Boston dietitian Katarina Mollo, MEd, RDN, LDN, has virtually no memory of life without celiac disease (CD). Diagnosed at age 4, Dr. Mollo has been on a gluten-free diet for 41 years, which she says has kept her healthy and may also be why she hasn’t developed other autoimmune diseases. It’s also played a part in her thinking about screening patients with CD.

“I think [physicians] should definitely be screening people with celiac disease for autoimmune disorders, especially if they see things like anemia or if a child has dropped on the growth chart and has nutrient deficiencies,” said Dr. Mollo, whose daughter also has the disease. “I would recommend that they see someone who specializes in celiac disease so they can get monitored and have regular follow-up checks for nutrient deficiencies and other autoimmune disorders.”

Dr. Mollo’s views on screening are echoed by many CD specialists and physicians, who cite multiple studies that have found that people with the disease face higher risks for diabetes, thyroid conditions, arthritis, and other autoimmune disorders.

Gastroenterologist Alessio Fasano, MD, with Massachusetts General Hospital, Boston, said there has been a “shift in the paradigm in thinking” about cross-screening for CD and autoimmune disorders. As result, he believes the answer to the question of whether to routinely do so is a no-brainer.

“The bottom line is, if you have CD, it [should be] routine that during your annual follow-ups you check for the possibility of the onset of other autoimmune disease. And people with other autoimmune diseases, like type 1 diabetes, should also be screened for CD because of the comorbidity,” said Dr. Fasano, professor of pediatrics and gastroenterology at Harvard Medical School and professor of nutrition at the Harvard School of Public Health, both in Boston. “This is what we call good clinical practice.”
 

Screening, despite lack of consensus guidelines

Other CD specialists differ on the need for universal cross-screening but agree that, at least in some cases, people with one autoimmune disorder should be tested for others.

Jolanda Denham, MD, a pediatric gastroenterologist affiliated with Nemours Children’s Hospital in Orlando, routinely recommends that her patients with CD be screened for certain autoimmune disorders – such as type 1 diabetes and autoimmune thyroid and liver diseases – even though medical organizations have not developed clear consensus or standard guidelines on cross-screening.

“There currently is no evidence to support the screening of celiac patients for all autoimmune and rheumatologic disorders,” she said. “It is true that celiac disease is an autoimmune disorder, and as such, there is a definite increased risk of these disorders in patients with celiac disease and vice versa.”

Echoing Dr. Denham, New York–based gastroenterologist Benjamin Lebwohl, MD, president of the Society for the Study of Celiac Disease, urges physicians to look beyond consensus guidelines and to err on the side of caution and make the best decisions for their patients on a case-by-case basis.

“Given the increased risk of certain autoimmune conditions in people with celiac disease, it behooves physicians to have a low threshold to evaluate for these conditions if any suggestive symptoms are present,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University, New York.

“Whether to screen for these conditions among people who are entirely without symptoms is less certain, and there is no consensus on that. But it is reasonable and common to include some basic tests with annual blood work, such as thyroid function and a liver profile, since both autoimmune thyroid disease and autoimmune liver disease can be silent early on and the patient would potentially benefit from identification and treatment of these conditions,” he said.

The American Diabetes Association and the International Society of Pediatric and Adolescent Diabetes do recommend that people with diabetes be screened for CD years after diagnosis, noted Robert Rapaport, MD, a pediatric endocrinologist, with Kravis Children’s Hospital, New York. But in a study published in 2021, he and colleagues found that this wasn’t occurring, which prompted them to recommend yearly screening.

“There is a consensus that in children with type 1 diabetes, we screen them for other autoimmune disorders, specifically for thyroid disease and celiac disease,” said Dr. Rapaport, who is also Emma Elizabeth Sullivan Professor of Pediatric Endocrinology and Diabetes at Icahn School of Medicine at Mount Sinai, New York. “But there is no consensus going the other way – for patients with celiac disease, what other autoimmune conditions they should be screened for.”

This hasn’t kept some doctors from extending cross-screening efforts to their patients.

“At our center, we screen ... for thyroid disease and autoimmune liver disease as part of routine healthcare maintenance for our celiac disease patients. We discuss symptoms of diabetes and send screening with [hemoglobin] A1c for anyone who has symptoms,” said Lui Edwin, MD, a pediatric gastroenterologist with Children’s Hospital Colorado, Aurora, and director of the Colorado Center for Celiac Disease, who delivered a lecture on CD-autoimmune screening at the International Celiac Disease Symposium in October.

“It is definitely worth screening for celiac disease in [those with] other autoimmune disorders,” Dr. Edwin added.

“The symptoms can be very heterogeneous. Diagnosing and treating celiac disease can make a huge impact with respect to symptoms, quality of life, and preventing disease-related complications,” he said.
 

Mounting evidence linking CD to autoimmune disorders

Many studies have linked CD to a variety of other autoimmune disorders. The association could be due to common genetic factors or because CD might lead to such conditions. Researchers have found that people diagnosed with CD later in life are more likely to develop other autoimmune disorders.

Going gluten free has preventive advantages

In a landmark 2012 study, researchers with the Celiac Disease Center at Columbia University stopped short of recommending routine screening for the general public or asymptomatic individuals in high-prevalence groups. But they concluded that more screening of symptomatic individuals – and close relatives – would speed treatment for those with more than one autoimmune disorder.

They also noted that some studies have found that a gluten-free diet might help prevent the development of other autoimmune disorders.

Marisa Gallant Stahl, MD, a gastroenterologist with Children’s Hospital Colorado, agreed that it is important that physicians keep gluten-free diets in mind when determining which patients to cross-screen.

“The literature is mixed, but some studies suggest that treating celiac disease with a gluten-free diet actually augments the treatment and control of other autoimmune disorders [and] adherence to a gluten-free diet does reduce the risk of cancer associated with celiac disease,” she said.

Dr. Denham agreed. “Strict adherence to a gluten-free diet definitely protects against the development of enteropathy-associated T-cell lymphoma but may be protective against non-Hodgkin’s lymphoma and adenocarcinoma of the small intestine as well. All three are associated with long-term nonadherence to a gluten-free diet.”

She also noted that a gluten-free diet may help people with CD manage other autoimmune disorders, which can be complicated by CD.

“Good control of celiac disease will help prevent complications that can worsen symptoms and outcomes of concomitant autoimmune and rheumatologic disorders,” she said.
 

Other factors to consider

Dr. Fasano added that autoimmune disorders can be complicated by CD in cases in which oral medications or healthful foods are not properly absorbed in the intestines.

“For example, with Hashimoto’s disease, if you have hormone replacement with oral treatments and your intestines are not 100% functional because you have inflammation, then you may have a problem [with] the absorption of medications like levothyroxine,” he said.

“It’s the same story with diabetes. You don’t take insulin by mouth, but glucose [control] strongly depends on several factors, mostly what comes from the diet, and if it’s erratic, that can be a problem. ... So, the treatment of autoimmune diseases can be influenced by celiac disease,” he said.

In addition, Dr. Fasano and others believe that people with CD and other autoimmune disorders should be managed by a team of experts who can personalize the care on the basis of specific needs of the individual patient. These should include specialists, dietitians, mental health counselors, and family social workers.

“It has to be a multidisciplinary approach to maintain the good health of an individual,” Dr. Fasano said. “Celiac disease is the quintessential example in which the primary care physician needs to be the quarterback of the team, the patient is active in his or her health, and [specialists] not only deliver personalized care but also preventive intervention, particularly the prevention of comorbidities.”

Financial disclosures for those quoted in this article were not available at the time of publication.

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

Boston dietitian Katarina Mollo, MEd, RDN, LDN, has virtually no memory of life without celiac disease (CD). Diagnosed at age 4, Dr. Mollo has been on a gluten-free diet for 41 years, which she says has kept her healthy and may also be why she hasn’t developed other autoimmune diseases. It’s also played a part in her thinking about screening patients with CD.

“I think [physicians] should definitely be screening people with celiac disease for autoimmune disorders, especially if they see things like anemia or if a child has dropped on the growth chart and has nutrient deficiencies,” said Dr. Mollo, whose daughter also has the disease. “I would recommend that they see someone who specializes in celiac disease so they can get monitored and have regular follow-up checks for nutrient deficiencies and other autoimmune disorders.”

Dr. Mollo’s views on screening are echoed by many CD specialists and physicians, who cite multiple studies that have found that people with the disease face higher risks for diabetes, thyroid conditions, arthritis, and other autoimmune disorders.

Gastroenterologist Alessio Fasano, MD, with Massachusetts General Hospital, Boston, said there has been a “shift in the paradigm in thinking” about cross-screening for CD and autoimmune disorders. As result, he believes the answer to the question of whether to routinely do so is a no-brainer.

“The bottom line is, if you have CD, it [should be] routine that during your annual follow-ups you check for the possibility of the onset of other autoimmune disease. And people with other autoimmune diseases, like type 1 diabetes, should also be screened for CD because of the comorbidity,” said Dr. Fasano, professor of pediatrics and gastroenterology at Harvard Medical School and professor of nutrition at the Harvard School of Public Health, both in Boston. “This is what we call good clinical practice.”
 

Screening, despite lack of consensus guidelines

Other CD specialists differ on the need for universal cross-screening but agree that, at least in some cases, people with one autoimmune disorder should be tested for others.

Jolanda Denham, MD, a pediatric gastroenterologist affiliated with Nemours Children’s Hospital in Orlando, routinely recommends that her patients with CD be screened for certain autoimmune disorders – such as type 1 diabetes and autoimmune thyroid and liver diseases – even though medical organizations have not developed clear consensus or standard guidelines on cross-screening.

“There currently is no evidence to support the screening of celiac patients for all autoimmune and rheumatologic disorders,” she said. “It is true that celiac disease is an autoimmune disorder, and as such, there is a definite increased risk of these disorders in patients with celiac disease and vice versa.”

Echoing Dr. Denham, New York–based gastroenterologist Benjamin Lebwohl, MD, president of the Society for the Study of Celiac Disease, urges physicians to look beyond consensus guidelines and to err on the side of caution and make the best decisions for their patients on a case-by-case basis.

“Given the increased risk of certain autoimmune conditions in people with celiac disease, it behooves physicians to have a low threshold to evaluate for these conditions if any suggestive symptoms are present,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University, New York.

“Whether to screen for these conditions among people who are entirely without symptoms is less certain, and there is no consensus on that. But it is reasonable and common to include some basic tests with annual blood work, such as thyroid function and a liver profile, since both autoimmune thyroid disease and autoimmune liver disease can be silent early on and the patient would potentially benefit from identification and treatment of these conditions,” he said.

The American Diabetes Association and the International Society of Pediatric and Adolescent Diabetes do recommend that people with diabetes be screened for CD years after diagnosis, noted Robert Rapaport, MD, a pediatric endocrinologist, with Kravis Children’s Hospital, New York. But in a study published in 2021, he and colleagues found that this wasn’t occurring, which prompted them to recommend yearly screening.

“There is a consensus that in children with type 1 diabetes, we screen them for other autoimmune disorders, specifically for thyroid disease and celiac disease,” said Dr. Rapaport, who is also Emma Elizabeth Sullivan Professor of Pediatric Endocrinology and Diabetes at Icahn School of Medicine at Mount Sinai, New York. “But there is no consensus going the other way – for patients with celiac disease, what other autoimmune conditions they should be screened for.”

This hasn’t kept some doctors from extending cross-screening efforts to their patients.

“At our center, we screen ... for thyroid disease and autoimmune liver disease as part of routine healthcare maintenance for our celiac disease patients. We discuss symptoms of diabetes and send screening with [hemoglobin] A1c for anyone who has symptoms,” said Lui Edwin, MD, a pediatric gastroenterologist with Children’s Hospital Colorado, Aurora, and director of the Colorado Center for Celiac Disease, who delivered a lecture on CD-autoimmune screening at the International Celiac Disease Symposium in October.

“It is definitely worth screening for celiac disease in [those with] other autoimmune disorders,” Dr. Edwin added.

“The symptoms can be very heterogeneous. Diagnosing and treating celiac disease can make a huge impact with respect to symptoms, quality of life, and preventing disease-related complications,” he said.
 

Mounting evidence linking CD to autoimmune disorders

Many studies have linked CD to a variety of other autoimmune disorders. The association could be due to common genetic factors or because CD might lead to such conditions. Researchers have found that people diagnosed with CD later in life are more likely to develop other autoimmune disorders.

Going gluten free has preventive advantages

In a landmark 2012 study, researchers with the Celiac Disease Center at Columbia University stopped short of recommending routine screening for the general public or asymptomatic individuals in high-prevalence groups. But they concluded that more screening of symptomatic individuals – and close relatives – would speed treatment for those with more than one autoimmune disorder.

They also noted that some studies have found that a gluten-free diet might help prevent the development of other autoimmune disorders.

Marisa Gallant Stahl, MD, a gastroenterologist with Children’s Hospital Colorado, agreed that it is important that physicians keep gluten-free diets in mind when determining which patients to cross-screen.

“The literature is mixed, but some studies suggest that treating celiac disease with a gluten-free diet actually augments the treatment and control of other autoimmune disorders [and] adherence to a gluten-free diet does reduce the risk of cancer associated with celiac disease,” she said.

Dr. Denham agreed. “Strict adherence to a gluten-free diet definitely protects against the development of enteropathy-associated T-cell lymphoma but may be protective against non-Hodgkin’s lymphoma and adenocarcinoma of the small intestine as well. All three are associated with long-term nonadherence to a gluten-free diet.”

She also noted that a gluten-free diet may help people with CD manage other autoimmune disorders, which can be complicated by CD.

“Good control of celiac disease will help prevent complications that can worsen symptoms and outcomes of concomitant autoimmune and rheumatologic disorders,” she said.
 

Other factors to consider

Dr. Fasano added that autoimmune disorders can be complicated by CD in cases in which oral medications or healthful foods are not properly absorbed in the intestines.

“For example, with Hashimoto’s disease, if you have hormone replacement with oral treatments and your intestines are not 100% functional because you have inflammation, then you may have a problem [with] the absorption of medications like levothyroxine,” he said.

“It’s the same story with diabetes. You don’t take insulin by mouth, but glucose [control] strongly depends on several factors, mostly what comes from the diet, and if it’s erratic, that can be a problem. ... So, the treatment of autoimmune diseases can be influenced by celiac disease,” he said.

In addition, Dr. Fasano and others believe that people with CD and other autoimmune disorders should be managed by a team of experts who can personalize the care on the basis of specific needs of the individual patient. These should include specialists, dietitians, mental health counselors, and family social workers.

“It has to be a multidisciplinary approach to maintain the good health of an individual,” Dr. Fasano said. “Celiac disease is the quintessential example in which the primary care physician needs to be the quarterback of the team, the patient is active in his or her health, and [specialists] not only deliver personalized care but also preventive intervention, particularly the prevention of comorbidities.”

Financial disclosures for those quoted in this article were not available at the time of publication.

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

Boston dietitian Katarina Mollo, MEd, RDN, LDN, has virtually no memory of life without celiac disease (CD). Diagnosed at age 4, Dr. Mollo has been on a gluten-free diet for 41 years, which she says has kept her healthy and may also be why she hasn’t developed other autoimmune diseases. It’s also played a part in her thinking about screening patients with CD.

“I think [physicians] should definitely be screening people with celiac disease for autoimmune disorders, especially if they see things like anemia or if a child has dropped on the growth chart and has nutrient deficiencies,” said Dr. Mollo, whose daughter also has the disease. “I would recommend that they see someone who specializes in celiac disease so they can get monitored and have regular follow-up checks for nutrient deficiencies and other autoimmune disorders.”

Dr. Mollo’s views on screening are echoed by many CD specialists and physicians, who cite multiple studies that have found that people with the disease face higher risks for diabetes, thyroid conditions, arthritis, and other autoimmune disorders.

Gastroenterologist Alessio Fasano, MD, with Massachusetts General Hospital, Boston, said there has been a “shift in the paradigm in thinking” about cross-screening for CD and autoimmune disorders. As result, he believes the answer to the question of whether to routinely do so is a no-brainer.

“The bottom line is, if you have CD, it [should be] routine that during your annual follow-ups you check for the possibility of the onset of other autoimmune disease. And people with other autoimmune diseases, like type 1 diabetes, should also be screened for CD because of the comorbidity,” said Dr. Fasano, professor of pediatrics and gastroenterology at Harvard Medical School and professor of nutrition at the Harvard School of Public Health, both in Boston. “This is what we call good clinical practice.”
 

Screening, despite lack of consensus guidelines

Other CD specialists differ on the need for universal cross-screening but agree that, at least in some cases, people with one autoimmune disorder should be tested for others.

Jolanda Denham, MD, a pediatric gastroenterologist affiliated with Nemours Children’s Hospital in Orlando, routinely recommends that her patients with CD be screened for certain autoimmune disorders – such as type 1 diabetes and autoimmune thyroid and liver diseases – even though medical organizations have not developed clear consensus or standard guidelines on cross-screening.

“There currently is no evidence to support the screening of celiac patients for all autoimmune and rheumatologic disorders,” she said. “It is true that celiac disease is an autoimmune disorder, and as such, there is a definite increased risk of these disorders in patients with celiac disease and vice versa.”

Echoing Dr. Denham, New York–based gastroenterologist Benjamin Lebwohl, MD, president of the Society for the Study of Celiac Disease, urges physicians to look beyond consensus guidelines and to err on the side of caution and make the best decisions for their patients on a case-by-case basis.

“Given the increased risk of certain autoimmune conditions in people with celiac disease, it behooves physicians to have a low threshold to evaluate for these conditions if any suggestive symptoms are present,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University, New York.

“Whether to screen for these conditions among people who are entirely without symptoms is less certain, and there is no consensus on that. But it is reasonable and common to include some basic tests with annual blood work, such as thyroid function and a liver profile, since both autoimmune thyroid disease and autoimmune liver disease can be silent early on and the patient would potentially benefit from identification and treatment of these conditions,” he said.

The American Diabetes Association and the International Society of Pediatric and Adolescent Diabetes do recommend that people with diabetes be screened for CD years after diagnosis, noted Robert Rapaport, MD, a pediatric endocrinologist, with Kravis Children’s Hospital, New York. But in a study published in 2021, he and colleagues found that this wasn’t occurring, which prompted them to recommend yearly screening.

“There is a consensus that in children with type 1 diabetes, we screen them for other autoimmune disorders, specifically for thyroid disease and celiac disease,” said Dr. Rapaport, who is also Emma Elizabeth Sullivan Professor of Pediatric Endocrinology and Diabetes at Icahn School of Medicine at Mount Sinai, New York. “But there is no consensus going the other way – for patients with celiac disease, what other autoimmune conditions they should be screened for.”

This hasn’t kept some doctors from extending cross-screening efforts to their patients.

“At our center, we screen ... for thyroid disease and autoimmune liver disease as part of routine healthcare maintenance for our celiac disease patients. We discuss symptoms of diabetes and send screening with [hemoglobin] A1c for anyone who has symptoms,” said Lui Edwin, MD, a pediatric gastroenterologist with Children’s Hospital Colorado, Aurora, and director of the Colorado Center for Celiac Disease, who delivered a lecture on CD-autoimmune screening at the International Celiac Disease Symposium in October.

“It is definitely worth screening for celiac disease in [those with] other autoimmune disorders,” Dr. Edwin added.

“The symptoms can be very heterogeneous. Diagnosing and treating celiac disease can make a huge impact with respect to symptoms, quality of life, and preventing disease-related complications,” he said.
 

Mounting evidence linking CD to autoimmune disorders

Many studies have linked CD to a variety of other autoimmune disorders. The association could be due to common genetic factors or because CD might lead to such conditions. Researchers have found that people diagnosed with CD later in life are more likely to develop other autoimmune disorders.

Going gluten free has preventive advantages

In a landmark 2012 study, researchers with the Celiac Disease Center at Columbia University stopped short of recommending routine screening for the general public or asymptomatic individuals in high-prevalence groups. But they concluded that more screening of symptomatic individuals – and close relatives – would speed treatment for those with more than one autoimmune disorder.

They also noted that some studies have found that a gluten-free diet might help prevent the development of other autoimmune disorders.

Marisa Gallant Stahl, MD, a gastroenterologist with Children’s Hospital Colorado, agreed that it is important that physicians keep gluten-free diets in mind when determining which patients to cross-screen.

“The literature is mixed, but some studies suggest that treating celiac disease with a gluten-free diet actually augments the treatment and control of other autoimmune disorders [and] adherence to a gluten-free diet does reduce the risk of cancer associated with celiac disease,” she said.

Dr. Denham agreed. “Strict adherence to a gluten-free diet definitely protects against the development of enteropathy-associated T-cell lymphoma but may be protective against non-Hodgkin’s lymphoma and adenocarcinoma of the small intestine as well. All three are associated with long-term nonadherence to a gluten-free diet.”

She also noted that a gluten-free diet may help people with CD manage other autoimmune disorders, which can be complicated by CD.

“Good control of celiac disease will help prevent complications that can worsen symptoms and outcomes of concomitant autoimmune and rheumatologic disorders,” she said.
 

Other factors to consider

Dr. Fasano added that autoimmune disorders can be complicated by CD in cases in which oral medications or healthful foods are not properly absorbed in the intestines.

“For example, with Hashimoto’s disease, if you have hormone replacement with oral treatments and your intestines are not 100% functional because you have inflammation, then you may have a problem [with] the absorption of medications like levothyroxine,” he said.

“It’s the same story with diabetes. You don’t take insulin by mouth, but glucose [control] strongly depends on several factors, mostly what comes from the diet, and if it’s erratic, that can be a problem. ... So, the treatment of autoimmune diseases can be influenced by celiac disease,” he said.

In addition, Dr. Fasano and others believe that people with CD and other autoimmune disorders should be managed by a team of experts who can personalize the care on the basis of specific needs of the individual patient. These should include specialists, dietitians, mental health counselors, and family social workers.

“It has to be a multidisciplinary approach to maintain the good health of an individual,” Dr. Fasano said. “Celiac disease is the quintessential example in which the primary care physician needs to be the quarterback of the team, the patient is active in his or her health, and [specialists] not only deliver personalized care but also preventive intervention, particularly the prevention of comorbidities.”

Financial disclosures for those quoted in this article were not available at the time of publication.

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

As many as 40% of patients with cancer develop hiccups – often unbeknownst to their oncologists. But even if recognized, hiccups may not be treated effectively, according to a national survey of cancer care clinicians.

When poorly controlled, persistent hiccups can affect a patient’s quality of life, with 40% of survey respondents considering chronic hiccups “much more” or “somewhat more” severe than nausea and vomiting.

Overall, the findings indicate that patients with cancer who develop persistent hiccups are “truly suffering,” the authors wrote.

The survey results were published online recently in the American Journal of Hospice and Palliative Medicine.

Hiccups may simply be a nuisance for most, but these spasms can become problematic for patients with cancer, leading to sleep deprivation, fatigue, aspiration pneumonia, compromised food intake, weight loss, pain, and even death.

Hiccups can develop when the nerve that controls the diaphragm becomes irritated, which can be triggered by certain chemotherapy drugs.

Yet few studies have focused on hiccups in patients with cancer and none, until now, has sought the perspectives of cancer care clinicians.

Aminah Jatoi, MD, medical oncologist with the Mayo Clinic in Rochester, Minn., and two Mayo colleagues developed a survey, alongside MeterHealth, which this news organization distributed to clinicians with an interest in cancer care.

The survey gauged clinicians’ awareness or lack of awareness about clinically significant hiccups as well as treatments for hiccups and whether they consider hiccups an unmet palliative need.

A total of 684 clinicians completed two eligibility screening questions, which required them to have cared for more than 10 patients with cancer in the past 6 months with clinically significant hiccups (defined as hiccups that lasted more than 48 hours or occurred from cancer or cancer care).

Among 113 eligible health care professionals, 90 completed the survey: 42 physicians, 29 nurses, 15 nurse practitioners, and 4 physician assistants.

The survey revealed three key issues.

The first is that hiccups appear to be an underrecognized issue.

Among health care professionals who answered the eligibility screening questions, fewer than 20% reported caring for more than 10 patients with cancer in the past 6 months who had persistent hiccups. Most of these clinicians reported caring for more than 1,000 patients per year.

Given that 15%-40% of patients with cancer report hiccups, this finding suggests that hiccups are not widely recognized by health care professionals.

Second: The survey data showed that hiccups often increase patients’ anxiety, fatigue, and sleep problems and can decrease productivity at work or school.

In fact, when comparing hiccups to nausea and vomiting – sometimes described as one of the most severe side effects of cancer care – 40% of respondents rated hiccups as “much more” or “somewhat more” severe than nausea and vomiting for their patients and 38% rated the severity of the two issues as “about the same.”

Finally, even when hiccups are recognized and treated, about 20% of respondents said that current therapies are not very effective, and more treatment options are needed.

Among the survey respondents, the most frequently prescribed medications for chronic hiccups were the antipsychotic chlorpromazine, the muscle relaxant baclofen (Lioresal), the antiemetic metoclopramide (Metozolv ODT, Reglan), and the anticonvulsants gabapentin (Neurontin) and carbamazepine (Tegretol).

Survey respondents who provided comments about current treatments for hiccups highlighted a range of challenges. One respondent said, “When current therapies do not work, it can be very demoralizing to our patients.”  Another said, “I feel like it is a gamble whether treatment for hiccups will work or not.”

Still another felt that while current treatments work “quite well to halt hiccups,” they come with side effects which can be “quite severe.”

These results “clearly point to the unmet needs of hiccups in patients with cancer and should prompt more research aimed at generating more palliative options,” the authors said.

This research had no commercial funding. MeterHealth reviewed the manuscript and provided input on the accuracy of methods and results. Dr. Jatoi reports serving on an advisory board for MeterHealth (honoraria to institution).

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

As many as 40% of patients with cancer develop hiccups – often unbeknownst to their oncologists. But even if recognized, hiccups may not be treated effectively, according to a national survey of cancer care clinicians.

When poorly controlled, persistent hiccups can affect a patient’s quality of life, with 40% of survey respondents considering chronic hiccups “much more” or “somewhat more” severe than nausea and vomiting.

Overall, the findings indicate that patients with cancer who develop persistent hiccups are “truly suffering,” the authors wrote.

The survey results were published online recently in the American Journal of Hospice and Palliative Medicine.

Hiccups may simply be a nuisance for most, but these spasms can become problematic for patients with cancer, leading to sleep deprivation, fatigue, aspiration pneumonia, compromised food intake, weight loss, pain, and even death.

Hiccups can develop when the nerve that controls the diaphragm becomes irritated, which can be triggered by certain chemotherapy drugs.

Yet few studies have focused on hiccups in patients with cancer and none, until now, has sought the perspectives of cancer care clinicians.

Aminah Jatoi, MD, medical oncologist with the Mayo Clinic in Rochester, Minn., and two Mayo colleagues developed a survey, alongside MeterHealth, which this news organization distributed to clinicians with an interest in cancer care.

The survey gauged clinicians’ awareness or lack of awareness about clinically significant hiccups as well as treatments for hiccups and whether they consider hiccups an unmet palliative need.

A total of 684 clinicians completed two eligibility screening questions, which required them to have cared for more than 10 patients with cancer in the past 6 months with clinically significant hiccups (defined as hiccups that lasted more than 48 hours or occurred from cancer or cancer care).

Among 113 eligible health care professionals, 90 completed the survey: 42 physicians, 29 nurses, 15 nurse practitioners, and 4 physician assistants.

The survey revealed three key issues.

The first is that hiccups appear to be an underrecognized issue.

Among health care professionals who answered the eligibility screening questions, fewer than 20% reported caring for more than 10 patients with cancer in the past 6 months who had persistent hiccups. Most of these clinicians reported caring for more than 1,000 patients per year.

Given that 15%-40% of patients with cancer report hiccups, this finding suggests that hiccups are not widely recognized by health care professionals.

Second: The survey data showed that hiccups often increase patients’ anxiety, fatigue, and sleep problems and can decrease productivity at work or school.

In fact, when comparing hiccups to nausea and vomiting – sometimes described as one of the most severe side effects of cancer care – 40% of respondents rated hiccups as “much more” or “somewhat more” severe than nausea and vomiting for their patients and 38% rated the severity of the two issues as “about the same.”

Finally, even when hiccups are recognized and treated, about 20% of respondents said that current therapies are not very effective, and more treatment options are needed.

Among the survey respondents, the most frequently prescribed medications for chronic hiccups were the antipsychotic chlorpromazine, the muscle relaxant baclofen (Lioresal), the antiemetic metoclopramide (Metozolv ODT, Reglan), and the anticonvulsants gabapentin (Neurontin) and carbamazepine (Tegretol).

Survey respondents who provided comments about current treatments for hiccups highlighted a range of challenges. One respondent said, “When current therapies do not work, it can be very demoralizing to our patients.”  Another said, “I feel like it is a gamble whether treatment for hiccups will work or not.”

Still another felt that while current treatments work “quite well to halt hiccups,” they come with side effects which can be “quite severe.”

These results “clearly point to the unmet needs of hiccups in patients with cancer and should prompt more research aimed at generating more palliative options,” the authors said.

This research had no commercial funding. MeterHealth reviewed the manuscript and provided input on the accuracy of methods and results. Dr. Jatoi reports serving on an advisory board for MeterHealth (honoraria to institution).

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

As many as 40% of patients with cancer develop hiccups – often unbeknownst to their oncologists. But even if recognized, hiccups may not be treated effectively, according to a national survey of cancer care clinicians.

When poorly controlled, persistent hiccups can affect a patient’s quality of life, with 40% of survey respondents considering chronic hiccups “much more” or “somewhat more” severe than nausea and vomiting.

Overall, the findings indicate that patients with cancer who develop persistent hiccups are “truly suffering,” the authors wrote.

The survey results were published online recently in the American Journal of Hospice and Palliative Medicine.

Hiccups may simply be a nuisance for most, but these spasms can become problematic for patients with cancer, leading to sleep deprivation, fatigue, aspiration pneumonia, compromised food intake, weight loss, pain, and even death.

Hiccups can develop when the nerve that controls the diaphragm becomes irritated, which can be triggered by certain chemotherapy drugs.

Yet few studies have focused on hiccups in patients with cancer and none, until now, has sought the perspectives of cancer care clinicians.

Aminah Jatoi, MD, medical oncologist with the Mayo Clinic in Rochester, Minn., and two Mayo colleagues developed a survey, alongside MeterHealth, which this news organization distributed to clinicians with an interest in cancer care.

The survey gauged clinicians’ awareness or lack of awareness about clinically significant hiccups as well as treatments for hiccups and whether they consider hiccups an unmet palliative need.

A total of 684 clinicians completed two eligibility screening questions, which required them to have cared for more than 10 patients with cancer in the past 6 months with clinically significant hiccups (defined as hiccups that lasted more than 48 hours or occurred from cancer or cancer care).

Among 113 eligible health care professionals, 90 completed the survey: 42 physicians, 29 nurses, 15 nurse practitioners, and 4 physician assistants.

The survey revealed three key issues.

The first is that hiccups appear to be an underrecognized issue.

Among health care professionals who answered the eligibility screening questions, fewer than 20% reported caring for more than 10 patients with cancer in the past 6 months who had persistent hiccups. Most of these clinicians reported caring for more than 1,000 patients per year.

Given that 15%-40% of patients with cancer report hiccups, this finding suggests that hiccups are not widely recognized by health care professionals.

Second: The survey data showed that hiccups often increase patients’ anxiety, fatigue, and sleep problems and can decrease productivity at work or school.

In fact, when comparing hiccups to nausea and vomiting – sometimes described as one of the most severe side effects of cancer care – 40% of respondents rated hiccups as “much more” or “somewhat more” severe than nausea and vomiting for their patients and 38% rated the severity of the two issues as “about the same.”

Finally, even when hiccups are recognized and treated, about 20% of respondents said that current therapies are not very effective, and more treatment options are needed.

Among the survey respondents, the most frequently prescribed medications for chronic hiccups were the antipsychotic chlorpromazine, the muscle relaxant baclofen (Lioresal), the antiemetic metoclopramide (Metozolv ODT, Reglan), and the anticonvulsants gabapentin (Neurontin) and carbamazepine (Tegretol).

Survey respondents who provided comments about current treatments for hiccups highlighted a range of challenges. One respondent said, “When current therapies do not work, it can be very demoralizing to our patients.”  Another said, “I feel like it is a gamble whether treatment for hiccups will work or not.”

Still another felt that while current treatments work “quite well to halt hiccups,” they come with side effects which can be “quite severe.”

These results “clearly point to the unmet needs of hiccups in patients with cancer and should prompt more research aimed at generating more palliative options,” the authors said.

This research had no commercial funding. MeterHealth reviewed the manuscript and provided input on the accuracy of methods and results. Dr. Jatoi reports serving on an advisory board for MeterHealth (honoraria to institution).

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

Emergency medicine providers worry more about committing medical errors that harm patients than about triggering malpractice lawsuits, according to a study published in JAMA Network Open.

The cross-sectional study was conducted by researchers from Soroka University Medical Center, Israel; the University of Massachusetts, Worcester; Beth Israel Deaconess Medical Center; Harvard Medical School, Boston; and the University of Massachusetts, Amherst.

Online survey responses were collected from 1,222 emergency department attending physicians and advanced practice clinicians (APCs) in acute care hospitals throughout Massachusetts from January to September 2020.

Participants were asked to rank their level of agreement – from “strongly disagree” to “strongly agree” – with two statements: “In my day-to-day practice, I am fearful of making a mistake which results in [1] harm to the patient” (fear of harm) and [2] “being sued” (fear of suit).

The average age of the participants was about 44 years; 54.2% were men, 45.1% were women, and 0.7% were of other gender. Approximately 70% of responses were from MDs or DOs, and the remainder were from nurse practitioners and physician assistants. Participants had between 5 and 19 years of experience (median, 10 years).

The study found that the mean score was greater with regard to fear of harm than to fear of suit, regardless of clinician type, experience, or sex and whether the survey was completed before or after the start of the COVID-19 pandemic. There was no significant difference in mean scores regarding fear of suit before the pandemic and after it.

“Our data show a significantly greater fear of harming a patient than a fear of a malpractice suit,” Linda Isbell, PhD, professor of psychology at the University of Massachusetts, Amherst, who is one of the study’s authors, told this news organization. “There is a genuine concern and fear of harming patients and a desire to provide the best care for the patient’s well-being.”

In general, fear-of-harm and fear-of-suit scores decreased as providers gained experience. Those with less than 5 years of experience reported the highest levels of both.

“Although our data do not specifically provide reasons why age may impact [fear] levels, it is possible that with more practice experience ... providers have a better sense of the likelihood of patient harm and malpractice and how to manage such outcomes should they happen,” says Dr. Isbell. She noted that a longitudinal study is necessary to confirm this hypothesis.

One exception was female APCs, whose fear-of-harm scores remained relatively steady across all experience levels. Among male APCs, fear of causing patient harm decreased among those with 5-14 years of experience but increased slightly at 14-44 years of experience.

While previous research typically focused on fear of malpractice as a significant driver of defensive medicine, such as testing excessively, this study examined providers’ fear of harming patients because of a medical error.

The findings suggest “that fear of harm should be considered with, and may be more consequential than, fear of suit in medical decision-making,” the authors note.

“[F]ear can motivate people to engage in more careful and thorough information processing, which can drive behaviors in systematic ways,” says Dr. Isbell. “It is possible that one’s fear of harming a patient is triggering a high level of vigilance, reflected in the practice of defensive medicine across different types of patients – some of whom may be better off with less testing and referrals.”

Rade B. Vukmir, MD, JD, FACEP, an emergency medicine physician and spokesman for the American College of Emergency Physicians, says defensive medicine is common in the specialty and that it occurs 20%-40% of the time.

“Early in practice, the proverbial worst sin is missing a diagnosis, so that’s where the overtesting mentality comes from,” he says. In addition, “there are cities where you can’t drive a mile without seeing a half dozen legal advertisements. That imposes a cost burden on the system, [adding] roughly 20% to the cost of overall care.”

Emergency medicine providers attempt to minimize testing, but between their role as “America’s safety net” and the difficult circumstances they often face when treating patients, it takes a while to strike a balance, Dr. Vukmir acknowledges.

“There’s a training correlation, which showed up [in this study]; as people got further advanced in training, they felt more comfortable and felt the need to do it less,” says Dr. Vukmir.

The study was funded by a grant from the Agency for Healthcare Research and Quality. Dr. Isbell reports no conflicts of interest. Dr. Vukmir has disclosed no relevant financial relationships.

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

Emergency medicine providers worry more about committing medical errors that harm patients than about triggering malpractice lawsuits, according to a study published in JAMA Network Open.

The cross-sectional study was conducted by researchers from Soroka University Medical Center, Israel; the University of Massachusetts, Worcester; Beth Israel Deaconess Medical Center; Harvard Medical School, Boston; and the University of Massachusetts, Amherst.

Online survey responses were collected from 1,222 emergency department attending physicians and advanced practice clinicians (APCs) in acute care hospitals throughout Massachusetts from January to September 2020.

Participants were asked to rank their level of agreement – from “strongly disagree” to “strongly agree” – with two statements: “In my day-to-day practice, I am fearful of making a mistake which results in [1] harm to the patient” (fear of harm) and [2] “being sued” (fear of suit).

The average age of the participants was about 44 years; 54.2% were men, 45.1% were women, and 0.7% were of other gender. Approximately 70% of responses were from MDs or DOs, and the remainder were from nurse practitioners and physician assistants. Participants had between 5 and 19 years of experience (median, 10 years).

The study found that the mean score was greater with regard to fear of harm than to fear of suit, regardless of clinician type, experience, or sex and whether the survey was completed before or after the start of the COVID-19 pandemic. There was no significant difference in mean scores regarding fear of suit before the pandemic and after it.

“Our data show a significantly greater fear of harming a patient than a fear of a malpractice suit,” Linda Isbell, PhD, professor of psychology at the University of Massachusetts, Amherst, who is one of the study’s authors, told this news organization. “There is a genuine concern and fear of harming patients and a desire to provide the best care for the patient’s well-being.”

In general, fear-of-harm and fear-of-suit scores decreased as providers gained experience. Those with less than 5 years of experience reported the highest levels of both.

“Although our data do not specifically provide reasons why age may impact [fear] levels, it is possible that with more practice experience ... providers have a better sense of the likelihood of patient harm and malpractice and how to manage such outcomes should they happen,” says Dr. Isbell. She noted that a longitudinal study is necessary to confirm this hypothesis.

One exception was female APCs, whose fear-of-harm scores remained relatively steady across all experience levels. Among male APCs, fear of causing patient harm decreased among those with 5-14 years of experience but increased slightly at 14-44 years of experience.

While previous research typically focused on fear of malpractice as a significant driver of defensive medicine, such as testing excessively, this study examined providers’ fear of harming patients because of a medical error.

The findings suggest “that fear of harm should be considered with, and may be more consequential than, fear of suit in medical decision-making,” the authors note.

“[F]ear can motivate people to engage in more careful and thorough information processing, which can drive behaviors in systematic ways,” says Dr. Isbell. “It is possible that one’s fear of harming a patient is triggering a high level of vigilance, reflected in the practice of defensive medicine across different types of patients – some of whom may be better off with less testing and referrals.”

Rade B. Vukmir, MD, JD, FACEP, an emergency medicine physician and spokesman for the American College of Emergency Physicians, says defensive medicine is common in the specialty and that it occurs 20%-40% of the time.

“Early in practice, the proverbial worst sin is missing a diagnosis, so that’s where the overtesting mentality comes from,” he says. In addition, “there are cities where you can’t drive a mile without seeing a half dozen legal advertisements. That imposes a cost burden on the system, [adding] roughly 20% to the cost of overall care.”

Emergency medicine providers attempt to minimize testing, but between their role as “America’s safety net” and the difficult circumstances they often face when treating patients, it takes a while to strike a balance, Dr. Vukmir acknowledges.

“There’s a training correlation, which showed up [in this study]; as people got further advanced in training, they felt more comfortable and felt the need to do it less,” says Dr. Vukmir.

The study was funded by a grant from the Agency for Healthcare Research and Quality. Dr. Isbell reports no conflicts of interest. Dr. Vukmir has disclosed no relevant financial relationships.

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

Emergency medicine providers worry more about committing medical errors that harm patients than about triggering malpractice lawsuits, according to a study published in JAMA Network Open.

The cross-sectional study was conducted by researchers from Soroka University Medical Center, Israel; the University of Massachusetts, Worcester; Beth Israel Deaconess Medical Center; Harvard Medical School, Boston; and the University of Massachusetts, Amherst.

Online survey responses were collected from 1,222 emergency department attending physicians and advanced practice clinicians (APCs) in acute care hospitals throughout Massachusetts from January to September 2020.

Participants were asked to rank their level of agreement – from “strongly disagree” to “strongly agree” – with two statements: “In my day-to-day practice, I am fearful of making a mistake which results in [1] harm to the patient” (fear of harm) and [2] “being sued” (fear of suit).

The average age of the participants was about 44 years; 54.2% were men, 45.1% were women, and 0.7% were of other gender. Approximately 70% of responses were from MDs or DOs, and the remainder were from nurse practitioners and physician assistants. Participants had between 5 and 19 years of experience (median, 10 years).

The study found that the mean score was greater with regard to fear of harm than to fear of suit, regardless of clinician type, experience, or sex and whether the survey was completed before or after the start of the COVID-19 pandemic. There was no significant difference in mean scores regarding fear of suit before the pandemic and after it.

“Our data show a significantly greater fear of harming a patient than a fear of a malpractice suit,” Linda Isbell, PhD, professor of psychology at the University of Massachusetts, Amherst, who is one of the study’s authors, told this news organization. “There is a genuine concern and fear of harming patients and a desire to provide the best care for the patient’s well-being.”

In general, fear-of-harm and fear-of-suit scores decreased as providers gained experience. Those with less than 5 years of experience reported the highest levels of both.

“Although our data do not specifically provide reasons why age may impact [fear] levels, it is possible that with more practice experience ... providers have a better sense of the likelihood of patient harm and malpractice and how to manage such outcomes should they happen,” says Dr. Isbell. She noted that a longitudinal study is necessary to confirm this hypothesis.

One exception was female APCs, whose fear-of-harm scores remained relatively steady across all experience levels. Among male APCs, fear of causing patient harm decreased among those with 5-14 years of experience but increased slightly at 14-44 years of experience.

While previous research typically focused on fear of malpractice as a significant driver of defensive medicine, such as testing excessively, this study examined providers’ fear of harming patients because of a medical error.

The findings suggest “that fear of harm should be considered with, and may be more consequential than, fear of suit in medical decision-making,” the authors note.

“[F]ear can motivate people to engage in more careful and thorough information processing, which can drive behaviors in systematic ways,” says Dr. Isbell. “It is possible that one’s fear of harming a patient is triggering a high level of vigilance, reflected in the practice of defensive medicine across different types of patients – some of whom may be better off with less testing and referrals.”

Rade B. Vukmir, MD, JD, FACEP, an emergency medicine physician and spokesman for the American College of Emergency Physicians, says defensive medicine is common in the specialty and that it occurs 20%-40% of the time.

“Early in practice, the proverbial worst sin is missing a diagnosis, so that’s where the overtesting mentality comes from,” he says. In addition, “there are cities where you can’t drive a mile without seeing a half dozen legal advertisements. That imposes a cost burden on the system, [adding] roughly 20% to the cost of overall care.”

Emergency medicine providers attempt to minimize testing, but between their role as “America’s safety net” and the difficult circumstances they often face when treating patients, it takes a while to strike a balance, Dr. Vukmir acknowledges.

“There’s a training correlation, which showed up [in this study]; as people got further advanced in training, they felt more comfortable and felt the need to do it less,” says Dr. Vukmir.

The study was funded by a grant from the Agency for Healthcare Research and Quality. Dr. Isbell reports no conflicts of interest. Dr. Vukmir has disclosed no relevant financial relationships.

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

Scans of the lungs of pot users have turned up an alarming surprise: Regular smokers of marijuana appear to be at greater risk for lung damage than are people who smoke tobacco alone.

“There’s a public perception that marijuana is safe,” said Giselle Revah, MD, a radiologist at the University of Ottawa. “This study is raising concern that this might not be true.”

Dr. Revah said she can often tell immediately if a CT scan is from a heavy or long-time cigarette smoker. But with the legalization and increased use of marijuana in Canada and many U.S. states, she began to wonder what cannabis use does to the lungs and whether she would be able to differentiate its effects from those of cigarette smoking.

She and her colleagues retrospectively examined chest CT scans from 56 marijuana smokers and compared them to scans of 57 nonsmokers and 33 users of tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than among nonsmokers (5%). When matched for age and sex, 93% of marijuana smokers had emphysema, vs. 67% of those who smoked tobacco only (P = .009).

Without age matching, rates of emphysema remained slightly higher among the marijuana users (75% vs. 67%), although the difference was no longer statistically significant. Yet more than 40% of the marijuana group was younger than 50 years, and all of the tobacco-only users were 50 or older – meaning that marijuana smokers may develop lung damage earlier or with less exposure, Dr. Revah said.

Dr. Revah added that her colleagues in family medicine have said the findings match their clinical experience. “In their practices, they have younger patients with emphysema,” she said.

Marijuana smokers also showed higher rates of airway inflammation, including bronchial thickening, bronchiectasis, and mucoid impaction, with and without sex- and age-matching, the researchers found.

The findings are “not even a little bit surprising,” according to Alan Kaplan, MD, a family physician in Ontario who has expertise in respiratory health. He is the author of a 2021 review on cannabis and lung health.

In an editorial accompanying the journal article by Dr. Revah and colleagues , pulmonary experts noted that the new data give context to a recent uptick in referrals for nontraumatic pneumothorax. The authors said they had received 22 of these referrals during the past 2 years but that they had received only 6 between 2012 and 2020. “Many, but not all, of these patients have a documented history of marijuana use,” they wrote.

One reason for the additional damage may be the way marijuana is inhaled, Dr. Kaplan said. Marijuana smokers “take a big breath in, and they really push it into lungs and hold pressure on it, which may actually cause alveoli to distend over time.”

Because most marijuana smokers in the study also smoked cigarettes, whether the observed damage was caused by marijuana alone or occurred through a synergy with tobacco is impossible to discern, Dr. Revah said.

Still, the results are striking, she said, because the marijuana group was compared to tobacco users who had an extensive smoking history – 25 to 100 pack-years – and who were from a high-risk lung cancer screening program.

Dr. Revah and her colleagues are now conducting a larger, prospective study to see whether they can confirm their findings.

“The message to physicians is to ask about cannabis smoking,” Dr. Kaplan said. In the past, people have been reluctant to admit to using cannabis. Even with legalization, they may be slow to tell their physicians. But clinicians should still try to identify frequent users, especially those who are predisposed for lung conditions. If they intend to use the drug, the advice should be, “There are safer ways to use cannabis,” he said.

Dr. Revah and Dr. Kaplan have disclosed no relevant financial relationships.

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

Scans of the lungs of pot users have turned up an alarming surprise: Regular smokers of marijuana appear to be at greater risk for lung damage than are people who smoke tobacco alone.

“There’s a public perception that marijuana is safe,” said Giselle Revah, MD, a radiologist at the University of Ottawa. “This study is raising concern that this might not be true.”

Dr. Revah said she can often tell immediately if a CT scan is from a heavy or long-time cigarette smoker. But with the legalization and increased use of marijuana in Canada and many U.S. states, she began to wonder what cannabis use does to the lungs and whether she would be able to differentiate its effects from those of cigarette smoking.

She and her colleagues retrospectively examined chest CT scans from 56 marijuana smokers and compared them to scans of 57 nonsmokers and 33 users of tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than among nonsmokers (5%). When matched for age and sex, 93% of marijuana smokers had emphysema, vs. 67% of those who smoked tobacco only (P = .009).

Without age matching, rates of emphysema remained slightly higher among the marijuana users (75% vs. 67%), although the difference was no longer statistically significant. Yet more than 40% of the marijuana group was younger than 50 years, and all of the tobacco-only users were 50 or older – meaning that marijuana smokers may develop lung damage earlier or with less exposure, Dr. Revah said.

Dr. Revah added that her colleagues in family medicine have said the findings match their clinical experience. “In their practices, they have younger patients with emphysema,” she said.

Marijuana smokers also showed higher rates of airway inflammation, including bronchial thickening, bronchiectasis, and mucoid impaction, with and without sex- and age-matching, the researchers found.

The findings are “not even a little bit surprising,” according to Alan Kaplan, MD, a family physician in Ontario who has expertise in respiratory health. He is the author of a 2021 review on cannabis and lung health.

In an editorial accompanying the journal article by Dr. Revah and colleagues , pulmonary experts noted that the new data give context to a recent uptick in referrals for nontraumatic pneumothorax. The authors said they had received 22 of these referrals during the past 2 years but that they had received only 6 between 2012 and 2020. “Many, but not all, of these patients have a documented history of marijuana use,” they wrote.

One reason for the additional damage may be the way marijuana is inhaled, Dr. Kaplan said. Marijuana smokers “take a big breath in, and they really push it into lungs and hold pressure on it, which may actually cause alveoli to distend over time.”

Because most marijuana smokers in the study also smoked cigarettes, whether the observed damage was caused by marijuana alone or occurred through a synergy with tobacco is impossible to discern, Dr. Revah said.

Still, the results are striking, she said, because the marijuana group was compared to tobacco users who had an extensive smoking history – 25 to 100 pack-years – and who were from a high-risk lung cancer screening program.

Dr. Revah and her colleagues are now conducting a larger, prospective study to see whether they can confirm their findings.

“The message to physicians is to ask about cannabis smoking,” Dr. Kaplan said. In the past, people have been reluctant to admit to using cannabis. Even with legalization, they may be slow to tell their physicians. But clinicians should still try to identify frequent users, especially those who are predisposed for lung conditions. If they intend to use the drug, the advice should be, “There are safer ways to use cannabis,” he said.

Dr. Revah and Dr. Kaplan have disclosed no relevant financial relationships.

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

Scans of the lungs of pot users have turned up an alarming surprise: Regular smokers of marijuana appear to be at greater risk for lung damage than are people who smoke tobacco alone.

“There’s a public perception that marijuana is safe,” said Giselle Revah, MD, a radiologist at the University of Ottawa. “This study is raising concern that this might not be true.”

Dr. Revah said she can often tell immediately if a CT scan is from a heavy or long-time cigarette smoker. But with the legalization and increased use of marijuana in Canada and many U.S. states, she began to wonder what cannabis use does to the lungs and whether she would be able to differentiate its effects from those of cigarette smoking.

She and her colleagues retrospectively examined chest CT scans from 56 marijuana smokers and compared them to scans of 57 nonsmokers and 33 users of tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than among nonsmokers (5%). When matched for age and sex, 93% of marijuana smokers had emphysema, vs. 67% of those who smoked tobacco only (P = .009).

Without age matching, rates of emphysema remained slightly higher among the marijuana users (75% vs. 67%), although the difference was no longer statistically significant. Yet more than 40% of the marijuana group was younger than 50 years, and all of the tobacco-only users were 50 or older – meaning that marijuana smokers may develop lung damage earlier or with less exposure, Dr. Revah said.

Dr. Revah added that her colleagues in family medicine have said the findings match their clinical experience. “In their practices, they have younger patients with emphysema,” she said.

Marijuana smokers also showed higher rates of airway inflammation, including bronchial thickening, bronchiectasis, and mucoid impaction, with and without sex- and age-matching, the researchers found.

The findings are “not even a little bit surprising,” according to Alan Kaplan, MD, a family physician in Ontario who has expertise in respiratory health. He is the author of a 2021 review on cannabis and lung health.

In an editorial accompanying the journal article by Dr. Revah and colleagues , pulmonary experts noted that the new data give context to a recent uptick in referrals for nontraumatic pneumothorax. The authors said they had received 22 of these referrals during the past 2 years but that they had received only 6 between 2012 and 2020. “Many, but not all, of these patients have a documented history of marijuana use,” they wrote.

One reason for the additional damage may be the way marijuana is inhaled, Dr. Kaplan said. Marijuana smokers “take a big breath in, and they really push it into lungs and hold pressure on it, which may actually cause alveoli to distend over time.”

Because most marijuana smokers in the study also smoked cigarettes, whether the observed damage was caused by marijuana alone or occurred through a synergy with tobacco is impossible to discern, Dr. Revah said.

Still, the results are striking, she said, because the marijuana group was compared to tobacco users who had an extensive smoking history – 25 to 100 pack-years – and who were from a high-risk lung cancer screening program.

Dr. Revah and her colleagues are now conducting a larger, prospective study to see whether they can confirm their findings.

“The message to physicians is to ask about cannabis smoking,” Dr. Kaplan said. In the past, people have been reluctant to admit to using cannabis. Even with legalization, they may be slow to tell their physicians. But clinicians should still try to identify frequent users, especially those who are predisposed for lung conditions. If they intend to use the drug, the advice should be, “There are safer ways to use cannabis,” he said.

Dr. Revah and Dr. Kaplan have disclosed no relevant financial relationships.

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

In most cases, passengers on an airline flight are representative of the general population, which means that anyone could have an emergency at any time.

A study published in the New England Journal of Medicine in 2013 showed that a medical emergency occurred in 1 per 604 flights, as determined on the basis of in-flight medical emergencies that resulted in calls to a physician-directed medical communications center, said Amy Faith Ho, MD, MPH of Integrative Emergency Services, Dallas–Fort Worth, in a presentation at the annual meeting of the American College of Emergency Physicians.

The study authors reviewed records of 11,920 in-flight medical emergencies between Jan. 1, 2008, and Oct. 31, 2010. The data showed that physician passengers provided medical assistance in nearly half of in-flight emergencies (48.1%) and that flights were diverted because of the emergency in 7.3% of cases.

The majority of the in-flight emergencies involved syncope or presyncope (37.4% of cases), followed by respiratory symptoms (12.1%) and nausea or vomiting (9.5%), according to the study.

The in-flight medical bag

Tools in a physician’s in-flight toolbox start with the first-aid kit. Airplanes also have an emergency medical kit (EMK), an oxygen tank, and an AED.

The minimum EMK contents are mandated by the Federal Aviation Administration, said Dr. Ho. The standard equipment includes a stethoscope, a sphygmomanometer, and three sizes of oropharyngeal airways. Other items include self-inflating manual resuscitation devices and CPR masks in thee sizes, alcohol sponges, gloves, adhesive tape, scissors, a tourniquet, as well as saline solution, needles, syringes, and an intravenous administration set consisting of tubing and two Y connectors.

An EMK also should contain the following medications: nonnarcotic analgesic tablets, antihistamine tablets, an injectable antihistamine, atropine, aspirin tablets, a bronchodilator, and epinephrine (both 1:1000; 1 injectable cc and 1:10,000; two injectable cc). Nitroglycerin tablets and 5 cc of 20 mg/mL injectable cardiac lidocaine are part of the mandated kit as well, according to Dr. Ho.

Some airlines carry additional supplies on all their flights, said Dr. Ho. Notably, American Airlines and British Airways carry EpiPens for adults and children, as well as opioid reversal medication (naloxone) and glucose for managing low blood sugar. American Airlines and Delta stock antiemetics, and Delta also carries naloxone. British Airways is unique in stocking additional cardiac medications, both oral and injectable.
 

How to handle an in-flight emergency

Physicians should always carry a copy of their medical license when traveling for documentation by the airline if they assist in a medical emergency during a flight, Dr. Ho emphasized. “Staff” personnel should be used. These include the flight attendants, medical ground control, and other passengers who might have useful skills, such as nursing, the ability to perform CPR, or therapy/counseling to calm a frightened patient. If needed, “crowdsource additional supplies from passengers,” such as a glucometer or pulse oximeter.

Legal lessons

Physicians are not obligated to assist during an in-flight medical emergency, said Dr. Ho. Legal jurisdiction can vary. In the United States, a bystander who assists in an emergency is generally protected by Good Samaritan laws; for international airlines, the laws may vary; those where the airline is based usually apply.

The Aviation Medical Assistance Act, passed in 1998, protects individuals from being sued for negligence while providing medical assistance, “unless the individual, while rendering such assistance, is guilty of gross negligence of willful misconduct,” Dr. Ho noted. The Aviation Medical Assistance Act also protects the airline itself “if the carrier in good faith believes that the passenger is a medically qualified individual.”

Dr. Ho disclosed no relevant financial relationships.

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

In most cases, passengers on an airline flight are representative of the general population, which means that anyone could have an emergency at any time.

A study published in the New England Journal of Medicine in 2013 showed that a medical emergency occurred in 1 per 604 flights, as determined on the basis of in-flight medical emergencies that resulted in calls to a physician-directed medical communications center, said Amy Faith Ho, MD, MPH of Integrative Emergency Services, Dallas–Fort Worth, in a presentation at the annual meeting of the American College of Emergency Physicians.

The study authors reviewed records of 11,920 in-flight medical emergencies between Jan. 1, 2008, and Oct. 31, 2010. The data showed that physician passengers provided medical assistance in nearly half of in-flight emergencies (48.1%) and that flights were diverted because of the emergency in 7.3% of cases.

The majority of the in-flight emergencies involved syncope or presyncope (37.4% of cases), followed by respiratory symptoms (12.1%) and nausea or vomiting (9.5%), according to the study.

The in-flight medical bag

Tools in a physician’s in-flight toolbox start with the first-aid kit. Airplanes also have an emergency medical kit (EMK), an oxygen tank, and an AED.

The minimum EMK contents are mandated by the Federal Aviation Administration, said Dr. Ho. The standard equipment includes a stethoscope, a sphygmomanometer, and three sizes of oropharyngeal airways. Other items include self-inflating manual resuscitation devices and CPR masks in thee sizes, alcohol sponges, gloves, adhesive tape, scissors, a tourniquet, as well as saline solution, needles, syringes, and an intravenous administration set consisting of tubing and two Y connectors.

An EMK also should contain the following medications: nonnarcotic analgesic tablets, antihistamine tablets, an injectable antihistamine, atropine, aspirin tablets, a bronchodilator, and epinephrine (both 1:1000; 1 injectable cc and 1:10,000; two injectable cc). Nitroglycerin tablets and 5 cc of 20 mg/mL injectable cardiac lidocaine are part of the mandated kit as well, according to Dr. Ho.

Some airlines carry additional supplies on all their flights, said Dr. Ho. Notably, American Airlines and British Airways carry EpiPens for adults and children, as well as opioid reversal medication (naloxone) and glucose for managing low blood sugar. American Airlines and Delta stock antiemetics, and Delta also carries naloxone. British Airways is unique in stocking additional cardiac medications, both oral and injectable.
 

How to handle an in-flight emergency

Physicians should always carry a copy of their medical license when traveling for documentation by the airline if they assist in a medical emergency during a flight, Dr. Ho emphasized. “Staff” personnel should be used. These include the flight attendants, medical ground control, and other passengers who might have useful skills, such as nursing, the ability to perform CPR, or therapy/counseling to calm a frightened patient. If needed, “crowdsource additional supplies from passengers,” such as a glucometer or pulse oximeter.

Legal lessons

Physicians are not obligated to assist during an in-flight medical emergency, said Dr. Ho. Legal jurisdiction can vary. In the United States, a bystander who assists in an emergency is generally protected by Good Samaritan laws; for international airlines, the laws may vary; those where the airline is based usually apply.

The Aviation Medical Assistance Act, passed in 1998, protects individuals from being sued for negligence while providing medical assistance, “unless the individual, while rendering such assistance, is guilty of gross negligence of willful misconduct,” Dr. Ho noted. The Aviation Medical Assistance Act also protects the airline itself “if the carrier in good faith believes that the passenger is a medically qualified individual.”

Dr. Ho disclosed no relevant financial relationships.

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

In most cases, passengers on an airline flight are representative of the general population, which means that anyone could have an emergency at any time.

A study published in the New England Journal of Medicine in 2013 showed that a medical emergency occurred in 1 per 604 flights, as determined on the basis of in-flight medical emergencies that resulted in calls to a physician-directed medical communications center, said Amy Faith Ho, MD, MPH of Integrative Emergency Services, Dallas–Fort Worth, in a presentation at the annual meeting of the American College of Emergency Physicians.

The study authors reviewed records of 11,920 in-flight medical emergencies between Jan. 1, 2008, and Oct. 31, 2010. The data showed that physician passengers provided medical assistance in nearly half of in-flight emergencies (48.1%) and that flights were diverted because of the emergency in 7.3% of cases.

The majority of the in-flight emergencies involved syncope or presyncope (37.4% of cases), followed by respiratory symptoms (12.1%) and nausea or vomiting (9.5%), according to the study.

The in-flight medical bag

Tools in a physician’s in-flight toolbox start with the first-aid kit. Airplanes also have an emergency medical kit (EMK), an oxygen tank, and an AED.

The minimum EMK contents are mandated by the Federal Aviation Administration, said Dr. Ho. The standard equipment includes a stethoscope, a sphygmomanometer, and three sizes of oropharyngeal airways. Other items include self-inflating manual resuscitation devices and CPR masks in thee sizes, alcohol sponges, gloves, adhesive tape, scissors, a tourniquet, as well as saline solution, needles, syringes, and an intravenous administration set consisting of tubing and two Y connectors.

An EMK also should contain the following medications: nonnarcotic analgesic tablets, antihistamine tablets, an injectable antihistamine, atropine, aspirin tablets, a bronchodilator, and epinephrine (both 1:1000; 1 injectable cc and 1:10,000; two injectable cc). Nitroglycerin tablets and 5 cc of 20 mg/mL injectable cardiac lidocaine are part of the mandated kit as well, according to Dr. Ho.

Some airlines carry additional supplies on all their flights, said Dr. Ho. Notably, American Airlines and British Airways carry EpiPens for adults and children, as well as opioid reversal medication (naloxone) and glucose for managing low blood sugar. American Airlines and Delta stock antiemetics, and Delta also carries naloxone. British Airways is unique in stocking additional cardiac medications, both oral and injectable.
 

How to handle an in-flight emergency

Physicians should always carry a copy of their medical license when traveling for documentation by the airline if they assist in a medical emergency during a flight, Dr. Ho emphasized. “Staff” personnel should be used. These include the flight attendants, medical ground control, and other passengers who might have useful skills, such as nursing, the ability to perform CPR, or therapy/counseling to calm a frightened patient. If needed, “crowdsource additional supplies from passengers,” such as a glucometer or pulse oximeter.

Legal lessons

Physicians are not obligated to assist during an in-flight medical emergency, said Dr. Ho. Legal jurisdiction can vary. In the United States, a bystander who assists in an emergency is generally protected by Good Samaritan laws; for international airlines, the laws may vary; those where the airline is based usually apply.

The Aviation Medical Assistance Act, passed in 1998, protects individuals from being sued for negligence while providing medical assistance, “unless the individual, while rendering such assistance, is guilty of gross negligence of willful misconduct,” Dr. Ho noted. The Aviation Medical Assistance Act also protects the airline itself “if the carrier in good faith believes that the passenger is a medically qualified individual.”

Dr. Ho disclosed no relevant financial relationships.

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

THE CASE

A 34-year-old man was referred to the sports medicine clinic for evaluation of lumbar radiculopathy. He had a 2-year history of chronic lower back pain that started while he was working on power line towers in Puerto Rico. The back pain was achy, burning, shooting, and stabbing in nature. He had been treated with anti-inflammatories by a company health care provider while in Puerto Rico, but he did not have any imaging done.

At that time, he had tingling and burning that radiated down his left leg to his ankle. The patient also had leg spasms—in his left leg more than his right—and needed a cane when walking. His symptoms did not worsen at any particular time of day or with activity. He had no history of eating exotic foods or sustaining any venomous bites/stings. Ultimately, the back pain and leg spasms forced him to leave his job and return home to Louisiana.

Upon presentation to the sports medicine clinic, he explained that things had worsened since his return home. The pain and burning in his left leg had increased and were now present in his right leg, as well (bilateral paresthesias). In addition, he said he was feeling anxious (and described symptoms of forgetfulness, confusion, and agitation), was sleeping less, and was experiencing worsening fatigue.

Work-ups over the course of the previous 2 years had shed little light on the cause of his symptoms. X-rays of his lumbar spine revealed moderate degenerative changes at L5-S1. A lab work-up was negative and included a complete blood count, testing for HIV and herpes, a hepatitis panel, an antinuclear antibody screen, a C-reactive protein test, and a comprehensive metabolic panel. Thyroid-stimulating hormone, creatine kinase, rapid plasma reagin, and human leukocyte antigen B27 tests were also normal.

Magnetic resonance imaging (MRI) revealed a cystic lesion in the right ilium near the sacroiliac joint. A more recent follow-up MRI and computed tomography scan of the pelvis found the cyst to be stable and well marginalized, with no cortical erosion. Attempts at physical therapy had been unsuccessful because of the pain and decreasing muscle strength in his lower extremities. The patient’s primary care provider was treating him with meloxicam 15 mg/d and duloxetine 60 mg/d, but that had not provided any relief.

Our physical examination revealed a patient who was in mild distress and had limited lumbar spine range of motion (secondary to pain in all planes) and significant paraspinal spasms on the right side in both the lumbar and thoracic regions. The patient had reduced vibratory sensation on his left side vs the right, with a 256-Hz tuning fork at the great toe, as well as reduced sensation to fine touch with a cotton swab and a positive Babinski sign bilaterally. Lower extremity reflexes were hyperreflexic on the left compared with the right. He had no pronator drift; Trendelenburg, straight leg raise, Hoover sign, and slump tests were all negative. His gait was antalgic with a cane, as he described bilateral paresthesias.

THE DIAGNOSIS

The differential diagnosis for low back pain is quite extensive and includes simple mechanical low back pain, lumbar radiculopathy, facet arthritis, spinal stenosis, spondylolysis/spondylolisthesis, and referred pain from the hip, knee, or upper back. It can also be caused by referred pain from visceral organs such as the liver, colon, or kidneys. Low back pain can also signal primary or metastatic disease. However, most of these potential diagnoses had been ruled out with imaging and lab tests.

Continue to: Two things caught our attention

Two things caught our attention. First: Mechanical low back pain and the associated discogenic radiculopathy would be unilateral, manifesting with asymmetric paresthesias and pain. Our patient had weakness in gait and pain and burning in both of his legs. Second: Our patient described decreased sleep and feeling anxious, with symptoms of forgetfulness, confusion, and agitation. These factors prompted us to look beyond the normal differential and consider a potential toxicity. A heavy metal screen was ordered, and the results were positive for arsenic toxicity.

DISCUSSION

Arsenic toxicity is a global health problem that affects millions of people.^1,2 Arsenic has been used for centuries in depilatories, cosmetics, poisons, and therapeutic agents. Today it is used as a treatment for leukemia and in several ayurvedic and homeopathic remedies.^3-7 It is a common earth element found in ground water and a waste product from mining and the manufacturing of glass, computer chips, wood preservatives, and various pesticides.^2,3,7,8

A great masquerader. Once in the body, arsenic can cause many serious ailments ranging from urinary tract, liver, and skin cancers to various peripheral and central nervous system disorders.² Arsenic can cause symmetrical peripheral neuropathy characterized by sensory nerves being more sensitive than motor nerves.^2,3,5,6 Clinically, it causes numbness and paresthesias of the distal extremities, with the lower extremities more severely affected.^3,6 Symptoms can develop within 2 hours to 2 years of exposure, with vomiting, diarrhea, or both preceding the onset of the neuropathy.^2,3,5,6 Arsenic is linked to forgetfulness, confusion, visual distortion, sleep disturbances, decreased concentration, disorientation, severe agitation, paranoid ideation, emotional lability, and decreases in locomotor activity.^3,5,6

Testing and treatment. Arsenic levels in the body are measured by blood and urine testing. Blood arsenic levels are typically detectable immediately after exposure and with continued exposure, but quickly normalize as the metal integrates into the nonvascular tissues. Urine arsenic levels can be detected for weeks. Normal levels for arsenic in both urine and blood are ≤ 12 µg/L.³ Anything greater than 12 µg/L is considered high; critically high values are those above 50 µg/L.^3,5 Our patient’s blood arsenic level was 13 µg/L.

Several of the patient’s symptoms prompted us to look beyond the normal differential and consider a potential toxicity.

Treatment involves removing the source of the arsenic. Chelation therapy should be pursued when urine arsenic levels are greater than 50 µg/L or when removing the source of the arsenic fails to reduce arsenic levels. Chelation therapy should be continued until urine arsenic levels are below 20 µg/L.^5,6

Continue to: After discussing potential sources of exposure

After discussing potential sources of exposure, our patient decided to move out of the house he shared with his ex-wife. He started to recover soon after moving out. Two weeks after his clinic visit, he no longer needed a cane to walk, and his blood arsenic level had dropped to 6 µg/L. Two months after his clinic visit, the patient’s blood arsenic level was undetectable. The patient’s peripheral neuropathy symptoms continued to improve.

The source of this patient’s arsenic exposure was never confirmed. The exposure could have occurred in Puerto Rico or in Louisiana. Even though no one else in the Louisiana home became ill, the patient was instructed to contact the local health department and water department to have the water tested. However, when he returned to the clinic for follow-up, he had not followed through.

THE TAKEAWAY

When evaluating causes of peripheral neuropathy, consider the possibility of heavy metal toxicity, which can be easily overlooked by the busy clinician. In this case, the patient initially experienced asymmetric paresthesia that gradually increased to burning pain and weakness, with reduced motor control bilaterally. This was significant because mechanical low back pain and the associated discogenic radiculopathy would be unilateral, manifesting with asymmetric paresthesias and pain.

Our patient’s leg symptoms, the constellation of forgetfulness, confusion, and agitation, and his sleep issues prompted us to look outside our normal differential. Fortunately, once arsenic exposure ceases, patients will gradually improve because arsenic is rapidly cleared from the bloodstream.^3,6

CORRESPONDENCE
Charles W. Webb, DO, CAQSM, FAMSSM, FAAFP, Department of Family Medicine, 1501 Kings Highway, PO Box 33932, Shreveport, LA 71130-3932; [email protected]

THE CASE

A 34-year-old man was referred to the sports medicine clinic for evaluation of lumbar radiculopathy. He had a 2-year history of chronic lower back pain that started while he was working on power line towers in Puerto Rico. The back pain was achy, burning, shooting, and stabbing in nature. He had been treated with anti-inflammatories by a company health care provider while in Puerto Rico, but he did not have any imaging done.

At that time, he had tingling and burning that radiated down his left leg to his ankle. The patient also had leg spasms—in his left leg more than his right—and needed a cane when walking. His symptoms did not worsen at any particular time of day or with activity. He had no history of eating exotic foods or sustaining any venomous bites/stings. Ultimately, the back pain and leg spasms forced him to leave his job and return home to Louisiana.

Upon presentation to the sports medicine clinic, he explained that things had worsened since his return home. The pain and burning in his left leg had increased and were now present in his right leg, as well (bilateral paresthesias). In addition, he said he was feeling anxious (and described symptoms of forgetfulness, confusion, and agitation), was sleeping less, and was experiencing worsening fatigue.

Work-ups over the course of the previous 2 years had shed little light on the cause of his symptoms. X-rays of his lumbar spine revealed moderate degenerative changes at L5-S1. A lab work-up was negative and included a complete blood count, testing for HIV and herpes, a hepatitis panel, an antinuclear antibody screen, a C-reactive protein test, and a comprehensive metabolic panel. Thyroid-stimulating hormone, creatine kinase, rapid plasma reagin, and human leukocyte antigen B27 tests were also normal.

Magnetic resonance imaging (MRI) revealed a cystic lesion in the right ilium near the sacroiliac joint. A more recent follow-up MRI and computed tomography scan of the pelvis found the cyst to be stable and well marginalized, with no cortical erosion. Attempts at physical therapy had been unsuccessful because of the pain and decreasing muscle strength in his lower extremities. The patient’s primary care provider was treating him with meloxicam 15 mg/d and duloxetine 60 mg/d, but that had not provided any relief.

Our physical examination revealed a patient who was in mild distress and had limited lumbar spine range of motion (secondary to pain in all planes) and significant paraspinal spasms on the right side in both the lumbar and thoracic regions. The patient had reduced vibratory sensation on his left side vs the right, with a 256-Hz tuning fork at the great toe, as well as reduced sensation to fine touch with a cotton swab and a positive Babinski sign bilaterally. Lower extremity reflexes were hyperreflexic on the left compared with the right. He had no pronator drift; Trendelenburg, straight leg raise, Hoover sign, and slump tests were all negative. His gait was antalgic with a cane, as he described bilateral paresthesias.

THE DIAGNOSIS

The differential diagnosis for low back pain is quite extensive and includes simple mechanical low back pain, lumbar radiculopathy, facet arthritis, spinal stenosis, spondylolysis/spondylolisthesis, and referred pain from the hip, knee, or upper back. It can also be caused by referred pain from visceral organs such as the liver, colon, or kidneys. Low back pain can also signal primary or metastatic disease. However, most of these potential diagnoses had been ruled out with imaging and lab tests.

Continue to: Two things caught our attention

Two things caught our attention. First: Mechanical low back pain and the associated discogenic radiculopathy would be unilateral, manifesting with asymmetric paresthesias and pain. Our patient had weakness in gait and pain and burning in both of his legs. Second: Our patient described decreased sleep and feeling anxious, with symptoms of forgetfulness, confusion, and agitation. These factors prompted us to look beyond the normal differential and consider a potential toxicity. A heavy metal screen was ordered, and the results were positive for arsenic toxicity.

DISCUSSION

Arsenic toxicity is a global health problem that affects millions of people.^1,2 Arsenic has been used for centuries in depilatories, cosmetics, poisons, and therapeutic agents. Today it is used as a treatment for leukemia and in several ayurvedic and homeopathic remedies.^3-7 It is a common earth element found in ground water and a waste product from mining and the manufacturing of glass, computer chips, wood preservatives, and various pesticides.^2,3,7,8

A great masquerader. Once in the body, arsenic can cause many serious ailments ranging from urinary tract, liver, and skin cancers to various peripheral and central nervous system disorders.² Arsenic can cause symmetrical peripheral neuropathy characterized by sensory nerves being more sensitive than motor nerves.^2,3,5,6 Clinically, it causes numbness and paresthesias of the distal extremities, with the lower extremities more severely affected.^3,6 Symptoms can develop within 2 hours to 2 years of exposure, with vomiting, diarrhea, or both preceding the onset of the neuropathy.^2,3,5,6 Arsenic is linked to forgetfulness, confusion, visual distortion, sleep disturbances, decreased concentration, disorientation, severe agitation, paranoid ideation, emotional lability, and decreases in locomotor activity.^3,5,6

Testing and treatment. Arsenic levels in the body are measured by blood and urine testing. Blood arsenic levels are typically detectable immediately after exposure and with continued exposure, but quickly normalize as the metal integrates into the nonvascular tissues. Urine arsenic levels can be detected for weeks. Normal levels for arsenic in both urine and blood are ≤ 12 µg/L.³ Anything greater than 12 µg/L is considered high; critically high values are those above 50 µg/L.^3,5 Our patient’s blood arsenic level was 13 µg/L.

Several of the patient’s symptoms prompted us to look beyond the normal differential and consider a potential toxicity.

Treatment involves removing the source of the arsenic. Chelation therapy should be pursued when urine arsenic levels are greater than 50 µg/L or when removing the source of the arsenic fails to reduce arsenic levels. Chelation therapy should be continued until urine arsenic levels are below 20 µg/L.^5,6

Continue to: After discussing potential sources of exposure

After discussing potential sources of exposure, our patient decided to move out of the house he shared with his ex-wife. He started to recover soon after moving out. Two weeks after his clinic visit, he no longer needed a cane to walk, and his blood arsenic level had dropped to 6 µg/L. Two months after his clinic visit, the patient’s blood arsenic level was undetectable. The patient’s peripheral neuropathy symptoms continued to improve.

The source of this patient’s arsenic exposure was never confirmed. The exposure could have occurred in Puerto Rico or in Louisiana. Even though no one else in the Louisiana home became ill, the patient was instructed to contact the local health department and water department to have the water tested. However, when he returned to the clinic for follow-up, he had not followed through.

THE TAKEAWAY

When evaluating causes of peripheral neuropathy, consider the possibility of heavy metal toxicity, which can be easily overlooked by the busy clinician. In this case, the patient initially experienced asymmetric paresthesia that gradually increased to burning pain and weakness, with reduced motor control bilaterally. This was significant because mechanical low back pain and the associated discogenic radiculopathy would be unilateral, manifesting with asymmetric paresthesias and pain.

Our patient’s leg symptoms, the constellation of forgetfulness, confusion, and agitation, and his sleep issues prompted us to look outside our normal differential. Fortunately, once arsenic exposure ceases, patients will gradually improve because arsenic is rapidly cleared from the bloodstream.^3,6

CORRESPONDENCE
Charles W. Webb, DO, CAQSM, FAMSSM, FAAFP, Department of Family Medicine, 1501 Kings Highway, PO Box 33932, Shreveport, LA 71130-3932; [email protected]

THE CASE

A 34-year-old man was referred to the sports medicine clinic for evaluation of lumbar radiculopathy. He had a 2-year history of chronic lower back pain that started while he was working on power line towers in Puerto Rico. The back pain was achy, burning, shooting, and stabbing in nature. He had been treated with anti-inflammatories by a company health care provider while in Puerto Rico, but he did not have any imaging done.

At that time, he had tingling and burning that radiated down his left leg to his ankle. The patient also had leg spasms—in his left leg more than his right—and needed a cane when walking. His symptoms did not worsen at any particular time of day or with activity. He had no history of eating exotic foods or sustaining any venomous bites/stings. Ultimately, the back pain and leg spasms forced him to leave his job and return home to Louisiana.

Upon presentation to the sports medicine clinic, he explained that things had worsened since his return home. The pain and burning in his left leg had increased and were now present in his right leg, as well (bilateral paresthesias). In addition, he said he was feeling anxious (and described symptoms of forgetfulness, confusion, and agitation), was sleeping less, and was experiencing worsening fatigue.

Work-ups over the course of the previous 2 years had shed little light on the cause of his symptoms. X-rays of his lumbar spine revealed moderate degenerative changes at L5-S1. A lab work-up was negative and included a complete blood count, testing for HIV and herpes, a hepatitis panel, an antinuclear antibody screen, a C-reactive protein test, and a comprehensive metabolic panel. Thyroid-stimulating hormone, creatine kinase, rapid plasma reagin, and human leukocyte antigen B27 tests were also normal.

Magnetic resonance imaging (MRI) revealed a cystic lesion in the right ilium near the sacroiliac joint. A more recent follow-up MRI and computed tomography scan of the pelvis found the cyst to be stable and well marginalized, with no cortical erosion. Attempts at physical therapy had been unsuccessful because of the pain and decreasing muscle strength in his lower extremities. The patient’s primary care provider was treating him with meloxicam 15 mg/d and duloxetine 60 mg/d, but that had not provided any relief.

Our physical examination revealed a patient who was in mild distress and had limited lumbar spine range of motion (secondary to pain in all planes) and significant paraspinal spasms on the right side in both the lumbar and thoracic regions. The patient had reduced vibratory sensation on his left side vs the right, with a 256-Hz tuning fork at the great toe, as well as reduced sensation to fine touch with a cotton swab and a positive Babinski sign bilaterally. Lower extremity reflexes were hyperreflexic on the left compared with the right. He had no pronator drift; Trendelenburg, straight leg raise, Hoover sign, and slump tests were all negative. His gait was antalgic with a cane, as he described bilateral paresthesias.

THE DIAGNOSIS

The differential diagnosis for low back pain is quite extensive and includes simple mechanical low back pain, lumbar radiculopathy, facet arthritis, spinal stenosis, spondylolysis/spondylolisthesis, and referred pain from the hip, knee, or upper back. It can also be caused by referred pain from visceral organs such as the liver, colon, or kidneys. Low back pain can also signal primary or metastatic disease. However, most of these potential diagnoses had been ruled out with imaging and lab tests.

Continue to: Two things caught our attention

Two things caught our attention. First: Mechanical low back pain and the associated discogenic radiculopathy would be unilateral, manifesting with asymmetric paresthesias and pain. Our patient had weakness in gait and pain and burning in both of his legs. Second: Our patient described decreased sleep and feeling anxious, with symptoms of forgetfulness, confusion, and agitation. These factors prompted us to look beyond the normal differential and consider a potential toxicity. A heavy metal screen was ordered, and the results were positive for arsenic toxicity.

DISCUSSION

Arsenic toxicity is a global health problem that affects millions of people.^1,2 Arsenic has been used for centuries in depilatories, cosmetics, poisons, and therapeutic agents. Today it is used as a treatment for leukemia and in several ayurvedic and homeopathic remedies.^3-7 It is a common earth element found in ground water and a waste product from mining and the manufacturing of glass, computer chips, wood preservatives, and various pesticides.^2,3,7,8

A great masquerader. Once in the body, arsenic can cause many serious ailments ranging from urinary tract, liver, and skin cancers to various peripheral and central nervous system disorders.² Arsenic can cause symmetrical peripheral neuropathy characterized by sensory nerves being more sensitive than motor nerves.^2,3,5,6 Clinically, it causes numbness and paresthesias of the distal extremities, with the lower extremities more severely affected.^3,6 Symptoms can develop within 2 hours to 2 years of exposure, with vomiting, diarrhea, or both preceding the onset of the neuropathy.^2,3,5,6 Arsenic is linked to forgetfulness, confusion, visual distortion, sleep disturbances, decreased concentration, disorientation, severe agitation, paranoid ideation, emotional lability, and decreases in locomotor activity.^3,5,6

Testing and treatment. Arsenic levels in the body are measured by blood and urine testing. Blood arsenic levels are typically detectable immediately after exposure and with continued exposure, but quickly normalize as the metal integrates into the nonvascular tissues. Urine arsenic levels can be detected for weeks. Normal levels for arsenic in both urine and blood are ≤ 12 µg/L.³ Anything greater than 12 µg/L is considered high; critically high values are those above 50 µg/L.^3,5 Our patient’s blood arsenic level was 13 µg/L.

Several of the patient’s symptoms prompted us to look beyond the normal differential and consider a potential toxicity.

Treatment involves removing the source of the arsenic. Chelation therapy should be pursued when urine arsenic levels are greater than 50 µg/L or when removing the source of the arsenic fails to reduce arsenic levels. Chelation therapy should be continued until urine arsenic levels are below 20 µg/L.^5,6

Continue to: After discussing potential sources of exposure

After discussing potential sources of exposure, our patient decided to move out of the house he shared with his ex-wife. He started to recover soon after moving out. Two weeks after his clinic visit, he no longer needed a cane to walk, and his blood arsenic level had dropped to 6 µg/L. Two months after his clinic visit, the patient’s blood arsenic level was undetectable. The patient’s peripheral neuropathy symptoms continued to improve.

The source of this patient’s arsenic exposure was never confirmed. The exposure could have occurred in Puerto Rico or in Louisiana. Even though no one else in the Louisiana home became ill, the patient was instructed to contact the local health department and water department to have the water tested. However, when he returned to the clinic for follow-up, he had not followed through.

THE TAKEAWAY

When evaluating causes of peripheral neuropathy, consider the possibility of heavy metal toxicity, which can be easily overlooked by the busy clinician. In this case, the patient initially experienced asymmetric paresthesia that gradually increased to burning pain and weakness, with reduced motor control bilaterally. This was significant because mechanical low back pain and the associated discogenic radiculopathy would be unilateral, manifesting with asymmetric paresthesias and pain.

Our patient’s leg symptoms, the constellation of forgetfulness, confusion, and agitation, and his sleep issues prompted us to look outside our normal differential. Fortunately, once arsenic exposure ceases, patients will gradually improve because arsenic is rapidly cleared from the bloodstream.^3,6

CORRESPONDENCE
Charles W. Webb, DO, CAQSM, FAMSSM, FAAFP, Department of Family Medicine, 1501 Kings Highway, PO Box 33932, Shreveport, LA 71130-3932; [email protected]

A 12-YEAR-OLD BOY presented to the hospital with a 2-day history of fever, cough, and painful blisters on swollen lips. On examination, he had multiple tense blisters with clear fluid on the buccal mucosa and inner lips (FIGURE 1A), as well as multiple discrete ulcers on his posterior pharynx. The patient had no other skin, eye, or urogenital involvement, but he was dehydrated. Respiratory examination was unremarkable. A complete blood count and metabolic panel were normal, as was a ­C-reactive protein (CRP) test (0.8 mg/L).

The preliminary diagnosis was primary herpetic gingivostomatitis, and treatment was initiated with intravenous (IV) acyclovir (10 mg/kg every 8 hours), IV fluids, and topical lidocaine gel and topical steroids for analgesia. However, the patient’s fever persisted over the next 4 days, with his temperature fluctuating between 101.3 °F and 104 °F, and he had a worsening productive cough. The blisters ruptured on Day 6 of illness, leaving hemorrhagic crusting on his lips (FIGURE 1B). Herpes simplex virus types 1 and 2 and polymerase chain reaction (PCR) testing were negative.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Further follow-up on Day 6 of illness revealed bibasilar crepitations along with an elevated CRP level of 40.5 mg/L and a positive mycoplasma antibody serology (titer > 1:1280; ­normal, < 1:80). The patient was given a diagnosis of pneumonia (due to infection with Mycoplasma pneumoniae) and M ­pneumoniae–induced rash and mucositis (MIRM).

MIRM was first proposed as a distinct clinical entity in 2015 to distinguish it from Stevens-Johnson syndrome and erythema multiforme.¹ MIRM is seen more commonly in children and young adults, with a male preponderance.¹

Within 3 days of initiating treatment with IV ceftriaxone, azithromycin, and methylprednisolone, our patient experienced marked improvement of his symptoms.

A small longitudinal study found that approximately 22.7% of children who have M pneumoniae infections present with mucocutaneous lesions, and of those cases, 6.8% are MIRM.²Chlamydia pneumoniae is another potential causal organism of mucositis resembling MIRM.³

Pathogenesis. The commonly accepted mechanism of MIRM is an immune response triggered by a distant infection. This leads to tissue damage via polyclonal B cell proliferation and subsequent immune complex deposition, complement activation, and cytokine overproduction. Molecular mimicry between M pneumoniae P1-adhesion molecules and keratinocyte antigens may also contribute to this pathway.

3 criteria to make the diagnosis

Canavan et al¹ have proposed the following criteria for the diagnosis of MIRM:

• Clinical symptoms, such as fever and cough, and laboratory findings of M pneumoniae infection (elevated M pneumoniae immunoglobulin M antibodies, positive cultures or PCR for M pneumoniae from oropharyngeal samples or bullae, and/or serial cold agglutinins) AND
• a rash to the mucosa that usually affects ≥ 2 sites (although rare cases may have fewer than 2 mucosal sites involved) AND
• skin detachment of less than 10% of the body surface area.

Continue to: The 3 variants of MIRM include...

The 3 variants of MIRM include:

• Classic MIRM has evidence of all 3 diagnostic criteria plus a nonmucosal rash, such as vesiculobullous lesions (77%), scattered target lesions (48%), papules (14%), macules (12%), and morbilliform eruptions (9%).⁴
• MIRM sine rash includes all 3 criteria but there is no significant cutaneous, nonmucosal rash. There may be “few fleeting morbilliform lesions or a few vesicles.”⁴
• Severe MIRM includes the first 2 criteria listed, but the cutaneous rash is extensive, with widespread nonmucosal blisters or flat atypical target lesions.⁴

Our patient had definitive clinical symptoms, laboratory evidence, and severe oral mucositis without significant cutaneous rash, thereby fulfilling the criteria for a diagnosis of MIRM sine rash variant.

These skin conditions were considered in the differential

The differential diagnosis for sudden onset of severe oral mucosal blisters in children includes herpes gingivostomatitis; hand, foot, and mouth disease; erythema multiforme; and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The presence of pulmonary symptoms and oropharyngeal mucositis, together with the laboratory markers currently proposed as MIRM diagnostic criteria, are important in helping differentiate MIRM from other items in the differential diagnosis.

Herpes gingivostomatitis would involve numerous ulcerations of the oral mucosa and tongue, as well as gum hypertrophy.

Hand, foot, and mouth disease is characterized by vesicular exanthems of the hands, legs, and buttocks.

Continue to: Erythema multiforme

Erythema multiforme appears as cutaneous target lesions on the limbs that spread in a centripetal manner following herpes simplex virus infection.

SJS/TEN manifests with severe mucositis and is commonly triggered by medications (eg, sulphonamides, beta-lactams, nonsteroidal anti-inflammatory drugs, and antiepileptics).

With antibiotics, the prognosis is good

There are no established guidelines for the treatment of MIRM. Antibiotics and supportive care are universally accepted. Immunosuppressive therapy (eg, systemic steroids) is frequently used in patients with MIRM who have extensive mucosal involvement, in an attempt to decrease inflammation and pain; however, evidence for such an approach is lacking. The hyperimmune reactions of the host to M pneumoniae infection include cytokine overproduction and T-cell activation, which promote both pulmonary and extrapulmonary manifestations. This forms the basis of immunosuppressive therapy, such as systemic corticosteroids, IV immunoglobulin, and cyclosporin A, particularly when MIRM is associated with pneumonia caused by infection with M pneumoniae.^1,5,6

The overall prognosis of MIRM is good. Recurrence has been reported in up to 8% of cases, the treatment of which remains the same. Mucocutaneous and ocular sequelae (oral or genital synechiae, corneal ulcerations, dry eyes, loss of eye lashes) have been reported in less than 9% of patients.¹ Other rare reported complications following the occurrence of MIRM include persistent cutaneous lesions, B cell lymphopenia, and restrictive lung disease or chronic obliterative bronchitis.

Our patient was started on IV ­ceftriaxone (50 mg/kg/d), azithromycin (10 mg/kg/d on the first day, then 5 mg/kg/d on the sub­sequent 5 days), and methylprednisolone (3 mg/kg/d) on Day 6 of illness. Within 3 days, there was marked improvement of mucositis and respiratory symptoms with resolution of fever. He was discharged on Day 10. At his outpatient follow-up 2 weeks later, the patient had made a complete recovery.

A 12-YEAR-OLD BOY presented to the hospital with a 2-day history of fever, cough, and painful blisters on swollen lips. On examination, he had multiple tense blisters with clear fluid on the buccal mucosa and inner lips (FIGURE 1A), as well as multiple discrete ulcers on his posterior pharynx. The patient had no other skin, eye, or urogenital involvement, but he was dehydrated. Respiratory examination was unremarkable. A complete blood count and metabolic panel were normal, as was a ­C-reactive protein (CRP) test (0.8 mg/L).

The preliminary diagnosis was primary herpetic gingivostomatitis, and treatment was initiated with intravenous (IV) acyclovir (10 mg/kg every 8 hours), IV fluids, and topical lidocaine gel and topical steroids for analgesia. However, the patient’s fever persisted over the next 4 days, with his temperature fluctuating between 101.3 °F and 104 °F, and he had a worsening productive cough. The blisters ruptured on Day 6 of illness, leaving hemorrhagic crusting on his lips (FIGURE 1B). Herpes simplex virus types 1 and 2 and polymerase chain reaction (PCR) testing were negative.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Further follow-up on Day 6 of illness revealed bibasilar crepitations along with an elevated CRP level of 40.5 mg/L and a positive mycoplasma antibody serology (titer > 1:1280; ­normal, < 1:80). The patient was given a diagnosis of pneumonia (due to infection with Mycoplasma pneumoniae) and M ­pneumoniae–induced rash and mucositis (MIRM).

MIRM was first proposed as a distinct clinical entity in 2015 to distinguish it from Stevens-Johnson syndrome and erythema multiforme.¹ MIRM is seen more commonly in children and young adults, with a male preponderance.¹

Within 3 days of initiating treatment with IV ceftriaxone, azithromycin, and methylprednisolone, our patient experienced marked improvement of his symptoms.

A small longitudinal study found that approximately 22.7% of children who have M pneumoniae infections present with mucocutaneous lesions, and of those cases, 6.8% are MIRM.²Chlamydia pneumoniae is another potential causal organism of mucositis resembling MIRM.³

Pathogenesis. The commonly accepted mechanism of MIRM is an immune response triggered by a distant infection. This leads to tissue damage via polyclonal B cell proliferation and subsequent immune complex deposition, complement activation, and cytokine overproduction. Molecular mimicry between M pneumoniae P1-adhesion molecules and keratinocyte antigens may also contribute to this pathway.

3 criteria to make the diagnosis

Canavan et al¹ have proposed the following criteria for the diagnosis of MIRM:

• Clinical symptoms, such as fever and cough, and laboratory findings of M pneumoniae infection (elevated M pneumoniae immunoglobulin M antibodies, positive cultures or PCR for M pneumoniae from oropharyngeal samples or bullae, and/or serial cold agglutinins) AND
• a rash to the mucosa that usually affects ≥ 2 sites (although rare cases may have fewer than 2 mucosal sites involved) AND
• skin detachment of less than 10% of the body surface area.

Continue to: The 3 variants of MIRM include...

The 3 variants of MIRM include:

• Classic MIRM has evidence of all 3 diagnostic criteria plus a nonmucosal rash, such as vesiculobullous lesions (77%), scattered target lesions (48%), papules (14%), macules (12%), and morbilliform eruptions (9%).⁴
• MIRM sine rash includes all 3 criteria but there is no significant cutaneous, nonmucosal rash. There may be “few fleeting morbilliform lesions or a few vesicles.”⁴
• Severe MIRM includes the first 2 criteria listed, but the cutaneous rash is extensive, with widespread nonmucosal blisters or flat atypical target lesions.⁴

Our patient had definitive clinical symptoms, laboratory evidence, and severe oral mucositis without significant cutaneous rash, thereby fulfilling the criteria for a diagnosis of MIRM sine rash variant.

These skin conditions were considered in the differential

The differential diagnosis for sudden onset of severe oral mucosal blisters in children includes herpes gingivostomatitis; hand, foot, and mouth disease; erythema multiforme; and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The presence of pulmonary symptoms and oropharyngeal mucositis, together with the laboratory markers currently proposed as MIRM diagnostic criteria, are important in helping differentiate MIRM from other items in the differential diagnosis.

Herpes gingivostomatitis would involve numerous ulcerations of the oral mucosa and tongue, as well as gum hypertrophy.

Hand, foot, and mouth disease is characterized by vesicular exanthems of the hands, legs, and buttocks.

Continue to: Erythema multiforme

Erythema multiforme appears as cutaneous target lesions on the limbs that spread in a centripetal manner following herpes simplex virus infection.

SJS/TEN manifests with severe mucositis and is commonly triggered by medications (eg, sulphonamides, beta-lactams, nonsteroidal anti-inflammatory drugs, and antiepileptics).

With antibiotics, the prognosis is good

There are no established guidelines for the treatment of MIRM. Antibiotics and supportive care are universally accepted. Immunosuppressive therapy (eg, systemic steroids) is frequently used in patients with MIRM who have extensive mucosal involvement, in an attempt to decrease inflammation and pain; however, evidence for such an approach is lacking. The hyperimmune reactions of the host to M pneumoniae infection include cytokine overproduction and T-cell activation, which promote both pulmonary and extrapulmonary manifestations. This forms the basis of immunosuppressive therapy, such as systemic corticosteroids, IV immunoglobulin, and cyclosporin A, particularly when MIRM is associated with pneumonia caused by infection with M pneumoniae.^1,5,6

The overall prognosis of MIRM is good. Recurrence has been reported in up to 8% of cases, the treatment of which remains the same. Mucocutaneous and ocular sequelae (oral or genital synechiae, corneal ulcerations, dry eyes, loss of eye lashes) have been reported in less than 9% of patients.¹ Other rare reported complications following the occurrence of MIRM include persistent cutaneous lesions, B cell lymphopenia, and restrictive lung disease or chronic obliterative bronchitis.

Our patient was started on IV ­ceftriaxone (50 mg/kg/d), azithromycin (10 mg/kg/d on the first day, then 5 mg/kg/d on the sub­sequent 5 days), and methylprednisolone (3 mg/kg/d) on Day 6 of illness. Within 3 days, there was marked improvement of mucositis and respiratory symptoms with resolution of fever. He was discharged on Day 10. At his outpatient follow-up 2 weeks later, the patient had made a complete recovery.

A 12-YEAR-OLD BOY presented to the hospital with a 2-day history of fever, cough, and painful blisters on swollen lips. On examination, he had multiple tense blisters with clear fluid on the buccal mucosa and inner lips (FIGURE 1A), as well as multiple discrete ulcers on his posterior pharynx. The patient had no other skin, eye, or urogenital involvement, but he was dehydrated. Respiratory examination was unremarkable. A complete blood count and metabolic panel were normal, as was a ­C-reactive protein (CRP) test (0.8 mg/L).

The preliminary diagnosis was primary herpetic gingivostomatitis, and treatment was initiated with intravenous (IV) acyclovir (10 mg/kg every 8 hours), IV fluids, and topical lidocaine gel and topical steroids for analgesia. However, the patient’s fever persisted over the next 4 days, with his temperature fluctuating between 101.3 °F and 104 °F, and he had a worsening productive cough. The blisters ruptured on Day 6 of illness, leaving hemorrhagic crusting on his lips (FIGURE 1B). Herpes simplex virus types 1 and 2 and polymerase chain reaction (PCR) testing were negative.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Further follow-up on Day 6 of illness revealed bibasilar crepitations along with an elevated CRP level of 40.5 mg/L and a positive mycoplasma antibody serology (titer > 1:1280; ­normal, < 1:80). The patient was given a diagnosis of pneumonia (due to infection with Mycoplasma pneumoniae) and M ­pneumoniae–induced rash and mucositis (MIRM).

MIRM was first proposed as a distinct clinical entity in 2015 to distinguish it from Stevens-Johnson syndrome and erythema multiforme.¹ MIRM is seen more commonly in children and young adults, with a male preponderance.¹

Within 3 days of initiating treatment with IV ceftriaxone, azithromycin, and methylprednisolone, our patient experienced marked improvement of his symptoms.

A small longitudinal study found that approximately 22.7% of children who have M pneumoniae infections present with mucocutaneous lesions, and of those cases, 6.8% are MIRM.²Chlamydia pneumoniae is another potential causal organism of mucositis resembling MIRM.³

Pathogenesis. The commonly accepted mechanism of MIRM is an immune response triggered by a distant infection. This leads to tissue damage via polyclonal B cell proliferation and subsequent immune complex deposition, complement activation, and cytokine overproduction. Molecular mimicry between M pneumoniae P1-adhesion molecules and keratinocyte antigens may also contribute to this pathway.

3 criteria to make the diagnosis

Canavan et al¹ have proposed the following criteria for the diagnosis of MIRM:

• Clinical symptoms, such as fever and cough, and laboratory findings of M pneumoniae infection (elevated M pneumoniae immunoglobulin M antibodies, positive cultures or PCR for M pneumoniae from oropharyngeal samples or bullae, and/or serial cold agglutinins) AND
• a rash to the mucosa that usually affects ≥ 2 sites (although rare cases may have fewer than 2 mucosal sites involved) AND
• skin detachment of less than 10% of the body surface area.

Continue to: The 3 variants of MIRM include...

The 3 variants of MIRM include:

• Classic MIRM has evidence of all 3 diagnostic criteria plus a nonmucosal rash, such as vesiculobullous lesions (77%), scattered target lesions (48%), papules (14%), macules (12%), and morbilliform eruptions (9%).⁴
• MIRM sine rash includes all 3 criteria but there is no significant cutaneous, nonmucosal rash. There may be “few fleeting morbilliform lesions or a few vesicles.”⁴
• Severe MIRM includes the first 2 criteria listed, but the cutaneous rash is extensive, with widespread nonmucosal blisters or flat atypical target lesions.⁴

Our patient had definitive clinical symptoms, laboratory evidence, and severe oral mucositis without significant cutaneous rash, thereby fulfilling the criteria for a diagnosis of MIRM sine rash variant.

These skin conditions were considered in the differential

The differential diagnosis for sudden onset of severe oral mucosal blisters in children includes herpes gingivostomatitis; hand, foot, and mouth disease; erythema multiforme; and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The presence of pulmonary symptoms and oropharyngeal mucositis, together with the laboratory markers currently proposed as MIRM diagnostic criteria, are important in helping differentiate MIRM from other items in the differential diagnosis.

Herpes gingivostomatitis would involve numerous ulcerations of the oral mucosa and tongue, as well as gum hypertrophy.

Hand, foot, and mouth disease is characterized by vesicular exanthems of the hands, legs, and buttocks.

Continue to: Erythema multiforme

Erythema multiforme appears as cutaneous target lesions on the limbs that spread in a centripetal manner following herpes simplex virus infection.

SJS/TEN manifests with severe mucositis and is commonly triggered by medications (eg, sulphonamides, beta-lactams, nonsteroidal anti-inflammatory drugs, and antiepileptics).

With antibiotics, the prognosis is good

There are no established guidelines for the treatment of MIRM. Antibiotics and supportive care are universally accepted. Immunosuppressive therapy (eg, systemic steroids) is frequently used in patients with MIRM who have extensive mucosal involvement, in an attempt to decrease inflammation and pain; however, evidence for such an approach is lacking. The hyperimmune reactions of the host to M pneumoniae infection include cytokine overproduction and T-cell activation, which promote both pulmonary and extrapulmonary manifestations. This forms the basis of immunosuppressive therapy, such as systemic corticosteroids, IV immunoglobulin, and cyclosporin A, particularly when MIRM is associated with pneumonia caused by infection with M pneumoniae.^1,5,6

The overall prognosis of MIRM is good. Recurrence has been reported in up to 8% of cases, the treatment of which remains the same. Mucocutaneous and ocular sequelae (oral or genital synechiae, corneal ulcerations, dry eyes, loss of eye lashes) have been reported in less than 9% of patients.¹ Other rare reported complications following the occurrence of MIRM include persistent cutaneous lesions, B cell lymphopenia, and restrictive lung disease or chronic obliterative bronchitis.

Our patient was started on IV ­ceftriaxone (50 mg/kg/d), azithromycin (10 mg/kg/d on the first day, then 5 mg/kg/d on the sub­sequent 5 days), and methylprednisolone (3 mg/kg/d) on Day 6 of illness. Within 3 days, there was marked improvement of mucositis and respiratory symptoms with resolution of fever. He was discharged on Day 10. At his outpatient follow-up 2 weeks later, the patient had made a complete recovery.

I work with medical students nearly every day that I see patients. I recently mentioned to a student that I have a limited working knowledge of the brand names of diabetes medications released in the past 10 years. Just like the M3s, I need the full generic name to know whether a medication is a GLP-1 inhibitor or a ­DPP-4 inhibitor, because I know that “flozins” are SGLT-2 inhibitors and ­“glutides” are GLP-1 agonists. The combined efforts of an ambulatory care pharmacist and some flashcards have helped me to better understand how they work and which ones to prescribe when. Meanwhile, the residents are capably counseling on the adverse effects of the latest diabetes agent, while I am googling its generic name.

The premise of science is continuous discovery. In the first 10 months of 2022, the US Food & Drug Administration approved more than 2 dozen new medications, almost 100 new generics, and new indications for dozens more.^1,2 The US Preventive Services Task Force (USPSTF) issued 13 new or reaffirmed recommendations in the first 10 months of 2022, and it is just one of dozens of bodies that issue guidelines relevant to primary care.³ PubMed indexes more than a million new articles each year. Learning new information and changing practice are crucial to being an effective clinician.

In this edition of JFP, Covey and Cagle⁴ write about updates to the USPSTF’s lung cancer screening guidelines. The authors reference changing evidence that led to the revised recommendations. When the original guideline was released in 2013, it drew on the best available evidence at the time.⁵ The National Lung Screening Trial, which looked at CT scanning compared with chest x-rays as screening tests for lung cancer, was groundbreaking in its methods and results.⁶ However, it was not without its flaws. It enrolled < 5% Black patients, and so the recommendations for age cutoffs and pack-year cutoffs were made based on the majority White population from the trial.

Not adopting the new lung cancer screening recommendations would exclude patients most at risk of lung cancer and allow disparities to grow.

Black patients experience a higher mortality from lung cancer and are diagnosed at an earlier age and a lower cumulative pack-year exposure than White patients.⁷ Other studies have explored the social and political factors that lead to these disparities, which range from access to care to racial segregation of neighborhoods and tobacco marketing practices.⁷ When the USPSTF performed its periodic update of the guideline, it had access to additional research. The updates reflect the new information.

Every physician has a responsibility to find a way to adapt to important new information in medicine. Not using ­SGLT-2 inhibitors in the management of diabetes would be substandard care, and my patients would suffer for it. Not adopting the new lung cancer screening recommendations would exclude patients most at risk of lung cancer and allow disparities in lung cancer morbidity and mortality to grow.^7,8Understanding the evidence behind the recommendations also reminds me that the guidelines will change again. These recommendations are no more static than the first guidelines were. I’ll be ready when the next update comes, and I’ll have the medical students and residents to keep me sharp.

I work with medical students nearly every day that I see patients. I recently mentioned to a student that I have a limited working knowledge of the brand names of diabetes medications released in the past 10 years. Just like the M3s, I need the full generic name to know whether a medication is a GLP-1 inhibitor or a ­DPP-4 inhibitor, because I know that “flozins” are SGLT-2 inhibitors and ­“glutides” are GLP-1 agonists. The combined efforts of an ambulatory care pharmacist and some flashcards have helped me to better understand how they work and which ones to prescribe when. Meanwhile, the residents are capably counseling on the adverse effects of the latest diabetes agent, while I am googling its generic name.

The premise of science is continuous discovery. In the first 10 months of 2022, the US Food & Drug Administration approved more than 2 dozen new medications, almost 100 new generics, and new indications for dozens more.^1,2 The US Preventive Services Task Force (USPSTF) issued 13 new or reaffirmed recommendations in the first 10 months of 2022, and it is just one of dozens of bodies that issue guidelines relevant to primary care.³ PubMed indexes more than a million new articles each year. Learning new information and changing practice are crucial to being an effective clinician.

In this edition of JFP, Covey and Cagle⁴ write about updates to the USPSTF’s lung cancer screening guidelines. The authors reference changing evidence that led to the revised recommendations. When the original guideline was released in 2013, it drew on the best available evidence at the time.⁵ The National Lung Screening Trial, which looked at CT scanning compared with chest x-rays as screening tests for lung cancer, was groundbreaking in its methods and results.⁶ However, it was not without its flaws. It enrolled < 5% Black patients, and so the recommendations for age cutoffs and pack-year cutoffs were made based on the majority White population from the trial.

Not adopting the new lung cancer screening recommendations would exclude patients most at risk of lung cancer and allow disparities to grow.

Black patients experience a higher mortality from lung cancer and are diagnosed at an earlier age and a lower cumulative pack-year exposure than White patients.⁷ Other studies have explored the social and political factors that lead to these disparities, which range from access to care to racial segregation of neighborhoods and tobacco marketing practices.⁷ When the USPSTF performed its periodic update of the guideline, it had access to additional research. The updates reflect the new information.

Every physician has a responsibility to find a way to adapt to important new information in medicine. Not using ­SGLT-2 inhibitors in the management of diabetes would be substandard care, and my patients would suffer for it. Not adopting the new lung cancer screening recommendations would exclude patients most at risk of lung cancer and allow disparities in lung cancer morbidity and mortality to grow.^7,8Understanding the evidence behind the recommendations also reminds me that the guidelines will change again. These recommendations are no more static than the first guidelines were. I’ll be ready when the next update comes, and I’ll have the medical students and residents to keep me sharp.

I work with medical students nearly every day that I see patients. I recently mentioned to a student that I have a limited working knowledge of the brand names of diabetes medications released in the past 10 years. Just like the M3s, I need the full generic name to know whether a medication is a GLP-1 inhibitor or a ­DPP-4 inhibitor, because I know that “flozins” are SGLT-2 inhibitors and ­“glutides” are GLP-1 agonists. The combined efforts of an ambulatory care pharmacist and some flashcards have helped me to better understand how they work and which ones to prescribe when. Meanwhile, the residents are capably counseling on the adverse effects of the latest diabetes agent, while I am googling its generic name.

The premise of science is continuous discovery. In the first 10 months of 2022, the US Food & Drug Administration approved more than 2 dozen new medications, almost 100 new generics, and new indications for dozens more.^1,2 The US Preventive Services Task Force (USPSTF) issued 13 new or reaffirmed recommendations in the first 10 months of 2022, and it is just one of dozens of bodies that issue guidelines relevant to primary care.³ PubMed indexes more than a million new articles each year. Learning new information and changing practice are crucial to being an effective clinician.

In this edition of JFP, Covey and Cagle⁴ write about updates to the USPSTF’s lung cancer screening guidelines. The authors reference changing evidence that led to the revised recommendations. When the original guideline was released in 2013, it drew on the best available evidence at the time.⁵ The National Lung Screening Trial, which looked at CT scanning compared with chest x-rays as screening tests for lung cancer, was groundbreaking in its methods and results.⁶ However, it was not without its flaws. It enrolled < 5% Black patients, and so the recommendations for age cutoffs and pack-year cutoffs were made based on the majority White population from the trial.

Not adopting the new lung cancer screening recommendations would exclude patients most at risk of lung cancer and allow disparities to grow.

Black patients experience a higher mortality from lung cancer and are diagnosed at an earlier age and a lower cumulative pack-year exposure than White patients.⁷ Other studies have explored the social and political factors that lead to these disparities, which range from access to care to racial segregation of neighborhoods and tobacco marketing practices.⁷ When the USPSTF performed its periodic update of the guideline, it had access to additional research. The updates reflect the new information.

Every physician has a responsibility to find a way to adapt to important new information in medicine. Not using ­SGLT-2 inhibitors in the management of diabetes would be substandard care, and my patients would suffer for it. Not adopting the new lung cancer screening recommendations would exclude patients most at risk of lung cancer and allow disparities in lung cancer morbidity and mortality to grow.^7,8Understanding the evidence behind the recommendations also reminds me that the guidelines will change again. These recommendations are no more static than the first guidelines were. I’ll be ready when the next update comes, and I’ll have the medical students and residents to keep me sharp.

ILLUSTRATIVE CASE

A frail 76-year-old woman with a history of hypertension and hyperlipidemia presents for evaluation of palpitations. An in-office electrocardiogram reveals that the patient is in AF. Her CHA₂DS₂-VASc score is 4 and her HAS-BLED score is 2.^2,3 Using shared decision making, you decide to start medications for her AF. You plan to initiate a beta-blocker for rate control and must now decide on anticoagulation. Which oral anticoagulant would you prescribe for this patient’s AF, given her frail status?

Frailty is defined as a state of vulnerability with a decreased ability to recover from an acute stressful event.⁴ The prevalence of frailty varies by the measurements used and the population studied. A 2021 meta-analysis found that frailty prevalence ranges from 12% to 24% worldwide in patients older than 50 years⁵ and may increase to > 30% among those ages 85 years and older.⁶ Frailty increases rates of AEs such as falls⁷ and fracture,⁸ leading to disability,⁹ decreased quality of life,¹⁰ increased utilization of health care,¹¹ and increased mortality.¹² A number of validated approaches are available to screen for and measure frailty.^13-18

Given the association with negative health outcomes and high health care utilization, frailty is an important clinical factor for physicians to consider when treating elderly patients. Frailty assessment may allow for more tailored treatment choices for patients, with a potential reduction in complications. Although CHA₂DS₂-VASc and HAS-BLED scores assist in the decision-making process of whether to start anticoagulation,these tools do not take frailty into consideration or guide anticoagulant choice.^2,3 The purpose of this study was to analyze how levels of frailty affect the association of 3 different direct oral anticoagulants (DOACs) vs warfarin with various AEs (death, stroke, or major bleeding).

STUDY SUMMARY

This DOAC rose above the others

This retrospective cohort study compared the safety of 3 DOACs—dabigatran, rivaroxaban, and apixaban—vs warfarin in Medicare beneficiaries with AF, using 1:1 propensity score (PS)–matched analysis. Eligible patients were ages 65 years or older, with a filled prescription for a DOAC or warfarin, no prior oral anticoagulant exposure in the previous 183 days, a diagnostic code of AF, and continuous enrollment in Medicare Parts A, B, and D only. Patients were excluded if they had missing demographic data, received hospice care, resided in a nursing facility at drug initiation, had another indication for anticoagulation, or had a contraindication to either a DOAC or warfarin.

Frailty was measured using a claims-based frailty index (CFI), which applies health care utilization data to estimate a frailty index, with cut points for nonfrailty, prefrailty, and frailty. The CFI score has 93 claims-based variables, including wheelchairs and durable medical equipment, open wounds, diseases such as chronic obstructive pulmonary disease and ischemic heart disease, and transportation services.^15-17 In this study, nonfrailty was defined as a CFI < 0.15, prefrailty as a CFI of 0.15 to 0.24, and frailty as a CFI ≥ 0.25.

Among older patients treated with anticoagulation for atrial fibrillation, apixaban had the lowest adverse event rate vs warfarin among frail patients, compared with dabigatran and rivaroxaban.

The primary outcome—a composite endpoint of death, ischemic stroke, or major bleeding—was measured for each of the DOAC–warfarin cohorts in the overall population and stratified by frailty classification. Patients were followed until the occurrence of a study outcome, Medicare disenrollment, the end of the study period, discontinuation of the index drug (defined as > 5 days), change to a different anticoagulant, admission to a nursing facility, enrollment in hospice, initiation of dialysis, or kidney transplant. The authors conducted a PS-matched analysis to reduce any imbalances in clinical characteristics between the DOAC- and warfarin-­treated groups, as well as a sensitivity analysis to assess the strength of the data findings using different assumptions.

The authors created 3 DOAC–warfarin cohorts: dabigatran (n = 81,863) vs warfarin (n = 256,722), rivaroxaban (n = 185,011) vs warfarin (n = 228,028), and apixaban (n = 222,478) vs warfarin (n = 206,031). After PS matching, the mean age in all cohorts was 76 to 77 years, about 50% were female, and 91% were White. The mean HAS-BLED score was 2 and the mean CHA₂DS₂-VASc score was 4. The mean CFI was 0.19 to 0.20, defined as prefrail. Patients classified as frail were older, more likely to be female, and more likely to have greater comorbidities, higher scores on CHA₂DS₂-VASc and HAS-BLED, and higher health care utilization.

Continue to: In the dabigatran-warfarin...

In the dabigatran–warfarin cohort (median follow-up, 72 days), the event rate of the composite endpoint per 1000 person-years (PY) was 63.5 for dabigatran and 65.6 for warfarin (hazard ratio [HR] = 0.98; 95% CI, 0.92 to 1.05; rate difference [RD] per 1000 PY = –2.2; 95% CI, –6.5 to 2.1). A lower rate of the composite endpoint was associated with dabigatran than warfarin for the nonfrail subgroup but not the prefrail or frail groups.

In the rivaroxaban–warfarin cohort (median follow-up, 82 days), the composite endpoint rate per 1000 PY was 77.8 for rivaroxaban and 83.7 for warfarin (HR = 0.98; 95% CI, 0.94 to 1.02; RD per 1000 PY = –5.9; 95% CI, –9.4 to –2.4). When stratifying by frailty category, both dabigatran and rivaroxaban were associated with a lower composite endpoint rate than warfarin for the nonfrail population only (HR = 0.81; 95% CI, 0.68 to 0.97, and HR = 0.88; 95% CI, 0.77 to 0.99, respectively).

In the apixaban–warfarin cohort (median follow-up, 84 days), the rate of the composite endpoint per 1000 PY was 60.1 for apixaban and 92.3 for warfarin (HR = 0.68; 95% CI, 0.65 to 0.72; RD per 1000 PY = –32.2; 95% CI, –36.1 to –28.3). The beneficial association for apixaban was present in all frailty categories, with an HR of 0.61 (95% CI, 0.52 to 0.71) for nonfrail patients, 0.66 (95% CI, 0.61 to 0.70) for prefrail patients, and 0.73 (95% CI, 0.67 to 0.80) for frail patients. Apixaban was the only DOAC with a relative reduction in the hazard of death, ischemic stroke, or major bleeding among all frailty groups.

WHAT’S NEW

Only apixaban had lower AE rates vs warfarin across frailty levels

Three DOACs (dabigatran, rivaroxaban, and apixaban) reduced the risk of death, ischemic stroke, or major bleeding compared with warfarin in older adults with AF, but only apixaban was associated with a relative reduction of these adverse outcomes in patients of all frailty classifications.

CAVEATS

Important data but RCTs are needed

The power of this observational study is considerable. However, it remains a retrospective observational study. The authors attempted to account for these limitations and potential confounders by performing a PS-matched analysis and sensitivity analysis; however, these findings should be confirmed with randomized controlled trials.

Continue to: Additionally, the study...

Additionally, the study collected data on each of the DOAC–warfarin cohorts for < 90 days. Trials to address long-term outcomes are warranted.

Finally, there was no control group in comparison with anticoagulation. It is possible that choosing not to use an anticoagulant is the best choice for frail elderly patients.

CHALLENGES TO IMPLEMENTATION

Doctors need a practical frailty scale, patients need an affordable Rx

Frailty is not often considered a measurable trait. The approach used in the study to determine the CFI is not a practical clinical tool. Studies comparing a frailty calculation software application or an easily implementable survey may help bring this clinically impactful information to the hands of primary care physicians. The Clinical Frailty Scale—a brief, 7-point scale based on the physician’s clinical impression of the patient—has been found to correlate with other established frailty measures¹⁸ and might be an option for busy clinicians. However, the current study did not utilize this measurement, and the validity of its use by primary care physicians in the outpatient setting requires further study.

Cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D.

In addition, cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D. The average monthly cost of the DOACs ranges from $560 for dabigatran¹⁹ to $600 for rivaroxaban²⁰ and $623 for apixaban.²¹ As always, the choice of anticoagulant therapy is a clinical judgment and a joint decision of the patient and physician.

ILLUSTRATIVE CASE

A frail 76-year-old woman with a history of hypertension and hyperlipidemia presents for evaluation of palpitations. An in-office electrocardiogram reveals that the patient is in AF. Her CHA₂DS₂-VASc score is 4 and her HAS-BLED score is 2.^2,3 Using shared decision making, you decide to start medications for her AF. You plan to initiate a beta-blocker for rate control and must now decide on anticoagulation. Which oral anticoagulant would you prescribe for this patient’s AF, given her frail status?

Frailty is defined as a state of vulnerability with a decreased ability to recover from an acute stressful event.⁴ The prevalence of frailty varies by the measurements used and the population studied. A 2021 meta-analysis found that frailty prevalence ranges from 12% to 24% worldwide in patients older than 50 years⁵ and may increase to > 30% among those ages 85 years and older.⁶ Frailty increases rates of AEs such as falls⁷ and fracture,⁸ leading to disability,⁹ decreased quality of life,¹⁰ increased utilization of health care,¹¹ and increased mortality.¹² A number of validated approaches are available to screen for and measure frailty.^13-18

Given the association with negative health outcomes and high health care utilization, frailty is an important clinical factor for physicians to consider when treating elderly patients. Frailty assessment may allow for more tailored treatment choices for patients, with a potential reduction in complications. Although CHA₂DS₂-VASc and HAS-BLED scores assist in the decision-making process of whether to start anticoagulation,these tools do not take frailty into consideration or guide anticoagulant choice.^2,3 The purpose of this study was to analyze how levels of frailty affect the association of 3 different direct oral anticoagulants (DOACs) vs warfarin with various AEs (death, stroke, or major bleeding).

STUDY SUMMARY

This DOAC rose above the others

This retrospective cohort study compared the safety of 3 DOACs—dabigatran, rivaroxaban, and apixaban—vs warfarin in Medicare beneficiaries with AF, using 1:1 propensity score (PS)–matched analysis. Eligible patients were ages 65 years or older, with a filled prescription for a DOAC or warfarin, no prior oral anticoagulant exposure in the previous 183 days, a diagnostic code of AF, and continuous enrollment in Medicare Parts A, B, and D only. Patients were excluded if they had missing demographic data, received hospice care, resided in a nursing facility at drug initiation, had another indication for anticoagulation, or had a contraindication to either a DOAC or warfarin.

Frailty was measured using a claims-based frailty index (CFI), which applies health care utilization data to estimate a frailty index, with cut points for nonfrailty, prefrailty, and frailty. The CFI score has 93 claims-based variables, including wheelchairs and durable medical equipment, open wounds, diseases such as chronic obstructive pulmonary disease and ischemic heart disease, and transportation services.^15-17 In this study, nonfrailty was defined as a CFI < 0.15, prefrailty as a CFI of 0.15 to 0.24, and frailty as a CFI ≥ 0.25.

Among older patients treated with anticoagulation for atrial fibrillation, apixaban had the lowest adverse event rate vs warfarin among frail patients, compared with dabigatran and rivaroxaban.

The primary outcome—a composite endpoint of death, ischemic stroke, or major bleeding—was measured for each of the DOAC–warfarin cohorts in the overall population and stratified by frailty classification. Patients were followed until the occurrence of a study outcome, Medicare disenrollment, the end of the study period, discontinuation of the index drug (defined as > 5 days), change to a different anticoagulant, admission to a nursing facility, enrollment in hospice, initiation of dialysis, or kidney transplant. The authors conducted a PS-matched analysis to reduce any imbalances in clinical characteristics between the DOAC- and warfarin-­treated groups, as well as a sensitivity analysis to assess the strength of the data findings using different assumptions.

The authors created 3 DOAC–warfarin cohorts: dabigatran (n = 81,863) vs warfarin (n = 256,722), rivaroxaban (n = 185,011) vs warfarin (n = 228,028), and apixaban (n = 222,478) vs warfarin (n = 206,031). After PS matching, the mean age in all cohorts was 76 to 77 years, about 50% were female, and 91% were White. The mean HAS-BLED score was 2 and the mean CHA₂DS₂-VASc score was 4. The mean CFI was 0.19 to 0.20, defined as prefrail. Patients classified as frail were older, more likely to be female, and more likely to have greater comorbidities, higher scores on CHA₂DS₂-VASc and HAS-BLED, and higher health care utilization.

Continue to: In the dabigatran-warfarin...

In the dabigatran–warfarin cohort (median follow-up, 72 days), the event rate of the composite endpoint per 1000 person-years (PY) was 63.5 for dabigatran and 65.6 for warfarin (hazard ratio [HR] = 0.98; 95% CI, 0.92 to 1.05; rate difference [RD] per 1000 PY = –2.2; 95% CI, –6.5 to 2.1). A lower rate of the composite endpoint was associated with dabigatran than warfarin for the nonfrail subgroup but not the prefrail or frail groups.

In the rivaroxaban–warfarin cohort (median follow-up, 82 days), the composite endpoint rate per 1000 PY was 77.8 for rivaroxaban and 83.7 for warfarin (HR = 0.98; 95% CI, 0.94 to 1.02; RD per 1000 PY = –5.9; 95% CI, –9.4 to –2.4). When stratifying by frailty category, both dabigatran and rivaroxaban were associated with a lower composite endpoint rate than warfarin for the nonfrail population only (HR = 0.81; 95% CI, 0.68 to 0.97, and HR = 0.88; 95% CI, 0.77 to 0.99, respectively).

In the apixaban–warfarin cohort (median follow-up, 84 days), the rate of the composite endpoint per 1000 PY was 60.1 for apixaban and 92.3 for warfarin (HR = 0.68; 95% CI, 0.65 to 0.72; RD per 1000 PY = –32.2; 95% CI, –36.1 to –28.3). The beneficial association for apixaban was present in all frailty categories, with an HR of 0.61 (95% CI, 0.52 to 0.71) for nonfrail patients, 0.66 (95% CI, 0.61 to 0.70) for prefrail patients, and 0.73 (95% CI, 0.67 to 0.80) for frail patients. Apixaban was the only DOAC with a relative reduction in the hazard of death, ischemic stroke, or major bleeding among all frailty groups.

WHAT’S NEW

Only apixaban had lower AE rates vs warfarin across frailty levels

Three DOACs (dabigatran, rivaroxaban, and apixaban) reduced the risk of death, ischemic stroke, or major bleeding compared with warfarin in older adults with AF, but only apixaban was associated with a relative reduction of these adverse outcomes in patients of all frailty classifications.

CAVEATS

Important data but RCTs are needed

The power of this observational study is considerable. However, it remains a retrospective observational study. The authors attempted to account for these limitations and potential confounders by performing a PS-matched analysis and sensitivity analysis; however, these findings should be confirmed with randomized controlled trials.

Continue to: Additionally, the study...

Additionally, the study collected data on each of the DOAC–warfarin cohorts for < 90 days. Trials to address long-term outcomes are warranted.

Finally, there was no control group in comparison with anticoagulation. It is possible that choosing not to use an anticoagulant is the best choice for frail elderly patients.

CHALLENGES TO IMPLEMENTATION

Doctors need a practical frailty scale, patients need an affordable Rx

Frailty is not often considered a measurable trait. The approach used in the study to determine the CFI is not a practical clinical tool. Studies comparing a frailty calculation software application or an easily implementable survey may help bring this clinically impactful information to the hands of primary care physicians. The Clinical Frailty Scale—a brief, 7-point scale based on the physician’s clinical impression of the patient—has been found to correlate with other established frailty measures¹⁸ and might be an option for busy clinicians. However, the current study did not utilize this measurement, and the validity of its use by primary care physicians in the outpatient setting requires further study.

Cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D.

In addition, cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D. The average monthly cost of the DOACs ranges from $560 for dabigatran¹⁹ to $600 for rivaroxaban²⁰ and $623 for apixaban.²¹ As always, the choice of anticoagulant therapy is a clinical judgment and a joint decision of the patient and physician.

ILLUSTRATIVE CASE

A frail 76-year-old woman with a history of hypertension and hyperlipidemia presents for evaluation of palpitations. An in-office electrocardiogram reveals that the patient is in AF. Her CHA₂DS₂-VASc score is 4 and her HAS-BLED score is 2.^2,3 Using shared decision making, you decide to start medications for her AF. You plan to initiate a beta-blocker for rate control and must now decide on anticoagulation. Which oral anticoagulant would you prescribe for this patient’s AF, given her frail status?

Frailty is defined as a state of vulnerability with a decreased ability to recover from an acute stressful event.⁴ The prevalence of frailty varies by the measurements used and the population studied. A 2021 meta-analysis found that frailty prevalence ranges from 12% to 24% worldwide in patients older than 50 years⁵ and may increase to > 30% among those ages 85 years and older.⁶ Frailty increases rates of AEs such as falls⁷ and fracture,⁸ leading to disability,⁹ decreased quality of life,¹⁰ increased utilization of health care,¹¹ and increased mortality.¹² A number of validated approaches are available to screen for and measure frailty.^13-18

Given the association with negative health outcomes and high health care utilization, frailty is an important clinical factor for physicians to consider when treating elderly patients. Frailty assessment may allow for more tailored treatment choices for patients, with a potential reduction in complications. Although CHA₂DS₂-VASc and HAS-BLED scores assist in the decision-making process of whether to start anticoagulation,these tools do not take frailty into consideration or guide anticoagulant choice.^2,3 The purpose of this study was to analyze how levels of frailty affect the association of 3 different direct oral anticoagulants (DOACs) vs warfarin with various AEs (death, stroke, or major bleeding).

STUDY SUMMARY

This DOAC rose above the others

This retrospective cohort study compared the safety of 3 DOACs—dabigatran, rivaroxaban, and apixaban—vs warfarin in Medicare beneficiaries with AF, using 1:1 propensity score (PS)–matched analysis. Eligible patients were ages 65 years or older, with a filled prescription for a DOAC or warfarin, no prior oral anticoagulant exposure in the previous 183 days, a diagnostic code of AF, and continuous enrollment in Medicare Parts A, B, and D only. Patients were excluded if they had missing demographic data, received hospice care, resided in a nursing facility at drug initiation, had another indication for anticoagulation, or had a contraindication to either a DOAC or warfarin.

Frailty was measured using a claims-based frailty index (CFI), which applies health care utilization data to estimate a frailty index, with cut points for nonfrailty, prefrailty, and frailty. The CFI score has 93 claims-based variables, including wheelchairs and durable medical equipment, open wounds, diseases such as chronic obstructive pulmonary disease and ischemic heart disease, and transportation services.^15-17 In this study, nonfrailty was defined as a CFI < 0.15, prefrailty as a CFI of 0.15 to 0.24, and frailty as a CFI ≥ 0.25.

Among older patients treated with anticoagulation for atrial fibrillation, apixaban had the lowest adverse event rate vs warfarin among frail patients, compared with dabigatran and rivaroxaban.

The primary outcome—a composite endpoint of death, ischemic stroke, or major bleeding—was measured for each of the DOAC–warfarin cohorts in the overall population and stratified by frailty classification. Patients were followed until the occurrence of a study outcome, Medicare disenrollment, the end of the study period, discontinuation of the index drug (defined as > 5 days), change to a different anticoagulant, admission to a nursing facility, enrollment in hospice, initiation of dialysis, or kidney transplant. The authors conducted a PS-matched analysis to reduce any imbalances in clinical characteristics between the DOAC- and warfarin-­treated groups, as well as a sensitivity analysis to assess the strength of the data findings using different assumptions.

The authors created 3 DOAC–warfarin cohorts: dabigatran (n = 81,863) vs warfarin (n = 256,722), rivaroxaban (n = 185,011) vs warfarin (n = 228,028), and apixaban (n = 222,478) vs warfarin (n = 206,031). After PS matching, the mean age in all cohorts was 76 to 77 years, about 50% were female, and 91% were White. The mean HAS-BLED score was 2 and the mean CHA₂DS₂-VASc score was 4. The mean CFI was 0.19 to 0.20, defined as prefrail. Patients classified as frail were older, more likely to be female, and more likely to have greater comorbidities, higher scores on CHA₂DS₂-VASc and HAS-BLED, and higher health care utilization.

Continue to: In the dabigatran-warfarin...

In the dabigatran–warfarin cohort (median follow-up, 72 days), the event rate of the composite endpoint per 1000 person-years (PY) was 63.5 for dabigatran and 65.6 for warfarin (hazard ratio [HR] = 0.98; 95% CI, 0.92 to 1.05; rate difference [RD] per 1000 PY = –2.2; 95% CI, –6.5 to 2.1). A lower rate of the composite endpoint was associated with dabigatran than warfarin for the nonfrail subgroup but not the prefrail or frail groups.

In the rivaroxaban–warfarin cohort (median follow-up, 82 days), the composite endpoint rate per 1000 PY was 77.8 for rivaroxaban and 83.7 for warfarin (HR = 0.98; 95% CI, 0.94 to 1.02; RD per 1000 PY = –5.9; 95% CI, –9.4 to –2.4). When stratifying by frailty category, both dabigatran and rivaroxaban were associated with a lower composite endpoint rate than warfarin for the nonfrail population only (HR = 0.81; 95% CI, 0.68 to 0.97, and HR = 0.88; 95% CI, 0.77 to 0.99, respectively).

In the apixaban–warfarin cohort (median follow-up, 84 days), the rate of the composite endpoint per 1000 PY was 60.1 for apixaban and 92.3 for warfarin (HR = 0.68; 95% CI, 0.65 to 0.72; RD per 1000 PY = –32.2; 95% CI, –36.1 to –28.3). The beneficial association for apixaban was present in all frailty categories, with an HR of 0.61 (95% CI, 0.52 to 0.71) for nonfrail patients, 0.66 (95% CI, 0.61 to 0.70) for prefrail patients, and 0.73 (95% CI, 0.67 to 0.80) for frail patients. Apixaban was the only DOAC with a relative reduction in the hazard of death, ischemic stroke, or major bleeding among all frailty groups.

WHAT’S NEW

Only apixaban had lower AE rates vs warfarin across frailty levels

Three DOACs (dabigatran, rivaroxaban, and apixaban) reduced the risk of death, ischemic stroke, or major bleeding compared with warfarin in older adults with AF, but only apixaban was associated with a relative reduction of these adverse outcomes in patients of all frailty classifications.

CAVEATS

Important data but RCTs are needed

The power of this observational study is considerable. However, it remains a retrospective observational study. The authors attempted to account for these limitations and potential confounders by performing a PS-matched analysis and sensitivity analysis; however, these findings should be confirmed with randomized controlled trials.

Continue to: Additionally, the study...

Additionally, the study collected data on each of the DOAC–warfarin cohorts for < 90 days. Trials to address long-term outcomes are warranted.

Finally, there was no control group in comparison with anticoagulation. It is possible that choosing not to use an anticoagulant is the best choice for frail elderly patients.

CHALLENGES TO IMPLEMENTATION

Doctors need a practical frailty scale, patients need an affordable Rx

Frailty is not often considered a measurable trait. The approach used in the study to determine the CFI is not a practical clinical tool. Studies comparing a frailty calculation software application or an easily implementable survey may help bring this clinically impactful information to the hands of primary care physicians. The Clinical Frailty Scale—a brief, 7-point scale based on the physician’s clinical impression of the patient—has been found to correlate with other established frailty measures¹⁸ and might be an option for busy clinicians. However, the current study did not utilize this measurement, and the validity of its use by primary care physicians in the outpatient setting requires further study.

Cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D.

In addition, cost may be a barrier for patients younger than 65 years or for those older than 65 years who do not qualify for Medicare or do not have Medicare Part D. The average monthly cost of the DOACs ranges from $560 for dabigatran¹⁹ to $600 for rivaroxaban²⁰ and $623 for apixaban.²¹ As always, the choice of anticoagulant therapy is a clinical judgment and a joint decision of the patient and physician.