Mixed Topics

Urgent recommendations from a European Academy of Allergy and Clinical Immunology (EAACI) task force are aimed at reducing antibiotic overuse with allergic disease.

Top recommendations include limiting antibiotic therapy in pregnancy and early childhood to help reduce the allergy epidemic in children, and restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, especially asthma and atopic dermatitis.

The review, by lead author Gerdien Tramper-Stranders, MD, PhD, department of pediatrics, Franciscus Gasthuis & Vlietland Hospital, Rotterdam, the Netherlands, and colleagues, was published online Aug. 13 in the journal Allergy.

Several studies have shown that use of antibiotics in childhood and during pregnancy is associated with disturbing the intestinal and respiratory microbiome, which in turn leads to dysbiosis and an increased risk of acquiring allergic diseases, the authors noted.

In addition, patients with allergic diseases such as asthma have a higher risk of being prescribed antibiotics for infections compared with the general population, despite lack of clear clinical benefit.

“In fact, there are no clear data supporting antibiotic prescriptions for acute exacerbations; and clinical and/or laboratory criteria are lacking,” the authors wrote.

Despite that lack of data, antibiotics are often prescribed for exacerbations along with oral corticosteroids, Dr. Tramper-Stranders said in an interview. Some patients may benefit from antibiotics in a flare-up, she said, but more research is needed to determine which ones.

Dr. Tramper-Stranders said Franciscus has begun a large study that includes patients with asthma exacerbations to find biomarkers that might predict the type or origin of exacerbation to personalize treatment.
 

Recommendations have global relevance

She said although the recommendations are coming from the EAACI group, they apply worldwide.

“Especially in countries outside Northern Europe, antibiotic use is tremendous, leading to high rates of antibiotic resistance; but also increasing the risk for developing allergic diseases when prescribed in infancy,” she said.

She pointed out that in the United States, as many as one in six children receive unnecessary antibiotics for an asthma exacerbation. Overtreatment in adults with flare-ups is also prevalent, at rates from 40%-50%.

Millie Kwan, MD, PhD, an allergy specialist at University of North Carolina in Chapel Hill, said in an interview that in the U.S. there’s been a culture change in the direction of antibiotic restraint – but there are still problems.

“It’s a lot easier for us to whip out our prescription pads and prescribe antibiotics for an asthma patient who’s having a flare-up or a patient who has atopic dermatitis before addressing the underlying mechanism directly,” Dr. Kwan said. She agreed that antibiotic overuse is prevalent in pregnancies in the U.S., and she said that starts with the high prevalence of cesarean births. Nearly one-third of all births in the U.S. are by C-section, twice the rate recommended by the World Health Organization.

“Just bypassing the birth canal actually changes what kind of microflora the infant is being exposed to,” Dr. Kwan said. “That’s the first huge problem.”

The second problem, she said, is the potential for overuse of antibiotics with the surgical procedure.

The researchers wrote that pre-, pro- or postbiotics might alter the course of allergic disease, but clear evidence is lacking.

Until now, Dr. Tramper-Stranders said, pre- or probiotic treatment in infancy, irrespective of previous antibiotic use, has not proved effective in preventing allergies.

Data describing the effect of pre- or probiotics after an antibiotic course are scarce, are limited to older children and adults, and are focused on short-term effects, such as diarrhea prevention, she explained.

Dr. Kwan says she agrees that current data are not strong enough to recommend one over another.

“We don’t even know what the normal amount of bacteria should be to constitute an environment where the immune system develops ‘normally,’ “ she said.

Antibiotics should be prescribed cautiously and by following current recommendations to use the narrowest spectrum available, the authors wrote. Future research in antibiotic stewardship should incorporate biomarker-guided therapy to determine which patients might benefit most from antibiotic therapy.

“Practicing antibiotic stewardship needs recurrent attention and we hope that with this initiative, we specifically reach allergy doctors who will rethink their next [antibiotic] prescription. Within our EAACI task force, we will next work on a guideline for rational antibiotic use in asthma,” Dr. Tramper-Stranders said.

The review’s authors and Dr. Kwan have disclosed no relevant financial relationships.

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

Urgent recommendations from a European Academy of Allergy and Clinical Immunology (EAACI) task force are aimed at reducing antibiotic overuse with allergic disease.

Top recommendations include limiting antibiotic therapy in pregnancy and early childhood to help reduce the allergy epidemic in children, and restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, especially asthma and atopic dermatitis.

The review, by lead author Gerdien Tramper-Stranders, MD, PhD, department of pediatrics, Franciscus Gasthuis & Vlietland Hospital, Rotterdam, the Netherlands, and colleagues, was published online Aug. 13 in the journal Allergy.

Several studies have shown that use of antibiotics in childhood and during pregnancy is associated with disturbing the intestinal and respiratory microbiome, which in turn leads to dysbiosis and an increased risk of acquiring allergic diseases, the authors noted.

In addition, patients with allergic diseases such as asthma have a higher risk of being prescribed antibiotics for infections compared with the general population, despite lack of clear clinical benefit.

“In fact, there are no clear data supporting antibiotic prescriptions for acute exacerbations; and clinical and/or laboratory criteria are lacking,” the authors wrote.

Despite that lack of data, antibiotics are often prescribed for exacerbations along with oral corticosteroids, Dr. Tramper-Stranders said in an interview. Some patients may benefit from antibiotics in a flare-up, she said, but more research is needed to determine which ones.

Dr. Tramper-Stranders said Franciscus has begun a large study that includes patients with asthma exacerbations to find biomarkers that might predict the type or origin of exacerbation to personalize treatment.
 

Recommendations have global relevance

She said although the recommendations are coming from the EAACI group, they apply worldwide.

“Especially in countries outside Northern Europe, antibiotic use is tremendous, leading to high rates of antibiotic resistance; but also increasing the risk for developing allergic diseases when prescribed in infancy,” she said.

She pointed out that in the United States, as many as one in six children receive unnecessary antibiotics for an asthma exacerbation. Overtreatment in adults with flare-ups is also prevalent, at rates from 40%-50%.

Millie Kwan, MD, PhD, an allergy specialist at University of North Carolina in Chapel Hill, said in an interview that in the U.S. there’s been a culture change in the direction of antibiotic restraint – but there are still problems.

“It’s a lot easier for us to whip out our prescription pads and prescribe antibiotics for an asthma patient who’s having a flare-up or a patient who has atopic dermatitis before addressing the underlying mechanism directly,” Dr. Kwan said. She agreed that antibiotic overuse is prevalent in pregnancies in the U.S., and she said that starts with the high prevalence of cesarean births. Nearly one-third of all births in the U.S. are by C-section, twice the rate recommended by the World Health Organization.

“Just bypassing the birth canal actually changes what kind of microflora the infant is being exposed to,” Dr. Kwan said. “That’s the first huge problem.”

The second problem, she said, is the potential for overuse of antibiotics with the surgical procedure.

The researchers wrote that pre-, pro- or postbiotics might alter the course of allergic disease, but clear evidence is lacking.

Until now, Dr. Tramper-Stranders said, pre- or probiotic treatment in infancy, irrespective of previous antibiotic use, has not proved effective in preventing allergies.

Data describing the effect of pre- or probiotics after an antibiotic course are scarce, are limited to older children and adults, and are focused on short-term effects, such as diarrhea prevention, she explained.

Dr. Kwan says she agrees that current data are not strong enough to recommend one over another.

“We don’t even know what the normal amount of bacteria should be to constitute an environment where the immune system develops ‘normally,’ “ she said.

Antibiotics should be prescribed cautiously and by following current recommendations to use the narrowest spectrum available, the authors wrote. Future research in antibiotic stewardship should incorporate biomarker-guided therapy to determine which patients might benefit most from antibiotic therapy.

“Practicing antibiotic stewardship needs recurrent attention and we hope that with this initiative, we specifically reach allergy doctors who will rethink their next [antibiotic] prescription. Within our EAACI task force, we will next work on a guideline for rational antibiotic use in asthma,” Dr. Tramper-Stranders said.

The review’s authors and Dr. Kwan have disclosed no relevant financial relationships.

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

Urgent recommendations from a European Academy of Allergy and Clinical Immunology (EAACI) task force are aimed at reducing antibiotic overuse with allergic disease.

Top recommendations include limiting antibiotic therapy in pregnancy and early childhood to help reduce the allergy epidemic in children, and restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, especially asthma and atopic dermatitis.

The review, by lead author Gerdien Tramper-Stranders, MD, PhD, department of pediatrics, Franciscus Gasthuis & Vlietland Hospital, Rotterdam, the Netherlands, and colleagues, was published online Aug. 13 in the journal Allergy.

Several studies have shown that use of antibiotics in childhood and during pregnancy is associated with disturbing the intestinal and respiratory microbiome, which in turn leads to dysbiosis and an increased risk of acquiring allergic diseases, the authors noted.

In addition, patients with allergic diseases such as asthma have a higher risk of being prescribed antibiotics for infections compared with the general population, despite lack of clear clinical benefit.

“In fact, there are no clear data supporting antibiotic prescriptions for acute exacerbations; and clinical and/or laboratory criteria are lacking,” the authors wrote.

Despite that lack of data, antibiotics are often prescribed for exacerbations along with oral corticosteroids, Dr. Tramper-Stranders said in an interview. Some patients may benefit from antibiotics in a flare-up, she said, but more research is needed to determine which ones.

Dr. Tramper-Stranders said Franciscus has begun a large study that includes patients with asthma exacerbations to find biomarkers that might predict the type or origin of exacerbation to personalize treatment.
 

Recommendations have global relevance

She said although the recommendations are coming from the EAACI group, they apply worldwide.

“Especially in countries outside Northern Europe, antibiotic use is tremendous, leading to high rates of antibiotic resistance; but also increasing the risk for developing allergic diseases when prescribed in infancy,” she said.

She pointed out that in the United States, as many as one in six children receive unnecessary antibiotics for an asthma exacerbation. Overtreatment in adults with flare-ups is also prevalent, at rates from 40%-50%.

Millie Kwan, MD, PhD, an allergy specialist at University of North Carolina in Chapel Hill, said in an interview that in the U.S. there’s been a culture change in the direction of antibiotic restraint – but there are still problems.

“It’s a lot easier for us to whip out our prescription pads and prescribe antibiotics for an asthma patient who’s having a flare-up or a patient who has atopic dermatitis before addressing the underlying mechanism directly,” Dr. Kwan said. She agreed that antibiotic overuse is prevalent in pregnancies in the U.S., and she said that starts with the high prevalence of cesarean births. Nearly one-third of all births in the U.S. are by C-section, twice the rate recommended by the World Health Organization.

“Just bypassing the birth canal actually changes what kind of microflora the infant is being exposed to,” Dr. Kwan said. “That’s the first huge problem.”

The second problem, she said, is the potential for overuse of antibiotics with the surgical procedure.

The researchers wrote that pre-, pro- or postbiotics might alter the course of allergic disease, but clear evidence is lacking.

Until now, Dr. Tramper-Stranders said, pre- or probiotic treatment in infancy, irrespective of previous antibiotic use, has not proved effective in preventing allergies.

Data describing the effect of pre- or probiotics after an antibiotic course are scarce, are limited to older children and adults, and are focused on short-term effects, such as diarrhea prevention, she explained.

Dr. Kwan says she agrees that current data are not strong enough to recommend one over another.

“We don’t even know what the normal amount of bacteria should be to constitute an environment where the immune system develops ‘normally,’ “ she said.

Antibiotics should be prescribed cautiously and by following current recommendations to use the narrowest spectrum available, the authors wrote. Future research in antibiotic stewardship should incorporate biomarker-guided therapy to determine which patients might benefit most from antibiotic therapy.

“Practicing antibiotic stewardship needs recurrent attention and we hope that with this initiative, we specifically reach allergy doctors who will rethink their next [antibiotic] prescription. Within our EAACI task force, we will next work on a guideline for rational antibiotic use in asthma,” Dr. Tramper-Stranders said.

The review’s authors and Dr. Kwan have disclosed no relevant financial relationships.

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

The Food and Drug Administration is urging health care providers to immediately stop use of and discard all Eco-Med ultrasound gels and lotions because of risk for bacterial contamination with Burkholderia cepacia complex (Bcc). Earlier this month, the Centers for Disease Control and Prevention and the FDA announced an outbreak of at least 15 Bcc infections associated with contaminated ultrasound gel, and, according to the FDA, Eco-Med ultrasound gels have now been linked to at least 59 infections, 48 of which were blood infections.

On Aug. 4, the Canadian pharmaceutical company, based in Etobicoke, Ont., initiated a voluntary recall of certain lots of EcoGel 200 Ultrasound gel because of contamination with Bcc, but now the FDA warns that all Eco-Med’s ultrasound gels and lotions are at risk.

“The FDA’s determination is based on concerns that the company did not complete its investigation of the issues, the root cause and extent of bacterial contamination was not identified, and multiple products could be affected by manufacturing issues associated with the company’s ultrasound gel (such as inappropriate testing of finished product, inadequate testing of raw materials, and a lack of environmental controls),” the FDA said in a letter to health care providers published Aug. 18.

The letter lists 25 products manufactured by Eco-Med that are sold by distributors in 10 different countries, including the United States and Canada. The list may not be completely comprehensive, the organization notes.

Eco-Med has ceased all operations and is no longer manufacturing or distributing products, according to the FDA statement. Both phone numbers listed for the company were not in operation at the time of reporting.

Beyond stopping use of and discarding Eco-Med products, the FDA recommends that health care providers and facilities stop purchases of Eco-Med products, contact distributors with product disposal questions, and follow professional society guidelines and CDC guidelines for ultrasound use and cleaning products. Providers are encouraged to report adverse events related to Eco-Med ultrasound gels or lotions through MedWatch: The FDA Safety Information and Adverse Event Reporting program.

Though Eco-Med is listed as one of the “prominent players in the ultrasound gel market,” according to a June 2020 report by Grand View Research, the announcement will likely not cause many issues, Lauren Golding, MD, chair of the American College of Radiology Commission on Ultrasound, said in an interview.

“Fortunately, several companies produce ultrasound gel. Barring unforeseen circumstances, we do not expect this FDA action to have a widespread impact on patients’ access to ultrasound exams in the United States,” she said.

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

The Food and Drug Administration is urging health care providers to immediately stop use of and discard all Eco-Med ultrasound gels and lotions because of risk for bacterial contamination with Burkholderia cepacia complex (Bcc). Earlier this month, the Centers for Disease Control and Prevention and the FDA announced an outbreak of at least 15 Bcc infections associated with contaminated ultrasound gel, and, according to the FDA, Eco-Med ultrasound gels have now been linked to at least 59 infections, 48 of which were blood infections.

On Aug. 4, the Canadian pharmaceutical company, based in Etobicoke, Ont., initiated a voluntary recall of certain lots of EcoGel 200 Ultrasound gel because of contamination with Bcc, but now the FDA warns that all Eco-Med’s ultrasound gels and lotions are at risk.

“The FDA’s determination is based on concerns that the company did not complete its investigation of the issues, the root cause and extent of bacterial contamination was not identified, and multiple products could be affected by manufacturing issues associated with the company’s ultrasound gel (such as inappropriate testing of finished product, inadequate testing of raw materials, and a lack of environmental controls),” the FDA said in a letter to health care providers published Aug. 18.

The letter lists 25 products manufactured by Eco-Med that are sold by distributors in 10 different countries, including the United States and Canada. The list may not be completely comprehensive, the organization notes.

Eco-Med has ceased all operations and is no longer manufacturing or distributing products, according to the FDA statement. Both phone numbers listed for the company were not in operation at the time of reporting.

Beyond stopping use of and discarding Eco-Med products, the FDA recommends that health care providers and facilities stop purchases of Eco-Med products, contact distributors with product disposal questions, and follow professional society guidelines and CDC guidelines for ultrasound use and cleaning products. Providers are encouraged to report adverse events related to Eco-Med ultrasound gels or lotions through MedWatch: The FDA Safety Information and Adverse Event Reporting program.

Though Eco-Med is listed as one of the “prominent players in the ultrasound gel market,” according to a June 2020 report by Grand View Research, the announcement will likely not cause many issues, Lauren Golding, MD, chair of the American College of Radiology Commission on Ultrasound, said in an interview.

“Fortunately, several companies produce ultrasound gel. Barring unforeseen circumstances, we do not expect this FDA action to have a widespread impact on patients’ access to ultrasound exams in the United States,” she said.

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

The Food and Drug Administration is urging health care providers to immediately stop use of and discard all Eco-Med ultrasound gels and lotions because of risk for bacterial contamination with Burkholderia cepacia complex (Bcc). Earlier this month, the Centers for Disease Control and Prevention and the FDA announced an outbreak of at least 15 Bcc infections associated with contaminated ultrasound gel, and, according to the FDA, Eco-Med ultrasound gels have now been linked to at least 59 infections, 48 of which were blood infections.

On Aug. 4, the Canadian pharmaceutical company, based in Etobicoke, Ont., initiated a voluntary recall of certain lots of EcoGel 200 Ultrasound gel because of contamination with Bcc, but now the FDA warns that all Eco-Med’s ultrasound gels and lotions are at risk.

“The FDA’s determination is based on concerns that the company did not complete its investigation of the issues, the root cause and extent of bacterial contamination was not identified, and multiple products could be affected by manufacturing issues associated with the company’s ultrasound gel (such as inappropriate testing of finished product, inadequate testing of raw materials, and a lack of environmental controls),” the FDA said in a letter to health care providers published Aug. 18.

The letter lists 25 products manufactured by Eco-Med that are sold by distributors in 10 different countries, including the United States and Canada. The list may not be completely comprehensive, the organization notes.

Eco-Med has ceased all operations and is no longer manufacturing or distributing products, according to the FDA statement. Both phone numbers listed for the company were not in operation at the time of reporting.

Beyond stopping use of and discarding Eco-Med products, the FDA recommends that health care providers and facilities stop purchases of Eco-Med products, contact distributors with product disposal questions, and follow professional society guidelines and CDC guidelines for ultrasound use and cleaning products. Providers are encouraged to report adverse events related to Eco-Med ultrasound gels or lotions through MedWatch: The FDA Safety Information and Adverse Event Reporting program.

Though Eco-Med is listed as one of the “prominent players in the ultrasound gel market,” according to a June 2020 report by Grand View Research, the announcement will likely not cause many issues, Lauren Golding, MD, chair of the American College of Radiology Commission on Ultrasound, said in an interview.

“Fortunately, several companies produce ultrasound gel. Barring unforeseen circumstances, we do not expect this FDA action to have a widespread impact on patients’ access to ultrasound exams in the United States,” she said.

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

The Food and Drug Administration has broadened the indication for dostarlimab-gxly (Jemperli), a PD-1 blocking antibody, to include all recurrent or advanced mismatch repair-deficient (dMMR) solid tumors that have progressed during or after treatment in cases in which there are no satisfactory alternative options, according to new labeling.

The agency approved the drug in April for dMMR recurrent or advanced endometrial cancer that has progressed during or following treatment with a platinum-containing regimen. The labeling notes that dMMR status for both indications must be determined through an FDA-approved test.

The accelerated approval “may be contingent upon verification and description of clinical benefit in a confirmatory” trial, the labeling says.

The new indication was based results from 209 patients in the GARNET trial. In that trial, the objective response rate was 41.6% across dMMR endometrial and other solid tumors. The complete response rate was 9.1%.

The median duration of response was 34.7 months. For 95% of patients who responded to treatment, the duration of response was 6 months or longer, according to a press release from the maker, GlaxoSmithKline.

In mismatch repair deficiency, tumors contain abnormalities that affect the proper repair of DNA. Prevalence in the United States is estimated to be 14%. The deficiency is particularly common in endometrial, colorectal, and other gastrointestinal cancers, the company said.

The drug was administered in GARNET as a 500-mg intravenous infusion every 3 weeks in four doses, followed by 1,000 mg once every 6 weeks until disease progression or unacceptable toxicity.

Common adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3 or 4 adverse reactions included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.

As with other PD-1/PD-L1 blockers, there’s also a possibility of severe and fatal immune-mediated adverse reactions in any organ system either during or after treatment, including immune-mediated pneumonitis, colitis, and hepatitis.

GlaxoSmithKline said it’s studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other agents for other advanced/metastatic cancers.

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

The Food and Drug Administration has broadened the indication for dostarlimab-gxly (Jemperli), a PD-1 blocking antibody, to include all recurrent or advanced mismatch repair-deficient (dMMR) solid tumors that have progressed during or after treatment in cases in which there are no satisfactory alternative options, according to new labeling.

The agency approved the drug in April for dMMR recurrent or advanced endometrial cancer that has progressed during or following treatment with a platinum-containing regimen. The labeling notes that dMMR status for both indications must be determined through an FDA-approved test.

The accelerated approval “may be contingent upon verification and description of clinical benefit in a confirmatory” trial, the labeling says.

The new indication was based results from 209 patients in the GARNET trial. In that trial, the objective response rate was 41.6% across dMMR endometrial and other solid tumors. The complete response rate was 9.1%.

The median duration of response was 34.7 months. For 95% of patients who responded to treatment, the duration of response was 6 months or longer, according to a press release from the maker, GlaxoSmithKline.

In mismatch repair deficiency, tumors contain abnormalities that affect the proper repair of DNA. Prevalence in the United States is estimated to be 14%. The deficiency is particularly common in endometrial, colorectal, and other gastrointestinal cancers, the company said.

The drug was administered in GARNET as a 500-mg intravenous infusion every 3 weeks in four doses, followed by 1,000 mg once every 6 weeks until disease progression or unacceptable toxicity.

Common adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3 or 4 adverse reactions included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.

As with other PD-1/PD-L1 blockers, there’s also a possibility of severe and fatal immune-mediated adverse reactions in any organ system either during or after treatment, including immune-mediated pneumonitis, colitis, and hepatitis.

GlaxoSmithKline said it’s studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other agents for other advanced/metastatic cancers.

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

The Food and Drug Administration has broadened the indication for dostarlimab-gxly (Jemperli), a PD-1 blocking antibody, to include all recurrent or advanced mismatch repair-deficient (dMMR) solid tumors that have progressed during or after treatment in cases in which there are no satisfactory alternative options, according to new labeling.

The agency approved the drug in April for dMMR recurrent or advanced endometrial cancer that has progressed during or following treatment with a platinum-containing regimen. The labeling notes that dMMR status for both indications must be determined through an FDA-approved test.

The accelerated approval “may be contingent upon verification and description of clinical benefit in a confirmatory” trial, the labeling says.

The new indication was based results from 209 patients in the GARNET trial. In that trial, the objective response rate was 41.6% across dMMR endometrial and other solid tumors. The complete response rate was 9.1%.

The median duration of response was 34.7 months. For 95% of patients who responded to treatment, the duration of response was 6 months or longer, according to a press release from the maker, GlaxoSmithKline.

In mismatch repair deficiency, tumors contain abnormalities that affect the proper repair of DNA. Prevalence in the United States is estimated to be 14%. The deficiency is particularly common in endometrial, colorectal, and other gastrointestinal cancers, the company said.

The drug was administered in GARNET as a 500-mg intravenous infusion every 3 weeks in four doses, followed by 1,000 mg once every 6 weeks until disease progression or unacceptable toxicity.

Common adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3 or 4 adverse reactions included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.

As with other PD-1/PD-L1 blockers, there’s also a possibility of severe and fatal immune-mediated adverse reactions in any organ system either during or after treatment, including immune-mediated pneumonitis, colitis, and hepatitis.

GlaxoSmithKline said it’s studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other agents for other advanced/metastatic cancers.

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

The Food and Drug Administration approved belzutifan (Welireg) for adult patients with von Hippel–Lindau disease (VHL) who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) that do not require immediate surgery.

Belzutifan is a selective small-molecule inhibitor of hypoxia-inducible factor and a first-in-class drug.

The new approval is based on safety and efficacy results from the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC with at least one measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNETs.

Patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity.

The overall response rate, which was the study’s primary endpoint, was 49% in patients with VHL-associated RCC. Additional efficacy endpoints included duration of response (DoR), which was not reached. So far, 56% of responders had DoR of at least 12 months. The median time to response was 8 months.

Among the patients in the study with other VHL-associated non-RCC tumors, 24 patients with CNS hemangioblastomas had an ORR of 63%, and 12 patients with pNETs had an ORR of 83%. Median DoR was not reached,with 73% and 50% of patients having response durations of at least 12 months for CNS hemangioblastomas and pNET, respectively.

The most common adverse reactions (≥20% of patients), according to the FDA, were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea.

Notably, anemia and hypoxia from belzutifan use can be severe. In Study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. Patients should be transfused as clinically indicated. Erythropoiesis-stimulating agents for anemia are not recommended in patients treated with belzutifan. In Study 004, hypoxia occurred in 1.6% of patients.

Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm; see full prescribing information for Welireg.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, and used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. The application was granted priority review by the FDA.

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

The Food and Drug Administration approved belzutifan (Welireg) for adult patients with von Hippel–Lindau disease (VHL) who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) that do not require immediate surgery.

Belzutifan is a selective small-molecule inhibitor of hypoxia-inducible factor and a first-in-class drug.

The new approval is based on safety and efficacy results from the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC with at least one measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNETs.

Patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity.

The overall response rate, which was the study’s primary endpoint, was 49% in patients with VHL-associated RCC. Additional efficacy endpoints included duration of response (DoR), which was not reached. So far, 56% of responders had DoR of at least 12 months. The median time to response was 8 months.

Among the patients in the study with other VHL-associated non-RCC tumors, 24 patients with CNS hemangioblastomas had an ORR of 63%, and 12 patients with pNETs had an ORR of 83%. Median DoR was not reached,with 73% and 50% of patients having response durations of at least 12 months for CNS hemangioblastomas and pNET, respectively.

The most common adverse reactions (≥20% of patients), according to the FDA, were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea.

Notably, anemia and hypoxia from belzutifan use can be severe. In Study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. Patients should be transfused as clinically indicated. Erythropoiesis-stimulating agents for anemia are not recommended in patients treated with belzutifan. In Study 004, hypoxia occurred in 1.6% of patients.

Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm; see full prescribing information for Welireg.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, and used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. The application was granted priority review by the FDA.

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

The Food and Drug Administration approved belzutifan (Welireg) for adult patients with von Hippel–Lindau disease (VHL) who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) that do not require immediate surgery.

Belzutifan is a selective small-molecule inhibitor of hypoxia-inducible factor and a first-in-class drug.

The new approval is based on safety and efficacy results from the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC with at least one measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNETs.

Patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity.

The overall response rate, which was the study’s primary endpoint, was 49% in patients with VHL-associated RCC. Additional efficacy endpoints included duration of response (DoR), which was not reached. So far, 56% of responders had DoR of at least 12 months. The median time to response was 8 months.

Among the patients in the study with other VHL-associated non-RCC tumors, 24 patients with CNS hemangioblastomas had an ORR of 63%, and 12 patients with pNETs had an ORR of 83%. Median DoR was not reached,with 73% and 50% of patients having response durations of at least 12 months for CNS hemangioblastomas and pNET, respectively.

The most common adverse reactions (≥20% of patients), according to the FDA, were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea.

Notably, anemia and hypoxia from belzutifan use can be severe. In Study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. Patients should be transfused as clinically indicated. Erythropoiesis-stimulating agents for anemia are not recommended in patients treated with belzutifan. In Study 004, hypoxia occurred in 1.6% of patients.

Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm; see full prescribing information for Welireg.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, and used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. The application was granted priority review by the FDA.

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

In medical school, I remember thinking that telling a patient “you have cancer” would be the most professionally challenging phrase I would ever utter. And don’t get me wrong – it certainly isn’t easy; but, compared with telling someone “you are infertile,” it’s a cakewalk.

Maybe it’s because people “have” cancer and cancer is something you “fight.” Or maybe because, unlike infertility, cancer has become a part of public life (think lapel pins and support groups) and is now easier to accept. On the other hand, someone “is” infertile. The condition is a source of embarrassment for the couple and is often hidden from society.

Here’s another concerning point of contrast: While the overall rate of cancer death has declined since the early 1990s, infertility is increasing. Reports now show that one in six couples have problems conceiving and the use of assisted reproductive technologies is increasing by 5%-10% per year. Many theories exist to explain these trends, chief among them the rise in average maternal age and the increasing incidence of obesity, as well as various other male- and female-specific factors.

But interestingly, recent data suggest that the most male of all male-specific factors – total sperm count – may be specifically to blame.

According to a recent meta-analysis, the average total sperm count in men declined by 59.3% between 1973 and 2011. While these data certainly have limitations – including the exclusion of non-English publications, the reliance on total sperm count and not sperm motility, and the potential bias of those patients willing to give a semen sample – the overall trend nevertheless seems to be clearly downward. What’s more concerning, if you believe the data presented, is that there does not appear to be a leveling off of the downward curve in total sperm count.

Think about that last statement. At the current rate of decline, the average sperm count will be zero in 2045. One of the lead authors on the meta-analysis, Hagai Levine, MD, MPH, goes so far as to state, “We should hope for the best and prepare for the worst.”

As a matter of personal philosophy, I’m not a huge fan of end-of-the-world predictions because they tend not to come true (think Montanism back in the 2nd century; the 2012 Mayan calendar scare; or my personal favorite, the Prophet Hen of Leeds). On the other hand, the overall trend of decreased total sperm count in the English-speaking world seems to be true and it raises the interesting question of why.

According to the Mayo Clinic, causes of decreased sperm count include everything from anatomical factors (like varicoceles and ejaculatory issues) and lifestyle issues (such as recreational drugs, weight gain, and emotional stress) to environmental exposures (heavy metal or radiation). The senior author of the aforementioned meta-analysis, Shanna Swan, PhD, has championed another theory: the widespread exposure to endocrine-disrupting chemicals in everyday plastics.

It turns out that at least two chemicals used in the plastics industry, bisphenol A and phthalates, can mimic the effect of estrogen when ingested into the body. Even low levels of these chemicals in our bodies can lead to health problems.

Consider for a moment the presence of plastics in your life: the plastic wrappings on your food, plastic containers for shampoos and beauty products, and even the coatings of our oral supplements. A study by the Centers for Disease Control and Prevention looked at the urine of people participating in the National Health and Nutrition Examination Survey and found detectable concentrations of both of these chemicals in nearly all participants.

In 2045, I intend to be retired. But in the meantime, I think we all need to be aware of the potential impact that various endocrine-disrupting chemicals could be having on humanity. We need more research. If indeed the connection between endocrine disruptors and decreased sperm count is borne out, changes in our environmental exposure to these chemicals need to be made.

Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs. He comes from a long line of doctors, but before entering medicine he served in the U.S. Navy as an officer aboard the USS Pittsburgh, a fast-attack submarine based out of New London, Conn. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom. Dr. Rosevear disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

In medical school, I remember thinking that telling a patient “you have cancer” would be the most professionally challenging phrase I would ever utter. And don’t get me wrong – it certainly isn’t easy; but, compared with telling someone “you are infertile,” it’s a cakewalk.

Maybe it’s because people “have” cancer and cancer is something you “fight.” Or maybe because, unlike infertility, cancer has become a part of public life (think lapel pins and support groups) and is now easier to accept. On the other hand, someone “is” infertile. The condition is a source of embarrassment for the couple and is often hidden from society.

Here’s another concerning point of contrast: While the overall rate of cancer death has declined since the early 1990s, infertility is increasing. Reports now show that one in six couples have problems conceiving and the use of assisted reproductive technologies is increasing by 5%-10% per year. Many theories exist to explain these trends, chief among them the rise in average maternal age and the increasing incidence of obesity, as well as various other male- and female-specific factors.

But interestingly, recent data suggest that the most male of all male-specific factors – total sperm count – may be specifically to blame.

According to a recent meta-analysis, the average total sperm count in men declined by 59.3% between 1973 and 2011. While these data certainly have limitations – including the exclusion of non-English publications, the reliance on total sperm count and not sperm motility, and the potential bias of those patients willing to give a semen sample – the overall trend nevertheless seems to be clearly downward. What’s more concerning, if you believe the data presented, is that there does not appear to be a leveling off of the downward curve in total sperm count.

Think about that last statement. At the current rate of decline, the average sperm count will be zero in 2045. One of the lead authors on the meta-analysis, Hagai Levine, MD, MPH, goes so far as to state, “We should hope for the best and prepare for the worst.”

As a matter of personal philosophy, I’m not a huge fan of end-of-the-world predictions because they tend not to come true (think Montanism back in the 2nd century; the 2012 Mayan calendar scare; or my personal favorite, the Prophet Hen of Leeds). On the other hand, the overall trend of decreased total sperm count in the English-speaking world seems to be true and it raises the interesting question of why.

According to the Mayo Clinic, causes of decreased sperm count include everything from anatomical factors (like varicoceles and ejaculatory issues) and lifestyle issues (such as recreational drugs, weight gain, and emotional stress) to environmental exposures (heavy metal or radiation). The senior author of the aforementioned meta-analysis, Shanna Swan, PhD, has championed another theory: the widespread exposure to endocrine-disrupting chemicals in everyday plastics.

It turns out that at least two chemicals used in the plastics industry, bisphenol A and phthalates, can mimic the effect of estrogen when ingested into the body. Even low levels of these chemicals in our bodies can lead to health problems.

Consider for a moment the presence of plastics in your life: the plastic wrappings on your food, plastic containers for shampoos and beauty products, and even the coatings of our oral supplements. A study by the Centers for Disease Control and Prevention looked at the urine of people participating in the National Health and Nutrition Examination Survey and found detectable concentrations of both of these chemicals in nearly all participants.

In 2045, I intend to be retired. But in the meantime, I think we all need to be aware of the potential impact that various endocrine-disrupting chemicals could be having on humanity. We need more research. If indeed the connection between endocrine disruptors and decreased sperm count is borne out, changes in our environmental exposure to these chemicals need to be made.

Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs. He comes from a long line of doctors, but before entering medicine he served in the U.S. Navy as an officer aboard the USS Pittsburgh, a fast-attack submarine based out of New London, Conn. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom. Dr. Rosevear disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

In medical school, I remember thinking that telling a patient “you have cancer” would be the most professionally challenging phrase I would ever utter. And don’t get me wrong – it certainly isn’t easy; but, compared with telling someone “you are infertile,” it’s a cakewalk.

Maybe it’s because people “have” cancer and cancer is something you “fight.” Or maybe because, unlike infertility, cancer has become a part of public life (think lapel pins and support groups) and is now easier to accept. On the other hand, someone “is” infertile. The condition is a source of embarrassment for the couple and is often hidden from society.

Here’s another concerning point of contrast: While the overall rate of cancer death has declined since the early 1990s, infertility is increasing. Reports now show that one in six couples have problems conceiving and the use of assisted reproductive technologies is increasing by 5%-10% per year. Many theories exist to explain these trends, chief among them the rise in average maternal age and the increasing incidence of obesity, as well as various other male- and female-specific factors.

But interestingly, recent data suggest that the most male of all male-specific factors – total sperm count – may be specifically to blame.

According to a recent meta-analysis, the average total sperm count in men declined by 59.3% between 1973 and 2011. While these data certainly have limitations – including the exclusion of non-English publications, the reliance on total sperm count and not sperm motility, and the potential bias of those patients willing to give a semen sample – the overall trend nevertheless seems to be clearly downward. What’s more concerning, if you believe the data presented, is that there does not appear to be a leveling off of the downward curve in total sperm count.

Think about that last statement. At the current rate of decline, the average sperm count will be zero in 2045. One of the lead authors on the meta-analysis, Hagai Levine, MD, MPH, goes so far as to state, “We should hope for the best and prepare for the worst.”

As a matter of personal philosophy, I’m not a huge fan of end-of-the-world predictions because they tend not to come true (think Montanism back in the 2nd century; the 2012 Mayan calendar scare; or my personal favorite, the Prophet Hen of Leeds). On the other hand, the overall trend of decreased total sperm count in the English-speaking world seems to be true and it raises the interesting question of why.

According to the Mayo Clinic, causes of decreased sperm count include everything from anatomical factors (like varicoceles and ejaculatory issues) and lifestyle issues (such as recreational drugs, weight gain, and emotional stress) to environmental exposures (heavy metal or radiation). The senior author of the aforementioned meta-analysis, Shanna Swan, PhD, has championed another theory: the widespread exposure to endocrine-disrupting chemicals in everyday plastics.

It turns out that at least two chemicals used in the plastics industry, bisphenol A and phthalates, can mimic the effect of estrogen when ingested into the body. Even low levels of these chemicals in our bodies can lead to health problems.

Consider for a moment the presence of plastics in your life: the plastic wrappings on your food, plastic containers for shampoos and beauty products, and even the coatings of our oral supplements. A study by the Centers for Disease Control and Prevention looked at the urine of people participating in the National Health and Nutrition Examination Survey and found detectable concentrations of both of these chemicals in nearly all participants.

In 2045, I intend to be retired. But in the meantime, I think we all need to be aware of the potential impact that various endocrine-disrupting chemicals could be having on humanity. We need more research. If indeed the connection between endocrine disruptors and decreased sperm count is borne out, changes in our environmental exposure to these chemicals need to be made.

Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs. He comes from a long line of doctors, but before entering medicine he served in the U.S. Navy as an officer aboard the USS Pittsburgh, a fast-attack submarine based out of New London, Conn. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom. Dr. Rosevear disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

New consensus recommendations address diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with advice that may also be helpful for patients with lingering symptoms following acute COVID-19 infection.

VioletaStoimenova/Getty Images

The document was published online Aug. 25, 2021, in the Mayo Clinic Proceedings by the 23-member U.S. ME/CFS Clinician Coalition, headed by Lucinda Bateman, MD, of the Bateman Horne Center of Excellence, Salt Lake City. The document is the culmination of work that began with a summit held at the center in March 2018.

The target audience is both generalist and specialist health care providers. While ME/CFS is estimated to affect up to 2.5 million Americans, more than 90% are either undiagnosed or misdiagnosed with other conditions such as depression. And those who are diagnosed often receive inappropriate, outdated treatments such as psychotherapy and exercise prescriptions.

“Despite myalgic encephalomyelitis/chronic fatigue syndrome affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful,” Dr. Bateman and colleagues wrote.

The urgency of appropriate recognition and management of ME/CFS has increased as growing numbers of people are exhibiting signs and symptoms of ME/CFS following acute COVID-19 infection. This isn’t surprising because the illness has long been linked to other infections, including Epstein-Barr virus, the authors noted.

The document covers the epidemiology, impact, and prognosis of ME/CFS, as well as etiology and pathophysiology. “Scientific studies demonstrate multiple dysfunctional organ systems, including neuro, immune, and metabolic, in ME/CFS. These findings are not explained merely by deconditioning,” document coauthor Lily Chu, MD, an independent consultant in Burlingame, Calif., said in an interview.

The document reviews the 2015 U.S. Institute of Medicine (now Academy of Medicine) diagnostic criteria that are now also recommended by the Centers for Disease Control and Prevention. They are based on four main symptoms: substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social or personal activities for longer than 6 months; postexertional malaise, a worsening of all current symptoms, that patients often describe as a “crash”; unrefreshing sleep; and cognitive impairment and/or orthostatic intolerance.

“The new diagnostic criteria focusing on the key symptom of postexertional malaise rather than chronic fatigue, which is common in many conditions, may make the diagnostic process quicker and more accurate. Diagnosis now is both an inclusionary and not just exclusionary process, so it’s not necessary to eliminate all causes of fatigue. Diagnose patients who fit the criteria and be alert for it in people with persistent symptoms post COVID,” Dr. Chu said.

The document provides advice for taking a clinical history to obtain the information necessary for making the diagnosis, including use of laboratory testing to rule out other conditions. Physical exams, while they may not reveal specific abnormalities, may help in identifying comorbidities and ruling out alternative diagnoses.

A long list of nonpharmacologic and pharmacologic treatment and management approaches is offered for each of the individual core and common ME/CFS symptoms, including postexertional malaise, orthostatic intolerance, sleep issues, cognitive dysfunction and fatigue, immune dysfunction, pain, and gastrointestinal issues.

The document recommends against using the “outdated standard of care” cognitive-behavioral therapy and graded exercise therapy as primary treatments for the illness. Instead, the authors recommend teaching patients “pacing,” an individualized approach to energy conservation aimed at minimizing the frequency, duration, and severity of postexertional malaise.

Clinicians are also advised to assess patients’ daily living needs and provide support, including acquiring handicap placards, work or school accommodations, and disability benefits.

“There are things clinicians can do now to help patients even without a disease-modifying treatment. These are actions they are already familiar with and carry out for people with other chronic diseases, which often have limited treatment options as well. Don’t underestimate the importance and value of supportive care for patients.” Dr. Chu said.

The recommendations are based primarily on clinical expertise because there are very few randomized trials, and much of the evidence from other types of trials has been flawed, document coauthor Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“The sad reality is there aren’t very many large randomized clinical trials with this illness and so what a group of very experienced clinicians did was to gather their collective experience and report it as that. It’s largely uncontrolled experience, but from people who have seen a lot of patients, for what it’s worth to the medical community.”

Dr. Komaroff also advised that clinicians watch out for ME/CFS in patients with long COVID. “If we find that those called long COVID meet ME/CFS criteria, the reason for knowing that is that there are already some treatments that according to experienced clinicians are helpful for ME/CFS, and it would be perfectly appropriate to try some of them in long COVID, particularly the ones that have minimal adverse reactions.”

The guidelines project was supported by the Open Medicine Foundation. Dr. Komaroff reported receiving personal fees from Serimmune outside the submitted work. Dr. Chu has no disclosures.

New consensus recommendations address diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with advice that may also be helpful for patients with lingering symptoms following acute COVID-19 infection.

VioletaStoimenova/Getty Images

The document was published online Aug. 25, 2021, in the Mayo Clinic Proceedings by the 23-member U.S. ME/CFS Clinician Coalition, headed by Lucinda Bateman, MD, of the Bateman Horne Center of Excellence, Salt Lake City. The document is the culmination of work that began with a summit held at the center in March 2018.

The target audience is both generalist and specialist health care providers. While ME/CFS is estimated to affect up to 2.5 million Americans, more than 90% are either undiagnosed or misdiagnosed with other conditions such as depression. And those who are diagnosed often receive inappropriate, outdated treatments such as psychotherapy and exercise prescriptions.

“Despite myalgic encephalomyelitis/chronic fatigue syndrome affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful,” Dr. Bateman and colleagues wrote.

The urgency of appropriate recognition and management of ME/CFS has increased as growing numbers of people are exhibiting signs and symptoms of ME/CFS following acute COVID-19 infection. This isn’t surprising because the illness has long been linked to other infections, including Epstein-Barr virus, the authors noted.

The document covers the epidemiology, impact, and prognosis of ME/CFS, as well as etiology and pathophysiology. “Scientific studies demonstrate multiple dysfunctional organ systems, including neuro, immune, and metabolic, in ME/CFS. These findings are not explained merely by deconditioning,” document coauthor Lily Chu, MD, an independent consultant in Burlingame, Calif., said in an interview.

The document reviews the 2015 U.S. Institute of Medicine (now Academy of Medicine) diagnostic criteria that are now also recommended by the Centers for Disease Control and Prevention. They are based on four main symptoms: substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social or personal activities for longer than 6 months; postexertional malaise, a worsening of all current symptoms, that patients often describe as a “crash”; unrefreshing sleep; and cognitive impairment and/or orthostatic intolerance.

“The new diagnostic criteria focusing on the key symptom of postexertional malaise rather than chronic fatigue, which is common in many conditions, may make the diagnostic process quicker and more accurate. Diagnosis now is both an inclusionary and not just exclusionary process, so it’s not necessary to eliminate all causes of fatigue. Diagnose patients who fit the criteria and be alert for it in people with persistent symptoms post COVID,” Dr. Chu said.

The document provides advice for taking a clinical history to obtain the information necessary for making the diagnosis, including use of laboratory testing to rule out other conditions. Physical exams, while they may not reveal specific abnormalities, may help in identifying comorbidities and ruling out alternative diagnoses.

A long list of nonpharmacologic and pharmacologic treatment and management approaches is offered for each of the individual core and common ME/CFS symptoms, including postexertional malaise, orthostatic intolerance, sleep issues, cognitive dysfunction and fatigue, immune dysfunction, pain, and gastrointestinal issues.

The document recommends against using the “outdated standard of care” cognitive-behavioral therapy and graded exercise therapy as primary treatments for the illness. Instead, the authors recommend teaching patients “pacing,” an individualized approach to energy conservation aimed at minimizing the frequency, duration, and severity of postexertional malaise.

Clinicians are also advised to assess patients’ daily living needs and provide support, including acquiring handicap placards, work or school accommodations, and disability benefits.

“There are things clinicians can do now to help patients even without a disease-modifying treatment. These are actions they are already familiar with and carry out for people with other chronic diseases, which often have limited treatment options as well. Don’t underestimate the importance and value of supportive care for patients.” Dr. Chu said.

The recommendations are based primarily on clinical expertise because there are very few randomized trials, and much of the evidence from other types of trials has been flawed, document coauthor Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“The sad reality is there aren’t very many large randomized clinical trials with this illness and so what a group of very experienced clinicians did was to gather their collective experience and report it as that. It’s largely uncontrolled experience, but from people who have seen a lot of patients, for what it’s worth to the medical community.”

Dr. Komaroff also advised that clinicians watch out for ME/CFS in patients with long COVID. “If we find that those called long COVID meet ME/CFS criteria, the reason for knowing that is that there are already some treatments that according to experienced clinicians are helpful for ME/CFS, and it would be perfectly appropriate to try some of them in long COVID, particularly the ones that have minimal adverse reactions.”

The guidelines project was supported by the Open Medicine Foundation. Dr. Komaroff reported receiving personal fees from Serimmune outside the submitted work. Dr. Chu has no disclosures.

New consensus recommendations address diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with advice that may also be helpful for patients with lingering symptoms following acute COVID-19 infection.

VioletaStoimenova/Getty Images

The document was published online Aug. 25, 2021, in the Mayo Clinic Proceedings by the 23-member U.S. ME/CFS Clinician Coalition, headed by Lucinda Bateman, MD, of the Bateman Horne Center of Excellence, Salt Lake City. The document is the culmination of work that began with a summit held at the center in March 2018.

The target audience is both generalist and specialist health care providers. While ME/CFS is estimated to affect up to 2.5 million Americans, more than 90% are either undiagnosed or misdiagnosed with other conditions such as depression. And those who are diagnosed often receive inappropriate, outdated treatments such as psychotherapy and exercise prescriptions.

“Despite myalgic encephalomyelitis/chronic fatigue syndrome affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful,” Dr. Bateman and colleagues wrote.

The urgency of appropriate recognition and management of ME/CFS has increased as growing numbers of people are exhibiting signs and symptoms of ME/CFS following acute COVID-19 infection. This isn’t surprising because the illness has long been linked to other infections, including Epstein-Barr virus, the authors noted.

The document covers the epidemiology, impact, and prognosis of ME/CFS, as well as etiology and pathophysiology. “Scientific studies demonstrate multiple dysfunctional organ systems, including neuro, immune, and metabolic, in ME/CFS. These findings are not explained merely by deconditioning,” document coauthor Lily Chu, MD, an independent consultant in Burlingame, Calif., said in an interview.

The document reviews the 2015 U.S. Institute of Medicine (now Academy of Medicine) diagnostic criteria that are now also recommended by the Centers for Disease Control and Prevention. They are based on four main symptoms: substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social or personal activities for longer than 6 months; postexertional malaise, a worsening of all current symptoms, that patients often describe as a “crash”; unrefreshing sleep; and cognitive impairment and/or orthostatic intolerance.

“The new diagnostic criteria focusing on the key symptom of postexertional malaise rather than chronic fatigue, which is common in many conditions, may make the diagnostic process quicker and more accurate. Diagnosis now is both an inclusionary and not just exclusionary process, so it’s not necessary to eliminate all causes of fatigue. Diagnose patients who fit the criteria and be alert for it in people with persistent symptoms post COVID,” Dr. Chu said.

The document provides advice for taking a clinical history to obtain the information necessary for making the diagnosis, including use of laboratory testing to rule out other conditions. Physical exams, while they may not reveal specific abnormalities, may help in identifying comorbidities and ruling out alternative diagnoses.

A long list of nonpharmacologic and pharmacologic treatment and management approaches is offered for each of the individual core and common ME/CFS symptoms, including postexertional malaise, orthostatic intolerance, sleep issues, cognitive dysfunction and fatigue, immune dysfunction, pain, and gastrointestinal issues.

The document recommends against using the “outdated standard of care” cognitive-behavioral therapy and graded exercise therapy as primary treatments for the illness. Instead, the authors recommend teaching patients “pacing,” an individualized approach to energy conservation aimed at minimizing the frequency, duration, and severity of postexertional malaise.

Clinicians are also advised to assess patients’ daily living needs and provide support, including acquiring handicap placards, work or school accommodations, and disability benefits.

“There are things clinicians can do now to help patients even without a disease-modifying treatment. These are actions they are already familiar with and carry out for people with other chronic diseases, which often have limited treatment options as well. Don’t underestimate the importance and value of supportive care for patients.” Dr. Chu said.

The recommendations are based primarily on clinical expertise because there are very few randomized trials, and much of the evidence from other types of trials has been flawed, document coauthor Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“The sad reality is there aren’t very many large randomized clinical trials with this illness and so what a group of very experienced clinicians did was to gather their collective experience and report it as that. It’s largely uncontrolled experience, but from people who have seen a lot of patients, for what it’s worth to the medical community.”

Dr. Komaroff also advised that clinicians watch out for ME/CFS in patients with long COVID. “If we find that those called long COVID meet ME/CFS criteria, the reason for knowing that is that there are already some treatments that according to experienced clinicians are helpful for ME/CFS, and it would be perfectly appropriate to try some of them in long COVID, particularly the ones that have minimal adverse reactions.”

The guidelines project was supported by the Open Medicine Foundation. Dr. Komaroff reported receiving personal fees from Serimmune outside the submitted work. Dr. Chu has no disclosures.

As long as I can remember, children have been notoriously wasteful when dining in school cafeterias. Even those children who bring their own food often return home in the afternoon with their lunches half eaten. Not surprisingly, the food tossed out is often the healthier portion of the meal. Schools have tried a variety of strategies to curb this wastage, including using volunteer student monitors to police and encourage ecologically based recycling.

The authors of a recent study published on JAMA Network Open observed that when elementary and middle-school students were allowed a 20-minute seated lunch period they consumed more food and there was significantly less waste of fruits and vegetable compared with when the students’ lunch period was limited to 10 minutes. Interestingly, there was no difference in the beverage and entrée consumption when the lunch period was doubled.

The authors postulate that younger children may not have acquired the dexterity to feed themselves optimally in the shorter lunch period. I’m not sure I buy that argument. It may be simply that the children ate and drank their favorites first and needed a bit more time to allow their little guts to move things along. But, regardless of the explanation, the investigators’ observations deserve further study.

When I was in high school our lunch period was a full hour, which allowed me to make the half mile walk to home and back to eat a home-prepared meal. The noon hour was when school clubs and committees met and there was a full schedule of diversions to fill out the hour. I don’t recall the seated portion of the lunch period having any time restriction.

By the time my own children were in middle school, lunch periods lasted no longer than 20 minutes. I was not surprised to learn from this recent study that in some schools the seated lunch period has been shortened to 10 minutes. In some cases the truncated lunch periods are a response to space and time limitations. I fear that occasionally, educators and administrators have found it so difficult to keep young children who are accustomed to watching television while they eat engaged that the periods have been shortened to minimize the chaos.

Here in Maine, the governor has just announced plans to offer free breakfast and lunch to every student in response to a federal initiative. If we intend to make nutrition a cornerstone of the educational process this study from the University of Illinois at Urbana-Champaign suggests that we must do more than simply provide the food at no cost. We must somehow carve out more time in the day for the children to eat a healthy diet.

But, where is this time going to come from? Many school systems have already cannibalized physical education to the point that most children are not getting a healthy amount of exercise. It is unfortunate that we have come to expect public school systems to solve all of our societal ills and compensate for less-than-healthy home environments. But that is the reality. If we think nutrition and physical activity are important components of our children’s educations then we must make the time necessary to provide them.

Will this mean longer school days? And will those longer days cost money? You bet they will, but that may be the price we have to pay for healthier, better educated children.
 

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

As long as I can remember, children have been notoriously wasteful when dining in school cafeterias. Even those children who bring their own food often return home in the afternoon with their lunches half eaten. Not surprisingly, the food tossed out is often the healthier portion of the meal. Schools have tried a variety of strategies to curb this wastage, including using volunteer student monitors to police and encourage ecologically based recycling.

The authors of a recent study published on JAMA Network Open observed that when elementary and middle-school students were allowed a 20-minute seated lunch period they consumed more food and there was significantly less waste of fruits and vegetable compared with when the students’ lunch period was limited to 10 minutes. Interestingly, there was no difference in the beverage and entrée consumption when the lunch period was doubled.

The authors postulate that younger children may not have acquired the dexterity to feed themselves optimally in the shorter lunch period. I’m not sure I buy that argument. It may be simply that the children ate and drank their favorites first and needed a bit more time to allow their little guts to move things along. But, regardless of the explanation, the investigators’ observations deserve further study.

When I was in high school our lunch period was a full hour, which allowed me to make the half mile walk to home and back to eat a home-prepared meal. The noon hour was when school clubs and committees met and there was a full schedule of diversions to fill out the hour. I don’t recall the seated portion of the lunch period having any time restriction.

By the time my own children were in middle school, lunch periods lasted no longer than 20 minutes. I was not surprised to learn from this recent study that in some schools the seated lunch period has been shortened to 10 minutes. In some cases the truncated lunch periods are a response to space and time limitations. I fear that occasionally, educators and administrators have found it so difficult to keep young children who are accustomed to watching television while they eat engaged that the periods have been shortened to minimize the chaos.

Here in Maine, the governor has just announced plans to offer free breakfast and lunch to every student in response to a federal initiative. If we intend to make nutrition a cornerstone of the educational process this study from the University of Illinois at Urbana-Champaign suggests that we must do more than simply provide the food at no cost. We must somehow carve out more time in the day for the children to eat a healthy diet.

But, where is this time going to come from? Many school systems have already cannibalized physical education to the point that most children are not getting a healthy amount of exercise. It is unfortunate that we have come to expect public school systems to solve all of our societal ills and compensate for less-than-healthy home environments. But that is the reality. If we think nutrition and physical activity are important components of our children’s educations then we must make the time necessary to provide them.

Will this mean longer school days? And will those longer days cost money? You bet they will, but that may be the price we have to pay for healthier, better educated children.
 

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

As long as I can remember, children have been notoriously wasteful when dining in school cafeterias. Even those children who bring their own food often return home in the afternoon with their lunches half eaten. Not surprisingly, the food tossed out is often the healthier portion of the meal. Schools have tried a variety of strategies to curb this wastage, including using volunteer student monitors to police and encourage ecologically based recycling.

The authors of a recent study published on JAMA Network Open observed that when elementary and middle-school students were allowed a 20-minute seated lunch period they consumed more food and there was significantly less waste of fruits and vegetable compared with when the students’ lunch period was limited to 10 minutes. Interestingly, there was no difference in the beverage and entrée consumption when the lunch period was doubled.

The authors postulate that younger children may not have acquired the dexterity to feed themselves optimally in the shorter lunch period. I’m not sure I buy that argument. It may be simply that the children ate and drank their favorites first and needed a bit more time to allow their little guts to move things along. But, regardless of the explanation, the investigators’ observations deserve further study.

When I was in high school our lunch period was a full hour, which allowed me to make the half mile walk to home and back to eat a home-prepared meal. The noon hour was when school clubs and committees met and there was a full schedule of diversions to fill out the hour. I don’t recall the seated portion of the lunch period having any time restriction.

By the time my own children were in middle school, lunch periods lasted no longer than 20 minutes. I was not surprised to learn from this recent study that in some schools the seated lunch period has been shortened to 10 minutes. In some cases the truncated lunch periods are a response to space and time limitations. I fear that occasionally, educators and administrators have found it so difficult to keep young children who are accustomed to watching television while they eat engaged that the periods have been shortened to minimize the chaos.

Here in Maine, the governor has just announced plans to offer free breakfast and lunch to every student in response to a federal initiative. If we intend to make nutrition a cornerstone of the educational process this study from the University of Illinois at Urbana-Champaign suggests that we must do more than simply provide the food at no cost. We must somehow carve out more time in the day for the children to eat a healthy diet.

But, where is this time going to come from? Many school systems have already cannibalized physical education to the point that most children are not getting a healthy amount of exercise. It is unfortunate that we have come to expect public school systems to solve all of our societal ills and compensate for less-than-healthy home environments. But that is the reality. If we think nutrition and physical activity are important components of our children’s educations then we must make the time necessary to provide them.

Will this mean longer school days? And will those longer days cost money? You bet they will, but that may be the price we have to pay for healthier, better educated children.
 

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

The Diagnosis: Generalized Bullous Fixed Drug Eruption

A punch biopsy from the left thigh revealed a vacuolar interface dermatitis with full-thickness necrosis of the epidermis and a patchy lichenoid inflammatory cell infiltrate in the superficial dermis consistent with a generalized bullous fixed drug eruption (GBFDE). The patient received supportive care and methylprednisolone with improvement of symptoms.

Generalized bullous fixed drug eruption is a rare, potentially life-threatening form of a fixed drug eruption (FDE), a cutaneous drug reaction that occurs in response to a causative medication. It typically presents with welldemarcated, dusky, erythematous patches or plaques that recur in the same sites with repeat exposure.¹ The pathogenesis of FDE has been hypothesized to involve epidermal CD8+ T cells, which are activated by drug exposure and release cytotoxic molecules including Fas, Fas ligand, perforin, and granzyme B, resulting in lysis of the surrounding keratinocytes.^1-3 Common eliciting drugs include nonsteroidal anti-inflammatory drugs, antibacterial agents (particularly trimethoprim-sulfamethoxazole), barbiturates, acetaminophen, and antimalarials.1 In addition to the findings seen in FDE, GBFDE is characterized by widespread bullous skin lesions.^1-4 Typical histologic patterns seen in GBFDE are dispersed epidermal apoptotic keratinocytes, prominent dermal eosinophilic and lymphocytic infiltrates, and dermal melanophages.³ Discontinuing the causative agent and diligent prevention of re-exposure are the most important steps in management, as additional exposures can increase the number of lesions and overall severity. Symptoms typically resolve 7 to 14 days after drug discontinuation, often with postinflammatory hyperpigmentation.³

Generalized bullous fixed drug eruption presents a diagnostic challenge, as it sometimes involves the oral mucosa and can exhibit the Nikolsky sign. Thus, it often is confused with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).^1,4 Stevens-Johnson syndrome and TEN are severe cutaneous drug eruptions that also can present with diffuse bullous skin lesions. Stevens-Johnson syndrome and TEN are thought to be a spectrum of the same disease that initially presents with dusky red macules that can coalesce, develop central blistering, and lead to skin detachment.⁵ Stevens-Johnson syndrome is defined as skin detachment of less than 10% body surface area (BSA); TEN is defined as skin detachment of more than 30% BSA. Stevens-Johnson syndrome/TEN overlap syndrome includes skin detachment of 10% to 30% BSA.⁵

Causative medications overlap substantially with GBFDE and include anticonvulsants, sulfa-containing drugs, antibiotics, nonsteroidal anti-inflammatory drugs, and uric acid–lowering agents. The histology of SJS/TEN also is quite similar to GBFDE, and these entities may be indistinguishable without clinical information.⁵ Lee et al¹ found that absence of grouped necrotic keratinocytes (fire flag sign), deep inflammatory infiltrates, notable pigment incontinence, and higher eosinophil counts appear to be more common in GBFDE than SJS/TEN. Constitutional symptoms and mucosal involvement also were more frequent in SJS/TEN.

The timing of clinical presentation and medical history can be useful in differentiating between SJS/TEN and GBFDE. In SJS/TEN, drug exposure typically occurs 1 to 3 weeks before onset of symptoms vs 30 minutes to 24 hours in GBFDE.³ Additionally, a history of similar eruption in the same location is pathognomonic for GBFDE. Although GBFDE has been thought to have a better prognosis than SJS/TEN, more recent data suggest mortality rates may be similar.³ A case-control study found a mortality rate of 22% (13/58) in patients with GBFDE compared to 28% (n=170) in SJS/TEN patients.⁴

Erythema multiforme (EM) is an uncommon immunemediated disorder that typically presents as targetoid lesions with central epidermal necrosis in an acral distribution. Erythema multiforme can arise from a variety of factors, but up to 90% of cases are due to infection, most commonly herpes simplex virus; medications account for less than 10% of cases.⁶ Previously, EM has been thought to be on the same disease spectrum as SJS and TEN. It is now clear that EM is a separate entity with similar mucosal erosions but different cutaneous findings,⁶ mainly typical target lesions that differ from the atypical targets seen in SJS.

Staphylococcal scalded skin syndrome is a blistering skin disorder associated with local Staphylococcus aureus infection. It most commonly is seen in children and rarely occurs in adults who are not on dialysis. Some Staphylococcus strains produce exfoliative toxins A and B, which are serine proteases that target and cleave desmoglein 1, a mediator of keratinocyte adhesion. Staphylococcal scalded skin syndrome initially presents with erythema accentuated in the skin folds that becomes generalized. The disruption of keratinocyte adhesion leads to bullae formation in areas of erythema and diffuse sheetlike desquamation. Pathology reveals subcorneal rather than subepidermal blistering, which is seen in GBFDE and SJS/TEN. Treatment involves antistaphylococcal antibiotics and supportive care. With proper treatment, most cases resolve within 2 to 3 weeks.⁷

Mycoplasma pneumoniae–induced rash and mucositis presents with prominent mucositis and can have cutaneous findings of sparse vesiculobullous or targetoid eruption.⁸ Mycoplasma pneumoniae typically infects the lungs and is a leading cause of community-acquired pneumonia. However, a subset of patients can have extrapulmonary disease presenting as mucocutaneous eruptions, which is preceded by an approximately weeklong prodrome of fever, cough, and malaise.⁷ Mycoplasma pneumoniae–induced rash and mucositis also affect children and young patients and is more common in males.⁸

The Diagnosis: Generalized Bullous Fixed Drug Eruption

A punch biopsy from the left thigh revealed a vacuolar interface dermatitis with full-thickness necrosis of the epidermis and a patchy lichenoid inflammatory cell infiltrate in the superficial dermis consistent with a generalized bullous fixed drug eruption (GBFDE). The patient received supportive care and methylprednisolone with improvement of symptoms.

Generalized bullous fixed drug eruption is a rare, potentially life-threatening form of a fixed drug eruption (FDE), a cutaneous drug reaction that occurs in response to a causative medication. It typically presents with welldemarcated, dusky, erythematous patches or plaques that recur in the same sites with repeat exposure.¹ The pathogenesis of FDE has been hypothesized to involve epidermal CD8+ T cells, which are activated by drug exposure and release cytotoxic molecules including Fas, Fas ligand, perforin, and granzyme B, resulting in lysis of the surrounding keratinocytes.^1-3 Common eliciting drugs include nonsteroidal anti-inflammatory drugs, antibacterial agents (particularly trimethoprim-sulfamethoxazole), barbiturates, acetaminophen, and antimalarials.1 In addition to the findings seen in FDE, GBFDE is characterized by widespread bullous skin lesions.^1-4 Typical histologic patterns seen in GBFDE are dispersed epidermal apoptotic keratinocytes, prominent dermal eosinophilic and lymphocytic infiltrates, and dermal melanophages.³ Discontinuing the causative agent and diligent prevention of re-exposure are the most important steps in management, as additional exposures can increase the number of lesions and overall severity. Symptoms typically resolve 7 to 14 days after drug discontinuation, often with postinflammatory hyperpigmentation.³

Generalized bullous fixed drug eruption presents a diagnostic challenge, as it sometimes involves the oral mucosa and can exhibit the Nikolsky sign. Thus, it often is confused with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).^1,4 Stevens-Johnson syndrome and TEN are severe cutaneous drug eruptions that also can present with diffuse bullous skin lesions. Stevens-Johnson syndrome and TEN are thought to be a spectrum of the same disease that initially presents with dusky red macules that can coalesce, develop central blistering, and lead to skin detachment.⁵ Stevens-Johnson syndrome is defined as skin detachment of less than 10% body surface area (BSA); TEN is defined as skin detachment of more than 30% BSA. Stevens-Johnson syndrome/TEN overlap syndrome includes skin detachment of 10% to 30% BSA.⁵

Causative medications overlap substantially with GBFDE and include anticonvulsants, sulfa-containing drugs, antibiotics, nonsteroidal anti-inflammatory drugs, and uric acid–lowering agents. The histology of SJS/TEN also is quite similar to GBFDE, and these entities may be indistinguishable without clinical information.⁵ Lee et al¹ found that absence of grouped necrotic keratinocytes (fire flag sign), deep inflammatory infiltrates, notable pigment incontinence, and higher eosinophil counts appear to be more common in GBFDE than SJS/TEN. Constitutional symptoms and mucosal involvement also were more frequent in SJS/TEN.

The timing of clinical presentation and medical history can be useful in differentiating between SJS/TEN and GBFDE. In SJS/TEN, drug exposure typically occurs 1 to 3 weeks before onset of symptoms vs 30 minutes to 24 hours in GBFDE.³ Additionally, a history of similar eruption in the same location is pathognomonic for GBFDE. Although GBFDE has been thought to have a better prognosis than SJS/TEN, more recent data suggest mortality rates may be similar.³ A case-control study found a mortality rate of 22% (13/58) in patients with GBFDE compared to 28% (n=170) in SJS/TEN patients.⁴

Erythema multiforme (EM) is an uncommon immunemediated disorder that typically presents as targetoid lesions with central epidermal necrosis in an acral distribution. Erythema multiforme can arise from a variety of factors, but up to 90% of cases are due to infection, most commonly herpes simplex virus; medications account for less than 10% of cases.⁶ Previously, EM has been thought to be on the same disease spectrum as SJS and TEN. It is now clear that EM is a separate entity with similar mucosal erosions but different cutaneous findings,⁶ mainly typical target lesions that differ from the atypical targets seen in SJS.

Staphylococcal scalded skin syndrome is a blistering skin disorder associated with local Staphylococcus aureus infection. It most commonly is seen in children and rarely occurs in adults who are not on dialysis. Some Staphylococcus strains produce exfoliative toxins A and B, which are serine proteases that target and cleave desmoglein 1, a mediator of keratinocyte adhesion. Staphylococcal scalded skin syndrome initially presents with erythema accentuated in the skin folds that becomes generalized. The disruption of keratinocyte adhesion leads to bullae formation in areas of erythema and diffuse sheetlike desquamation. Pathology reveals subcorneal rather than subepidermal blistering, which is seen in GBFDE and SJS/TEN. Treatment involves antistaphylococcal antibiotics and supportive care. With proper treatment, most cases resolve within 2 to 3 weeks.⁷

Mycoplasma pneumoniae–induced rash and mucositis presents with prominent mucositis and can have cutaneous findings of sparse vesiculobullous or targetoid eruption.⁸ Mycoplasma pneumoniae typically infects the lungs and is a leading cause of community-acquired pneumonia. However, a subset of patients can have extrapulmonary disease presenting as mucocutaneous eruptions, which is preceded by an approximately weeklong prodrome of fever, cough, and malaise.⁷ Mycoplasma pneumoniae–induced rash and mucositis also affect children and young patients and is more common in males.⁸

The Diagnosis: Generalized Bullous Fixed Drug Eruption

A punch biopsy from the left thigh revealed a vacuolar interface dermatitis with full-thickness necrosis of the epidermis and a patchy lichenoid inflammatory cell infiltrate in the superficial dermis consistent with a generalized bullous fixed drug eruption (GBFDE). The patient received supportive care and methylprednisolone with improvement of symptoms.

Generalized bullous fixed drug eruption is a rare, potentially life-threatening form of a fixed drug eruption (FDE), a cutaneous drug reaction that occurs in response to a causative medication. It typically presents with welldemarcated, dusky, erythematous patches or plaques that recur in the same sites with repeat exposure.¹ The pathogenesis of FDE has been hypothesized to involve epidermal CD8+ T cells, which are activated by drug exposure and release cytotoxic molecules including Fas, Fas ligand, perforin, and granzyme B, resulting in lysis of the surrounding keratinocytes.^1-3 Common eliciting drugs include nonsteroidal anti-inflammatory drugs, antibacterial agents (particularly trimethoprim-sulfamethoxazole), barbiturates, acetaminophen, and antimalarials.1 In addition to the findings seen in FDE, GBFDE is characterized by widespread bullous skin lesions.^1-4 Typical histologic patterns seen in GBFDE are dispersed epidermal apoptotic keratinocytes, prominent dermal eosinophilic and lymphocytic infiltrates, and dermal melanophages.³ Discontinuing the causative agent and diligent prevention of re-exposure are the most important steps in management, as additional exposures can increase the number of lesions and overall severity. Symptoms typically resolve 7 to 14 days after drug discontinuation, often with postinflammatory hyperpigmentation.³

Generalized bullous fixed drug eruption presents a diagnostic challenge, as it sometimes involves the oral mucosa and can exhibit the Nikolsky sign. Thus, it often is confused with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).^1,4 Stevens-Johnson syndrome and TEN are severe cutaneous drug eruptions that also can present with diffuse bullous skin lesions. Stevens-Johnson syndrome and TEN are thought to be a spectrum of the same disease that initially presents with dusky red macules that can coalesce, develop central blistering, and lead to skin detachment.⁵ Stevens-Johnson syndrome is defined as skin detachment of less than 10% body surface area (BSA); TEN is defined as skin detachment of more than 30% BSA. Stevens-Johnson syndrome/TEN overlap syndrome includes skin detachment of 10% to 30% BSA.⁵

Causative medications overlap substantially with GBFDE and include anticonvulsants, sulfa-containing drugs, antibiotics, nonsteroidal anti-inflammatory drugs, and uric acid–lowering agents. The histology of SJS/TEN also is quite similar to GBFDE, and these entities may be indistinguishable without clinical information.⁵ Lee et al¹ found that absence of grouped necrotic keratinocytes (fire flag sign), deep inflammatory infiltrates, notable pigment incontinence, and higher eosinophil counts appear to be more common in GBFDE than SJS/TEN. Constitutional symptoms and mucosal involvement also were more frequent in SJS/TEN.

The timing of clinical presentation and medical history can be useful in differentiating between SJS/TEN and GBFDE. In SJS/TEN, drug exposure typically occurs 1 to 3 weeks before onset of symptoms vs 30 minutes to 24 hours in GBFDE.³ Additionally, a history of similar eruption in the same location is pathognomonic for GBFDE. Although GBFDE has been thought to have a better prognosis than SJS/TEN, more recent data suggest mortality rates may be similar.³ A case-control study found a mortality rate of 22% (13/58) in patients with GBFDE compared to 28% (n=170) in SJS/TEN patients.⁴

Erythema multiforme (EM) is an uncommon immunemediated disorder that typically presents as targetoid lesions with central epidermal necrosis in an acral distribution. Erythema multiforme can arise from a variety of factors, but up to 90% of cases are due to infection, most commonly herpes simplex virus; medications account for less than 10% of cases.⁶ Previously, EM has been thought to be on the same disease spectrum as SJS and TEN. It is now clear that EM is a separate entity with similar mucosal erosions but different cutaneous findings,⁶ mainly typical target lesions that differ from the atypical targets seen in SJS.

Staphylococcal scalded skin syndrome is a blistering skin disorder associated with local Staphylococcus aureus infection. It most commonly is seen in children and rarely occurs in adults who are not on dialysis. Some Staphylococcus strains produce exfoliative toxins A and B, which are serine proteases that target and cleave desmoglein 1, a mediator of keratinocyte adhesion. Staphylococcal scalded skin syndrome initially presents with erythema accentuated in the skin folds that becomes generalized. The disruption of keratinocyte adhesion leads to bullae formation in areas of erythema and diffuse sheetlike desquamation. Pathology reveals subcorneal rather than subepidermal blistering, which is seen in GBFDE and SJS/TEN. Treatment involves antistaphylococcal antibiotics and supportive care. With proper treatment, most cases resolve within 2 to 3 weeks.⁷

Mycoplasma pneumoniae–induced rash and mucositis presents with prominent mucositis and can have cutaneous findings of sparse vesiculobullous or targetoid eruption.⁸ Mycoplasma pneumoniae typically infects the lungs and is a leading cause of community-acquired pneumonia. However, a subset of patients can have extrapulmonary disease presenting as mucocutaneous eruptions, which is preceded by an approximately weeklong prodrome of fever, cough, and malaise.⁷ Mycoplasma pneumoniae–induced rash and mucositis also affect children and young patients and is more common in males.⁸

It was a typical, busy evening shift in the emergency department (ED) when Steve Carroll, DO, an emergency medicine physician in the Philadelphia area, noticed an odd listing on the tracking board. In the waiting room, there was someone whose chief complaint was that she needed to have surgical drains pulled.

According to the woman’s chart, she’d undergone liposuction in Miami a week before. She came bearing a letter from her surgeon to an ED physician with specific instructions on when and how to remove the drains. The surgeon had effectively relinquished all follow-up care to the woman’s local ED.

Dr. Carroll searched the name of her surgeon and found that his site “specifically advertised medical tourism,” Dr. Carroll said. The site lured patients with the idea of recovering by the beach and that a local nurse would come to their room every day.

But when Dr. Carroll told the patient that her surgeon should be the one who removes the drains, she became concerned. She didn’t know that her surgeon wasn’t providing the standard of care, he said. Somewhat appalled that a board-certified plastic surgeon would place the burden of follow-up care on an ED doctor hundreds of miles away, Dr. Carroll posted the case to Twitter and several Facebook groups.

“Yes I could refuse to take [the drains] out but that’s not patient-centered care,” Dr. Carroll wrote in a Twitter thread. “It’s unfairly shifting routine outpatient surgical followup (and liability) onto me and extra cost to [the patient].” Comments from ED physicians and sympathetic surgeons across the country flowed in. Dr. Carroll quickly realized his situation was part of a much larger problem than he’d thought.

Dr. Carroll’s patient told him that the Miami surgery cost less than undergoing the surgery locally; that’s why she’d made the trip. She’s not alone. Traveling to get the lowest price for a plastic surgery procedure has been a rising phenomenon since the early 2000s, according to the American Society of Plastic Surgeons (ASPS). Many countries are actively fostering their medical tourism industries, as are states such as Florida.

People have long traveled to get the best medical care. But “medical tourism is completely different,” said Alan Matarasso, MD, FACS, a Manhattan-based plastic surgeon and member of the ASPS Executive Committee. “People [are] traveling to get a simultaneous vacation or lower cost,” he said.

Choosing facilities on the basis of these criteria comes with myriad problems, and the quality of medical care may be lower. It’s difficult to verify the credentials of the surgeons, anesthesiologists, and facilities involved. Medical records can be in a different language, and traveling immediately after surgery increases the risk for pulmonary embolism and death, not to mention the added complications of traveling and being a surgical patient during the COVID-19 pandemic, he said.

Typically, surgeons are protective of their patients. But Murtaza Akhter, MD, an emergency medicine physician based in Miami, says it’s the opposite with the medical tourism surgeons whose patients regularly end up in his ED. “There’s almost no ownership,” he said. “Every time, [the patients] say, ‘My doctor isn’t responding,’ or they said go to the ER.” And that’s before they’ve even made it out of Miami.

The most common cosmetic surgery complications Dr. Akhter sees occur in patients who’ve undergone so-called Brazilian butt lifts. They show up in his ED face down, suffering from severe blood loss. He has them undergo a transfusion and maybe some imaging, but if they need a higher degree of care, they have to be transferred. “There’s a reason it’s cheaper,” he said.

Medical tourism mishaps are such a regular occurrence in Miami that no one flinches when the patients show up in the ED, Dr. Akhter said. He had begun to think he was overreacting to the problem until he saw Dr. Carroll’s Twitter thread.

“Since it’s daily, I just thought maybe I had gone crazy and that it’s considered normal for plastic surgeons to do this. Thanks for making me feel sane again,” Dr. Akhter tweeted in a reply to Dr. Carroll.

There are no reliable data as to of how often or where such surgeries are occurring or of patients’ outcomes. But Nicholas Genes, MD, an ED physician in Manhattan, says he sees far more postsurgical patients who traveled for their procedures than ones who underwent surgery locally. He can’t say for certain whether that’s because procedures performed by doctors in New York City have fewer complications or the physicians just handle postprocedure problems themselves.

In a 2021 systematic review of aesthetic breast surgeries performed through medical tourism, researchers found that of 171 patients who traveled for surgery, 88 (51%) had a total of 106 complications that required returning to the operating room and undergoing general anesthesia. They also found that 39% of breast augmentation implant surgeries required either a unilateral or bilateral explantation procedure after patients returned home.

The rate of complications was higher than the study authors had expected. “These are totally elective procedures,” Dr. Matarasso said. “They should be optimized.” And high rates of complications come with hefty price tags.

The cost of managing these complications, which falls to the home healthcare system or the patient themselves, can range from $5,500 (determined on the basis of data from a 2019 study in the United Kingdom) to as much as $123,000, researchers in New York City calculated, if the patient develops a complicated mycobacterium infection.

“In your effort to get a good deal or around the system, you could still end up with a lot of extensive medical bills if something goes wrong,” Dr. Genes said.
 

The liability dilemma

Many of the ED physicians Dr. Carroll heard from said that they wouldn’t have treated the woman who needed to have drains removed. Unlike the Brazilian-butt-lifts-gone-wrong in Miami or the complications Dr. Genes sees in New York City, Dr. Carroll’s patient wasn’t in a state of emergency. Most ED physicians said they would have sent her on her way to find a surgeon.

“In general, we shouldn’t be doing things we aren’t trained to do. It’s sort of a slippery slope,” Dr. Genes said. He’s comfortable with removing stitches, but for surgical drains and plastic apparatuses, “I don’t feel particularly well trained. I’d have to consult a colleague in general surgery,” he said. When he does get one of these patients, he works the phones to find a plastic surgeon who will see the patient, something he says their original plastic surgeon should have done.

“Sitting there with the patient, I felt a little bad for her,” Dr. Carroll said. “I knew if I didn’t do it, it would be weeks while she bounced around to urgent care, primary care, and finally found a surgeon.” But by removing the drains, he did shift some of the liability to himself. “If she developed a wound infection, then I’m on the hook for [that],” he said. “If I send her away, I have less liability but didn’t quite do the right thing for the patient.”

In replies to Dr. Carroll’s thread, some doctors debated whether these types of cases, particularly those in which surgeons forgo follow-up care, could be considered medical abandonment. Legal experts say that’s not exactly the case, at least it would not be the case with Dr. Carroll’s patient.

“I don’t think they’ve abandoned the patient; I think they’ve abandoned care,” said Michael Flynn, JD, professor of personal injury law at Nova Southeastern University, in Fort Lauderdale–Davie, Fla. “And that abandonment of follow-up care, if it falls below the standard of what medical professionals should do, then it’s malpractice.”

“The doctor didn’t just walk away and become unreachable,” said Bernard Black, JD, a medical malpractice attorney and law professor at Northwestern University, in Evanston, Ill. Technically, the surgeon referred the patient to the ED. Mr. Black agreed that it sounds more like a question of malpractice, “but without real damages, there’s no claim.”

Even if not illegal, sending these patients to the ED is still highly unethical, Dr. Carroll said. The authors of a 2014 article in Aesthetic Plastic Surgery concur: “It is the duty and ethical responsibility of plastic surgeons to prevent unnecessary complications following tourism medicine by adequately counseling patients, defining perioperative treatment protocols, and reporting complications to regional and specialty-specific governing bodies,” they write.

Sometimes patients need to travel, Dr. Matarasso said. Recently, three out-of-state patients came to him for procedures. Two stayed in Manhattan until their follow-up care was finished; he arranged care elsewhere for the third. It’s the operating surgeon’s job to connect patients with someone who can provide follow-up care when they go home, Dr. Matarasso said. If a surgeon doesn’t have a connection in a patient’s home city, the ASPS has a referral service to help, he said.

“My frustration was never with the patient,” Dr. Carroll said. “No one should feel bad about coming to an ED for literally anything, and I mean that. My frustration is with the surgeon who didn’t go the one extra step to arrange her follow-up.”

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

It was a typical, busy evening shift in the emergency department (ED) when Steve Carroll, DO, an emergency medicine physician in the Philadelphia area, noticed an odd listing on the tracking board. In the waiting room, there was someone whose chief complaint was that she needed to have surgical drains pulled.

According to the woman’s chart, she’d undergone liposuction in Miami a week before. She came bearing a letter from her surgeon to an ED physician with specific instructions on when and how to remove the drains. The surgeon had effectively relinquished all follow-up care to the woman’s local ED.

Dr. Carroll searched the name of her surgeon and found that his site “specifically advertised medical tourism,” Dr. Carroll said. The site lured patients with the idea of recovering by the beach and that a local nurse would come to their room every day.

But when Dr. Carroll told the patient that her surgeon should be the one who removes the drains, she became concerned. She didn’t know that her surgeon wasn’t providing the standard of care, he said. Somewhat appalled that a board-certified plastic surgeon would place the burden of follow-up care on an ED doctor hundreds of miles away, Dr. Carroll posted the case to Twitter and several Facebook groups.

“Yes I could refuse to take [the drains] out but that’s not patient-centered care,” Dr. Carroll wrote in a Twitter thread. “It’s unfairly shifting routine outpatient surgical followup (and liability) onto me and extra cost to [the patient].” Comments from ED physicians and sympathetic surgeons across the country flowed in. Dr. Carroll quickly realized his situation was part of a much larger problem than he’d thought.

Dr. Carroll’s patient told him that the Miami surgery cost less than undergoing the surgery locally; that’s why she’d made the trip. She’s not alone. Traveling to get the lowest price for a plastic surgery procedure has been a rising phenomenon since the early 2000s, according to the American Society of Plastic Surgeons (ASPS). Many countries are actively fostering their medical tourism industries, as are states such as Florida.

People have long traveled to get the best medical care. But “medical tourism is completely different,” said Alan Matarasso, MD, FACS, a Manhattan-based plastic surgeon and member of the ASPS Executive Committee. “People [are] traveling to get a simultaneous vacation or lower cost,” he said.

Choosing facilities on the basis of these criteria comes with myriad problems, and the quality of medical care may be lower. It’s difficult to verify the credentials of the surgeons, anesthesiologists, and facilities involved. Medical records can be in a different language, and traveling immediately after surgery increases the risk for pulmonary embolism and death, not to mention the added complications of traveling and being a surgical patient during the COVID-19 pandemic, he said.

Typically, surgeons are protective of their patients. But Murtaza Akhter, MD, an emergency medicine physician based in Miami, says it’s the opposite with the medical tourism surgeons whose patients regularly end up in his ED. “There’s almost no ownership,” he said. “Every time, [the patients] say, ‘My doctor isn’t responding,’ or they said go to the ER.” And that’s before they’ve even made it out of Miami.

The most common cosmetic surgery complications Dr. Akhter sees occur in patients who’ve undergone so-called Brazilian butt lifts. They show up in his ED face down, suffering from severe blood loss. He has them undergo a transfusion and maybe some imaging, but if they need a higher degree of care, they have to be transferred. “There’s a reason it’s cheaper,” he said.

Medical tourism mishaps are such a regular occurrence in Miami that no one flinches when the patients show up in the ED, Dr. Akhter said. He had begun to think he was overreacting to the problem until he saw Dr. Carroll’s Twitter thread.

“Since it’s daily, I just thought maybe I had gone crazy and that it’s considered normal for plastic surgeons to do this. Thanks for making me feel sane again,” Dr. Akhter tweeted in a reply to Dr. Carroll.

There are no reliable data as to of how often or where such surgeries are occurring or of patients’ outcomes. But Nicholas Genes, MD, an ED physician in Manhattan, says he sees far more postsurgical patients who traveled for their procedures than ones who underwent surgery locally. He can’t say for certain whether that’s because procedures performed by doctors in New York City have fewer complications or the physicians just handle postprocedure problems themselves.

In a 2021 systematic review of aesthetic breast surgeries performed through medical tourism, researchers found that of 171 patients who traveled for surgery, 88 (51%) had a total of 106 complications that required returning to the operating room and undergoing general anesthesia. They also found that 39% of breast augmentation implant surgeries required either a unilateral or bilateral explantation procedure after patients returned home.

The rate of complications was higher than the study authors had expected. “These are totally elective procedures,” Dr. Matarasso said. “They should be optimized.” And high rates of complications come with hefty price tags.

The cost of managing these complications, which falls to the home healthcare system or the patient themselves, can range from $5,500 (determined on the basis of data from a 2019 study in the United Kingdom) to as much as $123,000, researchers in New York City calculated, if the patient develops a complicated mycobacterium infection.

“In your effort to get a good deal or around the system, you could still end up with a lot of extensive medical bills if something goes wrong,” Dr. Genes said.
 

The liability dilemma

Many of the ED physicians Dr. Carroll heard from said that they wouldn’t have treated the woman who needed to have drains removed. Unlike the Brazilian-butt-lifts-gone-wrong in Miami or the complications Dr. Genes sees in New York City, Dr. Carroll’s patient wasn’t in a state of emergency. Most ED physicians said they would have sent her on her way to find a surgeon.

“In general, we shouldn’t be doing things we aren’t trained to do. It’s sort of a slippery slope,” Dr. Genes said. He’s comfortable with removing stitches, but for surgical drains and plastic apparatuses, “I don’t feel particularly well trained. I’d have to consult a colleague in general surgery,” he said. When he does get one of these patients, he works the phones to find a plastic surgeon who will see the patient, something he says their original plastic surgeon should have done.

“Sitting there with the patient, I felt a little bad for her,” Dr. Carroll said. “I knew if I didn’t do it, it would be weeks while she bounced around to urgent care, primary care, and finally found a surgeon.” But by removing the drains, he did shift some of the liability to himself. “If she developed a wound infection, then I’m on the hook for [that],” he said. “If I send her away, I have less liability but didn’t quite do the right thing for the patient.”

In replies to Dr. Carroll’s thread, some doctors debated whether these types of cases, particularly those in which surgeons forgo follow-up care, could be considered medical abandonment. Legal experts say that’s not exactly the case, at least it would not be the case with Dr. Carroll’s patient.

“I don’t think they’ve abandoned the patient; I think they’ve abandoned care,” said Michael Flynn, JD, professor of personal injury law at Nova Southeastern University, in Fort Lauderdale–Davie, Fla. “And that abandonment of follow-up care, if it falls below the standard of what medical professionals should do, then it’s malpractice.”

“The doctor didn’t just walk away and become unreachable,” said Bernard Black, JD, a medical malpractice attorney and law professor at Northwestern University, in Evanston, Ill. Technically, the surgeon referred the patient to the ED. Mr. Black agreed that it sounds more like a question of malpractice, “but without real damages, there’s no claim.”

Even if not illegal, sending these patients to the ED is still highly unethical, Dr. Carroll said. The authors of a 2014 article in Aesthetic Plastic Surgery concur: “It is the duty and ethical responsibility of plastic surgeons to prevent unnecessary complications following tourism medicine by adequately counseling patients, defining perioperative treatment protocols, and reporting complications to regional and specialty-specific governing bodies,” they write.

Sometimes patients need to travel, Dr. Matarasso said. Recently, three out-of-state patients came to him for procedures. Two stayed in Manhattan until their follow-up care was finished; he arranged care elsewhere for the third. It’s the operating surgeon’s job to connect patients with someone who can provide follow-up care when they go home, Dr. Matarasso said. If a surgeon doesn’t have a connection in a patient’s home city, the ASPS has a referral service to help, he said.

“My frustration was never with the patient,” Dr. Carroll said. “No one should feel bad about coming to an ED for literally anything, and I mean that. My frustration is with the surgeon who didn’t go the one extra step to arrange her follow-up.”

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

It was a typical, busy evening shift in the emergency department (ED) when Steve Carroll, DO, an emergency medicine physician in the Philadelphia area, noticed an odd listing on the tracking board. In the waiting room, there was someone whose chief complaint was that she needed to have surgical drains pulled.

According to the woman’s chart, she’d undergone liposuction in Miami a week before. She came bearing a letter from her surgeon to an ED physician with specific instructions on when and how to remove the drains. The surgeon had effectively relinquished all follow-up care to the woman’s local ED.

Dr. Carroll searched the name of her surgeon and found that his site “specifically advertised medical tourism,” Dr. Carroll said. The site lured patients with the idea of recovering by the beach and that a local nurse would come to their room every day.

But when Dr. Carroll told the patient that her surgeon should be the one who removes the drains, she became concerned. She didn’t know that her surgeon wasn’t providing the standard of care, he said. Somewhat appalled that a board-certified plastic surgeon would place the burden of follow-up care on an ED doctor hundreds of miles away, Dr. Carroll posted the case to Twitter and several Facebook groups.

“Yes I could refuse to take [the drains] out but that’s not patient-centered care,” Dr. Carroll wrote in a Twitter thread. “It’s unfairly shifting routine outpatient surgical followup (and liability) onto me and extra cost to [the patient].” Comments from ED physicians and sympathetic surgeons across the country flowed in. Dr. Carroll quickly realized his situation was part of a much larger problem than he’d thought.

Dr. Carroll’s patient told him that the Miami surgery cost less than undergoing the surgery locally; that’s why she’d made the trip. She’s not alone. Traveling to get the lowest price for a plastic surgery procedure has been a rising phenomenon since the early 2000s, according to the American Society of Plastic Surgeons (ASPS). Many countries are actively fostering their medical tourism industries, as are states such as Florida.

People have long traveled to get the best medical care. But “medical tourism is completely different,” said Alan Matarasso, MD, FACS, a Manhattan-based plastic surgeon and member of the ASPS Executive Committee. “People [are] traveling to get a simultaneous vacation or lower cost,” he said.

Choosing facilities on the basis of these criteria comes with myriad problems, and the quality of medical care may be lower. It’s difficult to verify the credentials of the surgeons, anesthesiologists, and facilities involved. Medical records can be in a different language, and traveling immediately after surgery increases the risk for pulmonary embolism and death, not to mention the added complications of traveling and being a surgical patient during the COVID-19 pandemic, he said.

Typically, surgeons are protective of their patients. But Murtaza Akhter, MD, an emergency medicine physician based in Miami, says it’s the opposite with the medical tourism surgeons whose patients regularly end up in his ED. “There’s almost no ownership,” he said. “Every time, [the patients] say, ‘My doctor isn’t responding,’ or they said go to the ER.” And that’s before they’ve even made it out of Miami.

The most common cosmetic surgery complications Dr. Akhter sees occur in patients who’ve undergone so-called Brazilian butt lifts. They show up in his ED face down, suffering from severe blood loss. He has them undergo a transfusion and maybe some imaging, but if they need a higher degree of care, they have to be transferred. “There’s a reason it’s cheaper,” he said.

Medical tourism mishaps are such a regular occurrence in Miami that no one flinches when the patients show up in the ED, Dr. Akhter said. He had begun to think he was overreacting to the problem until he saw Dr. Carroll’s Twitter thread.

“Since it’s daily, I just thought maybe I had gone crazy and that it’s considered normal for plastic surgeons to do this. Thanks for making me feel sane again,” Dr. Akhter tweeted in a reply to Dr. Carroll.

There are no reliable data as to of how often or where such surgeries are occurring or of patients’ outcomes. But Nicholas Genes, MD, an ED physician in Manhattan, says he sees far more postsurgical patients who traveled for their procedures than ones who underwent surgery locally. He can’t say for certain whether that’s because procedures performed by doctors in New York City have fewer complications or the physicians just handle postprocedure problems themselves.

In a 2021 systematic review of aesthetic breast surgeries performed through medical tourism, researchers found that of 171 patients who traveled for surgery, 88 (51%) had a total of 106 complications that required returning to the operating room and undergoing general anesthesia. They also found that 39% of breast augmentation implant surgeries required either a unilateral or bilateral explantation procedure after patients returned home.

The rate of complications was higher than the study authors had expected. “These are totally elective procedures,” Dr. Matarasso said. “They should be optimized.” And high rates of complications come with hefty price tags.

The cost of managing these complications, which falls to the home healthcare system or the patient themselves, can range from $5,500 (determined on the basis of data from a 2019 study in the United Kingdom) to as much as $123,000, researchers in New York City calculated, if the patient develops a complicated mycobacterium infection.

“In your effort to get a good deal or around the system, you could still end up with a lot of extensive medical bills if something goes wrong,” Dr. Genes said.
 

The liability dilemma

Many of the ED physicians Dr. Carroll heard from said that they wouldn’t have treated the woman who needed to have drains removed. Unlike the Brazilian-butt-lifts-gone-wrong in Miami or the complications Dr. Genes sees in New York City, Dr. Carroll’s patient wasn’t in a state of emergency. Most ED physicians said they would have sent her on her way to find a surgeon.

“In general, we shouldn’t be doing things we aren’t trained to do. It’s sort of a slippery slope,” Dr. Genes said. He’s comfortable with removing stitches, but for surgical drains and plastic apparatuses, “I don’t feel particularly well trained. I’d have to consult a colleague in general surgery,” he said. When he does get one of these patients, he works the phones to find a plastic surgeon who will see the patient, something he says their original plastic surgeon should have done.

“Sitting there with the patient, I felt a little bad for her,” Dr. Carroll said. “I knew if I didn’t do it, it would be weeks while she bounced around to urgent care, primary care, and finally found a surgeon.” But by removing the drains, he did shift some of the liability to himself. “If she developed a wound infection, then I’m on the hook for [that],” he said. “If I send her away, I have less liability but didn’t quite do the right thing for the patient.”

In replies to Dr. Carroll’s thread, some doctors debated whether these types of cases, particularly those in which surgeons forgo follow-up care, could be considered medical abandonment. Legal experts say that’s not exactly the case, at least it would not be the case with Dr. Carroll’s patient.

“I don’t think they’ve abandoned the patient; I think they’ve abandoned care,” said Michael Flynn, JD, professor of personal injury law at Nova Southeastern University, in Fort Lauderdale–Davie, Fla. “And that abandonment of follow-up care, if it falls below the standard of what medical professionals should do, then it’s malpractice.”

“The doctor didn’t just walk away and become unreachable,” said Bernard Black, JD, a medical malpractice attorney and law professor at Northwestern University, in Evanston, Ill. Technically, the surgeon referred the patient to the ED. Mr. Black agreed that it sounds more like a question of malpractice, “but without real damages, there’s no claim.”

Even if not illegal, sending these patients to the ED is still highly unethical, Dr. Carroll said. The authors of a 2014 article in Aesthetic Plastic Surgery concur: “It is the duty and ethical responsibility of plastic surgeons to prevent unnecessary complications following tourism medicine by adequately counseling patients, defining perioperative treatment protocols, and reporting complications to regional and specialty-specific governing bodies,” they write.

Sometimes patients need to travel, Dr. Matarasso said. Recently, three out-of-state patients came to him for procedures. Two stayed in Manhattan until their follow-up care was finished; he arranged care elsewhere for the third. It’s the operating surgeon’s job to connect patients with someone who can provide follow-up care when they go home, Dr. Matarasso said. If a surgeon doesn’t have a connection in a patient’s home city, the ASPS has a referral service to help, he said.

“My frustration was never with the patient,” Dr. Carroll said. “No one should feel bad about coming to an ED for literally anything, and I mean that. My frustration is with the surgeon who didn’t go the one extra step to arrange her follow-up.”

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

Editor’s note: In this article, we present an archetypal ethics challenge in hospital medicine. The authors, members of the SHM’s Ethics Special Interest Group and clinical ethics consultants at their respective hospitals, will comment on the questions and practical approaches for hospitalists.

Ms. S, an 82-year-old woman with severe dementia, was initially hospitalized in the ICU with acute on chronic respiratory failure. Prior to admission, Ms. S lived with her daughter, who is her primary caregiver. Ms. S is able to say her daughter’s name, and answer “yes” and “no” to simple questions. She is bed bound, incontinent of urine and feces, and dependent on her daughter for all ADLs.

This admission, Ms. S has been re-intubated 4 times for recurrent respiratory failure. The nursing staff are distressed that she is suffering physically. Her daughter requests to continue all intensive, life-prolonging treatment including mechanical ventilation and artificial nutrition.

During sign out, your colleague remarks that his grandmother was in a similar situation and that his family chose to pursue comfort care. He questions whether Ms. S has any quality of life and asks if you think further intensive care is futile.

On your first day caring for Ms. S, you contact her primary care provider. Her PCP reports that Ms. S and her daughter completed an advance directive (AD) 10 years ago which documents a preference for all life prolonging treatment.
 

Question #1: What are the ethical challenges?

Dr. Chase: In caring for Ms. S, we face a common ethical challenge: how to respect the patient’s prior preferences (autonomy) when the currently requested treatments have diminishing benefits (beneficence) and escalating harms (non-maleficence). Life-prolonging care can have diminishing returns at the end of life. Ms. S’s loss of decision-making capacity adds a layer of complexity. Her AD was completed when she was able to consider decisions about her care, and she might make different decisions in her current state of health. Shared decision-making with a surrogate can be complicated by a surrogate’s anxiety with making life-altering decisions or their desire to avoid guilt or loneliness. Health care professionals face the limits of scientific knowledge in delivering accurate prognostic estimates, probabilities of recovery, and likelihood of benefit from interventions. In addition to the guideposts of ethical principles, some hospitals have policies which advise clinicians to avoid non-beneficial care.

Such situations are emotionally intense and can trigger distress among patients, families, caregivers and health care professionals. Conscious and unconscious bias about a patient’s perceived quality of life undermines equity and can play a role in our recommendations for patients of advanced age, with cognitive impairment, and those who live with a disability.
 

Question #2: How might you meet the patient’s medical needs in line with her goals?

Dr. Khawaja: In order to provide care consistent with the patient’s goals, the first step is to clarify these goals with Ms. S’s surrogate decision-maker, her daughter. In a previously autonomous but presently incapacitated patient, the previously expressed preferences in the form of a written AD should be respected. However, the AD is only a set of preferences completed at a particular time, not medical orders. The clinician and surrogate must consider how to apply the AD to the current clinical circumstances. The clinician should verify that the clinical circumstances specified in the AD have been met and evaluate if the patient’s preferences have changed since she originally completed the AD.

Surrogates are asked to use a Substituted Judgement Standard (i.e., what would the patient choose in this situation if known). This may differ from what the surrogate wants. If not known, surrogates are asked to use the Best Interest Standard (i.e., what would bring the most net benefit to the patient by weighing benefits and risks of treatment options). I often ask the surrogate, “Tell us about your loved one.” Or, “Knowing your loved one, what do you think would be the most important for her right now?”¹

I would also caution against bias in judging quality of life in patients with dementia, and using the term “futility,” as these concepts are inherently subjective. In general, when a colleague raises the issue of futility, I begin by asking, “…futile to achieve what goal?” That can help clarify some of the disagreement as some goals can be accomplished while others cannot.

Finally, I work to include other members of our team in these discussions. The distress of nurses, social workers, and others are important to acknowledge, validate, and involve in the problem-solving process.
 

Question #3: If you were Ms. S’s hospitalist, what would you do?

Dr. Khawaja: As the hospitalist caring for Ms. S, I would use the “four boxes” model as a helpful, clinically relevant and systematic approach to managing ethical concerns.²

This “four boxes” model gives us a practical framework to address these ethical principles by asking questions in four domains.

Medical indications: What is the nature of her current illness, and is it reversible or not? What is the probability of success of treatment options like mechanical ventilation? Are there adverse effects of treatment?

Patient preferences: Since Ms. S lacks capacity, does her daughter understand the benefits and burdens of treatment? What are the goals of treatment? Prolonging life? Minimizing discomfort? Spending time with loved ones? What burdens would the patient be willing to endure to reach her goals?

Quality of life: What would the patient’s quality of life be with and without the treatments?

Contextual features: My priorities would be building a relationship of trust with Ms. S’s daughter – by educating her about her mother’s clinical status, addressing her concerns and questions, and supporting her as we work through patient-centered decisions about what is best for her mother. Honest communication is a must, even if it means acknowledging uncertainties about the course of disease and prognosis.

These are not easy decisions for surrogates to make. They should be given time to process information and to make what they believe are the best decisions for their loved ones. It is critical for clinicians to provide honest and complete clinical information and to avoid value judgments, bias, or unreasonable time pressure. While one-on-one conversations are central, I find that multidisciplinary meetings allow all stakeholders to ask and answer vital questions and ideally to reach consensus in treatment planning.

Dr. Chase: In caring for Ms. S, I would use a structured approach to discussions with her daughter, such as the “SPIKES” protocol.³ Using open ended questions, I would ask about the patient’s and her daughter’s goals, values, and fears and provide support about the responsibility for shared-decision making and the difficulty of uncertainty. Reflecting statements can help in confirming understanding and showing attention (e.g. “I hear that avoiding discomfort would be important to your mother.”)

I find it helpful to emphasize my commitment to honesty and non-abandonment (a common fear among patients and families). By offering to provide recommendations about both disease-directed and palliative, comfort-focused interventions, the patient’s daughter has an opportunity to engage voluntarily in discussion. When asked about care that may have marginal benefit, I suggest time-limited trials.⁴ I do not offer non-beneficial treatments and if asked about such treatments, I note the underlying motive and why the treatment is not feasible (“I see that you are hoping that your mother will live longer, but I am concerned that tube feeding will not help because…”), offer preferable alternatives, and leave space for questions and emotions. It is important not to force a premature resolution of the situation through unilateral or coercive decisions⁵ (i.e., going off service does not mean I have to wrap up the existential crisis which is occurring.) A broader challenge is the grief and other emotions which accompany illness and death. I can neither prevent death nor grief, but I can offer my professional guidance and provide a supportive space for the patient and family to experience this transition. By acknowledging this, I center myself with the patient and family and we can work together toward a common goal of providing compassionate and ethical care.

Dr. Chase is associate professor, Department of Family and Community Medicine, University of California San Francisco; and co-chair, Ethics Committee, San Francisco General Hospital. Dr. Khawaja is assistant professor, Department of Internal Medicine, Baylor College of Medicine, Houston, and a member of the Ethics Committee of the Society of General Internal Medicine.

References

1. Sulmasy DP, Snyder L. Substituted interests and best judgments: an integrated model of surrogate decision making. JAMA. 2010 Nov 3;304(17):1946-7. doi: 10.1001/jama.2010.159.

2. Jonsen AR, Siegler M, Winslade WJ. Clinical ethics: A practical approach to ethical decisions in clinical medicine. 6th ed. New York: McGraw Hill Medical; 2006.

3. Baile WF, et al. SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer. Oncologist. 2000;5(4):302–311. doi: 10.1634/theoncologist.5-4-302.

4. Chang DW, et al. Evaluation of time-limited trials among critically ill patients with advanced medical illnesses and reduction of nonbeneficial ICU treatments. JAMA Intern Med. 2021;181(6):786–794. doi: 10.1001/jamainternmed.2021.1000.

5. Sedig, L. What’s the role of autonomy in patient-and family-centered care when patients and family members don’t agree? AMA J Ethics. 2016;18(1):12-17. doi: 10.1001/journalofethics.2017.18.1.ecas2-1601.

Editor’s note: In this article, we present an archetypal ethics challenge in hospital medicine. The authors, members of the SHM’s Ethics Special Interest Group and clinical ethics consultants at their respective hospitals, will comment on the questions and practical approaches for hospitalists.

Ms. S, an 82-year-old woman with severe dementia, was initially hospitalized in the ICU with acute on chronic respiratory failure. Prior to admission, Ms. S lived with her daughter, who is her primary caregiver. Ms. S is able to say her daughter’s name, and answer “yes” and “no” to simple questions. She is bed bound, incontinent of urine and feces, and dependent on her daughter for all ADLs.

This admission, Ms. S has been re-intubated 4 times for recurrent respiratory failure. The nursing staff are distressed that she is suffering physically. Her daughter requests to continue all intensive, life-prolonging treatment including mechanical ventilation and artificial nutrition.

During sign out, your colleague remarks that his grandmother was in a similar situation and that his family chose to pursue comfort care. He questions whether Ms. S has any quality of life and asks if you think further intensive care is futile.

On your first day caring for Ms. S, you contact her primary care provider. Her PCP reports that Ms. S and her daughter completed an advance directive (AD) 10 years ago which documents a preference for all life prolonging treatment.
 

Question #1: What are the ethical challenges?

Dr. Chase: In caring for Ms. S, we face a common ethical challenge: how to respect the patient’s prior preferences (autonomy) when the currently requested treatments have diminishing benefits (beneficence) and escalating harms (non-maleficence). Life-prolonging care can have diminishing returns at the end of life. Ms. S’s loss of decision-making capacity adds a layer of complexity. Her AD was completed when she was able to consider decisions about her care, and she might make different decisions in her current state of health. Shared decision-making with a surrogate can be complicated by a surrogate’s anxiety with making life-altering decisions or their desire to avoid guilt or loneliness. Health care professionals face the limits of scientific knowledge in delivering accurate prognostic estimates, probabilities of recovery, and likelihood of benefit from interventions. In addition to the guideposts of ethical principles, some hospitals have policies which advise clinicians to avoid non-beneficial care.

Such situations are emotionally intense and can trigger distress among patients, families, caregivers and health care professionals. Conscious and unconscious bias about a patient’s perceived quality of life undermines equity and can play a role in our recommendations for patients of advanced age, with cognitive impairment, and those who live with a disability.
 

Question #2: How might you meet the patient’s medical needs in line with her goals?

Dr. Khawaja: In order to provide care consistent with the patient’s goals, the first step is to clarify these goals with Ms. S’s surrogate decision-maker, her daughter. In a previously autonomous but presently incapacitated patient, the previously expressed preferences in the form of a written AD should be respected. However, the AD is only a set of preferences completed at a particular time, not medical orders. The clinician and surrogate must consider how to apply the AD to the current clinical circumstances. The clinician should verify that the clinical circumstances specified in the AD have been met and evaluate if the patient’s preferences have changed since she originally completed the AD.

Surrogates are asked to use a Substituted Judgement Standard (i.e., what would the patient choose in this situation if known). This may differ from what the surrogate wants. If not known, surrogates are asked to use the Best Interest Standard (i.e., what would bring the most net benefit to the patient by weighing benefits and risks of treatment options). I often ask the surrogate, “Tell us about your loved one.” Or, “Knowing your loved one, what do you think would be the most important for her right now?”¹

I would also caution against bias in judging quality of life in patients with dementia, and using the term “futility,” as these concepts are inherently subjective. In general, when a colleague raises the issue of futility, I begin by asking, “…futile to achieve what goal?” That can help clarify some of the disagreement as some goals can be accomplished while others cannot.

Finally, I work to include other members of our team in these discussions. The distress of nurses, social workers, and others are important to acknowledge, validate, and involve in the problem-solving process.
 

Question #3: If you were Ms. S’s hospitalist, what would you do?

Dr. Khawaja: As the hospitalist caring for Ms. S, I would use the “four boxes” model as a helpful, clinically relevant and systematic approach to managing ethical concerns.²

This “four boxes” model gives us a practical framework to address these ethical principles by asking questions in four domains.

Medical indications: What is the nature of her current illness, and is it reversible or not? What is the probability of success of treatment options like mechanical ventilation? Are there adverse effects of treatment?

Patient preferences: Since Ms. S lacks capacity, does her daughter understand the benefits and burdens of treatment? What are the goals of treatment? Prolonging life? Minimizing discomfort? Spending time with loved ones? What burdens would the patient be willing to endure to reach her goals?

Quality of life: What would the patient’s quality of life be with and without the treatments?

Contextual features: My priorities would be building a relationship of trust with Ms. S’s daughter – by educating her about her mother’s clinical status, addressing her concerns and questions, and supporting her as we work through patient-centered decisions about what is best for her mother. Honest communication is a must, even if it means acknowledging uncertainties about the course of disease and prognosis.

These are not easy decisions for surrogates to make. They should be given time to process information and to make what they believe are the best decisions for their loved ones. It is critical for clinicians to provide honest and complete clinical information and to avoid value judgments, bias, or unreasonable time pressure. While one-on-one conversations are central, I find that multidisciplinary meetings allow all stakeholders to ask and answer vital questions and ideally to reach consensus in treatment planning.

Dr. Chase: In caring for Ms. S, I would use a structured approach to discussions with her daughter, such as the “SPIKES” protocol.³ Using open ended questions, I would ask about the patient’s and her daughter’s goals, values, and fears and provide support about the responsibility for shared-decision making and the difficulty of uncertainty. Reflecting statements can help in confirming understanding and showing attention (e.g. “I hear that avoiding discomfort would be important to your mother.”)

I find it helpful to emphasize my commitment to honesty and non-abandonment (a common fear among patients and families). By offering to provide recommendations about both disease-directed and palliative, comfort-focused interventions, the patient’s daughter has an opportunity to engage voluntarily in discussion. When asked about care that may have marginal benefit, I suggest time-limited trials.⁴ I do not offer non-beneficial treatments and if asked about such treatments, I note the underlying motive and why the treatment is not feasible (“I see that you are hoping that your mother will live longer, but I am concerned that tube feeding will not help because…”), offer preferable alternatives, and leave space for questions and emotions. It is important not to force a premature resolution of the situation through unilateral or coercive decisions⁵ (i.e., going off service does not mean I have to wrap up the existential crisis which is occurring.) A broader challenge is the grief and other emotions which accompany illness and death. I can neither prevent death nor grief, but I can offer my professional guidance and provide a supportive space for the patient and family to experience this transition. By acknowledging this, I center myself with the patient and family and we can work together toward a common goal of providing compassionate and ethical care.

Dr. Chase is associate professor, Department of Family and Community Medicine, University of California San Francisco; and co-chair, Ethics Committee, San Francisco General Hospital. Dr. Khawaja is assistant professor, Department of Internal Medicine, Baylor College of Medicine, Houston, and a member of the Ethics Committee of the Society of General Internal Medicine.

References

1. Sulmasy DP, Snyder L. Substituted interests and best judgments: an integrated model of surrogate decision making. JAMA. 2010 Nov 3;304(17):1946-7. doi: 10.1001/jama.2010.159.

2. Jonsen AR, Siegler M, Winslade WJ. Clinical ethics: A practical approach to ethical decisions in clinical medicine. 6th ed. New York: McGraw Hill Medical; 2006.

3. Baile WF, et al. SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer. Oncologist. 2000;5(4):302–311. doi: 10.1634/theoncologist.5-4-302.

4. Chang DW, et al. Evaluation of time-limited trials among critically ill patients with advanced medical illnesses and reduction of nonbeneficial ICU treatments. JAMA Intern Med. 2021;181(6):786–794. doi: 10.1001/jamainternmed.2021.1000.

5. Sedig, L. What’s the role of autonomy in patient-and family-centered care when patients and family members don’t agree? AMA J Ethics. 2016;18(1):12-17. doi: 10.1001/journalofethics.2017.18.1.ecas2-1601.

Editor’s note: In this article, we present an archetypal ethics challenge in hospital medicine. The authors, members of the SHM’s Ethics Special Interest Group and clinical ethics consultants at their respective hospitals, will comment on the questions and practical approaches for hospitalists.

Ms. S, an 82-year-old woman with severe dementia, was initially hospitalized in the ICU with acute on chronic respiratory failure. Prior to admission, Ms. S lived with her daughter, who is her primary caregiver. Ms. S is able to say her daughter’s name, and answer “yes” and “no” to simple questions. She is bed bound, incontinent of urine and feces, and dependent on her daughter for all ADLs.

This admission, Ms. S has been re-intubated 4 times for recurrent respiratory failure. The nursing staff are distressed that she is suffering physically. Her daughter requests to continue all intensive, life-prolonging treatment including mechanical ventilation and artificial nutrition.

During sign out, your colleague remarks that his grandmother was in a similar situation and that his family chose to pursue comfort care. He questions whether Ms. S has any quality of life and asks if you think further intensive care is futile.

On your first day caring for Ms. S, you contact her primary care provider. Her PCP reports that Ms. S and her daughter completed an advance directive (AD) 10 years ago which documents a preference for all life prolonging treatment.
 

Question #1: What are the ethical challenges?

Dr. Chase: In caring for Ms. S, we face a common ethical challenge: how to respect the patient’s prior preferences (autonomy) when the currently requested treatments have diminishing benefits (beneficence) and escalating harms (non-maleficence). Life-prolonging care can have diminishing returns at the end of life. Ms. S’s loss of decision-making capacity adds a layer of complexity. Her AD was completed when she was able to consider decisions about her care, and she might make different decisions in her current state of health. Shared decision-making with a surrogate can be complicated by a surrogate’s anxiety with making life-altering decisions or their desire to avoid guilt or loneliness. Health care professionals face the limits of scientific knowledge in delivering accurate prognostic estimates, probabilities of recovery, and likelihood of benefit from interventions. In addition to the guideposts of ethical principles, some hospitals have policies which advise clinicians to avoid non-beneficial care.

Such situations are emotionally intense and can trigger distress among patients, families, caregivers and health care professionals. Conscious and unconscious bias about a patient’s perceived quality of life undermines equity and can play a role in our recommendations for patients of advanced age, with cognitive impairment, and those who live with a disability.
 

Question #2: How might you meet the patient’s medical needs in line with her goals?

Dr. Khawaja: In order to provide care consistent with the patient’s goals, the first step is to clarify these goals with Ms. S’s surrogate decision-maker, her daughter. In a previously autonomous but presently incapacitated patient, the previously expressed preferences in the form of a written AD should be respected. However, the AD is only a set of preferences completed at a particular time, not medical orders. The clinician and surrogate must consider how to apply the AD to the current clinical circumstances. The clinician should verify that the clinical circumstances specified in the AD have been met and evaluate if the patient’s preferences have changed since she originally completed the AD.

Surrogates are asked to use a Substituted Judgement Standard (i.e., what would the patient choose in this situation if known). This may differ from what the surrogate wants. If not known, surrogates are asked to use the Best Interest Standard (i.e., what would bring the most net benefit to the patient by weighing benefits and risks of treatment options). I often ask the surrogate, “Tell us about your loved one.” Or, “Knowing your loved one, what do you think would be the most important for her right now?”¹

I would also caution against bias in judging quality of life in patients with dementia, and using the term “futility,” as these concepts are inherently subjective. In general, when a colleague raises the issue of futility, I begin by asking, “…futile to achieve what goal?” That can help clarify some of the disagreement as some goals can be accomplished while others cannot.

Finally, I work to include other members of our team in these discussions. The distress of nurses, social workers, and others are important to acknowledge, validate, and involve in the problem-solving process.
 

Question #3: If you were Ms. S’s hospitalist, what would you do?

Dr. Khawaja: As the hospitalist caring for Ms. S, I would use the “four boxes” model as a helpful, clinically relevant and systematic approach to managing ethical concerns.²

This “four boxes” model gives us a practical framework to address these ethical principles by asking questions in four domains.

Medical indications: What is the nature of her current illness, and is it reversible or not? What is the probability of success of treatment options like mechanical ventilation? Are there adverse effects of treatment?

Patient preferences: Since Ms. S lacks capacity, does her daughter understand the benefits and burdens of treatment? What are the goals of treatment? Prolonging life? Minimizing discomfort? Spending time with loved ones? What burdens would the patient be willing to endure to reach her goals?

Quality of life: What would the patient’s quality of life be with and without the treatments?

Contextual features: My priorities would be building a relationship of trust with Ms. S’s daughter – by educating her about her mother’s clinical status, addressing her concerns and questions, and supporting her as we work through patient-centered decisions about what is best for her mother. Honest communication is a must, even if it means acknowledging uncertainties about the course of disease and prognosis.

These are not easy decisions for surrogates to make. They should be given time to process information and to make what they believe are the best decisions for their loved ones. It is critical for clinicians to provide honest and complete clinical information and to avoid value judgments, bias, or unreasonable time pressure. While one-on-one conversations are central, I find that multidisciplinary meetings allow all stakeholders to ask and answer vital questions and ideally to reach consensus in treatment planning.

Dr. Chase: In caring for Ms. S, I would use a structured approach to discussions with her daughter, such as the “SPIKES” protocol.³ Using open ended questions, I would ask about the patient’s and her daughter’s goals, values, and fears and provide support about the responsibility for shared-decision making and the difficulty of uncertainty. Reflecting statements can help in confirming understanding and showing attention (e.g. “I hear that avoiding discomfort would be important to your mother.”)

I find it helpful to emphasize my commitment to honesty and non-abandonment (a common fear among patients and families). By offering to provide recommendations about both disease-directed and palliative, comfort-focused interventions, the patient’s daughter has an opportunity to engage voluntarily in discussion. When asked about care that may have marginal benefit, I suggest time-limited trials.⁴ I do not offer non-beneficial treatments and if asked about such treatments, I note the underlying motive and why the treatment is not feasible (“I see that you are hoping that your mother will live longer, but I am concerned that tube feeding will not help because…”), offer preferable alternatives, and leave space for questions and emotions. It is important not to force a premature resolution of the situation through unilateral or coercive decisions⁵ (i.e., going off service does not mean I have to wrap up the existential crisis which is occurring.) A broader challenge is the grief and other emotions which accompany illness and death. I can neither prevent death nor grief, but I can offer my professional guidance and provide a supportive space for the patient and family to experience this transition. By acknowledging this, I center myself with the patient and family and we can work together toward a common goal of providing compassionate and ethical care.

Dr. Chase is associate professor, Department of Family and Community Medicine, University of California San Francisco; and co-chair, Ethics Committee, San Francisco General Hospital. Dr. Khawaja is assistant professor, Department of Internal Medicine, Baylor College of Medicine, Houston, and a member of the Ethics Committee of the Society of General Internal Medicine.

References

1. Sulmasy DP, Snyder L. Substituted interests and best judgments: an integrated model of surrogate decision making. JAMA. 2010 Nov 3;304(17):1946-7. doi: 10.1001/jama.2010.159.

2. Jonsen AR, Siegler M, Winslade WJ. Clinical ethics: A practical approach to ethical decisions in clinical medicine. 6th ed. New York: McGraw Hill Medical; 2006.

3. Baile WF, et al. SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer. Oncologist. 2000;5(4):302–311. doi: 10.1634/theoncologist.5-4-302.

4. Chang DW, et al. Evaluation of time-limited trials among critically ill patients with advanced medical illnesses and reduction of nonbeneficial ICU treatments. JAMA Intern Med. 2021;181(6):786–794. doi: 10.1001/jamainternmed.2021.1000.

5. Sedig, L. What’s the role of autonomy in patient-and family-centered care when patients and family members don’t agree? AMA J Ethics. 2016;18(1):12-17. doi: 10.1001/journalofethics.2017.18.1.ecas2-1601.