadherence to endocrine therapy, differences in tumor biologic factors, and differences in the tumor microenvironment between men and women, they noted, in the discussion section.
 

What Drives the Risk?

Key factors for breast cancer-specific mortality were age, tumor stage, and tumor grade.

The cumulative 20-year risk of BCSM in the current study was 12.4%, 26.2%, and 46.0% for stage I, II, and III, respectively. The adjusted BCSM risk was increased in patients younger than 50 years, those with grade II or III/IV tumors, and those with stage II or III disease.
 

What Are the Limitations?

The current study by Leone and colleagues was limited by the relatively small subgroup sample of men with stage III and N3 disease, lack of data on the use of systemic therapies, and lack of data on human epidermal growth factor receptor 2 gene (ERBB2), the researchers wrote. However, the long-term follow-up strengthened the results, and the study is the first known to assess 20-year BCSM risk in men with nonmetastatic HR+ breast cancer.

What Do Oncologists Need to Know About the Study?

The study findings indicate that the risk of breast cancer mortality persists for 20 years in men with hormone receptor–positive breast cancer, Dr. J.P. Leone said in an interview. As in women, the risk depends on traditional clinicopathologic factors, he noted.

“However, the kinetics of that risk appears to be different between men and women. In order to reduce the breast cancer mortality risk in men with hormone receptor–positive breast cancer, it will be important for men to consider the benefits of the treatment options that may be indicated for their specific situation,” he said.

“I think early detection is also very important,” he emphasized. To that end, increased awareness of the possibility for breast cancer in men, as well as prompt intervention when breast cancer is suspected, will help to improve early detection when the risk of breast cancer mortality is lower, he added.
 

What Are the Next Steps for Research?

“I think our study underscores the need for additional research to improve our adjuvant therapy options in both men and women with hormone receptor-positive breast cancer, to reduce the risk of long-term mortality,” he said.

The study received no outside funding. Lead author Julieta Leone had no financial conflicts to disclose. Dr. José P. Leone disclosed receiving institutional grants from Kazia Therapeutics and Seagen unrelated to the current study.

Breast cancer-specific mortality risk in men with hormone receptor–positive breast cancer persists for at least 20 years, but patterns of breast cancer–specific mortality (BCSM) are distinct from those in women, a new study finds.

Previous studies in women with hormone receptor–positive (HR+) breast cancer have shown a risk of distant recurrence and death for at least 20 years after diagnosis, but data for men are limited, wrote Julieta Leone, MD, of the Dana Farber Cancer Institute, Boston, and colleagues.
 

What is Known About Hormone Receptor–Positive Breast Cancer Mortality in Men vs. Women?

Invasive breast cancer in men is rare and consequently understudied, the researchers wrote. Previous studies of BCSM in men with more than 5 years’ follow-up consist mainly of case series at single institutions, the researchers wrote in JAMA Oncology (2024 Feb 29. doi: 10.1001/jamaoncol.2023.7194).

“We believed it would be important to study this issue to help inform the management of men with breast cancer,” corresponding author, José P. Leone, MD, said in an interview.

In 2021, Dr. J.P. Leone and colleagues published a study in Breast Cancer Research and Treatment that examined the 20-year risk of BCSM in women that included more than 36,000 individuals who had survived for 5 years, with a median of 14 years’ follow-up.

In that study of women, the BCSM risk at 20 years was significantly higher for those with HR-negative tumors, but the risk was still elevated for both types. Patients with stage IIIC HR-positive disease had four times the risk of BCSM over 20 years and those with stage IIIC HR-negative disease had seven times the risk of BCSM over 20 years compared with the risk of death not related to breast cancer, the researchers wrote.

Another study of nearly 2,400 men with breast cancer (mainly HR+) by Dr. J.P. Leone and colleagues showed that cancer stage, tumor subtype, and race were associated with overall survival and breast cancer-specific survival.
 

What Does the New Study Add?

The current study included 2,836 men diagnosed with stage I to stage III HR+ breast cancer between 1990 and 2008, using data from the Surveillance, Epidemiology, and End Results (SEER) database.

“We found that in men with breast cancer, the risk of breast cancer mortality persists for at least 20 years and that [the risk] depends on traditional clinicopathologic factors, such as age, tumor size, nodal status and tumor grade,” Dr. J.P. Leone said in an interview.

“The prolonged risk [of breast-cancer specific mortality] over 20 years that we observed in our study is similar to that previously reported in women; however, the kinetics of the risk over the 20-year period appears different in men,” he emphasized.

The men in the study, especially those with a higher stage of disease, appeared to have a bimodal distribution of the BRCA mortality risk, he said.

Two peaks were identified, he explained; an early peak in mortality risk at approximately 4 years from diagnosis and another at approximately 11 years after diagnosis.

Although women with breast cancer had a prolonged risk of breast cancer mortality, “the kinetics of the risk does not include 2 peaks, even in women with higher stage of disease.” In women with higher stage breast cancer, the peak mortality risk occurs approximately 5 years after diagnosis, he said.

The reasons for the later peak in men remain unclear, the researchers wrote in the study, but possible explanations include nonadherence to endocrine therapy, differences in tumor biologic factors, and differences in the tumor microenvironment between men and women, they noted, in the discussion section.
 

What Drives the Risk?

Key factors for breast cancer-specific mortality were age, tumor stage, and tumor grade.

The cumulative 20-year risk of BCSM in the current study was 12.4%, 26.2%, and 46.0% for stage I, II, and III, respectively. The adjusted BCSM risk was increased in patients younger than 50 years, those with grade II or III/IV tumors, and those with stage II or III disease.
 

What Are the Limitations?

The current study by Leone and colleagues was limited by the relatively small subgroup sample of men with stage III and N3 disease, lack of data on the use of systemic therapies, and lack of data on human epidermal growth factor receptor 2 gene (ERBB2), the researchers wrote. However, the long-term follow-up strengthened the results, and the study is the first known to assess 20-year BCSM risk in men with nonmetastatic HR+ breast cancer.

What Do Oncologists Need to Know About the Study?

The study findings indicate that the risk of breast cancer mortality persists for 20 years in men with hormone receptor–positive breast cancer, Dr. J.P. Leone said in an interview. As in women, the risk depends on traditional clinicopathologic factors, he noted.

“However, the kinetics of that risk appears to be different between men and women. In order to reduce the breast cancer mortality risk in men with hormone receptor–positive breast cancer, it will be important for men to consider the benefits of the treatment options that may be indicated for their specific situation,” he said.

“I think early detection is also very important,” he emphasized. To that end, increased awareness of the possibility for breast cancer in men, as well as prompt intervention when breast cancer is suspected, will help to improve early detection when the risk of breast cancer mortality is lower, he added.
 

What Are the Next Steps for Research?

“I think our study underscores the need for additional research to improve our adjuvant therapy options in both men and women with hormone receptor-positive breast cancer, to reduce the risk of long-term mortality,” he said.

The study received no outside funding. Lead author Julieta Leone had no financial conflicts to disclose. Dr. José P. Leone disclosed receiving institutional grants from Kazia Therapeutics and Seagen unrelated to the current study.

While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”

Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.

“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.

Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress. 
 

Adrenal Fatigue, Burnout, or Adrenal Insufficiency?

Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”

Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.

More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.

He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.

“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.

The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.

“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.

Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.

“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said. 

This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.

While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.

“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.

Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.

“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”

Recognizing and Managing Patient Frustration

The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.

Dr. Rao empathizes with the situation that many people, often young women, find themselves in.

“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”

This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.

But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.

“We truly are what we eat, and we are what we think,” she noted.

The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.” 

“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”

Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.

“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”

Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.

A version of this article appeared on Medscape.com.

While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”

Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.

“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.

Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress. 
 

Adrenal Fatigue, Burnout, or Adrenal Insufficiency?

Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”

Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.

More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.

He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.

“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.

The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.

“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.

Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.

“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said. 

This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.

While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.

“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.

Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.

“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”

Recognizing and Managing Patient Frustration

The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.

Dr. Rao empathizes with the situation that many people, often young women, find themselves in.

“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”

This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.

But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.

“We truly are what we eat, and we are what we think,” she noted.

The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.” 

“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”

Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.

“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”

Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.

A version of this article appeared on Medscape.com.

While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”

Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.

“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.

Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress. 
 

Adrenal Fatigue, Burnout, or Adrenal Insufficiency?

Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”

Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.

More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.

He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.

“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.

The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.

“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.

Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.

“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said. 

This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.

While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.

“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.

Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.

“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”

Recognizing and Managing Patient Frustration

The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.

Dr. Rao empathizes with the situation that many people, often young women, find themselves in.

“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”

This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.

But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.

“We truly are what we eat, and we are what we think,” she noted.

The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.” 

“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”

Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.

“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”

Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.

A version of this article appeared on Medscape.com.

Jason Black, MD, trained in family medicine, worked for Kaiser Permanente, and subsequently completed a fellowship in geriatrics. Today, he treats frail elderly patients, mostly residents of nursing homes and assisted living facilities or living in their own homes, for Gilchrist, a hospice and palliative care organization serving Baltimore and central Maryland.

“I’m practicing family medicine to the extent that I’m treating the family unit, including the anxieties of the adult children, and finding solutions for the parents,” said Dr. Black, one of Gilchrist’s 62 employed providers, one third of whom are physicians. One of his most important roles is medication reconciliation and deprescribing.

Palliative care, a medical specialty that focuses on clarifying the treatment goals of seriously ill patients, helping with end-of-life planning, and emphasizing pain and symptom management, has been growing in recent years. Already well-established in most US hospitals, it is expanding in community settings, often as an extension of hospice programs.

Now, by adding primary care physicians and practices to their service mix, palliative care groups are better meeting the needs of a neglected — and costly — population of frail elders. In doing so, they also are better able to find a niche in the rapidly evolving alphabet soup of value-based care and its varieties of shared savings for providers who post positive outcomes.

Most patients Dr. Black sees find it difficult to visit their doctors in a clinic setting, although they face a variety of medical needs and chronic conditions of aging. They may have a prognosis of several years to live and, thus, do not qualify for hospice care. To him, a palliative approach offers the satisfaction of focusing on what is most important to patients at this difficult time in their lives, rather than predetermined clinical metrics like blood pressure or blood glucose. “It takes a lot of work, but it feels important and rewarding,” he said.

A recent survey of community-dwelling older adults in Ontario, Canada, found most patients fail to receive this treatment homes in the final 3 months of life.
 

Continuums of Patients and Models

Gilchrist started as a nonprofit, hospital-affiliated hospice program in 1994 and in 2000 took on the management of a geriatric medicine practice for its parent, Greater Baltimore Medical Center. Today, its physicians and nurse practitioners see a range of patients in geriatric primary care, palliative medicine, and hospice, according to its chief medical officer, Mark J. Gloth, DO.

“As people progress in their disease, their location — where they call home — may change as well,” Dr. Gloth said. “We offer a continuum of care in order to not lose people through those transitions. That’s the core of our mission — making sure we are there to escort people through the difficult moments in their lives.”

Models for value-based care encompass accountable care organizations (ACOs), including the ACO REACH (Realizing Equity, Access, and Community Health) high-needs model for traditional Medicare patients, and Medicare Shared Savings Programs for fee-for-service beneficiaries. These value-based models offer a variety of opportunities for the palliative care organization to share in savings resulting from keeping the patient out of the hospital or emergency room and other quality and cost benchmarks.
 

Coming Together to Meet Needs

Gilchrist is one of nine hospice and palliative organizations that have joined to form their own multistate ACO, Responsive Care Solutions, focused on the clinical needs of frail elderly Medicare beneficiaries. Hospice of the Valley in Phoenix has Geriatric Solutions, a frail elder physician practice. And Capital Caring Health, a hospice and palliative care agency serving metro Washington, DC, has deployed several physicians and nurse practitioners on the road doing primary care at home, said Heidi Young, MD, its Primary Care at Home Lead Physician.

“Five years ago, we started our primary care practice under the umbrella of a 40-year-old hospice organization because we thought we needed to prepare for the changes that are coming to the hospice model,” Dr. Young said. “The thought was that we’re not just a hospice organization; we’re an advanced illness organization. We will come to your home, whatever that is, and provide your primary care.”

The greatest potential gains for a hospice organization are from assuming 100% risk for a large population of patients, keeping them out of the hospital to lower the costs of their care, then reaping those gains under a value-based profit-sharing model, Dr. Young said.

“Our program is still new and working toward getting more patients aligned into value-based models,” she said. “It’s a work in progress.”
 

A Foot in Each World

Agencies like Capital Caring and Gilchrist derive the largest share of their physician income from billing Medicare Part B and other insurers per visit. But that billing is not enough to break even on physician services.

With hopes for a value-based future, Gilchrist also gets grants from elder-facing charitable foundations to cover up to 40% of the costs of its home-based primary care, according to its president, Catherine Hamel. Hospice care continues to be paid on a per-diem basis by Medicare for eligible terminally ill patients, including Medicare Advantage patients, although the Centers for Medicare & Medicaid Services is reportedly considering new models for the hospice benefit.

The National Partnership for Healthcare and Hospice Innovation (NPHI) is a trade group representing more than 100 nonprofit, hospice-based organizations participating in palliative care and value-based care.

For a hospice to be successful in the evolving post–acute care/end-of-life care landscape, it can no longer rely solely on its hospice line of business, no matter how high-quality, said Ethan McChesney, policy director for the Washington, DC-based nonprofit.

NPHI members have developed their own palliative care programs, and perhaps, a quarter have primary care at home practices, Mr. McChesney said. Some of them acquired existing primary care practices in their service area with which they already had relationships; others created their own.

For hospice organizations building a continuum of services for the seriously ill, adding a primary care at home practice is a natural fit, he said. “You can provide all the services you would as a traditional primary care practice while you have the opportunity to establish long-term relationships with patients and their caregivers that lend themselves to palliative care referrals and then hospice referrals downstream [when the patient becomes eligible for hospice care].” Often, this primary medical care is a mix of in-person and telehealth.

Cameron Muir, MD, NPHI’s chief innovation officer, noted that the hamster wheel for primary care doctors has been spinning faster and faster, with reimbursement going down and costs going up.

But with home-based primary care for frail elders under value-based models, Dr. Muir said, the clinician is paid not for making more visits but for taking great care of the patient: “And I’m actually saving Medicare money and getting credit for the hospitalizations that were avoided.”
 

A version of this article appeared on Medscape.com.

Jason Black, MD, trained in family medicine, worked for Kaiser Permanente, and subsequently completed a fellowship in geriatrics. Today, he treats frail elderly patients, mostly residents of nursing homes and assisted living facilities or living in their own homes, for Gilchrist, a hospice and palliative care organization serving Baltimore and central Maryland.

“I’m practicing family medicine to the extent that I’m treating the family unit, including the anxieties of the adult children, and finding solutions for the parents,” said Dr. Black, one of Gilchrist’s 62 employed providers, one third of whom are physicians. One of his most important roles is medication reconciliation and deprescribing.

Palliative care, a medical specialty that focuses on clarifying the treatment goals of seriously ill patients, helping with end-of-life planning, and emphasizing pain and symptom management, has been growing in recent years. Already well-established in most US hospitals, it is expanding in community settings, often as an extension of hospice programs.

Now, by adding primary care physicians and practices to their service mix, palliative care groups are better meeting the needs of a neglected — and costly — population of frail elders. In doing so, they also are better able to find a niche in the rapidly evolving alphabet soup of value-based care and its varieties of shared savings for providers who post positive outcomes.

Most patients Dr. Black sees find it difficult to visit their doctors in a clinic setting, although they face a variety of medical needs and chronic conditions of aging. They may have a prognosis of several years to live and, thus, do not qualify for hospice care. To him, a palliative approach offers the satisfaction of focusing on what is most important to patients at this difficult time in their lives, rather than predetermined clinical metrics like blood pressure or blood glucose. “It takes a lot of work, but it feels important and rewarding,” he said.

A recent survey of community-dwelling older adults in Ontario, Canada, found most patients fail to receive this treatment homes in the final 3 months of life.
 

Continuums of Patients and Models

Gilchrist started as a nonprofit, hospital-affiliated hospice program in 1994 and in 2000 took on the management of a geriatric medicine practice for its parent, Greater Baltimore Medical Center. Today, its physicians and nurse practitioners see a range of patients in geriatric primary care, palliative medicine, and hospice, according to its chief medical officer, Mark J. Gloth, DO.

“As people progress in their disease, their location — where they call home — may change as well,” Dr. Gloth said. “We offer a continuum of care in order to not lose people through those transitions. That’s the core of our mission — making sure we are there to escort people through the difficult moments in their lives.”

Models for value-based care encompass accountable care organizations (ACOs), including the ACO REACH (Realizing Equity, Access, and Community Health) high-needs model for traditional Medicare patients, and Medicare Shared Savings Programs for fee-for-service beneficiaries. These value-based models offer a variety of opportunities for the palliative care organization to share in savings resulting from keeping the patient out of the hospital or emergency room and other quality and cost benchmarks.
 

Coming Together to Meet Needs

Gilchrist is one of nine hospice and palliative organizations that have joined to form their own multistate ACO, Responsive Care Solutions, focused on the clinical needs of frail elderly Medicare beneficiaries. Hospice of the Valley in Phoenix has Geriatric Solutions, a frail elder physician practice. And Capital Caring Health, a hospice and palliative care agency serving metro Washington, DC, has deployed several physicians and nurse practitioners on the road doing primary care at home, said Heidi Young, MD, its Primary Care at Home Lead Physician.

“Five years ago, we started our primary care practice under the umbrella of a 40-year-old hospice organization because we thought we needed to prepare for the changes that are coming to the hospice model,” Dr. Young said. “The thought was that we’re not just a hospice organization; we’re an advanced illness organization. We will come to your home, whatever that is, and provide your primary care.”

The greatest potential gains for a hospice organization are from assuming 100% risk for a large population of patients, keeping them out of the hospital to lower the costs of their care, then reaping those gains under a value-based profit-sharing model, Dr. Young said.

“Our program is still new and working toward getting more patients aligned into value-based models,” she said. “It’s a work in progress.”
 

A Foot in Each World

Agencies like Capital Caring and Gilchrist derive the largest share of their physician income from billing Medicare Part B and other insurers per visit. But that billing is not enough to break even on physician services.

With hopes for a value-based future, Gilchrist also gets grants from elder-facing charitable foundations to cover up to 40% of the costs of its home-based primary care, according to its president, Catherine Hamel. Hospice care continues to be paid on a per-diem basis by Medicare for eligible terminally ill patients, including Medicare Advantage patients, although the Centers for Medicare & Medicaid Services is reportedly considering new models for the hospice benefit.

The National Partnership for Healthcare and Hospice Innovation (NPHI) is a trade group representing more than 100 nonprofit, hospice-based organizations participating in palliative care and value-based care.

For a hospice to be successful in the evolving post–acute care/end-of-life care landscape, it can no longer rely solely on its hospice line of business, no matter how high-quality, said Ethan McChesney, policy director for the Washington, DC-based nonprofit.

NPHI members have developed their own palliative care programs, and perhaps, a quarter have primary care at home practices, Mr. McChesney said. Some of them acquired existing primary care practices in their service area with which they already had relationships; others created their own.

For hospice organizations building a continuum of services for the seriously ill, adding a primary care at home practice is a natural fit, he said. “You can provide all the services you would as a traditional primary care practice while you have the opportunity to establish long-term relationships with patients and their caregivers that lend themselves to palliative care referrals and then hospice referrals downstream [when the patient becomes eligible for hospice care].” Often, this primary medical care is a mix of in-person and telehealth.

Cameron Muir, MD, NPHI’s chief innovation officer, noted that the hamster wheel for primary care doctors has been spinning faster and faster, with reimbursement going down and costs going up.

But with home-based primary care for frail elders under value-based models, Dr. Muir said, the clinician is paid not for making more visits but for taking great care of the patient: “And I’m actually saving Medicare money and getting credit for the hospitalizations that were avoided.”
 

A version of this article appeared on Medscape.com.

Jason Black, MD, trained in family medicine, worked for Kaiser Permanente, and subsequently completed a fellowship in geriatrics. Today, he treats frail elderly patients, mostly residents of nursing homes and assisted living facilities or living in their own homes, for Gilchrist, a hospice and palliative care organization serving Baltimore and central Maryland.

“I’m practicing family medicine to the extent that I’m treating the family unit, including the anxieties of the adult children, and finding solutions for the parents,” said Dr. Black, one of Gilchrist’s 62 employed providers, one third of whom are physicians. One of his most important roles is medication reconciliation and deprescribing.

Palliative care, a medical specialty that focuses on clarifying the treatment goals of seriously ill patients, helping with end-of-life planning, and emphasizing pain and symptom management, has been growing in recent years. Already well-established in most US hospitals, it is expanding in community settings, often as an extension of hospice programs.

Now, by adding primary care physicians and practices to their service mix, palliative care groups are better meeting the needs of a neglected — and costly — population of frail elders. In doing so, they also are better able to find a niche in the rapidly evolving alphabet soup of value-based care and its varieties of shared savings for providers who post positive outcomes.

Most patients Dr. Black sees find it difficult to visit their doctors in a clinic setting, although they face a variety of medical needs and chronic conditions of aging. They may have a prognosis of several years to live and, thus, do not qualify for hospice care. To him, a palliative approach offers the satisfaction of focusing on what is most important to patients at this difficult time in their lives, rather than predetermined clinical metrics like blood pressure or blood glucose. “It takes a lot of work, but it feels important and rewarding,” he said.

A recent survey of community-dwelling older adults in Ontario, Canada, found most patients fail to receive this treatment homes in the final 3 months of life.
 

Continuums of Patients and Models

Gilchrist started as a nonprofit, hospital-affiliated hospice program in 1994 and in 2000 took on the management of a geriatric medicine practice for its parent, Greater Baltimore Medical Center. Today, its physicians and nurse practitioners see a range of patients in geriatric primary care, palliative medicine, and hospice, according to its chief medical officer, Mark J. Gloth, DO.

“As people progress in their disease, their location — where they call home — may change as well,” Dr. Gloth said. “We offer a continuum of care in order to not lose people through those transitions. That’s the core of our mission — making sure we are there to escort people through the difficult moments in their lives.”

Models for value-based care encompass accountable care organizations (ACOs), including the ACO REACH (Realizing Equity, Access, and Community Health) high-needs model for traditional Medicare patients, and Medicare Shared Savings Programs for fee-for-service beneficiaries. These value-based models offer a variety of opportunities for the palliative care organization to share in savings resulting from keeping the patient out of the hospital or emergency room and other quality and cost benchmarks.
 

Coming Together to Meet Needs

Gilchrist is one of nine hospice and palliative organizations that have joined to form their own multistate ACO, Responsive Care Solutions, focused on the clinical needs of frail elderly Medicare beneficiaries. Hospice of the Valley in Phoenix has Geriatric Solutions, a frail elder physician practice. And Capital Caring Health, a hospice and palliative care agency serving metro Washington, DC, has deployed several physicians and nurse practitioners on the road doing primary care at home, said Heidi Young, MD, its Primary Care at Home Lead Physician.

“Five years ago, we started our primary care practice under the umbrella of a 40-year-old hospice organization because we thought we needed to prepare for the changes that are coming to the hospice model,” Dr. Young said. “The thought was that we’re not just a hospice organization; we’re an advanced illness organization. We will come to your home, whatever that is, and provide your primary care.”

The greatest potential gains for a hospice organization are from assuming 100% risk for a large population of patients, keeping them out of the hospital to lower the costs of their care, then reaping those gains under a value-based profit-sharing model, Dr. Young said.

“Our program is still new and working toward getting more patients aligned into value-based models,” she said. “It’s a work in progress.”
 

A Foot in Each World

Agencies like Capital Caring and Gilchrist derive the largest share of their physician income from billing Medicare Part B and other insurers per visit. But that billing is not enough to break even on physician services.

With hopes for a value-based future, Gilchrist also gets grants from elder-facing charitable foundations to cover up to 40% of the costs of its home-based primary care, according to its president, Catherine Hamel. Hospice care continues to be paid on a per-diem basis by Medicare for eligible terminally ill patients, including Medicare Advantage patients, although the Centers for Medicare & Medicaid Services is reportedly considering new models for the hospice benefit.

The National Partnership for Healthcare and Hospice Innovation (NPHI) is a trade group representing more than 100 nonprofit, hospice-based organizations participating in palliative care and value-based care.

For a hospice to be successful in the evolving post–acute care/end-of-life care landscape, it can no longer rely solely on its hospice line of business, no matter how high-quality, said Ethan McChesney, policy director for the Washington, DC-based nonprofit.

NPHI members have developed their own palliative care programs, and perhaps, a quarter have primary care at home practices, Mr. McChesney said. Some of them acquired existing primary care practices in their service area with which they already had relationships; others created their own.

For hospice organizations building a continuum of services for the seriously ill, adding a primary care at home practice is a natural fit, he said. “You can provide all the services you would as a traditional primary care practice while you have the opportunity to establish long-term relationships with patients and their caregivers that lend themselves to palliative care referrals and then hospice referrals downstream [when the patient becomes eligible for hospice care].” Often, this primary medical care is a mix of in-person and telehealth.

Cameron Muir, MD, NPHI’s chief innovation officer, noted that the hamster wheel for primary care doctors has been spinning faster and faster, with reimbursement going down and costs going up.

But with home-based primary care for frail elders under value-based models, Dr. Muir said, the clinician is paid not for making more visits but for taking great care of the patient: “And I’m actually saving Medicare money and getting credit for the hospitalizations that were avoided.”
 

A version of this article appeared on Medscape.com.

Thanks to decades of successful vector control strategies, vector-borne transmission of Chagas disease has significantly decreased in many regions. Oral ingestion of Trypanosoma cruzi through contaminated food and beverages, however, is increasing. Unlike vector transmission, oral transmission of Chagas disease entails high lethality in pediatric and adult populations.

“The oral transmission of Chagas disease is becoming a much more recognized route, and it is crucial to understand that people can die from this type of transmission,” Norman L. Beatty, MD, assistant professor of infectious diseases and global medicine at the University of Florida College of Medicine in Gainesville, Florida, told this news organization. Dr. Beatty is the lead author of a recent article on the subject.

In regions where the parasite circulates in the environment, people are consuming foods, fruit juices, and possibly wild animal meat that may be contaminated. “As we experience changes in our environment and in the way we consume food, it is crucial to consider how food preparation is carried out in areas where T cruzi transmission occurs in the environment,” said Dr. Beatty. “And as organic farming methods without insecticides become increasingly common, more research is needed in these areas, both in Latin America and in the United States, to understand if oral transmission of T cruzi is occurring.”

In the Amazon basin, foodborne transmission is already the leading cause of acute Chagas disease. It has been described in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, and Venezuela.

Dr. Beatty’s colleagues recently treated a Brazilian patient at the hospital in Florida. “He came to our hospital very ill, with acute myocarditis after consuming contaminated açaí.” Clarifying that there is widespread awareness about oral transmission in Brazil, he stated, “We are concerned that it may not be recognized in other areas of Latin America.”

Mexico and regions of Central America have little to no information on oral transmission, but it is likely occurring, and cases may be going undetected in the region, said Dr. Beatty.

He investigated the issue in Colombia as part of an international collaboration involving the University of Antioquia, aiming to find ways to mitigate oral transmission and create a model that can be used throughout Latin America and the United States. For the Colombia study, they reviewed all cases reported to the Ministry of Health and Social Protection, and oral transmission turned out to be more common than the research group expected. “Still, I imagine that in certain areas with limited resources…there are many more cases that are not being reported.

“A myth I would like to dispel is that Chagas disease is not being transmitted in the United States,” Dr. Beatty added. He mentioned that at least 30 American states have vectors, and in Florida, it was documented that triatomines invaded homes and bit residents. In addition, 30% of these insects are infected with T cruzi. Research is underway to determine whether Floridians are becoming infected and if they are also at risk of contracting Chagas disease orally, said Dr. Beatty. “In the United States, we know very little about how many people are infected and what the infection routes are. Much more research is needed.”

Roberto Chuit, MD, PhD, a doctor in public health and an external consultant for the Pan American Health Organization (PAHO), agreed that this route of food contamination, which occurs because of vector-borne parasites, was until recently masked or hidden by the predominance of vector presence. Just as it began to gain importance as other transmission routes were controlled, “it now has extremely high importance in the Americas, as does vertical transmission,” he said.

In 2023, more than 50 years after the first description of oral transmission, the PAHO expert meeting proposed to alert health services and the broader community about the severity and potential lethality of oral Chagas disease outbreaks to elicit immediate responses and mitigation measures. The body also proposed conducting studies to provide detailed information on the contamination source and the wild vectors present in oral transmission foci.
 

Unique Clinical Manifestations

The exacerbated signs and symptoms of oral infection (see sidebar) are attributed to the high parasite loads in contaminated food and beverages. A single crushed triatomine along with a food or beverage harboring T cruzi can contain an estimated 600,000 metacyclic trypomastigotes, compared with 3000-4000 per µL when infection occurs by triatomine fecal matter. The robust systemic immune response observed in patients with acute oral Chagas disease is thought to result from more efficient transmission after penetration through the oral, pharyngeal, and gastric mucosae.
 

Seven Things to Know About Orally Transmitted Chagas Disease

1. It presents with exacerbated symptoms and rapid disease progression in immunocompetent individuals. This presentation is not common in vector-borne, congenital, or transfusion-related transmission. It can cause fulminant myocarditis and heart failure, meningoencephalitis, or potentially fatal shock due to parasitemia.

2. Most patients (71%-100%) with acute oral Chagas present with fever.

3. Electrocardiographic abnormalities, specifically ventricular depolarization alterations and pericardial involvement, are observed in most patients.

4. Facial edema, which typically affects the entire face and parts of the lips, is present in 57%-100% of patients with acute oral Chagas disease. In those with acute symptoms from vector transmission, unilateral periorbital swelling (Romaña’s sign) is more common.

5. Other notable systemic symptoms include edema of the lower extremities, myalgia, generalized lymphadenopathy, abdominal discomfort, dyspnea, vomiting, diarrhea, hepatomegaly, splenomegaly, headache, chest pain, cutaneous erythematous rash, jaundice, arthralgia, epistaxis, hematemesis, melena, and palpitations.

6. The incubation period after oral ingestion of products contaminated with Trypanosoma cruzi is approximately 3-22 days, in contrast to 4-15 days for vector-borne transmission and 8-160 days for transfusion and transplant-related transmission.

7. Patients need antiparasitic drugs immediately.
 

Thinking Epidemiologically

Dr. Chuit recalled that suspicion of food contamination should be based on epidemiology, especially in outbreaks affecting several people and in regions where Chagas vectors have been described. Sometimes, however, a single careless tourist consumes contaminated products.

“The difficulty is that many times it is not considered, and if it is not considered, the search for the parasite is not requested,” said Dr. Chuit. He added that it is common for the professional to consider Chagas disease only if viral and bacterial isolation tests are negative. Clinicians sometimes consider Chagas disease because the patient has not responded to regular treatments for other causes, such as antibiotics and hydration.

Epidemiology is important, especially when Chagas disease is diagnosed in groups or a family, because they are usually not isolated cases but outbreaks of 3-40 cases, according to Dr. Chuit. “Under these conditions, it must be quickly considered…that this parasite may be involved.”

One of the difficulties is that the source of these oral transmissions is not recognized most of the time. In general, the sources are usually foods that are more likely to be contaminated by insects or insect feces, such as orange juice or sugarcane. But in fact, any food or beverage left unattended could be contaminated by vectors or possible secretions from infected marsupial odoriferous glands.

An analysis of 32 outbreaks from 1965 to 2022 showed that the main foods involved in oral transmission were homemade fruit juices. But different vector species were identified, and the reservoirs were mainly dogs, rodents, and large American opossums (Didelphis).

The largest oral Chagas outbreak was linked to the consumption of contaminated guava juice in a primary school in Caracas, Venezuela. Nonindustrially produced açaí is a common source of orally acquired Chagas disease in Brazil. In Colombia, Chagas disease has been associated with the consumption of palm wine, sugar cane, and tangerine juice. Other oral transmission routes include consuming meat from wild animals and ingesting blood from infected armadillos, which is related to a traditional medicine practice.
 

Deadly Yet Easily Treatable

In the outbreak of 119 confirmed and suspected cases in Venezuela, 20.3% required hospitalization, and a 5-year-old child died of acute myocarditis. These percentages differ from those reported in vector transmission, which is asymptomatic in the acute phase for 95%-99% of cases or will only develop a mild febrile illness that resolves on its own.

“Not all cases will present as severe, because depending on the inoculum, there may be individuals with subclinical situations. But any food poisoning that occurs in endemic areas, where food is not properly controlled, and these street foods are associated with processes in jungle areas, raises the possibility that T cruzi is involved and should be considered as a differential diagnosis,» noted Dr. Chuit. “The treatment is highly effective, and people recover quickly.”

“The most important thing about oral transmission of Chagas is that someone infected in this way needs antiparasitic drugs immediately. We can cure them if we treat them immediately,” said Dr. Beatty, adding that treatment is sometimes delayed due to lack of access to appropriate antiparasitic drugs. “Here in the United States and in Latin America, it is quite common for healthcare professionals not to understand the differences between vector, vertical, and oral transmission. By not treating these patients, they become ill quickly.”

Dr. Beatty and Dr. Chuit declared no relevant financial conflicts of interest.

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Thanks to decades of successful vector control strategies, vector-borne transmission of Chagas disease has significantly decreased in many regions. Oral ingestion of Trypanosoma cruzi through contaminated food and beverages, however, is increasing. Unlike vector transmission, oral transmission of Chagas disease entails high lethality in pediatric and adult populations.

“The oral transmission of Chagas disease is becoming a much more recognized route, and it is crucial to understand that people can die from this type of transmission,” Norman L. Beatty, MD, assistant professor of infectious diseases and global medicine at the University of Florida College of Medicine in Gainesville, Florida, told this news organization. Dr. Beatty is the lead author of a recent article on the subject.

In regions where the parasite circulates in the environment, people are consuming foods, fruit juices, and possibly wild animal meat that may be contaminated. “As we experience changes in our environment and in the way we consume food, it is crucial to consider how food preparation is carried out in areas where T cruzi transmission occurs in the environment,” said Dr. Beatty. “And as organic farming methods without insecticides become increasingly common, more research is needed in these areas, both in Latin America and in the United States, to understand if oral transmission of T cruzi is occurring.”

In the Amazon basin, foodborne transmission is already the leading cause of acute Chagas disease. It has been described in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, and Venezuela.

Dr. Beatty’s colleagues recently treated a Brazilian patient at the hospital in Florida. “He came to our hospital very ill, with acute myocarditis after consuming contaminated açaí.” Clarifying that there is widespread awareness about oral transmission in Brazil, he stated, “We are concerned that it may not be recognized in other areas of Latin America.”

Mexico and regions of Central America have little to no information on oral transmission, but it is likely occurring, and cases may be going undetected in the region, said Dr. Beatty.

He investigated the issue in Colombia as part of an international collaboration involving the University of Antioquia, aiming to find ways to mitigate oral transmission and create a model that can be used throughout Latin America and the United States. For the Colombia study, they reviewed all cases reported to the Ministry of Health and Social Protection, and oral transmission turned out to be more common than the research group expected. “Still, I imagine that in certain areas with limited resources…there are many more cases that are not being reported.

“A myth I would like to dispel is that Chagas disease is not being transmitted in the United States,” Dr. Beatty added. He mentioned that at least 30 American states have vectors, and in Florida, it was documented that triatomines invaded homes and bit residents. In addition, 30% of these insects are infected with T cruzi. Research is underway to determine whether Floridians are becoming infected and if they are also at risk of contracting Chagas disease orally, said Dr. Beatty. “In the United States, we know very little about how many people are infected and what the infection routes are. Much more research is needed.”

Roberto Chuit, MD, PhD, a doctor in public health and an external consultant for the Pan American Health Organization (PAHO), agreed that this route of food contamination, which occurs because of vector-borne parasites, was until recently masked or hidden by the predominance of vector presence. Just as it began to gain importance as other transmission routes were controlled, “it now has extremely high importance in the Americas, as does vertical transmission,” he said.

In 2023, more than 50 years after the first description of oral transmission, the PAHO expert meeting proposed to alert health services and the broader community about the severity and potential lethality of oral Chagas disease outbreaks to elicit immediate responses and mitigation measures. The body also proposed conducting studies to provide detailed information on the contamination source and the wild vectors present in oral transmission foci.
 

Unique Clinical Manifestations

The exacerbated signs and symptoms of oral infection (see sidebar) are attributed to the high parasite loads in contaminated food and beverages. A single crushed triatomine along with a food or beverage harboring T cruzi can contain an estimated 600,000 metacyclic trypomastigotes, compared with 3000-4000 per µL when infection occurs by triatomine fecal matter. The robust systemic immune response observed in patients with acute oral Chagas disease is thought to result from more efficient transmission after penetration through the oral, pharyngeal, and gastric mucosae.
 

Seven Things to Know About Orally Transmitted Chagas Disease

1. It presents with exacerbated symptoms and rapid disease progression in immunocompetent individuals. This presentation is not common in vector-borne, congenital, or transfusion-related transmission. It can cause fulminant myocarditis and heart failure, meningoencephalitis, or potentially fatal shock due to parasitemia.

2. Most patients (71%-100%) with acute oral Chagas present with fever.

3. Electrocardiographic abnormalities, specifically ventricular depolarization alterations and pericardial involvement, are observed in most patients.

4. Facial edema, which typically affects the entire face and parts of the lips, is present in 57%-100% of patients with acute oral Chagas disease. In those with acute symptoms from vector transmission, unilateral periorbital swelling (Romaña’s sign) is more common.

5. Other notable systemic symptoms include edema of the lower extremities, myalgia, generalized lymphadenopathy, abdominal discomfort, dyspnea, vomiting, diarrhea, hepatomegaly, splenomegaly, headache, chest pain, cutaneous erythematous rash, jaundice, arthralgia, epistaxis, hematemesis, melena, and palpitations.

6. The incubation period after oral ingestion of products contaminated with Trypanosoma cruzi is approximately 3-22 days, in contrast to 4-15 days for vector-borne transmission and 8-160 days for transfusion and transplant-related transmission.

7. Patients need antiparasitic drugs immediately.
 

Thinking Epidemiologically

Dr. Chuit recalled that suspicion of food contamination should be based on epidemiology, especially in outbreaks affecting several people and in regions where Chagas vectors have been described. Sometimes, however, a single careless tourist consumes contaminated products.

“The difficulty is that many times it is not considered, and if it is not considered, the search for the parasite is not requested,” said Dr. Chuit. He added that it is common for the professional to consider Chagas disease only if viral and bacterial isolation tests are negative. Clinicians sometimes consider Chagas disease because the patient has not responded to regular treatments for other causes, such as antibiotics and hydration.

Epidemiology is important, especially when Chagas disease is diagnosed in groups or a family, because they are usually not isolated cases but outbreaks of 3-40 cases, according to Dr. Chuit. “Under these conditions, it must be quickly considered…that this parasite may be involved.”

One of the difficulties is that the source of these oral transmissions is not recognized most of the time. In general, the sources are usually foods that are more likely to be contaminated by insects or insect feces, such as orange juice or sugarcane. But in fact, any food or beverage left unattended could be contaminated by vectors or possible secretions from infected marsupial odoriferous glands.

An analysis of 32 outbreaks from 1965 to 2022 showed that the main foods involved in oral transmission were homemade fruit juices. But different vector species were identified, and the reservoirs were mainly dogs, rodents, and large American opossums (Didelphis).

The largest oral Chagas outbreak was linked to the consumption of contaminated guava juice in a primary school in Caracas, Venezuela. Nonindustrially produced açaí is a common source of orally acquired Chagas disease in Brazil. In Colombia, Chagas disease has been associated with the consumption of palm wine, sugar cane, and tangerine juice. Other oral transmission routes include consuming meat from wild animals and ingesting blood from infected armadillos, which is related to a traditional medicine practice.
 

Deadly Yet Easily Treatable

In the outbreak of 119 confirmed and suspected cases in Venezuela, 20.3% required hospitalization, and a 5-year-old child died of acute myocarditis. These percentages differ from those reported in vector transmission, which is asymptomatic in the acute phase for 95%-99% of cases or will only develop a mild febrile illness that resolves on its own.

“Not all cases will present as severe, because depending on the inoculum, there may be individuals with subclinical situations. But any food poisoning that occurs in endemic areas, where food is not properly controlled, and these street foods are associated with processes in jungle areas, raises the possibility that T cruzi is involved and should be considered as a differential diagnosis,» noted Dr. Chuit. “The treatment is highly effective, and people recover quickly.”

“The most important thing about oral transmission of Chagas is that someone infected in this way needs antiparasitic drugs immediately. We can cure them if we treat them immediately,” said Dr. Beatty, adding that treatment is sometimes delayed due to lack of access to appropriate antiparasitic drugs. “Here in the United States and in Latin America, it is quite common for healthcare professionals not to understand the differences between vector, vertical, and oral transmission. By not treating these patients, they become ill quickly.”

Dr. Beatty and Dr. Chuit declared no relevant financial conflicts of interest.

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Thanks to decades of successful vector control strategies, vector-borne transmission of Chagas disease has significantly decreased in many regions. Oral ingestion of Trypanosoma cruzi through contaminated food and beverages, however, is increasing. Unlike vector transmission, oral transmission of Chagas disease entails high lethality in pediatric and adult populations.

“The oral transmission of Chagas disease is becoming a much more recognized route, and it is crucial to understand that people can die from this type of transmission,” Norman L. Beatty, MD, assistant professor of infectious diseases and global medicine at the University of Florida College of Medicine in Gainesville, Florida, told this news organization. Dr. Beatty is the lead author of a recent article on the subject.

In regions where the parasite circulates in the environment, people are consuming foods, fruit juices, and possibly wild animal meat that may be contaminated. “As we experience changes in our environment and in the way we consume food, it is crucial to consider how food preparation is carried out in areas where T cruzi transmission occurs in the environment,” said Dr. Beatty. “And as organic farming methods without insecticides become increasingly common, more research is needed in these areas, both in Latin America and in the United States, to understand if oral transmission of T cruzi is occurring.”

In the Amazon basin, foodborne transmission is already the leading cause of acute Chagas disease. It has been described in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, and Venezuela.

Dr. Beatty’s colleagues recently treated a Brazilian patient at the hospital in Florida. “He came to our hospital very ill, with acute myocarditis after consuming contaminated açaí.” Clarifying that there is widespread awareness about oral transmission in Brazil, he stated, “We are concerned that it may not be recognized in other areas of Latin America.”

Mexico and regions of Central America have little to no information on oral transmission, but it is likely occurring, and cases may be going undetected in the region, said Dr. Beatty.

He investigated the issue in Colombia as part of an international collaboration involving the University of Antioquia, aiming to find ways to mitigate oral transmission and create a model that can be used throughout Latin America and the United States. For the Colombia study, they reviewed all cases reported to the Ministry of Health and Social Protection, and oral transmission turned out to be more common than the research group expected. “Still, I imagine that in certain areas with limited resources…there are many more cases that are not being reported.

“A myth I would like to dispel is that Chagas disease is not being transmitted in the United States,” Dr. Beatty added. He mentioned that at least 30 American states have vectors, and in Florida, it was documented that triatomines invaded homes and bit residents. In addition, 30% of these insects are infected with T cruzi. Research is underway to determine whether Floridians are becoming infected and if they are also at risk of contracting Chagas disease orally, said Dr. Beatty. “In the United States, we know very little about how many people are infected and what the infection routes are. Much more research is needed.”

Roberto Chuit, MD, PhD, a doctor in public health and an external consultant for the Pan American Health Organization (PAHO), agreed that this route of food contamination, which occurs because of vector-borne parasites, was until recently masked or hidden by the predominance of vector presence. Just as it began to gain importance as other transmission routes were controlled, “it now has extremely high importance in the Americas, as does vertical transmission,” he said.

In 2023, more than 50 years after the first description of oral transmission, the PAHO expert meeting proposed to alert health services and the broader community about the severity and potential lethality of oral Chagas disease outbreaks to elicit immediate responses and mitigation measures. The body also proposed conducting studies to provide detailed information on the contamination source and the wild vectors present in oral transmission foci.
 

Unique Clinical Manifestations

The exacerbated signs and symptoms of oral infection (see sidebar) are attributed to the high parasite loads in contaminated food and beverages. A single crushed triatomine along with a food or beverage harboring T cruzi can contain an estimated 600,000 metacyclic trypomastigotes, compared with 3000-4000 per µL when infection occurs by triatomine fecal matter. The robust systemic immune response observed in patients with acute oral Chagas disease is thought to result from more efficient transmission after penetration through the oral, pharyngeal, and gastric mucosae.
 

Seven Things to Know About Orally Transmitted Chagas Disease

1. It presents with exacerbated symptoms and rapid disease progression in immunocompetent individuals. This presentation is not common in vector-borne, congenital, or transfusion-related transmission. It can cause fulminant myocarditis and heart failure, meningoencephalitis, or potentially fatal shock due to parasitemia.

2. Most patients (71%-100%) with acute oral Chagas present with fever.

3. Electrocardiographic abnormalities, specifically ventricular depolarization alterations and pericardial involvement, are observed in most patients.

4. Facial edema, which typically affects the entire face and parts of the lips, is present in 57%-100% of patients with acute oral Chagas disease. In those with acute symptoms from vector transmission, unilateral periorbital swelling (Romaña’s sign) is more common.

5. Other notable systemic symptoms include edema of the lower extremities, myalgia, generalized lymphadenopathy, abdominal discomfort, dyspnea, vomiting, diarrhea, hepatomegaly, splenomegaly, headache, chest pain, cutaneous erythematous rash, jaundice, arthralgia, epistaxis, hematemesis, melena, and palpitations.

6. The incubation period after oral ingestion of products contaminated with Trypanosoma cruzi is approximately 3-22 days, in contrast to 4-15 days for vector-borne transmission and 8-160 days for transfusion and transplant-related transmission.

7. Patients need antiparasitic drugs immediately.
 

Thinking Epidemiologically

Dr. Chuit recalled that suspicion of food contamination should be based on epidemiology, especially in outbreaks affecting several people and in regions where Chagas vectors have been described. Sometimes, however, a single careless tourist consumes contaminated products.

“The difficulty is that many times it is not considered, and if it is not considered, the search for the parasite is not requested,” said Dr. Chuit. He added that it is common for the professional to consider Chagas disease only if viral and bacterial isolation tests are negative. Clinicians sometimes consider Chagas disease because the patient has not responded to regular treatments for other causes, such as antibiotics and hydration.

Epidemiology is important, especially when Chagas disease is diagnosed in groups or a family, because they are usually not isolated cases but outbreaks of 3-40 cases, according to Dr. Chuit. “Under these conditions, it must be quickly considered…that this parasite may be involved.”

One of the difficulties is that the source of these oral transmissions is not recognized most of the time. In general, the sources are usually foods that are more likely to be contaminated by insects or insect feces, such as orange juice or sugarcane. But in fact, any food or beverage left unattended could be contaminated by vectors or possible secretions from infected marsupial odoriferous glands.

An analysis of 32 outbreaks from 1965 to 2022 showed that the main foods involved in oral transmission were homemade fruit juices. But different vector species were identified, and the reservoirs were mainly dogs, rodents, and large American opossums (Didelphis).

The largest oral Chagas outbreak was linked to the consumption of contaminated guava juice in a primary school in Caracas, Venezuela. Nonindustrially produced açaí is a common source of orally acquired Chagas disease in Brazil. In Colombia, Chagas disease has been associated with the consumption of palm wine, sugar cane, and tangerine juice. Other oral transmission routes include consuming meat from wild animals and ingesting blood from infected armadillos, which is related to a traditional medicine practice.
 

Deadly Yet Easily Treatable

In the outbreak of 119 confirmed and suspected cases in Venezuela, 20.3% required hospitalization, and a 5-year-old child died of acute myocarditis. These percentages differ from those reported in vector transmission, which is asymptomatic in the acute phase for 95%-99% of cases or will only develop a mild febrile illness that resolves on its own.

“Not all cases will present as severe, because depending on the inoculum, there may be individuals with subclinical situations. But any food poisoning that occurs in endemic areas, where food is not properly controlled, and these street foods are associated with processes in jungle areas, raises the possibility that T cruzi is involved and should be considered as a differential diagnosis,» noted Dr. Chuit. “The treatment is highly effective, and people recover quickly.”

“The most important thing about oral transmission of Chagas is that someone infected in this way needs antiparasitic drugs immediately. We can cure them if we treat them immediately,” said Dr. Beatty, adding that treatment is sometimes delayed due to lack of access to appropriate antiparasitic drugs. “Here in the United States and in Latin America, it is quite common for healthcare professionals not to understand the differences between vector, vertical, and oral transmission. By not treating these patients, they become ill quickly.”

Dr. Beatty and Dr. Chuit declared no relevant financial conflicts of interest.

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted. 
Persons with severe COPD frequently report fears of suffocation and death, as well as anxieties about abandoning family and friends, and these negative, intrusive thoughts can have an adverse effect on COPD outcomes. 
Disease-related mental distress can lead to increased disability, more frequent use of costly health care resources, higher morbidity, and elevated risk of death, investigators say. 
"Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients," wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.  

Fears of dying (and living)  

The causes of depression and anxiety among patients with obstructive pulmonary disorders are multi-factorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Sweden.  
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease. 
"Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety," the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014. 
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones. 
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease, so called "life anxiety." 
The patients also reported "counterweights" to anxiety as a way of coping. For some this involved trust in their health care professionals and adherence to medication, inhalers, and supplemental oxygen. 
"The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants," Dr. Strang and colleagues reported. 
Others reported avoiding talking about death, sleeping more, or using humor to "laugh off this difficult subject." 

Screening and diagnosis 

Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don't have the time to add screening to their already crammed schedules. In addition, "the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders)," can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant health care burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted. 
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Johannes and colleagues, and the COPD Anxiety Questionnaire. 
The COPD Assessment Testand Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said. 
"In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression," Dr. Garfield said. 

Listen to patients and families 

Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York. 
"I think just listening to the patient, that's a little bit forgotten yet so important," he said in an interview with Chest Physician.  
"When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory 'how's your breathing? Any chest pain?' and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say 'Hey, I'm nervous, hey I'm worried about my family, hey I'm worried if I die what's going to happen to my wife and kids,' and that's something I think is invaluable." 
It's also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient's stresses and anxieties, he said. 

Pulmonary Rehabilitation 

All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases. 
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms. 
"I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients," Dr. Garfield said. "It's physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation - improving strength and coordination, but  also it helps our patients get as much as possible out of what they've got." 
For example, patients can be taught how to decrease their respiratory rate when they're feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.  
"Once your into medical interventions, pulmonary rehab is phenomenal," Dr. Saleh said.  
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but "unfortunately it's not as available as we like," he said. 
Many patients don't live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4 to 12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged. 
"You have to sit [with the patient] and be honest and tell them it's a lot of diligence involved and you have to be really motivated," he said. 
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents. 
"SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy," Dr. Johannes and colleagues wrote. 

Defiant joy 

Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al called "a defiant joy." 
 "It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands or that tomorrow might be better," the investigators wrote. 
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.

Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted. 
Persons with severe COPD frequently report fears of suffocation and death, as well as anxieties about abandoning family and friends, and these negative, intrusive thoughts can have an adverse effect on COPD outcomes. 
Disease-related mental distress can lead to increased disability, more frequent use of costly health care resources, higher morbidity, and elevated risk of death, investigators say. 
"Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients," wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.  

Fears of dying (and living)  

The causes of depression and anxiety among patients with obstructive pulmonary disorders are multi-factorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Sweden.  
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease. 
"Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety," the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014. 
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones. 
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease, so called "life anxiety." 
The patients also reported "counterweights" to anxiety as a way of coping. For some this involved trust in their health care professionals and adherence to medication, inhalers, and supplemental oxygen. 
"The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants," Dr. Strang and colleagues reported. 
Others reported avoiding talking about death, sleeping more, or using humor to "laugh off this difficult subject." 

Screening and diagnosis 

Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don't have the time to add screening to their already crammed schedules. In addition, "the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders)," can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant health care burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted. 
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Johannes and colleagues, and the COPD Anxiety Questionnaire. 
The COPD Assessment Testand Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said. 
"In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression," Dr. Garfield said. 

Listen to patients and families 

Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York. 
"I think just listening to the patient, that's a little bit forgotten yet so important," he said in an interview with Chest Physician.  
"When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory 'how's your breathing? Any chest pain?' and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say 'Hey, I'm nervous, hey I'm worried about my family, hey I'm worried if I die what's going to happen to my wife and kids,' and that's something I think is invaluable." 
It's also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient's stresses and anxieties, he said. 

Pulmonary Rehabilitation 

All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases. 
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms. 
"I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients," Dr. Garfield said. "It's physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation - improving strength and coordination, but  also it helps our patients get as much as possible out of what they've got." 
For example, patients can be taught how to decrease their respiratory rate when they're feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.  
"Once your into medical interventions, pulmonary rehab is phenomenal," Dr. Saleh said.  
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but "unfortunately it's not as available as we like," he said. 
Many patients don't live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4 to 12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged. 
"You have to sit [with the patient] and be honest and tell them it's a lot of diligence involved and you have to be really motivated," he said. 
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents. 
"SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy," Dr. Johannes and colleagues wrote. 

Defiant joy 

Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al called "a defiant joy." 
 "It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands or that tomorrow might be better," the investigators wrote. 
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.

Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted. 
Persons with severe COPD frequently report fears of suffocation and death, as well as anxieties about abandoning family and friends, and these negative, intrusive thoughts can have an adverse effect on COPD outcomes. 
Disease-related mental distress can lead to increased disability, more frequent use of costly health care resources, higher morbidity, and elevated risk of death, investigators say. 
"Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients," wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.  

Fears of dying (and living)  

The causes of depression and anxiety among patients with obstructive pulmonary disorders are multi-factorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Sweden.  
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease. 
"Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety," the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014. 
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones. 
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease, so called "life anxiety." 
The patients also reported "counterweights" to anxiety as a way of coping. For some this involved trust in their health care professionals and adherence to medication, inhalers, and supplemental oxygen. 
"The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants," Dr. Strang and colleagues reported. 
Others reported avoiding talking about death, sleeping more, or using humor to "laugh off this difficult subject." 

Screening and diagnosis 

Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don't have the time to add screening to their already crammed schedules. In addition, "the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders)," can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant health care burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted. 
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Johannes and colleagues, and the COPD Anxiety Questionnaire. 
The COPD Assessment Testand Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said. 
"In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression," Dr. Garfield said. 

Listen to patients and families 

Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York. 
"I think just listening to the patient, that's a little bit forgotten yet so important," he said in an interview with Chest Physician.  
"When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory 'how's your breathing? Any chest pain?' and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say 'Hey, I'm nervous, hey I'm worried about my family, hey I'm worried if I die what's going to happen to my wife and kids,' and that's something I think is invaluable." 
It's also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient's stresses and anxieties, he said. 

Pulmonary Rehabilitation 

All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases. 
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms. 
"I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients," Dr. Garfield said. "It's physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation - improving strength and coordination, but  also it helps our patients get as much as possible out of what they've got." 
For example, patients can be taught how to decrease their respiratory rate when they're feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.  
"Once your into medical interventions, pulmonary rehab is phenomenal," Dr. Saleh said.  
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but "unfortunately it's not as available as we like," he said. 
Many patients don't live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4 to 12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged. 
"You have to sit [with the patient] and be honest and tell them it's a lot of diligence involved and you have to be really motivated," he said. 
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents. 
"SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy," Dr. Johannes and colleagues wrote. 

Defiant joy 

Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al called "a defiant joy." 
 "It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands or that tomorrow might be better," the investigators wrote. 
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.

After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”

Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.

What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.

“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.

Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.

Emerging ‘Menstrual Science’ Could Be Key

There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.

Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.

Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.

Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.

How Gender and Long COVID Intertwine

The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).

It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.

Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.

Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.

Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.

Sex-Specific Symptoms and Marginalized Communities

Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.

In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.

However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.

For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.

The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”

Where It All Leads

The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.

“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.

This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.

“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.

“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.

A version of this article appeared on Medscape.com.

Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.

After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”

Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.

What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.

“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.

Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.

Emerging ‘Menstrual Science’ Could Be Key

There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.

Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.

Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.

Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.

How Gender and Long COVID Intertwine

The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).

It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.

Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.

Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.

Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.

Sex-Specific Symptoms and Marginalized Communities

Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.

In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.

However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.

For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.

The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”

Where It All Leads

The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.

“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.

This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.

“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.

“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.

A version of this article appeared on Medscape.com.

Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.

After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”

Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.

What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.

“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.

Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.

Emerging ‘Menstrual Science’ Could Be Key

There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.

Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.

Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.

Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.

How Gender and Long COVID Intertwine

The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).

It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.

Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.

Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.

Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.

Sex-Specific Symptoms and Marginalized Communities

Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.

In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.

However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.

For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.

The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”

Where It All Leads

The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.

“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.

This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.

“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.

“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.

A version of this article appeared on Medscape.com.

In January 2023, Mark Lewis, MD, stood with the door slammed in his face. His partner in the practice had had enough. She accused him of sugarcoating prognoses and leaving her to tell patients the whole truth.

The reality was he just didn’t know how to grieve.

Dr. Lewis was well acquainted with cancer grief long before he became an oncologist. Dr. Lewis’ father died of a rare, hereditary cancer syndrome when he was only 14. The condition, which causes tumors to grow in the endocrine glands, can be hard to identify and, if found late, deadly.

In some ways, Dr. Lewis’ career caring for patients with advanced cancers was born out of that first loss. He centered his practice around helping patients diagnosed at late stages, like his father.

But that comes at a cost. Many patients will die.

Dr. Lewis’ encounter with his colleague led him to inventory his practice. He found that well over half of his patients died within 2 years following their advanced cancer diagnosis.

To stave off the grief of so many losses, Dr. Lewis became an eternal optimist in the clinic, in search of the Hail Mary chemotherapy, any way to eke out a few more months only to be ambushed by grief when a patient did finally pass.

At funerals — which he made every effort to attend — Dr. Lewis couldn’t help but think, “If I had done my job better, none of us with be here.” His grief started to mingle with this sense of guilt.

It became a cycle: Denial shrouded in optimism, grief, then a toxic guilt. The pattern became untenable for his colleagues. And his partner finally called him out.

Few medical specialties draw physicians as close to their patients as oncology. The long courses of treatment-spanning years can foster an intimacy that is comforting for patients and fulfilling for physicians. But that closeness can also set doctors up for an acute grief when the end of life comes.

Experts agree that no amount of training in medical school prepares an oncologist to navigate the grief that comes with losing patients. Five oncologists spoke with this news organization about the boundaries they rely on to sustain their careers.
 

Don’t Go to Funerals

Don Dizon, MD, who specializes in women’s cancers, established an essential boundary 20 years ago: Never go to funerals. In his early days at Memorial Sloan Kettering Cancer Center, the death of each patient dealt him a crushing blow. He’d go to the funerals in search of closure, but that only added to the weight of his grief.

“When I started in oncology, I just remember the most tragic cases were the ones I was taking care of,” recalled Dr. Dizon, now director of the Pelvic Malignancies Program at Lifespan Cancer Institute in Lincoln, Rhode Island.

Dr. Dizon recalled one young mother who was diagnosed with ovarian cancer. She responded to treatment, but it was short-lived, and her cancer progressed, he said. Multiple treatments followed, but none were effective. Eventually, Dr. Dizon had to tell her that “there’s nothing left to try.”

At her funeral, watching her grieving husband with their daughter who had just started to walk, Dr. Dizon was overwhelmed with despair.

“When you have to do this multiple times a year,” the grief becomes untenable, he said. Sensing the difficulty I was having as a new attending, “my boss stopped sending me patients because he knew I was in trouble emotionally.”

That’s when Dr. Dizon started looking for other ways to get closure.

Today, he tries to say his goodbyes before a patient dies. After the final treatment or before hospice, Dr. Dizon has a parting conversation with his patients to express the privilege of caring for them and all he learned from them. These talks help him and his patient connect in their last moments together.
 

The Price of Wildly Happy Days

Molly Taylor, MD, MS, a pediatric oncologist in Seattle, sees the deeply sad days as the price an oncologist pays to be witness to the “wildly happy ones.”

Dr. Taylor has gone to patients’ funerals, has even been asked to speak at them, but she has also attended patients’ weddings.

To some degree, doctors get good at compartmentalizing, and they become accustomed to tragedy, she said. But there are some patients who stick with you, “and that is a whole other level of grief,” Dr. Taylor said.

Several years into her practice, one of Dr. Taylor’s patients, someone who reminded her of her own child, died. The death came as a surprise, and the finality of it took her breath away, she said. The sadness only deepened as days went by. “I felt that mother’s grief and still do,” she said.

The patient’s funeral was one of the most difficult moments in her career as an oncologist. Even weeks later, she caught herself picturing the family huddled together that day.

Taking long walks, commiserating with colleagues who get it, and watching the occasional cat video can help take the immediate sting away. But the pain of losing a patient can be long lasting and processing that grief can be a lonely endeavor.

“We need space to recognize grief for all providers, all the people that touch these patients’ lives — the nurses, the translators, the cleaning staff,” Dr. Taylor said. Otherwise, you start to believe you’re the only one feeling the weight of the loss.

While it doesn’t make the losses any less poignant, Dr. Taylor finds solace in the good moments: Patient graduations and weddings, survivors who now volunteer at the hospital, and a patient who had a baby of her own this past year. If facing grief daily has taught Dr. Taylor anything, it is to not let the good moments pass unnoticed.
 

Towing the Line

Ten years ago, Tina Rizack, MD, walked into the ICU to see a young mother holding her 6-year-old daughter. The mother had necrotizing fasciitis that had gone undiagnosed.

As Dr. Rizack stood in the doorway watching the embrace, she saw a grim future: A child without her mother. This realization hit too close to home, she said. “I still think about that case.”

In her training, Dr. Rizack, now medical director of hematology/oncology at St. Anne’s in Fall River, Massachusetts, worked with a social worker who taught her how to deal with these tough cases — most importantly, how to not take them home with her.

Over the years, Dr. Rizack learned how to build and sustain a firm barrier between work and outside work.

She doesn’t go to funerals or give out her cell phone number. If charts need to be done, she prefers to stay late at the clinic instead of bringing them home.

And she invests in the simple moments that help her detach from the day-to-day in the clinic — rooting for her kids at their games, carving out time for family meals most days, and having relaxed movie nights on the couch.

“It’s hard sometimes,” she said. But “I really do need the line.” Because without it, she can’t show up for her patients the way she wants and needs to.

Establishing the work-life boundary means that when at work, Dr. Rizack can be all in for her patients. Even after her patients’ treatment ends, she makes sure to check on them at home or in hospice. For her, sticking with patients over the long term offers some closure.

“I want to love work, and if I’m there all the time, I’m not going to love it,” she said.
 

Trading Funerals for the Bedside

Like many other oncologists, Charles Blanke, MD, finds that going to patients’ funerals makes the loss seem more profound. Being at the bedside when they die is not as painful, he said. In fact, being there when his patients die offers him some comfort. He rarely misses a patient’s death because now Dr. Blanke’s patients can schedule their departure.

An oncologist at the Knight Cancer Institute in Portland, Oregon, Dr. Blanke specializes in end-of-life care with an emphasis on death with dignity, also known as medical aid in dying. He admits it’s not a role every physician is comfortable with.

“If you’re paralyzed by grief, you can’t do this for a living,” he said. But he’s able to do the work because he genuinely feels he’s helping patients get “the relief they so strongly desire” in their last moments.

When cancer care can’t give them the life they wanted, he can give them control over when and how they die. And the ability to honor their last wishes offers him some closure as well.

“You know what kind of end they have. You know it was peaceful. You see them achieve the thing that was the most important to them,” he said.

Despite this process, he still encounters some circumstances utterly heart-wrenching — the very young patients who have advanced disease. Some of these patients choose to die because they can’t afford to continue treatment. Others don’t have a support system. In these instances, Dr. Blanke is often the only one in the room.

Believe it or not, he said, the paperwork — and there’s a lot of it in his line of work — helps remind Dr. Blanke that patients’ last wishes are being honored.
 

Making Changes

After Dr. Lewis was confronted by his partner, he began to face the shortcomings of his own coping strategies. His practice hired a social worker to help staff process difficult experiences. After the loss of every patient, the practice comes together to share and process the loss.

For him, funerals remain helpful, providing a sort of solace, so he continues to go when he can. But how to grieve is something each doctor has to figure out, he said.

Deaths still hit hard, especially the ones he doesn’t see coming. The patients who remind him of his dad can also be hard. They restart a cycle of grief from his teenage years.

The difference now is he has space to voice those concerns and someone objective to help his process.

“It’s a privilege to prepare [patients for death] and help them build their legacy,” he said. But it’s also an unrelenting challenge to navigate that grief, he said.

Still, the grief lets Dr. Lewis know he’s still engaged.

“The day I don’t feel something is probably the day I need to take a break or walk away.”
 

A version of this article appeared on Medscape.com.

In January 2023, Mark Lewis, MD, stood with the door slammed in his face. His partner in the practice had had enough. She accused him of sugarcoating prognoses and leaving her to tell patients the whole truth.

The reality was he just didn’t know how to grieve.

Dr. Lewis was well acquainted with cancer grief long before he became an oncologist. Dr. Lewis’ father died of a rare, hereditary cancer syndrome when he was only 14. The condition, which causes tumors to grow in the endocrine glands, can be hard to identify and, if found late, deadly.

In some ways, Dr. Lewis’ career caring for patients with advanced cancers was born out of that first loss. He centered his practice around helping patients diagnosed at late stages, like his father.

But that comes at a cost. Many patients will die.

Dr. Lewis’ encounter with his colleague led him to inventory his practice. He found that well over half of his patients died within 2 years following their advanced cancer diagnosis.

To stave off the grief of so many losses, Dr. Lewis became an eternal optimist in the clinic, in search of the Hail Mary chemotherapy, any way to eke out a few more months only to be ambushed by grief when a patient did finally pass.

At funerals — which he made every effort to attend — Dr. Lewis couldn’t help but think, “If I had done my job better, none of us with be here.” His grief started to mingle with this sense of guilt.

It became a cycle: Denial shrouded in optimism, grief, then a toxic guilt. The pattern became untenable for his colleagues. And his partner finally called him out.

Few medical specialties draw physicians as close to their patients as oncology. The long courses of treatment-spanning years can foster an intimacy that is comforting for patients and fulfilling for physicians. But that closeness can also set doctors up for an acute grief when the end of life comes.

Experts agree that no amount of training in medical school prepares an oncologist to navigate the grief that comes with losing patients. Five oncologists spoke with this news organization about the boundaries they rely on to sustain their careers.
 

Don’t Go to Funerals

Don Dizon, MD, who specializes in women’s cancers, established an essential boundary 20 years ago: Never go to funerals. In his early days at Memorial Sloan Kettering Cancer Center, the death of each patient dealt him a crushing blow. He’d go to the funerals in search of closure, but that only added to the weight of his grief.

“When I started in oncology, I just remember the most tragic cases were the ones I was taking care of,” recalled Dr. Dizon, now director of the Pelvic Malignancies Program at Lifespan Cancer Institute in Lincoln, Rhode Island.

Dr. Dizon recalled one young mother who was diagnosed with ovarian cancer. She responded to treatment, but it was short-lived, and her cancer progressed, he said. Multiple treatments followed, but none were effective. Eventually, Dr. Dizon had to tell her that “there’s nothing left to try.”

At her funeral, watching her grieving husband with their daughter who had just started to walk, Dr. Dizon was overwhelmed with despair.

“When you have to do this multiple times a year,” the grief becomes untenable, he said. Sensing the difficulty I was having as a new attending, “my boss stopped sending me patients because he knew I was in trouble emotionally.”

That’s when Dr. Dizon started looking for other ways to get closure.

Today, he tries to say his goodbyes before a patient dies. After the final treatment or before hospice, Dr. Dizon has a parting conversation with his patients to express the privilege of caring for them and all he learned from them. These talks help him and his patient connect in their last moments together.
 

The Price of Wildly Happy Days

Molly Taylor, MD, MS, a pediatric oncologist in Seattle, sees the deeply sad days as the price an oncologist pays to be witness to the “wildly happy ones.”

Dr. Taylor has gone to patients’ funerals, has even been asked to speak at them, but she has also attended patients’ weddings.

To some degree, doctors get good at compartmentalizing, and they become accustomed to tragedy, she said. But there are some patients who stick with you, “and that is a whole other level of grief,” Dr. Taylor said.

Several years into her practice, one of Dr. Taylor’s patients, someone who reminded her of her own child, died. The death came as a surprise, and the finality of it took her breath away, she said. The sadness only deepened as days went by. “I felt that mother’s grief and still do,” she said.

The patient’s funeral was one of the most difficult moments in her career as an oncologist. Even weeks later, she caught herself picturing the family huddled together that day.

Taking long walks, commiserating with colleagues who get it, and watching the occasional cat video can help take the immediate sting away. But the pain of losing a patient can be long lasting and processing that grief can be a lonely endeavor.

“We need space to recognize grief for all providers, all the people that touch these patients’ lives — the nurses, the translators, the cleaning staff,” Dr. Taylor said. Otherwise, you start to believe you’re the only one feeling the weight of the loss.

While it doesn’t make the losses any less poignant, Dr. Taylor finds solace in the good moments: Patient graduations and weddings, survivors who now volunteer at the hospital, and a patient who had a baby of her own this past year. If facing grief daily has taught Dr. Taylor anything, it is to not let the good moments pass unnoticed.
 

Towing the Line

Ten years ago, Tina Rizack, MD, walked into the ICU to see a young mother holding her 6-year-old daughter. The mother had necrotizing fasciitis that had gone undiagnosed.

As Dr. Rizack stood in the doorway watching the embrace, she saw a grim future: A child without her mother. This realization hit too close to home, she said. “I still think about that case.”

In her training, Dr. Rizack, now medical director of hematology/oncology at St. Anne’s in Fall River, Massachusetts, worked with a social worker who taught her how to deal with these tough cases — most importantly, how to not take them home with her.

Over the years, Dr. Rizack learned how to build and sustain a firm barrier between work and outside work.

She doesn’t go to funerals or give out her cell phone number. If charts need to be done, she prefers to stay late at the clinic instead of bringing them home.

And she invests in the simple moments that help her detach from the day-to-day in the clinic — rooting for her kids at their games, carving out time for family meals most days, and having relaxed movie nights on the couch.

“It’s hard sometimes,” she said. But “I really do need the line.” Because without it, she can’t show up for her patients the way she wants and needs to.

Establishing the work-life boundary means that when at work, Dr. Rizack can be all in for her patients. Even after her patients’ treatment ends, she makes sure to check on them at home or in hospice. For her, sticking with patients over the long term offers some closure.

“I want to love work, and if I’m there all the time, I’m not going to love it,” she said.
 

Trading Funerals for the Bedside

Like many other oncologists, Charles Blanke, MD, finds that going to patients’ funerals makes the loss seem more profound. Being at the bedside when they die is not as painful, he said. In fact, being there when his patients die offers him some comfort. He rarely misses a patient’s death because now Dr. Blanke’s patients can schedule their departure.

An oncologist at the Knight Cancer Institute in Portland, Oregon, Dr. Blanke specializes in end-of-life care with an emphasis on death with dignity, also known as medical aid in dying. He admits it’s not a role every physician is comfortable with.

“If you’re paralyzed by grief, you can’t do this for a living,” he said. But he’s able to do the work because he genuinely feels he’s helping patients get “the relief they so strongly desire” in their last moments.

When cancer care can’t give them the life they wanted, he can give them control over when and how they die. And the ability to honor their last wishes offers him some closure as well.

“You know what kind of end they have. You know it was peaceful. You see them achieve the thing that was the most important to them,” he said.

Despite this process, he still encounters some circumstances utterly heart-wrenching — the very young patients who have advanced disease. Some of these patients choose to die because they can’t afford to continue treatment. Others don’t have a support system. In these instances, Dr. Blanke is often the only one in the room.

Believe it or not, he said, the paperwork — and there’s a lot of it in his line of work — helps remind Dr. Blanke that patients’ last wishes are being honored.
 

Making Changes

After Dr. Lewis was confronted by his partner, he began to face the shortcomings of his own coping strategies. His practice hired a social worker to help staff process difficult experiences. After the loss of every patient, the practice comes together to share and process the loss.

For him, funerals remain helpful, providing a sort of solace, so he continues to go when he can. But how to grieve is something each doctor has to figure out, he said.

Deaths still hit hard, especially the ones he doesn’t see coming. The patients who remind him of his dad can also be hard. They restart a cycle of grief from his teenage years.

The difference now is he has space to voice those concerns and someone objective to help his process.

“It’s a privilege to prepare [patients for death] and help them build their legacy,” he said. But it’s also an unrelenting challenge to navigate that grief, he said.

Still, the grief lets Dr. Lewis know he’s still engaged.

“The day I don’t feel something is probably the day I need to take a break or walk away.”
 

A version of this article appeared on Medscape.com.

In January 2023, Mark Lewis, MD, stood with the door slammed in his face. His partner in the practice had had enough. She accused him of sugarcoating prognoses and leaving her to tell patients the whole truth.

The reality was he just didn’t know how to grieve.

Dr. Lewis was well acquainted with cancer grief long before he became an oncologist. Dr. Lewis’ father died of a rare, hereditary cancer syndrome when he was only 14. The condition, which causes tumors to grow in the endocrine glands, can be hard to identify and, if found late, deadly.

In some ways, Dr. Lewis’ career caring for patients with advanced cancers was born out of that first loss. He centered his practice around helping patients diagnosed at late stages, like his father.

But that comes at a cost. Many patients will die.

Dr. Lewis’ encounter with his colleague led him to inventory his practice. He found that well over half of his patients died within 2 years following their advanced cancer diagnosis.

To stave off the grief of so many losses, Dr. Lewis became an eternal optimist in the clinic, in search of the Hail Mary chemotherapy, any way to eke out a few more months only to be ambushed by grief when a patient did finally pass.

At funerals — which he made every effort to attend — Dr. Lewis couldn’t help but think, “If I had done my job better, none of us with be here.” His grief started to mingle with this sense of guilt.

It became a cycle: Denial shrouded in optimism, grief, then a toxic guilt. The pattern became untenable for his colleagues. And his partner finally called him out.

Few medical specialties draw physicians as close to their patients as oncology. The long courses of treatment-spanning years can foster an intimacy that is comforting for patients and fulfilling for physicians. But that closeness can also set doctors up for an acute grief when the end of life comes.

Experts agree that no amount of training in medical school prepares an oncologist to navigate the grief that comes with losing patients. Five oncologists spoke with this news organization about the boundaries they rely on to sustain their careers.
 

Don’t Go to Funerals

Don Dizon, MD, who specializes in women’s cancers, established an essential boundary 20 years ago: Never go to funerals. In his early days at Memorial Sloan Kettering Cancer Center, the death of each patient dealt him a crushing blow. He’d go to the funerals in search of closure, but that only added to the weight of his grief.

“When I started in oncology, I just remember the most tragic cases were the ones I was taking care of,” recalled Dr. Dizon, now director of the Pelvic Malignancies Program at Lifespan Cancer Institute in Lincoln, Rhode Island.

Dr. Dizon recalled one young mother who was diagnosed with ovarian cancer. She responded to treatment, but it was short-lived, and her cancer progressed, he said. Multiple treatments followed, but none were effective. Eventually, Dr. Dizon had to tell her that “there’s nothing left to try.”

At her funeral, watching her grieving husband with their daughter who had just started to walk, Dr. Dizon was overwhelmed with despair.

“When you have to do this multiple times a year,” the grief becomes untenable, he said. Sensing the difficulty I was having as a new attending, “my boss stopped sending me patients because he knew I was in trouble emotionally.”

That’s when Dr. Dizon started looking for other ways to get closure.

Today, he tries to say his goodbyes before a patient dies. After the final treatment or before hospice, Dr. Dizon has a parting conversation with his patients to express the privilege of caring for them and all he learned from them. These talks help him and his patient connect in their last moments together.
 

The Price of Wildly Happy Days

Molly Taylor, MD, MS, a pediatric oncologist in Seattle, sees the deeply sad days as the price an oncologist pays to be witness to the “wildly happy ones.”

Dr. Taylor has gone to patients’ funerals, has even been asked to speak at them, but she has also attended patients’ weddings.

To some degree, doctors get good at compartmentalizing, and they become accustomed to tragedy, she said. But there are some patients who stick with you, “and that is a whole other level of grief,” Dr. Taylor said.

Several years into her practice, one of Dr. Taylor’s patients, someone who reminded her of her own child, died. The death came as a surprise, and the finality of it took her breath away, she said. The sadness only deepened as days went by. “I felt that mother’s grief and still do,” she said.

The patient’s funeral was one of the most difficult moments in her career as an oncologist. Even weeks later, she caught herself picturing the family huddled together that day.

Taking long walks, commiserating with colleagues who get it, and watching the occasional cat video can help take the immediate sting away. But the pain of losing a patient can be long lasting and processing that grief can be a lonely endeavor.

“We need space to recognize grief for all providers, all the people that touch these patients’ lives — the nurses, the translators, the cleaning staff,” Dr. Taylor said. Otherwise, you start to believe you’re the only one feeling the weight of the loss.

While it doesn’t make the losses any less poignant, Dr. Taylor finds solace in the good moments: Patient graduations and weddings, survivors who now volunteer at the hospital, and a patient who had a baby of her own this past year. If facing grief daily has taught Dr. Taylor anything, it is to not let the good moments pass unnoticed.
 

Towing the Line

Ten years ago, Tina Rizack, MD, walked into the ICU to see a young mother holding her 6-year-old daughter. The mother had necrotizing fasciitis that had gone undiagnosed.

As Dr. Rizack stood in the doorway watching the embrace, she saw a grim future: A child without her mother. This realization hit too close to home, she said. “I still think about that case.”

In her training, Dr. Rizack, now medical director of hematology/oncology at St. Anne’s in Fall River, Massachusetts, worked with a social worker who taught her how to deal with these tough cases — most importantly, how to not take them home with her.

Over the years, Dr. Rizack learned how to build and sustain a firm barrier between work and outside work.

She doesn’t go to funerals or give out her cell phone number. If charts need to be done, she prefers to stay late at the clinic instead of bringing them home.

And she invests in the simple moments that help her detach from the day-to-day in the clinic — rooting for her kids at their games, carving out time for family meals most days, and having relaxed movie nights on the couch.

“It’s hard sometimes,” she said. But “I really do need the line.” Because without it, she can’t show up for her patients the way she wants and needs to.

Establishing the work-life boundary means that when at work, Dr. Rizack can be all in for her patients. Even after her patients’ treatment ends, she makes sure to check on them at home or in hospice. For her, sticking with patients over the long term offers some closure.

“I want to love work, and if I’m there all the time, I’m not going to love it,” she said.
 

Trading Funerals for the Bedside

Like many other oncologists, Charles Blanke, MD, finds that going to patients’ funerals makes the loss seem more profound. Being at the bedside when they die is not as painful, he said. In fact, being there when his patients die offers him some comfort. He rarely misses a patient’s death because now Dr. Blanke’s patients can schedule their departure.

An oncologist at the Knight Cancer Institute in Portland, Oregon, Dr. Blanke specializes in end-of-life care with an emphasis on death with dignity, also known as medical aid in dying. He admits it’s not a role every physician is comfortable with.

“If you’re paralyzed by grief, you can’t do this for a living,” he said. But he’s able to do the work because he genuinely feels he’s helping patients get “the relief they so strongly desire” in their last moments.

When cancer care can’t give them the life they wanted, he can give them control over when and how they die. And the ability to honor their last wishes offers him some closure as well.

“You know what kind of end they have. You know it was peaceful. You see them achieve the thing that was the most important to them,” he said.

Despite this process, he still encounters some circumstances utterly heart-wrenching — the very young patients who have advanced disease. Some of these patients choose to die because they can’t afford to continue treatment. Others don’t have a support system. In these instances, Dr. Blanke is often the only one in the room.

Believe it or not, he said, the paperwork — and there’s a lot of it in his line of work — helps remind Dr. Blanke that patients’ last wishes are being honored.
 

Making Changes

After Dr. Lewis was confronted by his partner, he began to face the shortcomings of his own coping strategies. His practice hired a social worker to help staff process difficult experiences. After the loss of every patient, the practice comes together to share and process the loss.

For him, funerals remain helpful, providing a sort of solace, so he continues to go when he can. But how to grieve is something each doctor has to figure out, he said.

Deaths still hit hard, especially the ones he doesn’t see coming. The patients who remind him of his dad can also be hard. They restart a cycle of grief from his teenage years.

The difference now is he has space to voice those concerns and someone objective to help his process.

“It’s a privilege to prepare [patients for death] and help them build their legacy,” he said. But it’s also an unrelenting challenge to navigate that grief, he said.

Still, the grief lets Dr. Lewis know he’s still engaged.

“The day I don’t feel something is probably the day I need to take a break or walk away.”
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has used its expedited withdrawal process to rescind its approval of melphalan flufenamide (also called melflufen; Pepaxto, Oncopeptides AB), which it had approved for combined use with dexamethasone to treat some patients with multiple myeloma.

But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.

Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):

“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?

Melphalan Flufenamide is finally completely withdrawn by @US_FDA

But approval by @EMA_News stays.

How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?

Modern day miracle?”
 

EMA: Pepaxti’s Benefits Exceed Its Risks

The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:

“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.

Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.

“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.

The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.

“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
 

Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’

David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.

Liza Simonsson

“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”

Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”

“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
 

FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks

In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.

OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.

In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.

Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:

“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”

“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.

The US Food and Drug Administration (FDA) has used its expedited withdrawal process to rescind its approval of melphalan flufenamide (also called melflufen; Pepaxto, Oncopeptides AB), which it had approved for combined use with dexamethasone to treat some patients with multiple myeloma.

But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.

Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):

“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?

Melphalan Flufenamide is finally completely withdrawn by @US_FDA

But approval by @EMA_News stays.

How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?

Modern day miracle?”
 

EMA: Pepaxti’s Benefits Exceed Its Risks

The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:

“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.

Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.

“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.

The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.

“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
 

Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’

David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.

Liza Simonsson

“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”

Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”

“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
 

FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks

In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.

OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.

In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.

Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:

“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”

“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.

The US Food and Drug Administration (FDA) has used its expedited withdrawal process to rescind its approval of melphalan flufenamide (also called melflufen; Pepaxto, Oncopeptides AB), which it had approved for combined use with dexamethasone to treat some patients with multiple myeloma.

But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.

Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):

“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?

Melphalan Flufenamide is finally completely withdrawn by @US_FDA

But approval by @EMA_News stays.

How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?

Modern day miracle?”
 

EMA: Pepaxti’s Benefits Exceed Its Risks

The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:

“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.

Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.

“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.

The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.

“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
 

Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’

David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.

Liza Simonsson

“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”

Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”

“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
 

FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks

In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.

OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.

In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.

Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:

“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”

“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.