Rheumatology News

The U.S. Food and Drug Administration (FDA) has authorized booster doses for the Moderna and Johnson & Johnson COVID-19 vaccines, while also allowing boosters to be given interchangeably with any of the other vaccines, in people who are eligible to get them.

The move to amend the Emergency Use Authorization for these vaccines gives the vaccine experts on the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices latitude to recommend a mix-and-match strategy if they feel the science supports it.

The committee convenes Oct. 21 for a day-long meeting to make its recommendations for additional doses.

People who’ve previously received two doses of the Moderna mRNA vaccine, which is now called Spikevax, are eligible for a third dose of any COVID-19 vaccine if they are 6 months past their second dose and are:

• 65 years of age or older
• 18 to 64 years of age, but at high risk for severe COVID-19 because of an underlying health condition
• 18 to 64 years of age and at high risk for exposure to the SARS-CoV-2 virus because they live in a group setting, such as a prison or care home, or work in a risky occupation, such as healthcare

People who’ve previously received a dose of the Johnson & Johnson vaccine are eligible for a second dose of any COVID-19 vaccine if they are over the age of 18 and at least 2 months past their vaccination.

“Today’s actions demonstrate our commitment to public health in proactively fighting against the COVID-19 pandemic,” said Acting FDA Commissioner Janet Woodcock, MD, in a news release. “As the pandemic continues to impact the country, science has shown that vaccination continues to be the safest and most effective way to prevent COVID-19, including the most serious consequences of the disease, such as hospitalization and death.

“The available data suggest waning immunity in some populations who are fully vaccinated. The availability of these authorized boosters is important for continued protection against COVID-19 disease.”

A version of this article was first published on Medscape.com.

The U.S. Food and Drug Administration (FDA) has authorized booster doses for the Moderna and Johnson & Johnson COVID-19 vaccines, while also allowing boosters to be given interchangeably with any of the other vaccines, in people who are eligible to get them.

The move to amend the Emergency Use Authorization for these vaccines gives the vaccine experts on the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices latitude to recommend a mix-and-match strategy if they feel the science supports it.

The committee convenes Oct. 21 for a day-long meeting to make its recommendations for additional doses.

People who’ve previously received two doses of the Moderna mRNA vaccine, which is now called Spikevax, are eligible for a third dose of any COVID-19 vaccine if they are 6 months past their second dose and are:

• 65 years of age or older
• 18 to 64 years of age, but at high risk for severe COVID-19 because of an underlying health condition
• 18 to 64 years of age and at high risk for exposure to the SARS-CoV-2 virus because they live in a group setting, such as a prison or care home, or work in a risky occupation, such as healthcare

People who’ve previously received a dose of the Johnson & Johnson vaccine are eligible for a second dose of any COVID-19 vaccine if they are over the age of 18 and at least 2 months past their vaccination.

“Today’s actions demonstrate our commitment to public health in proactively fighting against the COVID-19 pandemic,” said Acting FDA Commissioner Janet Woodcock, MD, in a news release. “As the pandemic continues to impact the country, science has shown that vaccination continues to be the safest and most effective way to prevent COVID-19, including the most serious consequences of the disease, such as hospitalization and death.

“The available data suggest waning immunity in some populations who are fully vaccinated. The availability of these authorized boosters is important for continued protection against COVID-19 disease.”

A version of this article was first published on Medscape.com.

The U.S. Food and Drug Administration (FDA) has authorized booster doses for the Moderna and Johnson & Johnson COVID-19 vaccines, while also allowing boosters to be given interchangeably with any of the other vaccines, in people who are eligible to get them.

The move to amend the Emergency Use Authorization for these vaccines gives the vaccine experts on the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices latitude to recommend a mix-and-match strategy if they feel the science supports it.

The committee convenes Oct. 21 for a day-long meeting to make its recommendations for additional doses.

People who’ve previously received two doses of the Moderna mRNA vaccine, which is now called Spikevax, are eligible for a third dose of any COVID-19 vaccine if they are 6 months past their second dose and are:

• 65 years of age or older
• 18 to 64 years of age, but at high risk for severe COVID-19 because of an underlying health condition
• 18 to 64 years of age and at high risk for exposure to the SARS-CoV-2 virus because they live in a group setting, such as a prison or care home, or work in a risky occupation, such as healthcare

People who’ve previously received a dose of the Johnson & Johnson vaccine are eligible for a second dose of any COVID-19 vaccine if they are over the age of 18 and at least 2 months past their vaccination.

“Today’s actions demonstrate our commitment to public health in proactively fighting against the COVID-19 pandemic,” said Acting FDA Commissioner Janet Woodcock, MD, in a news release. “As the pandemic continues to impact the country, science has shown that vaccination continues to be the safest and most effective way to prevent COVID-19, including the most serious consequences of the disease, such as hospitalization and death.

“The available data suggest waning immunity in some populations who are fully vaccinated. The availability of these authorized boosters is important for continued protection against COVID-19 disease.”

A version of this article was first published on Medscape.com.

Although early menopause is linked to increased risks in bone loss and fracture, new research indicates that, even among the majority of women who have menopause after age 45, the time since the final menstrual period can be a stronger predictor than chronological age for key risks in bone health and fracture.

Steve Debenport/Getty Images

In a large longitudinal cohort, the number of years since a woman’s final menstrual period specifically showed a stronger association with femoral neck bone mineral density (BMD) than chronological age, while an earlier age at menopause – even among those over 45 years, was linked to an increased risk of fracture.

“Most of our clinical tools to predict osteoporosis-related outcomes use chronological age,” first author Albert Shieh, MD, told this news organization.

“Our findings suggest that more research should be done to examine whether ovarian age (time since final menstrual period) should be used in these tools as well.”

An increased focus on the significance of age at the time of the final menstrual period, compared with chronological age, has gained interest in risk assessment because of the known acceleration in the decline of BMD that occurs 1 year prior to the final menstrual period and continues at a rapid pace for 3 years afterwards before slowing.

To further investigate the association with BMD, Dr. Shieh, an endocrinologist specializing in osteoporosis at the University of California, Los Angeles, and his colleagues turned to data from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study of ambulatory women with pre- or early perimenopausal baseline data and 15 annual follow-up assessments.

Outcomes regarding postmenopausal lumbar spine (LS) or femoral neck (FN) BMD were evaluated in 1,038 women, while the time to fracture in relation to the final menstrual period was separately evaluated in 1,554 women.

In both cohorts, the women had a known final menstrual period at age 45 or older, and on average, their final menstrual period occurred at age 52.

After a multivariate adjustment for age, body mass index, and various other factors, they found that each additional year after a woman’s final menstrual period was associated with a significant (0.006 g/cm²) reduction in postmenopausal lumbar spine BMD and a 0.004 g/cm² reduction femoral neck BMD (both P < .0001).

Conversely, chronological age was not associated with a change in femoral neck BMD when evaluated independently of years since the final menstrual period, the researchers reported in the Journal of Clinical Endocrinology and Metabolism.

Regarding lumbar spine BMD, chronological age was unexpectedly associated not just with change, but in fact with increases in lumbar spine BMD (P < .0001 per year). However, the authors speculate the change “is likely a reflection of age-associated degenerative changes causing false elevations in BMD measured by dual-energy x-ray absorptiometry.”

Fracture risk with earlier menopause

In terms of the fracture risk analysis, despite the women all being aged 45 or older, earlier age at menopause was still tied to an increased risk of incident fracture, with a 5% increase in risk for each earlier year in age at the time of the final menstrual period (P = .02).

Compared with women who had their final menstrual period at age 55, for instance, those who finished menstruating at age 47 had a 6.3% greater 20-year cumulative fracture risk, the authors note.

While previous findings from the Malmo Perimenopausal Study showed menopause prior to the age of 47 to be associated with an 83% and 59% greater risk of densitometric osteoporosis and fracture, respectively, by age 77, the authors note that the new study is unique in including only women who had a final menstrual period over the age of 45, therefore reducing the potential confounding of data on women under 45.

The new results “add to a growing body of literature suggesting that the endocrine changes that occur during the menopause transition trigger a pathophysiologic cascade that leads to organ dysfunction,” the authors note.

In terms of implications in risk assessment, “future studies should examine whether years since the final menstrual period predicts major osteoporotic fractures and hip fractures, specifically, and, if so, whether replacing chronological age with years since the final menstrual period improves the performance of clinical prediction tools, such as FRAX [Fracture Risk Assessment Tool],” they add.

Addition to guidelines?

Commenting on the findings, Peter Ebeling, MD, the current president of the American Society of Bone and Mineral Research, noted that the study importantly “confirms what we had previously anticipated, that in women with menopause who are 45 years of age or older a lower age of final menstrual period is associated with lower spine and hip BMD and more fractures.”

“We had already known this for women with premature ovarian insufficiency or an early menopause, and this extends the observation to the vast majority of women – more than 90% – with a normal menopause age,” said Dr. Ebeling, professor of medicine at Monash Health, Monash University, in Melbourne.

Despite the known importance of the time since final menstrual period, guidelines still focus on age in terms of chronology, rather than biology, emphasizing the risk among women over 50, in general, rather than the time since the last menstrual period, he noted.

“There is an important difference [between those two], as shown by this study,” he said. “Guidelines could be easily adapted to reflect this.”

Specifically, the association between lower age of final menstrual period and lower spine and hip BMD and more fractures requires “more formal assessment to determine whether adding age of final menstrual period to existing fracture risk calculator tools, like FRAX, can improve absolute fracture risk prediction,” Dr. Ebeling noted.

The authors and Dr. Ebeling had no disclosures to report.

Although early menopause is linked to increased risks in bone loss and fracture, new research indicates that, even among the majority of women who have menopause after age 45, the time since the final menstrual period can be a stronger predictor than chronological age for key risks in bone health and fracture.

Steve Debenport/Getty Images

In a large longitudinal cohort, the number of years since a woman’s final menstrual period specifically showed a stronger association with femoral neck bone mineral density (BMD) than chronological age, while an earlier age at menopause – even among those over 45 years, was linked to an increased risk of fracture.

“Most of our clinical tools to predict osteoporosis-related outcomes use chronological age,” first author Albert Shieh, MD, told this news organization.

“Our findings suggest that more research should be done to examine whether ovarian age (time since final menstrual period) should be used in these tools as well.”

An increased focus on the significance of age at the time of the final menstrual period, compared with chronological age, has gained interest in risk assessment because of the known acceleration in the decline of BMD that occurs 1 year prior to the final menstrual period and continues at a rapid pace for 3 years afterwards before slowing.

To further investigate the association with BMD, Dr. Shieh, an endocrinologist specializing in osteoporosis at the University of California, Los Angeles, and his colleagues turned to data from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study of ambulatory women with pre- or early perimenopausal baseline data and 15 annual follow-up assessments.

Outcomes regarding postmenopausal lumbar spine (LS) or femoral neck (FN) BMD were evaluated in 1,038 women, while the time to fracture in relation to the final menstrual period was separately evaluated in 1,554 women.

In both cohorts, the women had a known final menstrual period at age 45 or older, and on average, their final menstrual period occurred at age 52.

After a multivariate adjustment for age, body mass index, and various other factors, they found that each additional year after a woman’s final menstrual period was associated with a significant (0.006 g/cm²) reduction in postmenopausal lumbar spine BMD and a 0.004 g/cm² reduction femoral neck BMD (both P < .0001).

Conversely, chronological age was not associated with a change in femoral neck BMD when evaluated independently of years since the final menstrual period, the researchers reported in the Journal of Clinical Endocrinology and Metabolism.

Regarding lumbar spine BMD, chronological age was unexpectedly associated not just with change, but in fact with increases in lumbar spine BMD (P < .0001 per year). However, the authors speculate the change “is likely a reflection of age-associated degenerative changes causing false elevations in BMD measured by dual-energy x-ray absorptiometry.”

Fracture risk with earlier menopause

In terms of the fracture risk analysis, despite the women all being aged 45 or older, earlier age at menopause was still tied to an increased risk of incident fracture, with a 5% increase in risk for each earlier year in age at the time of the final menstrual period (P = .02).

Compared with women who had their final menstrual period at age 55, for instance, those who finished menstruating at age 47 had a 6.3% greater 20-year cumulative fracture risk, the authors note.

While previous findings from the Malmo Perimenopausal Study showed menopause prior to the age of 47 to be associated with an 83% and 59% greater risk of densitometric osteoporosis and fracture, respectively, by age 77, the authors note that the new study is unique in including only women who had a final menstrual period over the age of 45, therefore reducing the potential confounding of data on women under 45.

The new results “add to a growing body of literature suggesting that the endocrine changes that occur during the menopause transition trigger a pathophysiologic cascade that leads to organ dysfunction,” the authors note.

In terms of implications in risk assessment, “future studies should examine whether years since the final menstrual period predicts major osteoporotic fractures and hip fractures, specifically, and, if so, whether replacing chronological age with years since the final menstrual period improves the performance of clinical prediction tools, such as FRAX [Fracture Risk Assessment Tool],” they add.

Addition to guidelines?

Commenting on the findings, Peter Ebeling, MD, the current president of the American Society of Bone and Mineral Research, noted that the study importantly “confirms what we had previously anticipated, that in women with menopause who are 45 years of age or older a lower age of final menstrual period is associated with lower spine and hip BMD and more fractures.”

“We had already known this for women with premature ovarian insufficiency or an early menopause, and this extends the observation to the vast majority of women – more than 90% – with a normal menopause age,” said Dr. Ebeling, professor of medicine at Monash Health, Monash University, in Melbourne.

Despite the known importance of the time since final menstrual period, guidelines still focus on age in terms of chronology, rather than biology, emphasizing the risk among women over 50, in general, rather than the time since the last menstrual period, he noted.

“There is an important difference [between those two], as shown by this study,” he said. “Guidelines could be easily adapted to reflect this.”

Specifically, the association between lower age of final menstrual period and lower spine and hip BMD and more fractures requires “more formal assessment to determine whether adding age of final menstrual period to existing fracture risk calculator tools, like FRAX, can improve absolute fracture risk prediction,” Dr. Ebeling noted.

The authors and Dr. Ebeling had no disclosures to report.

Although early menopause is linked to increased risks in bone loss and fracture, new research indicates that, even among the majority of women who have menopause after age 45, the time since the final menstrual period can be a stronger predictor than chronological age for key risks in bone health and fracture.

Steve Debenport/Getty Images

In a large longitudinal cohort, the number of years since a woman’s final menstrual period specifically showed a stronger association with femoral neck bone mineral density (BMD) than chronological age, while an earlier age at menopause – even among those over 45 years, was linked to an increased risk of fracture.

“Most of our clinical tools to predict osteoporosis-related outcomes use chronological age,” first author Albert Shieh, MD, told this news organization.

“Our findings suggest that more research should be done to examine whether ovarian age (time since final menstrual period) should be used in these tools as well.”

An increased focus on the significance of age at the time of the final menstrual period, compared with chronological age, has gained interest in risk assessment because of the known acceleration in the decline of BMD that occurs 1 year prior to the final menstrual period and continues at a rapid pace for 3 years afterwards before slowing.

To further investigate the association with BMD, Dr. Shieh, an endocrinologist specializing in osteoporosis at the University of California, Los Angeles, and his colleagues turned to data from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study of ambulatory women with pre- or early perimenopausal baseline data and 15 annual follow-up assessments.

Outcomes regarding postmenopausal lumbar spine (LS) or femoral neck (FN) BMD were evaluated in 1,038 women, while the time to fracture in relation to the final menstrual period was separately evaluated in 1,554 women.

In both cohorts, the women had a known final menstrual period at age 45 or older, and on average, their final menstrual period occurred at age 52.

After a multivariate adjustment for age, body mass index, and various other factors, they found that each additional year after a woman’s final menstrual period was associated with a significant (0.006 g/cm²) reduction in postmenopausal lumbar spine BMD and a 0.004 g/cm² reduction femoral neck BMD (both P < .0001).

Conversely, chronological age was not associated with a change in femoral neck BMD when evaluated independently of years since the final menstrual period, the researchers reported in the Journal of Clinical Endocrinology and Metabolism.

Regarding lumbar spine BMD, chronological age was unexpectedly associated not just with change, but in fact with increases in lumbar spine BMD (P < .0001 per year). However, the authors speculate the change “is likely a reflection of age-associated degenerative changes causing false elevations in BMD measured by dual-energy x-ray absorptiometry.”

Fracture risk with earlier menopause

In terms of the fracture risk analysis, despite the women all being aged 45 or older, earlier age at menopause was still tied to an increased risk of incident fracture, with a 5% increase in risk for each earlier year in age at the time of the final menstrual period (P = .02).

Compared with women who had their final menstrual period at age 55, for instance, those who finished menstruating at age 47 had a 6.3% greater 20-year cumulative fracture risk, the authors note.

While previous findings from the Malmo Perimenopausal Study showed menopause prior to the age of 47 to be associated with an 83% and 59% greater risk of densitometric osteoporosis and fracture, respectively, by age 77, the authors note that the new study is unique in including only women who had a final menstrual period over the age of 45, therefore reducing the potential confounding of data on women under 45.

The new results “add to a growing body of literature suggesting that the endocrine changes that occur during the menopause transition trigger a pathophysiologic cascade that leads to organ dysfunction,” the authors note.

In terms of implications in risk assessment, “future studies should examine whether years since the final menstrual period predicts major osteoporotic fractures and hip fractures, specifically, and, if so, whether replacing chronological age with years since the final menstrual period improves the performance of clinical prediction tools, such as FRAX [Fracture Risk Assessment Tool],” they add.

Addition to guidelines?

Commenting on the findings, Peter Ebeling, MD, the current president of the American Society of Bone and Mineral Research, noted that the study importantly “confirms what we had previously anticipated, that in women with menopause who are 45 years of age or older a lower age of final menstrual period is associated with lower spine and hip BMD and more fractures.”

“We had already known this for women with premature ovarian insufficiency or an early menopause, and this extends the observation to the vast majority of women – more than 90% – with a normal menopause age,” said Dr. Ebeling, professor of medicine at Monash Health, Monash University, in Melbourne.

Despite the known importance of the time since final menstrual period, guidelines still focus on age in terms of chronology, rather than biology, emphasizing the risk among women over 50, in general, rather than the time since the last menstrual period, he noted.

“There is an important difference [between those two], as shown by this study,” he said. “Guidelines could be easily adapted to reflect this.”

Specifically, the association between lower age of final menstrual period and lower spine and hip BMD and more fractures requires “more formal assessment to determine whether adding age of final menstrual period to existing fracture risk calculator tools, like FRAX, can improve absolute fracture risk prediction,” Dr. Ebeling noted.

The authors and Dr. Ebeling had no disclosures to report.

A large international team of experts has developed two comprehensive guidelines for diagnosing, evaluating, and managing hypoparathyroidism and hyperparathyroidism, which replace guidelines issued 5 and 7 years ago.

Aliya A. Khan, MD, presented an overview of the hypoparathyroidism guidelines and John P. Bilezikian, MD, presented key aspects of the hyperparathyroidism guidelines at the American Society of Bone and Mineral Research (ASBMR) 2021 Annual Meeting.

The guidelines will be published as 17 articles in two issues of the society’s Journal of Bone and Mineral Research in 2022 – one on hypoparathyroidism and the other on hyperparathyroidism.

The work represents an “unprecedented effort” by more than 100 experts from 16 countries (United States, Canada, Australia, Brazil, China, Denmark, France, Germany, India, Italy, Israel, Lebanon, Singapore, Spain, Sweden, and the United Kingdom), Dr. Bilezikian told this news organization in an interview.

More than 100 international and national endocrine and osteoporosis organizations, societies, and patient advocacy groups from more than 50 countries have expressed interest in endorsing the guidelines.
 

Management of hypoparathyroidism

The new guidelines on hypoparathyroidism replace the guidelines issued in 2016 that were developed at the First International Conference on the Management of Hypoparathyroidism, Dr. Khan, from McMaster University, Hamilton, Ont., said in an email.

There was a need for new hypoparathyroidism guidelines, she explained, because of the better understanding of associated complications, how to predict who will develop hypoparathyroidism postoperatively (and how to prevent this), how and when to investigate a genetic cause further, when to consider parathyroid hormone (PTH) replacement therapy (and the benefits of the various molecules available today as well as those being evaluated in clinical research), and how to diagnose and manage hypoparathyroidism during pregnancy and lactation.

The experts in hypoparathyroidism were divided into four task forces that covered epidemiology and financial burden, etiology and pathophysiology, genetics and diagnosis, and patient evaluation and management.

The guidelines, developed over the past 18 months, provide detailed evidence-based graded (strong to weak) as well as ungraded (current practice) recommendations.

Summarizing a few key takeaways, Dr. Khan noted the guidelines recommend that clinicians treating patients with hypoparathyroidism should:

• Diagnose hypoparathyroidism if serum calcium corrected for albumin is low in the presence of a low or inappropriately normal PTH confirmed on two occasions 2 weeks apart (which may be supported by other specified abnormalities).
• Determine the cause for the hypoparathyroidism (which includes postsurgery, genetic variant, autoimmune, radiation, or idiopathic causes).
• Evaluate target organ damage.
• Try to achieve treatment goals and minimize risks for long-term complications.
• Consider PTH replacement therapy if patients have inadequate control, with symptoms of hypocalcemia or hypercalcemia, high phosphate, kidney disease, or high urine calcium, or poor quality of life. 

The guideline strongly recommends using PTH measurements after total thyroidectomy to try to predict which patients will develop permanent postsurgical hypoparathyroidism.

It provides a clinical approach for establishing the genetic etiology of hypoparathyroidism.

A meta-analysis of 81 studies identified that the most common symptoms/complications of chronic hypoparathyroidism were, in descending order, cataract (24%), infection (18%), nephrolithiasis, renal insufficiency, seizures, depression, ischemic heart disease, and arrhythmias.

Based on the best available evidence, the guideline advises that “clinicians need to carefully determine why a patient has hypoparathyroidism and develop an individualized treatment plan with conventional therapy consisting of calcium, active vitamin D, hydrochlorothiazide, and plain vitamin D,” Dr. Khan continued.

“If a patient has poorly controlled hypoparathyroidism with many symptoms or is not doing well, then clinicians must consider PTH replacement therapy, since this will replace the missing hormone, lower the urine calcium losses, bring the serum calcium back up to the normal reference range, and lower phosphate (which appears to be associated with kidney calcification and may also contribute to basal ganglia calcification and calcium deposits in the eye),” she noted.

The guideline also discusses the optimal way to monitor and treat patients during pregnancy, delivery, and breastfeeding to optimize outcomes for mother and baby. The key points are closer patient monitoring with normalization of calcium, urine calcium, phosphate, and vitamin D.  
 

Management of primary hyperparathyroidism

There was a need to update the previous 2014 guidelines developed at the Fourth International Workshop on the Management of Primary Hyperparathyroidism because, among other things, recent studies have provided new evidence about the different clinical phenotypes of primary hyperparathyroidism and ways the disease affects the skeleton and kidneys, Dr. Bilezikian, from the College of Physicians and Surgeons, Columbia University, New York, explained.

The experts in hyperparathyroidism were divided into four task forces that covered epidemiology, pathophysiology and genetics; classical and nonclassical disease manifestations; surgical aspects; and patient evaluation and management.

As part of these topics, the experts reviewed biochemical, skeletal, and renal findings, nonclassical features (such as neurocognitive complaints), nutritional and pharmacologic approaches, and disease course with or without surgical or medical intervention.

They made recommendations for diagnosis of hypercalcemic and normocalcemic phenotypes, differential diagnosis, evaluation of the skeleton and the kidney, indications for surgery, role of parathyroid imaging, indications for pharmacologic intervention, and monitoring.

“Consider the way this disease has appeared to change in the last 50 years,” said Dr. Bilezikian. In the 1940s, 50s, and 60s, patients with hyperparathyroidism were really sick and had severe bone disease and kidney disease. Then in the 70s, 80s, and 90s, the disease was more often discovered because of a screening test; high serum calcium was a hallmark of finding asymptomatic hyperparathyroidism.

In recent years, hyperparathyroidism is often discovered incidentally, when examining the skeleton or kidneys, he continued.

Primary hyperparathyroidism can now be subdivided into three types: patients who have target organ (kidney, bone) involvement, patients who don’t have this, and patients who have normocalcemic primary hyperparathyroidism.

The guideline discusses new medications that have become available for hyperparathyroidism, as well as surgery (the only cure), including how preoperative imaging can identify the overactive parathyroid gland, and the guidelines go into detail about how to monitor a patient and why a clinician would or would not recommend surgery, Dr. Bilezikian explained.

In the end, treatment is tailored to the individual.

Last, the guideline identifies eight areas where more research is needed.

The guidelines were funded by unrestricted educational grants from Amolyt, Ascendis, Calcilytix, and Takeda. Dr. Khan has reported participating on advisory boards for Alexion, Amgen, Amolyt, and Takeda, being a consultant for Amgen, receiving grants from Alexion, Amgen, Takeda, and Ascendis, being an investigator for Alexion, Amgen, Takeda, Ascendis, and Chugai, and being a speaker for Alexion, Amgen, Takeda, and Ultragenyx. Dr. Bilezikian has reported no relevant financial relationships.

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

A large international team of experts has developed two comprehensive guidelines for diagnosing, evaluating, and managing hypoparathyroidism and hyperparathyroidism, which replace guidelines issued 5 and 7 years ago.

Aliya A. Khan, MD, presented an overview of the hypoparathyroidism guidelines and John P. Bilezikian, MD, presented key aspects of the hyperparathyroidism guidelines at the American Society of Bone and Mineral Research (ASBMR) 2021 Annual Meeting.

The guidelines will be published as 17 articles in two issues of the society’s Journal of Bone and Mineral Research in 2022 – one on hypoparathyroidism and the other on hyperparathyroidism.

The work represents an “unprecedented effort” by more than 100 experts from 16 countries (United States, Canada, Australia, Brazil, China, Denmark, France, Germany, India, Italy, Israel, Lebanon, Singapore, Spain, Sweden, and the United Kingdom), Dr. Bilezikian told this news organization in an interview.

More than 100 international and national endocrine and osteoporosis organizations, societies, and patient advocacy groups from more than 50 countries have expressed interest in endorsing the guidelines.
 

Management of hypoparathyroidism

The new guidelines on hypoparathyroidism replace the guidelines issued in 2016 that were developed at the First International Conference on the Management of Hypoparathyroidism, Dr. Khan, from McMaster University, Hamilton, Ont., said in an email.

There was a need for new hypoparathyroidism guidelines, she explained, because of the better understanding of associated complications, how to predict who will develop hypoparathyroidism postoperatively (and how to prevent this), how and when to investigate a genetic cause further, when to consider parathyroid hormone (PTH) replacement therapy (and the benefits of the various molecules available today as well as those being evaluated in clinical research), and how to diagnose and manage hypoparathyroidism during pregnancy and lactation.

The experts in hypoparathyroidism were divided into four task forces that covered epidemiology and financial burden, etiology and pathophysiology, genetics and diagnosis, and patient evaluation and management.

The guidelines, developed over the past 18 months, provide detailed evidence-based graded (strong to weak) as well as ungraded (current practice) recommendations.

Summarizing a few key takeaways, Dr. Khan noted the guidelines recommend that clinicians treating patients with hypoparathyroidism should:

• Diagnose hypoparathyroidism if serum calcium corrected for albumin is low in the presence of a low or inappropriately normal PTH confirmed on two occasions 2 weeks apart (which may be supported by other specified abnormalities).
• Determine the cause for the hypoparathyroidism (which includes postsurgery, genetic variant, autoimmune, radiation, or idiopathic causes).
• Evaluate target organ damage.
• Try to achieve treatment goals and minimize risks for long-term complications.
• Consider PTH replacement therapy if patients have inadequate control, with symptoms of hypocalcemia or hypercalcemia, high phosphate, kidney disease, or high urine calcium, or poor quality of life. 

The guideline strongly recommends using PTH measurements after total thyroidectomy to try to predict which patients will develop permanent postsurgical hypoparathyroidism.

It provides a clinical approach for establishing the genetic etiology of hypoparathyroidism.

A meta-analysis of 81 studies identified that the most common symptoms/complications of chronic hypoparathyroidism were, in descending order, cataract (24%), infection (18%), nephrolithiasis, renal insufficiency, seizures, depression, ischemic heart disease, and arrhythmias.

Based on the best available evidence, the guideline advises that “clinicians need to carefully determine why a patient has hypoparathyroidism and develop an individualized treatment plan with conventional therapy consisting of calcium, active vitamin D, hydrochlorothiazide, and plain vitamin D,” Dr. Khan continued.

“If a patient has poorly controlled hypoparathyroidism with many symptoms or is not doing well, then clinicians must consider PTH replacement therapy, since this will replace the missing hormone, lower the urine calcium losses, bring the serum calcium back up to the normal reference range, and lower phosphate (which appears to be associated with kidney calcification and may also contribute to basal ganglia calcification and calcium deposits in the eye),” she noted.

The guideline also discusses the optimal way to monitor and treat patients during pregnancy, delivery, and breastfeeding to optimize outcomes for mother and baby. The key points are closer patient monitoring with normalization of calcium, urine calcium, phosphate, and vitamin D.  
 

Management of primary hyperparathyroidism

There was a need to update the previous 2014 guidelines developed at the Fourth International Workshop on the Management of Primary Hyperparathyroidism because, among other things, recent studies have provided new evidence about the different clinical phenotypes of primary hyperparathyroidism and ways the disease affects the skeleton and kidneys, Dr. Bilezikian, from the College of Physicians and Surgeons, Columbia University, New York, explained.

The experts in hyperparathyroidism were divided into four task forces that covered epidemiology, pathophysiology and genetics; classical and nonclassical disease manifestations; surgical aspects; and patient evaluation and management.

As part of these topics, the experts reviewed biochemical, skeletal, and renal findings, nonclassical features (such as neurocognitive complaints), nutritional and pharmacologic approaches, and disease course with or without surgical or medical intervention.

They made recommendations for diagnosis of hypercalcemic and normocalcemic phenotypes, differential diagnosis, evaluation of the skeleton and the kidney, indications for surgery, role of parathyroid imaging, indications for pharmacologic intervention, and monitoring.

“Consider the way this disease has appeared to change in the last 50 years,” said Dr. Bilezikian. In the 1940s, 50s, and 60s, patients with hyperparathyroidism were really sick and had severe bone disease and kidney disease. Then in the 70s, 80s, and 90s, the disease was more often discovered because of a screening test; high serum calcium was a hallmark of finding asymptomatic hyperparathyroidism.

In recent years, hyperparathyroidism is often discovered incidentally, when examining the skeleton or kidneys, he continued.

Primary hyperparathyroidism can now be subdivided into three types: patients who have target organ (kidney, bone) involvement, patients who don’t have this, and patients who have normocalcemic primary hyperparathyroidism.

The guideline discusses new medications that have become available for hyperparathyroidism, as well as surgery (the only cure), including how preoperative imaging can identify the overactive parathyroid gland, and the guidelines go into detail about how to monitor a patient and why a clinician would or would not recommend surgery, Dr. Bilezikian explained.

In the end, treatment is tailored to the individual.

Last, the guideline identifies eight areas where more research is needed.

The guidelines were funded by unrestricted educational grants from Amolyt, Ascendis, Calcilytix, and Takeda. Dr. Khan has reported participating on advisory boards for Alexion, Amgen, Amolyt, and Takeda, being a consultant for Amgen, receiving grants from Alexion, Amgen, Takeda, and Ascendis, being an investigator for Alexion, Amgen, Takeda, Ascendis, and Chugai, and being a speaker for Alexion, Amgen, Takeda, and Ultragenyx. Dr. Bilezikian has reported no relevant financial relationships.

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

A large international team of experts has developed two comprehensive guidelines for diagnosing, evaluating, and managing hypoparathyroidism and hyperparathyroidism, which replace guidelines issued 5 and 7 years ago.

Aliya A. Khan, MD, presented an overview of the hypoparathyroidism guidelines and John P. Bilezikian, MD, presented key aspects of the hyperparathyroidism guidelines at the American Society of Bone and Mineral Research (ASBMR) 2021 Annual Meeting.

The guidelines will be published as 17 articles in two issues of the society’s Journal of Bone and Mineral Research in 2022 – one on hypoparathyroidism and the other on hyperparathyroidism.

The work represents an “unprecedented effort” by more than 100 experts from 16 countries (United States, Canada, Australia, Brazil, China, Denmark, France, Germany, India, Italy, Israel, Lebanon, Singapore, Spain, Sweden, and the United Kingdom), Dr. Bilezikian told this news organization in an interview.

More than 100 international and national endocrine and osteoporosis organizations, societies, and patient advocacy groups from more than 50 countries have expressed interest in endorsing the guidelines.
 

Management of hypoparathyroidism

The new guidelines on hypoparathyroidism replace the guidelines issued in 2016 that were developed at the First International Conference on the Management of Hypoparathyroidism, Dr. Khan, from McMaster University, Hamilton, Ont., said in an email.

There was a need for new hypoparathyroidism guidelines, she explained, because of the better understanding of associated complications, how to predict who will develop hypoparathyroidism postoperatively (and how to prevent this), how and when to investigate a genetic cause further, when to consider parathyroid hormone (PTH) replacement therapy (and the benefits of the various molecules available today as well as those being evaluated in clinical research), and how to diagnose and manage hypoparathyroidism during pregnancy and lactation.

The experts in hypoparathyroidism were divided into four task forces that covered epidemiology and financial burden, etiology and pathophysiology, genetics and diagnosis, and patient evaluation and management.

The guidelines, developed over the past 18 months, provide detailed evidence-based graded (strong to weak) as well as ungraded (current practice) recommendations.

Summarizing a few key takeaways, Dr. Khan noted the guidelines recommend that clinicians treating patients with hypoparathyroidism should:

• Diagnose hypoparathyroidism if serum calcium corrected for albumin is low in the presence of a low or inappropriately normal PTH confirmed on two occasions 2 weeks apart (which may be supported by other specified abnormalities).
• Determine the cause for the hypoparathyroidism (which includes postsurgery, genetic variant, autoimmune, radiation, or idiopathic causes).
• Evaluate target organ damage.
• Try to achieve treatment goals and minimize risks for long-term complications.
• Consider PTH replacement therapy if patients have inadequate control, with symptoms of hypocalcemia or hypercalcemia, high phosphate, kidney disease, or high urine calcium, or poor quality of life. 

The guideline strongly recommends using PTH measurements after total thyroidectomy to try to predict which patients will develop permanent postsurgical hypoparathyroidism.

It provides a clinical approach for establishing the genetic etiology of hypoparathyroidism.

A meta-analysis of 81 studies identified that the most common symptoms/complications of chronic hypoparathyroidism were, in descending order, cataract (24%), infection (18%), nephrolithiasis, renal insufficiency, seizures, depression, ischemic heart disease, and arrhythmias.

Based on the best available evidence, the guideline advises that “clinicians need to carefully determine why a patient has hypoparathyroidism and develop an individualized treatment plan with conventional therapy consisting of calcium, active vitamin D, hydrochlorothiazide, and plain vitamin D,” Dr. Khan continued.

“If a patient has poorly controlled hypoparathyroidism with many symptoms or is not doing well, then clinicians must consider PTH replacement therapy, since this will replace the missing hormone, lower the urine calcium losses, bring the serum calcium back up to the normal reference range, and lower phosphate (which appears to be associated with kidney calcification and may also contribute to basal ganglia calcification and calcium deposits in the eye),” she noted.

The guideline also discusses the optimal way to monitor and treat patients during pregnancy, delivery, and breastfeeding to optimize outcomes for mother and baby. The key points are closer patient monitoring with normalization of calcium, urine calcium, phosphate, and vitamin D.  
 

Management of primary hyperparathyroidism

There was a need to update the previous 2014 guidelines developed at the Fourth International Workshop on the Management of Primary Hyperparathyroidism because, among other things, recent studies have provided new evidence about the different clinical phenotypes of primary hyperparathyroidism and ways the disease affects the skeleton and kidneys, Dr. Bilezikian, from the College of Physicians and Surgeons, Columbia University, New York, explained.

The experts in hyperparathyroidism were divided into four task forces that covered epidemiology, pathophysiology and genetics; classical and nonclassical disease manifestations; surgical aspects; and patient evaluation and management.

As part of these topics, the experts reviewed biochemical, skeletal, and renal findings, nonclassical features (such as neurocognitive complaints), nutritional and pharmacologic approaches, and disease course with or without surgical or medical intervention.

They made recommendations for diagnosis of hypercalcemic and normocalcemic phenotypes, differential diagnosis, evaluation of the skeleton and the kidney, indications for surgery, role of parathyroid imaging, indications for pharmacologic intervention, and monitoring.

“Consider the way this disease has appeared to change in the last 50 years,” said Dr. Bilezikian. In the 1940s, 50s, and 60s, patients with hyperparathyroidism were really sick and had severe bone disease and kidney disease. Then in the 70s, 80s, and 90s, the disease was more often discovered because of a screening test; high serum calcium was a hallmark of finding asymptomatic hyperparathyroidism.

In recent years, hyperparathyroidism is often discovered incidentally, when examining the skeleton or kidneys, he continued.

Primary hyperparathyroidism can now be subdivided into three types: patients who have target organ (kidney, bone) involvement, patients who don’t have this, and patients who have normocalcemic primary hyperparathyroidism.

The guideline discusses new medications that have become available for hyperparathyroidism, as well as surgery (the only cure), including how preoperative imaging can identify the overactive parathyroid gland, and the guidelines go into detail about how to monitor a patient and why a clinician would or would not recommend surgery, Dr. Bilezikian explained.

In the end, treatment is tailored to the individual.

Last, the guideline identifies eight areas where more research is needed.

The guidelines were funded by unrestricted educational grants from Amolyt, Ascendis, Calcilytix, and Takeda. Dr. Khan has reported participating on advisory boards for Alexion, Amgen, Amolyt, and Takeda, being a consultant for Amgen, receiving grants from Alexion, Amgen, Takeda, and Ascendis, being an investigator for Alexion, Amgen, Takeda, Ascendis, and Chugai, and being a speaker for Alexion, Amgen, Takeda, and Ultragenyx. Dr. Bilezikian has reported no relevant financial relationships.

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

The U.S. Food and Drug Administration (FDA) has approved a combination pill containing celecoxib and tramadol (Seglentis) for the treatment of adults with acute pain severe enough to require an opioid analgesic and for which alternative treatments fail to provide adequate pain relief.

Celecoxib is a nonsteroidal anti-inflammatory drug and tramadol is an opioid agonist. Seglentis contains 56 mg of celecoxib and 44 mg of tramadol.

“The unique co-crystal formulation of Seglentis provides effective pain relief via a multimodal approach,” Craig A. Sponseller, MD, chief medical officer of Kowa Pharmaceuticals America, said in a news release.

Esteve Pharmaceuticals has entered into an agreement with Kowa Pharmaceuticals America to commercialize the pain medicine in the United States, with a launch planned for early 2022.

“Seglentis uses four different and complementary mechanisms of analgesia and offers healthcare providers an important option to treat acute pain in adults that is severe enough to require opioid treatment and for which alternative treatments are inadequate,” Dr. Sponseller said.

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, the FDA will require a Risk Evaluation and Mitigation Strategy (REMS) for Seglentis.

The label states that the drug should be initiated as two tablets every 12 hours as needed and should be prescribed for the shortest duration consistent with individual patient treatment goals.

Patients should be monitored for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with Seglentis.

Prescribers should discuss naloxone (Narcan) with patients and consider prescribing the opioid antagonist naloxone based on the patient’s risk factors for overdose.

Full prescribing information is available online.

A version of this article was first published on Medscape.com.

The U.S. Food and Drug Administration (FDA) has approved a combination pill containing celecoxib and tramadol (Seglentis) for the treatment of adults with acute pain severe enough to require an opioid analgesic and for which alternative treatments fail to provide adequate pain relief.

Celecoxib is a nonsteroidal anti-inflammatory drug and tramadol is an opioid agonist. Seglentis contains 56 mg of celecoxib and 44 mg of tramadol.

“The unique co-crystal formulation of Seglentis provides effective pain relief via a multimodal approach,” Craig A. Sponseller, MD, chief medical officer of Kowa Pharmaceuticals America, said in a news release.

Esteve Pharmaceuticals has entered into an agreement with Kowa Pharmaceuticals America to commercialize the pain medicine in the United States, with a launch planned for early 2022.

“Seglentis uses four different and complementary mechanisms of analgesia and offers healthcare providers an important option to treat acute pain in adults that is severe enough to require opioid treatment and for which alternative treatments are inadequate,” Dr. Sponseller said.

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, the FDA will require a Risk Evaluation and Mitigation Strategy (REMS) for Seglentis.

The label states that the drug should be initiated as two tablets every 12 hours as needed and should be prescribed for the shortest duration consistent with individual patient treatment goals.

Patients should be monitored for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with Seglentis.

Prescribers should discuss naloxone (Narcan) with patients and consider prescribing the opioid antagonist naloxone based on the patient’s risk factors for overdose.

Full prescribing information is available online.

A version of this article was first published on Medscape.com.

The U.S. Food and Drug Administration (FDA) has approved a combination pill containing celecoxib and tramadol (Seglentis) for the treatment of adults with acute pain severe enough to require an opioid analgesic and for which alternative treatments fail to provide adequate pain relief.

Celecoxib is a nonsteroidal anti-inflammatory drug and tramadol is an opioid agonist. Seglentis contains 56 mg of celecoxib and 44 mg of tramadol.

“The unique co-crystal formulation of Seglentis provides effective pain relief via a multimodal approach,” Craig A. Sponseller, MD, chief medical officer of Kowa Pharmaceuticals America, said in a news release.

Esteve Pharmaceuticals has entered into an agreement with Kowa Pharmaceuticals America to commercialize the pain medicine in the United States, with a launch planned for early 2022.

“Seglentis uses four different and complementary mechanisms of analgesia and offers healthcare providers an important option to treat acute pain in adults that is severe enough to require opioid treatment and for which alternative treatments are inadequate,” Dr. Sponseller said.

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, the FDA will require a Risk Evaluation and Mitigation Strategy (REMS) for Seglentis.

The label states that the drug should be initiated as two tablets every 12 hours as needed and should be prescribed for the shortest duration consistent with individual patient treatment goals.

Patients should be monitored for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with Seglentis.

Prescribers should discuss naloxone (Narcan) with patients and consider prescribing the opioid antagonist naloxone based on the patient’s risk factors for overdose.

Full prescribing information is available online.

A version of this article was first published on Medscape.com.

Tramadol is increasingly used to manage chronic noncancer pain, but as compared with opioids, it appears to be linked to a higher risk for adverse outcomes, according to new data.

Among a cohort of patients who received a prescription for either tramadol or codeine for orthopedic-related pain, tramadol was significantly associated with a higher risk of mortality, cardiovascular events, and fractures.

However, there was no significant difference in the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders between the two drugs.

“However, this is a retrospective cohort study, and despite it providing information that would otherwise be impossible to gather – such as from randomized controlled trials – clinicians should not solely base their decision on this study,” cautioned lead author Carlen Reyes, MD, PhD, of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol), Barcelona.

Dr. Reyes noted that the intake of tramadol and codeine was analyzed using the number of “packages” that were dispensed, as an approximation of the real intake. “Logically we could think that the more packages dispensed of one drug, the more dose the patient is taking, but this is not always true given the availability of different doses commercialized of tramadol and different doses prescribed,” she said. “Given that we did not account for the real dose prescribed, we can only suspect an increased risk of these outcomes and reinforce the need for further prospective studies with more specific dose-response analysis comparing tramadol and codeine.”

The paper was published Oct. 19 in JAMA.

Tramadol has been considered to be a relatively safe opioid and was even strongly recommended by the American Academy of Orthopaedic Surgeons for patients experiencing symptomatic knee osteoarthritis. The authors point out that studies looking at opioid use from 2019 to 2020 show that tramadol was the most prescribed opioid in England, the Netherlands, and Spain.

In the United States, the age-adjusted rate of drug overdose deaths from synthetic opioids rose from 1.0 per 100 000 in 2013 to 11.4 in 2019. Most of these deaths were attributable to fentanyl but some were also related to tramadol.

But despite its wide use in managing chronic noncancer pain, results of recent studies suggest adverse outcomes as compared with other agents. Last year, one study found that older patients who received tramadol had a significant increase in the risk of hip fracture vs. those using NSAIDs or codeine. Another study, also published in 2020, showed that patients with osteoarthritis who were treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs.

In the current paper, Dr. Reyes and colleagues evaluated the association of tramadol with mortality and other adverse clinical outcomes in outpatient settings, compared with codeine.

They conducted a retrospective, population-based, propensity score–matched cohort study using a primary care database that routinely collects medical records and pharmacy dispensations for more than 80% of the population of Catalonia, Spain. The cohort included people 18 years or older who had been prescribed tramadol or codeine from 2007 to 2017 and were followed up to Dec. 31, 2017.

After propensity score matching, the final analysis included 368,960 participants: 184,480 in the tramadol arm and 184,480 in the codeine arm.

The mean age of patients was 52.7 years in the tramadol arm and 53.5 years in the codeine arm, and the prevalence of cancer was 3.2% and 3.3%, respectively. The most common diagnoses in this cohort were back pain (47.5% vs. 48.5%), neck/shoulder pain (28.6% vs. 29.5%), and osteoarthritis (15.3% vs. 15.5%). The most commonly used drugs were ibuprofen (34.4% vs. 34.3%) and paracetamol/acetaminophen (37.1% vs. 36.8%)

Higher risk of adverse outcomes

As compared with codeine, tramadol use was significantly associated with a higher risk of mortality (13.00 vs. 5.61 per 1,000 person-years; hazard ratio, 2.31; 95% confidence interval, 2.08-2.56); absolute rate differences (7.37 per 1,000 person-years; 95% CI, 6.09-8.78), cardiovascular events (10.03 vs. 8.67 per 1,000 person-years; HR, 1.15; 95% CI, 1.05-1.27; ARD, 1.36 per 1,000 person-years; 95% CI, 0.45-2.36), and fractures (12.26 vs. 8.13 per 1,000 person-years; HR, 1.50; 95% CI, 1.37-1.65; ARD, 4.10 per 1,000 person-years; 95% CI, 3.02-5.29).

A subgroup and sensitivity analysis showed that the increased mortality risk associated with tramadol was significantly higher in younger persons vs. older ones (HR, 3.14; 95% CI, 1.82-5.41 vs. 2.39; 95% CI, 2.20-2.60]; P < .001 for interaction). In addition, women had a significantly greater risk of cardiovascular events versus men (HR, 1.32; 95% CI, 1.19-1.46] vs. 1.03; 95% CI, 0.9-1.13]; P < .001 for interaction).
 

Potential for confounding

Weighing in on the data, Daniel Solomon, MD, MPH, chief of clinical sciences, division of rheumatology, Brigham and Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, noted that because it is extremely unlikely that anyone will ever conduct a large, head-to-head safety trial comparing different opioids, the results of this paper are important to consider.

“However, as the authors appropriately caution, this type of analysis is limited by the strong potential for residual confounding,” he said. “In other words, even though the authors used state-of-the-art methods to limit imbalances between the patients initiating tramadol versus codeine, there is strong reason to believe that imbalances that may account for the differences in adverse events exist.”

For example, he noted that if one looks at the distribution of comorbid conditions in the before-matching group, tramadol initiators demonstrate a higher frequency of chronic kidney disease, diabetes, and overall chronic comorbid diseases. “This suggests to me that prescribers apply selection criteria when choosing who to prescribe which opioid,” Dr. Solomon explained.

“While the authors’ use of propensity score matching limits confounding, it only can improve balance for measured confounders,” he said. “Other factors not measured in this type of data set – blood pressure, pain, physical activity, tobacco use, body mass index – may still demonstrate imbalances even after matching.”

But after these limitations are taken into consideration, the results remain concerning, Dr. Solomon emphasized, particularly the all-cause mortality excess of tramadol versus codeine users. “This study did not include cause of death, which would help the reader understand why users of tramadol were dying more frequently,” he added. “It also might help in understanding whether this is a true biologic effect or residual confounding.”

Perceived safety

In an accompanying editorial, Howard S. Kim, MD, MS, and colleagues from Northwestern University, Chicago, write that the greatest risk of tramadol may involve the perception that it is “inherently safer than other opioids.”

“In actuality, the mechanisms of action and variable metabolism of tramadol in a given population create considerable therapeutic uncertainty and introduce additional risk exposure,” they say, as demonstrated in the current study.

Therefore, when clinicians determine that an opioid is needed for pain relief, it may be a better option to select a pure opioid agonist that has a more predictable therapeutic effect and known adverse effect profile, such as morphine or hydrocodone. “This would allow clinicians and patients to more properly weigh the risks and benefits of initiating opioid therapy through shared decision-making and prompt the level of counseling on safe use, storage, and disposal practices that all opioids deserve,” write the editorialists.

The study was funded by the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Reyes has disclosed no relevant financial relationships. Dr. Solomon disclosed salary support from research contracts to his hospital from Amgen, AbbVie, Moderna, the Rheumatology Research Foundation, and National Institutes of Health; and royalties from UpToDate. Dr. Kim reported unrelated grant support from the Agency for Healthcare Research and Quality.
 

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

Tramadol is increasingly used to manage chronic noncancer pain, but as compared with opioids, it appears to be linked to a higher risk for adverse outcomes, according to new data.

Among a cohort of patients who received a prescription for either tramadol or codeine for orthopedic-related pain, tramadol was significantly associated with a higher risk of mortality, cardiovascular events, and fractures.

However, there was no significant difference in the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders between the two drugs.

“However, this is a retrospective cohort study, and despite it providing information that would otherwise be impossible to gather – such as from randomized controlled trials – clinicians should not solely base their decision on this study,” cautioned lead author Carlen Reyes, MD, PhD, of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol), Barcelona.

Dr. Reyes noted that the intake of tramadol and codeine was analyzed using the number of “packages” that were dispensed, as an approximation of the real intake. “Logically we could think that the more packages dispensed of one drug, the more dose the patient is taking, but this is not always true given the availability of different doses commercialized of tramadol and different doses prescribed,” she said. “Given that we did not account for the real dose prescribed, we can only suspect an increased risk of these outcomes and reinforce the need for further prospective studies with more specific dose-response analysis comparing tramadol and codeine.”

The paper was published Oct. 19 in JAMA.

Tramadol has been considered to be a relatively safe opioid and was even strongly recommended by the American Academy of Orthopaedic Surgeons for patients experiencing symptomatic knee osteoarthritis. The authors point out that studies looking at opioid use from 2019 to 2020 show that tramadol was the most prescribed opioid in England, the Netherlands, and Spain.

In the United States, the age-adjusted rate of drug overdose deaths from synthetic opioids rose from 1.0 per 100 000 in 2013 to 11.4 in 2019. Most of these deaths were attributable to fentanyl but some were also related to tramadol.

But despite its wide use in managing chronic noncancer pain, results of recent studies suggest adverse outcomes as compared with other agents. Last year, one study found that older patients who received tramadol had a significant increase in the risk of hip fracture vs. those using NSAIDs or codeine. Another study, also published in 2020, showed that patients with osteoarthritis who were treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs.

In the current paper, Dr. Reyes and colleagues evaluated the association of tramadol with mortality and other adverse clinical outcomes in outpatient settings, compared with codeine.

They conducted a retrospective, population-based, propensity score–matched cohort study using a primary care database that routinely collects medical records and pharmacy dispensations for more than 80% of the population of Catalonia, Spain. The cohort included people 18 years or older who had been prescribed tramadol or codeine from 2007 to 2017 and were followed up to Dec. 31, 2017.

After propensity score matching, the final analysis included 368,960 participants: 184,480 in the tramadol arm and 184,480 in the codeine arm.

The mean age of patients was 52.7 years in the tramadol arm and 53.5 years in the codeine arm, and the prevalence of cancer was 3.2% and 3.3%, respectively. The most common diagnoses in this cohort were back pain (47.5% vs. 48.5%), neck/shoulder pain (28.6% vs. 29.5%), and osteoarthritis (15.3% vs. 15.5%). The most commonly used drugs were ibuprofen (34.4% vs. 34.3%) and paracetamol/acetaminophen (37.1% vs. 36.8%)

Higher risk of adverse outcomes

As compared with codeine, tramadol use was significantly associated with a higher risk of mortality (13.00 vs. 5.61 per 1,000 person-years; hazard ratio, 2.31; 95% confidence interval, 2.08-2.56); absolute rate differences (7.37 per 1,000 person-years; 95% CI, 6.09-8.78), cardiovascular events (10.03 vs. 8.67 per 1,000 person-years; HR, 1.15; 95% CI, 1.05-1.27; ARD, 1.36 per 1,000 person-years; 95% CI, 0.45-2.36), and fractures (12.26 vs. 8.13 per 1,000 person-years; HR, 1.50; 95% CI, 1.37-1.65; ARD, 4.10 per 1,000 person-years; 95% CI, 3.02-5.29).

A subgroup and sensitivity analysis showed that the increased mortality risk associated with tramadol was significantly higher in younger persons vs. older ones (HR, 3.14; 95% CI, 1.82-5.41 vs. 2.39; 95% CI, 2.20-2.60]; P < .001 for interaction). In addition, women had a significantly greater risk of cardiovascular events versus men (HR, 1.32; 95% CI, 1.19-1.46] vs. 1.03; 95% CI, 0.9-1.13]; P < .001 for interaction).
 

Potential for confounding

Weighing in on the data, Daniel Solomon, MD, MPH, chief of clinical sciences, division of rheumatology, Brigham and Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, noted that because it is extremely unlikely that anyone will ever conduct a large, head-to-head safety trial comparing different opioids, the results of this paper are important to consider.

“However, as the authors appropriately caution, this type of analysis is limited by the strong potential for residual confounding,” he said. “In other words, even though the authors used state-of-the-art methods to limit imbalances between the patients initiating tramadol versus codeine, there is strong reason to believe that imbalances that may account for the differences in adverse events exist.”

For example, he noted that if one looks at the distribution of comorbid conditions in the before-matching group, tramadol initiators demonstrate a higher frequency of chronic kidney disease, diabetes, and overall chronic comorbid diseases. “This suggests to me that prescribers apply selection criteria when choosing who to prescribe which opioid,” Dr. Solomon explained.

“While the authors’ use of propensity score matching limits confounding, it only can improve balance for measured confounders,” he said. “Other factors not measured in this type of data set – blood pressure, pain, physical activity, tobacco use, body mass index – may still demonstrate imbalances even after matching.”

But after these limitations are taken into consideration, the results remain concerning, Dr. Solomon emphasized, particularly the all-cause mortality excess of tramadol versus codeine users. “This study did not include cause of death, which would help the reader understand why users of tramadol were dying more frequently,” he added. “It also might help in understanding whether this is a true biologic effect or residual confounding.”

Perceived safety

In an accompanying editorial, Howard S. Kim, MD, MS, and colleagues from Northwestern University, Chicago, write that the greatest risk of tramadol may involve the perception that it is “inherently safer than other opioids.”

“In actuality, the mechanisms of action and variable metabolism of tramadol in a given population create considerable therapeutic uncertainty and introduce additional risk exposure,” they say, as demonstrated in the current study.

Therefore, when clinicians determine that an opioid is needed for pain relief, it may be a better option to select a pure opioid agonist that has a more predictable therapeutic effect and known adverse effect profile, such as morphine or hydrocodone. “This would allow clinicians and patients to more properly weigh the risks and benefits of initiating opioid therapy through shared decision-making and prompt the level of counseling on safe use, storage, and disposal practices that all opioids deserve,” write the editorialists.

The study was funded by the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Reyes has disclosed no relevant financial relationships. Dr. Solomon disclosed salary support from research contracts to his hospital from Amgen, AbbVie, Moderna, the Rheumatology Research Foundation, and National Institutes of Health; and royalties from UpToDate. Dr. Kim reported unrelated grant support from the Agency for Healthcare Research and Quality.
 

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

Tramadol is increasingly used to manage chronic noncancer pain, but as compared with opioids, it appears to be linked to a higher risk for adverse outcomes, according to new data.

Among a cohort of patients who received a prescription for either tramadol or codeine for orthopedic-related pain, tramadol was significantly associated with a higher risk of mortality, cardiovascular events, and fractures.

However, there was no significant difference in the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders between the two drugs.

“However, this is a retrospective cohort study, and despite it providing information that would otherwise be impossible to gather – such as from randomized controlled trials – clinicians should not solely base their decision on this study,” cautioned lead author Carlen Reyes, MD, PhD, of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol), Barcelona.

Dr. Reyes noted that the intake of tramadol and codeine was analyzed using the number of “packages” that were dispensed, as an approximation of the real intake. “Logically we could think that the more packages dispensed of one drug, the more dose the patient is taking, but this is not always true given the availability of different doses commercialized of tramadol and different doses prescribed,” she said. “Given that we did not account for the real dose prescribed, we can only suspect an increased risk of these outcomes and reinforce the need for further prospective studies with more specific dose-response analysis comparing tramadol and codeine.”

The paper was published Oct. 19 in JAMA.

Tramadol has been considered to be a relatively safe opioid and was even strongly recommended by the American Academy of Orthopaedic Surgeons for patients experiencing symptomatic knee osteoarthritis. The authors point out that studies looking at opioid use from 2019 to 2020 show that tramadol was the most prescribed opioid in England, the Netherlands, and Spain.

In the United States, the age-adjusted rate of drug overdose deaths from synthetic opioids rose from 1.0 per 100 000 in 2013 to 11.4 in 2019. Most of these deaths were attributable to fentanyl but some were also related to tramadol.

But despite its wide use in managing chronic noncancer pain, results of recent studies suggest adverse outcomes as compared with other agents. Last year, one study found that older patients who received tramadol had a significant increase in the risk of hip fracture vs. those using NSAIDs or codeine. Another study, also published in 2020, showed that patients with osteoarthritis who were treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs.

In the current paper, Dr. Reyes and colleagues evaluated the association of tramadol with mortality and other adverse clinical outcomes in outpatient settings, compared with codeine.

They conducted a retrospective, population-based, propensity score–matched cohort study using a primary care database that routinely collects medical records and pharmacy dispensations for more than 80% of the population of Catalonia, Spain. The cohort included people 18 years or older who had been prescribed tramadol or codeine from 2007 to 2017 and were followed up to Dec. 31, 2017.

After propensity score matching, the final analysis included 368,960 participants: 184,480 in the tramadol arm and 184,480 in the codeine arm.

The mean age of patients was 52.7 years in the tramadol arm and 53.5 years in the codeine arm, and the prevalence of cancer was 3.2% and 3.3%, respectively. The most common diagnoses in this cohort were back pain (47.5% vs. 48.5%), neck/shoulder pain (28.6% vs. 29.5%), and osteoarthritis (15.3% vs. 15.5%). The most commonly used drugs were ibuprofen (34.4% vs. 34.3%) and paracetamol/acetaminophen (37.1% vs. 36.8%)

Higher risk of adverse outcomes

As compared with codeine, tramadol use was significantly associated with a higher risk of mortality (13.00 vs. 5.61 per 1,000 person-years; hazard ratio, 2.31; 95% confidence interval, 2.08-2.56); absolute rate differences (7.37 per 1,000 person-years; 95% CI, 6.09-8.78), cardiovascular events (10.03 vs. 8.67 per 1,000 person-years; HR, 1.15; 95% CI, 1.05-1.27; ARD, 1.36 per 1,000 person-years; 95% CI, 0.45-2.36), and fractures (12.26 vs. 8.13 per 1,000 person-years; HR, 1.50; 95% CI, 1.37-1.65; ARD, 4.10 per 1,000 person-years; 95% CI, 3.02-5.29).

A subgroup and sensitivity analysis showed that the increased mortality risk associated with tramadol was significantly higher in younger persons vs. older ones (HR, 3.14; 95% CI, 1.82-5.41 vs. 2.39; 95% CI, 2.20-2.60]; P < .001 for interaction). In addition, women had a significantly greater risk of cardiovascular events versus men (HR, 1.32; 95% CI, 1.19-1.46] vs. 1.03; 95% CI, 0.9-1.13]; P < .001 for interaction).
 

Potential for confounding

Weighing in on the data, Daniel Solomon, MD, MPH, chief of clinical sciences, division of rheumatology, Brigham and Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, noted that because it is extremely unlikely that anyone will ever conduct a large, head-to-head safety trial comparing different opioids, the results of this paper are important to consider.

“However, as the authors appropriately caution, this type of analysis is limited by the strong potential for residual confounding,” he said. “In other words, even though the authors used state-of-the-art methods to limit imbalances between the patients initiating tramadol versus codeine, there is strong reason to believe that imbalances that may account for the differences in adverse events exist.”

For example, he noted that if one looks at the distribution of comorbid conditions in the before-matching group, tramadol initiators demonstrate a higher frequency of chronic kidney disease, diabetes, and overall chronic comorbid diseases. “This suggests to me that prescribers apply selection criteria when choosing who to prescribe which opioid,” Dr. Solomon explained.

“While the authors’ use of propensity score matching limits confounding, it only can improve balance for measured confounders,” he said. “Other factors not measured in this type of data set – blood pressure, pain, physical activity, tobacco use, body mass index – may still demonstrate imbalances even after matching.”

But after these limitations are taken into consideration, the results remain concerning, Dr. Solomon emphasized, particularly the all-cause mortality excess of tramadol versus codeine users. “This study did not include cause of death, which would help the reader understand why users of tramadol were dying more frequently,” he added. “It also might help in understanding whether this is a true biologic effect or residual confounding.”

Perceived safety

In an accompanying editorial, Howard S. Kim, MD, MS, and colleagues from Northwestern University, Chicago, write that the greatest risk of tramadol may involve the perception that it is “inherently safer than other opioids.”

“In actuality, the mechanisms of action and variable metabolism of tramadol in a given population create considerable therapeutic uncertainty and introduce additional risk exposure,” they say, as demonstrated in the current study.

Therefore, when clinicians determine that an opioid is needed for pain relief, it may be a better option to select a pure opioid agonist that has a more predictable therapeutic effect and known adverse effect profile, such as morphine or hydrocodone. “This would allow clinicians and patients to more properly weigh the risks and benefits of initiating opioid therapy through shared decision-making and prompt the level of counseling on safe use, storage, and disposal practices that all opioids deserve,” write the editorialists.

The study was funded by the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Reyes has disclosed no relevant financial relationships. Dr. Solomon disclosed salary support from research contracts to his hospital from Amgen, AbbVie, Moderna, the Rheumatology Research Foundation, and National Institutes of Health; and royalties from UpToDate. Dr. Kim reported unrelated grant support from the Agency for Healthcare Research and Quality.
 

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

Women with systemic lupus erythematous (SLE) who are at risk for preeclampsia may benefit from timely treatment with low-dose aspirin and perhaps hydroxychloroquine, according to German researchers.

©American Heart Association

In a prospective, real-world study of 190 pregnancies in 148 women (average age, 30 years), the use of low-dose aspirin starting around the 16th week of gestation was associated with a lower risk for preeclampsia than was no aspirin use (adjusted odds ratio [aOR], 0.21; P < .05).

The use of hydroxychloroquine starting in the first trimester had a “moderating effect,” said Isabell Haase, MD, a senior clinician scientist in the department of rheumatology at Hiller-Research Unit, Düsseldorf, Germany. Although this was not a statistically significant effect (aOR, 0.47; P = .21), the association strengthened if only high-risk pregnancies were considered (aOR, 0.28; P = .075).

“I think this once more shows us that counseling and risk assessment in our lupus patients is very important to find out those with the highest risk and treat them as good as possible,” Dr. Haase said at an international congress on systemic lupus erythematosus.

Preeclampsia and lupus

“Women with SLE face a high risk of preeclampsia because of their autoimmune disease,” Dr. Haase explained. “This [risk] can be further increased if a woman carries additional risk factors, like hypertension or lupus nephritis.”

Low-dose aspirin is known to protect against the development of preeclampsia in women without autoimmune disease if started before the 16th gestational week of pregnancy, Dr. Haase added. That is why it’s recommended by both the American College of Rheumatology and the European Alliance of Associations for Rheumatology.

“For hydroxychloroquine, we only have some small studies and its mechanism of action that lead us to the idea that it could also have a beneficial effect on preeclampsia in lupus patients,” she said.
 

Study design and results

The aim of the study was to see in a real-world cohort whether there was any beneficial effect of either aspirin or hydroxychloroquine regarding the development of preeclampsia.

The researchers used prospectively collected data from pregnancies seen at an outpatient pregnancy clinic during 1995-2019. They used multiple logistic regression to determine whether there was any effect of four treatments on the development of preeclampsia: aspirin (n = 39 patients) or hydroxychloroquine (n = 39) alone, in combination (n = 43), or neither drug (n = 69).

Overall, 56% of the women had significant risk factors for preeclampsia, including a prior history, multifetal gestation, chronic hypertension, lupus nephritis, or antiphospholipid antibodies (aPL). A further 28% had moderate risk factors, including not having had children, a body mass index >30 kg/m², and being older than 35 years.

The overall rate of preeclampsia in the study population was 13.2%, “which is in line with other studies in lupus pregnancies,” Dr. Haase said. Rates in each of the four treatment groups were 15.4% with aspirin alone, 7.7% with hydroxychloroquine alone, 14% with both drugs, and 14.5% with neither.

The odds of developing preeclampsia were lower with both aspirin and hydroxychloroquine. Factors that raised the odds were high disease activity in the first trimester (aOR, 4.55), a BMI of >30 kg/m² (aOR, 6.14), having high-risk aPL or antiphospholipid syndrome (aOR, 8.02), and a history of preeclampsia (aOR, 9.78).

Only high disease activity in the first trimester and BMI >30 kg/m² remained independent predictors of preeclampsia when the researchers considered only high-risk pregnancies (aOR, 7.74 for high disease activity in first trimester and 10.04 for a high BMI).

The results are “really impressive,” said Angela Tincani, MD, senior consultant at the Rheumatology and Clinical Immunology Unit of ASST–Spedali Civili di Brescia, in Italy.

Dr. Tincani observed that the study had covered a “large number of years” (1995-2020).

“I think that our attitude in looking after lupus patients [changed] during this time,” she said.

“As an example, I think that we probably use less corticosteroids now than in the 90s,” she said.

When asked whether changes in practices have influenced the findings, she acknowledged, “You can see that the prescription of the different medications has changed a lot. We also thought that we have to take into account the years as a confounder, but we haven’t statistically analyzed that, but it’s definitely something that we are going to do next.”

The study received no outside funding. Dr. Haase has received travel fees from AbbVie, Celgene, Chugai, Janssen-Cilag, Eli Lilly, and Medac. Dr. Tincani has disclosed no relevant financial relationships.

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

Women with systemic lupus erythematous (SLE) who are at risk for preeclampsia may benefit from timely treatment with low-dose aspirin and perhaps hydroxychloroquine, according to German researchers.

©American Heart Association

In a prospective, real-world study of 190 pregnancies in 148 women (average age, 30 years), the use of low-dose aspirin starting around the 16th week of gestation was associated with a lower risk for preeclampsia than was no aspirin use (adjusted odds ratio [aOR], 0.21; P < .05).

The use of hydroxychloroquine starting in the first trimester had a “moderating effect,” said Isabell Haase, MD, a senior clinician scientist in the department of rheumatology at Hiller-Research Unit, Düsseldorf, Germany. Although this was not a statistically significant effect (aOR, 0.47; P = .21), the association strengthened if only high-risk pregnancies were considered (aOR, 0.28; P = .075).

“I think this once more shows us that counseling and risk assessment in our lupus patients is very important to find out those with the highest risk and treat them as good as possible,” Dr. Haase said at an international congress on systemic lupus erythematosus.

Preeclampsia and lupus

“Women with SLE face a high risk of preeclampsia because of their autoimmune disease,” Dr. Haase explained. “This [risk] can be further increased if a woman carries additional risk factors, like hypertension or lupus nephritis.”

Low-dose aspirin is known to protect against the development of preeclampsia in women without autoimmune disease if started before the 16th gestational week of pregnancy, Dr. Haase added. That is why it’s recommended by both the American College of Rheumatology and the European Alliance of Associations for Rheumatology.

“For hydroxychloroquine, we only have some small studies and its mechanism of action that lead us to the idea that it could also have a beneficial effect on preeclampsia in lupus patients,” she said.
 

Study design and results

The aim of the study was to see in a real-world cohort whether there was any beneficial effect of either aspirin or hydroxychloroquine regarding the development of preeclampsia.

The researchers used prospectively collected data from pregnancies seen at an outpatient pregnancy clinic during 1995-2019. They used multiple logistic regression to determine whether there was any effect of four treatments on the development of preeclampsia: aspirin (n = 39 patients) or hydroxychloroquine (n = 39) alone, in combination (n = 43), or neither drug (n = 69).

Overall, 56% of the women had significant risk factors for preeclampsia, including a prior history, multifetal gestation, chronic hypertension, lupus nephritis, or antiphospholipid antibodies (aPL). A further 28% had moderate risk factors, including not having had children, a body mass index >30 kg/m², and being older than 35 years.

The overall rate of preeclampsia in the study population was 13.2%, “which is in line with other studies in lupus pregnancies,” Dr. Haase said. Rates in each of the four treatment groups were 15.4% with aspirin alone, 7.7% with hydroxychloroquine alone, 14% with both drugs, and 14.5% with neither.

The odds of developing preeclampsia were lower with both aspirin and hydroxychloroquine. Factors that raised the odds were high disease activity in the first trimester (aOR, 4.55), a BMI of >30 kg/m² (aOR, 6.14), having high-risk aPL or antiphospholipid syndrome (aOR, 8.02), and a history of preeclampsia (aOR, 9.78).

Only high disease activity in the first trimester and BMI >30 kg/m² remained independent predictors of preeclampsia when the researchers considered only high-risk pregnancies (aOR, 7.74 for high disease activity in first trimester and 10.04 for a high BMI).

The results are “really impressive,” said Angela Tincani, MD, senior consultant at the Rheumatology and Clinical Immunology Unit of ASST–Spedali Civili di Brescia, in Italy.

Dr. Tincani observed that the study had covered a “large number of years” (1995-2020).

“I think that our attitude in looking after lupus patients [changed] during this time,” she said.

“As an example, I think that we probably use less corticosteroids now than in the 90s,” she said.

When asked whether changes in practices have influenced the findings, she acknowledged, “You can see that the prescription of the different medications has changed a lot. We also thought that we have to take into account the years as a confounder, but we haven’t statistically analyzed that, but it’s definitely something that we are going to do next.”

The study received no outside funding. Dr. Haase has received travel fees from AbbVie, Celgene, Chugai, Janssen-Cilag, Eli Lilly, and Medac. Dr. Tincani has disclosed no relevant financial relationships.

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

Women with systemic lupus erythematous (SLE) who are at risk for preeclampsia may benefit from timely treatment with low-dose aspirin and perhaps hydroxychloroquine, according to German researchers.

©American Heart Association

In a prospective, real-world study of 190 pregnancies in 148 women (average age, 30 years), the use of low-dose aspirin starting around the 16th week of gestation was associated with a lower risk for preeclampsia than was no aspirin use (adjusted odds ratio [aOR], 0.21; P < .05).

The use of hydroxychloroquine starting in the first trimester had a “moderating effect,” said Isabell Haase, MD, a senior clinician scientist in the department of rheumatology at Hiller-Research Unit, Düsseldorf, Germany. Although this was not a statistically significant effect (aOR, 0.47; P = .21), the association strengthened if only high-risk pregnancies were considered (aOR, 0.28; P = .075).

“I think this once more shows us that counseling and risk assessment in our lupus patients is very important to find out those with the highest risk and treat them as good as possible,” Dr. Haase said at an international congress on systemic lupus erythematosus.

Preeclampsia and lupus

“Women with SLE face a high risk of preeclampsia because of their autoimmune disease,” Dr. Haase explained. “This [risk] can be further increased if a woman carries additional risk factors, like hypertension or lupus nephritis.”

Low-dose aspirin is known to protect against the development of preeclampsia in women without autoimmune disease if started before the 16th gestational week of pregnancy, Dr. Haase added. That is why it’s recommended by both the American College of Rheumatology and the European Alliance of Associations for Rheumatology.

“For hydroxychloroquine, we only have some small studies and its mechanism of action that lead us to the idea that it could also have a beneficial effect on preeclampsia in lupus patients,” she said.
 

Study design and results

The aim of the study was to see in a real-world cohort whether there was any beneficial effect of either aspirin or hydroxychloroquine regarding the development of preeclampsia.

The researchers used prospectively collected data from pregnancies seen at an outpatient pregnancy clinic during 1995-2019. They used multiple logistic regression to determine whether there was any effect of four treatments on the development of preeclampsia: aspirin (n = 39 patients) or hydroxychloroquine (n = 39) alone, in combination (n = 43), or neither drug (n = 69).

Overall, 56% of the women had significant risk factors for preeclampsia, including a prior history, multifetal gestation, chronic hypertension, lupus nephritis, or antiphospholipid antibodies (aPL). A further 28% had moderate risk factors, including not having had children, a body mass index >30 kg/m², and being older than 35 years.

The overall rate of preeclampsia in the study population was 13.2%, “which is in line with other studies in lupus pregnancies,” Dr. Haase said. Rates in each of the four treatment groups were 15.4% with aspirin alone, 7.7% with hydroxychloroquine alone, 14% with both drugs, and 14.5% with neither.

The odds of developing preeclampsia were lower with both aspirin and hydroxychloroquine. Factors that raised the odds were high disease activity in the first trimester (aOR, 4.55), a BMI of >30 kg/m² (aOR, 6.14), having high-risk aPL or antiphospholipid syndrome (aOR, 8.02), and a history of preeclampsia (aOR, 9.78).

Only high disease activity in the first trimester and BMI >30 kg/m² remained independent predictors of preeclampsia when the researchers considered only high-risk pregnancies (aOR, 7.74 for high disease activity in first trimester and 10.04 for a high BMI).

The results are “really impressive,” said Angela Tincani, MD, senior consultant at the Rheumatology and Clinical Immunology Unit of ASST–Spedali Civili di Brescia, in Italy.

Dr. Tincani observed that the study had covered a “large number of years” (1995-2020).

“I think that our attitude in looking after lupus patients [changed] during this time,” she said.

“As an example, I think that we probably use less corticosteroids now than in the 90s,” she said.

When asked whether changes in practices have influenced the findings, she acknowledged, “You can see that the prescription of the different medications has changed a lot. We also thought that we have to take into account the years as a confounder, but we haven’t statistically analyzed that, but it’s definitely something that we are going to do next.”

The study received no outside funding. Dr. Haase has received travel fees from AbbVie, Celgene, Chugai, Janssen-Cilag, Eli Lilly, and Medac. Dr. Tincani has disclosed no relevant financial relationships.

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

Let me tell you a story. In 5 billion years the sun will run out of hydrogen, the fuel it is currently burning to power my solar panels amongst other things. At that time, the sun will no longer be able to keep its core contracted and will expand into a fiery, red giant, engulfing earth and obliterating any sign that we ever existed. No buildings. No blog posts. No mausoleums. No stories. Nothing of us will remain.

Well, here for a moment anyway, I’ve gotten you to think about something other than COVID. You’re welcome.

Fascinatingly, the image in your mind’s eye right now of a barren scorched landscape was put there by me. Simply by placing a few words together I have caused new thoughts in your head. You might even share this story with someone else – I would have actually changed your behavior through the power of language. This miraculous phenomenon seems to be unique to us humans; we are the only ones who can create whole worlds in another individual’s head just by making a few sounds. We in medicine have the privilege of experiencing this miracle every day.

Last week, a 97-year-old pale, frail, white man saw me for a basal cell carcinoma on his cheek. While performing a simple electrodesiccation and curettage, I asked if he remembers getting a lot of sunburns when he was young. He certainly remembered one. On a blustery sunny day, he fell asleep for hours on the deck of the USS West Virginia while in the Philippines. As a radio man, he was exhausted from days of conflict and he recalled how warm breezes lulled him asleep. He was so sunburned that for days he forgot how afraid he was of the Japanese.

After listening to his story, I had an image in my mind of palm trees swaying in the tropical winds while hundreds of hulking gray castles sat hidden in the vast surrounding oceans awaiting one of the greatest naval conflicts in history. I got to hear it from surely one of the last remaining people in existence to be able to tell that story. Listening to a patient’s tales is one of the benefits of being a physician. Not only do they help bond us with our patients, but also help lessen our burden of having to make diagnosis after diagnosis and write note after note for hours on end. Somehow performing yet another biopsy that day is made just a bit easier if I’m also learning about what it was like at the Battle of Leyte Gulf.

Encouraging patients to talk more can be risky. No physician, not even allergists, can afford to be waylaid by a retiree with nothing else to do today. But meaningful encounters can not only be a vaccine against burnout, they also lead to better patient adherence and satisfaction. Sometimes, there is simply not time. But often there is a little window during a procedure or when you’re reasonably caught up and don’t expect delays ahead. When patients say that a doctor really listened to me, it is often not their medical history, but their life story they mean. And like every story, they literally transform us, the listener. In a true physical sense, their stories live on in me, and now that I’ve shared this one in writing, also with you for perpetuity. That is at least for the next 5 billion years when it, too, will be swallowed by the sun, leaving only a crispy, smoking rock where we once existed.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Let me tell you a story. In 5 billion years the sun will run out of hydrogen, the fuel it is currently burning to power my solar panels amongst other things. At that time, the sun will no longer be able to keep its core contracted and will expand into a fiery, red giant, engulfing earth and obliterating any sign that we ever existed. No buildings. No blog posts. No mausoleums. No stories. Nothing of us will remain.

Well, here for a moment anyway, I’ve gotten you to think about something other than COVID. You’re welcome.

Fascinatingly, the image in your mind’s eye right now of a barren scorched landscape was put there by me. Simply by placing a few words together I have caused new thoughts in your head. You might even share this story with someone else – I would have actually changed your behavior through the power of language. This miraculous phenomenon seems to be unique to us humans; we are the only ones who can create whole worlds in another individual’s head just by making a few sounds. We in medicine have the privilege of experiencing this miracle every day.

Last week, a 97-year-old pale, frail, white man saw me for a basal cell carcinoma on his cheek. While performing a simple electrodesiccation and curettage, I asked if he remembers getting a lot of sunburns when he was young. He certainly remembered one. On a blustery sunny day, he fell asleep for hours on the deck of the USS West Virginia while in the Philippines. As a radio man, he was exhausted from days of conflict and he recalled how warm breezes lulled him asleep. He was so sunburned that for days he forgot how afraid he was of the Japanese.

After listening to his story, I had an image in my mind of palm trees swaying in the tropical winds while hundreds of hulking gray castles sat hidden in the vast surrounding oceans awaiting one of the greatest naval conflicts in history. I got to hear it from surely one of the last remaining people in existence to be able to tell that story. Listening to a patient’s tales is one of the benefits of being a physician. Not only do they help bond us with our patients, but also help lessen our burden of having to make diagnosis after diagnosis and write note after note for hours on end. Somehow performing yet another biopsy that day is made just a bit easier if I’m also learning about what it was like at the Battle of Leyte Gulf.

Encouraging patients to talk more can be risky. No physician, not even allergists, can afford to be waylaid by a retiree with nothing else to do today. But meaningful encounters can not only be a vaccine against burnout, they also lead to better patient adherence and satisfaction. Sometimes, there is simply not time. But often there is a little window during a procedure or when you’re reasonably caught up and don’t expect delays ahead. When patients say that a doctor really listened to me, it is often not their medical history, but their life story they mean. And like every story, they literally transform us, the listener. In a true physical sense, their stories live on in me, and now that I’ve shared this one in writing, also with you for perpetuity. That is at least for the next 5 billion years when it, too, will be swallowed by the sun, leaving only a crispy, smoking rock where we once existed.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Let me tell you a story. In 5 billion years the sun will run out of hydrogen, the fuel it is currently burning to power my solar panels amongst other things. At that time, the sun will no longer be able to keep its core contracted and will expand into a fiery, red giant, engulfing earth and obliterating any sign that we ever existed. No buildings. No blog posts. No mausoleums. No stories. Nothing of us will remain.

Well, here for a moment anyway, I’ve gotten you to think about something other than COVID. You’re welcome.

Fascinatingly, the image in your mind’s eye right now of a barren scorched landscape was put there by me. Simply by placing a few words together I have caused new thoughts in your head. You might even share this story with someone else – I would have actually changed your behavior through the power of language. This miraculous phenomenon seems to be unique to us humans; we are the only ones who can create whole worlds in another individual’s head just by making a few sounds. We in medicine have the privilege of experiencing this miracle every day.

Last week, a 97-year-old pale, frail, white man saw me for a basal cell carcinoma on his cheek. While performing a simple electrodesiccation and curettage, I asked if he remembers getting a lot of sunburns when he was young. He certainly remembered one. On a blustery sunny day, he fell asleep for hours on the deck of the USS West Virginia while in the Philippines. As a radio man, he was exhausted from days of conflict and he recalled how warm breezes lulled him asleep. He was so sunburned that for days he forgot how afraid he was of the Japanese.

After listening to his story, I had an image in my mind of palm trees swaying in the tropical winds while hundreds of hulking gray castles sat hidden in the vast surrounding oceans awaiting one of the greatest naval conflicts in history. I got to hear it from surely one of the last remaining people in existence to be able to tell that story. Listening to a patient’s tales is one of the benefits of being a physician. Not only do they help bond us with our patients, but also help lessen our burden of having to make diagnosis after diagnosis and write note after note for hours on end. Somehow performing yet another biopsy that day is made just a bit easier if I’m also learning about what it was like at the Battle of Leyte Gulf.

Encouraging patients to talk more can be risky. No physician, not even allergists, can afford to be waylaid by a retiree with nothing else to do today. But meaningful encounters can not only be a vaccine against burnout, they also lead to better patient adherence and satisfaction. Sometimes, there is simply not time. But often there is a little window during a procedure or when you’re reasonably caught up and don’t expect delays ahead. When patients say that a doctor really listened to me, it is often not their medical history, but their life story they mean. And like every story, they literally transform us, the listener. In a true physical sense, their stories live on in me, and now that I’ve shared this one in writing, also with you for perpetuity. That is at least for the next 5 billion years when it, too, will be swallowed by the sun, leaving only a crispy, smoking rock where we once existed.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

People with systemic lupus erythematosus (SLE) have a threefold greater likelihood of having up to five or more comorbidities in comparison with people in the general population, according to the results of two separate U.S. population-based studies.

The higher rate of comorbidities seen included many of those commonly reported before, such as cardiovascular and renal disease, but also some that may be less frequently associated with SLE, notably chronic obstructive pulmonary disease (COPD) and cardiac arrhythmias.

“In the past, the characterization of SLE comorbidities has relied on individual comorbidity assessment,” Alí Duarte García, MD, said at the 14th International Congress on Systemic Lupus Erythematosus, held together will the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“However, a patient-centric approach where a patient as a whole is seen and how many comorbidities they accrue has not been performed.” added Duarte García, who is a rheumatologist at the Mayo Clinic in Rochester, Minn.


 

Multiple conditions “overrepresented” in SLE patients

Dr. Duarte García reported the findings of one of the studies, both of which used data from the Rochester Epidemiology Project, a record-linkage system that collates clinical and hospital data from individuals who live in 19 counties in southeast Minnesota and eight counties in western Wisconsin; these patients have agreed to share their medical records for research.

The study population included 479 individuals diagnosed with SLE according to joint 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology criteria. These were matched by age, sex, race, and county to 479 individuals without SLE.

The mean age of the study population was 53 years, 82% were women, and 86% were White.

“We defined multimorbidity as those patients who have two or more comorbidities and substantial multimorbidity as those patients who have five or more comorbidities,” Dr. Duarte García explained.

A previously published list of 44 categories of comorbidities was used to classify the multimorbidity seen, and 27 of these were “overrepresented” in patients with SLE.

Patients with SLE averaged 5.3 comorbidities, whereas control study subjects had 2.9. Comparing SLE with non-SLE individuals, the odds ratio for having two or more comorbid conditions was 2.96, and for five or more comorbidities it was 3.06.

The highest odds ratio comparing SLE with non-SLE individuals was seen for pulmonary disorders (39.0).

Dr. Duarte García highlighted four comorbidities that occurred in SLE patients that were perhaps more unusual: congestive heart failure (OR, 13.3), valvular heart disease (OR, 4.2), cardiac arrhythmias (OR, 2.85), and COPD (OR, 2.7).

“Given the association of multimorbidity with poor outcomes, care delivery strategies to manage multimorbidity are needed in SLE,” Dr. Duarte García concluded.
 

Similar findings seen in cutaneous lupus

There is also an excess of comorbid conditions in people with cutaneous lupus erythematosus (CLE), Mehmet Hocaoglu, MD, said in reporting the findings of the second study.

Dr. Hocaoglu, an internal medicine resident at the University of Maryland Medical Center in Baltimore, and part of the same team of researchers as Dr. Duarte García, noted that in skin-related lupus the risk of multimorbidity was about doubled.

For this separate analysis, a total of 303 patients with cutaneous lupus had been matched to 303 controls from the general population. Odds ratios for having two or more or five or more comorbidities were a respective 2.27 and 1.65.

Among the comorbidities seen that were higher in those with cutaneous lupus than in the general population subjects were fibromyalgia, liver disease, hypertension, anemia, hypothyroidism, and COPD.

“Further research is definitely needed to identify if the driver of this multimorbidity in CLE patients is the disease itself or the treatments CLE patients are receiving or a multifactorial cause that is driving the disease association,” Dr. Hocaoglu said.
 

Comment and perspective

“Comorbidities that are not appropriate to the general population, compared to SLE,” seem to have been included in the overall SLE and the cutaneous lupus analyses, Raquel Faria, MD, suggested.

Dr. Faria, an internal medicine consultant at Unidade de Imunologia Clínica – Centro Hospitalar Universitário Porto (Portugal), chaired the poster discussion session in which the two studies had been presented.

She wondered if the researchers had analyzed the data while accounting for “the comorbidities that you knew are due to activity in lupus, like anemia?”

The number of patients with SLE who had pulmonary circulation disorders – 7.5% vs. 0.2% of the general population – also caught Dr. Faria’s attention.

That’s “a really huge number,” Dr. Faria pointed out, “I think it is pretty overrepresented.”

Dr. Duarte García acknowledged that they “took a very broad approach” in using a “very large comorbidity index.”

“What we were observing initially is precisely what you’re mentioning,” he responded to Dr. Faria.

“We were pulling patients who were having disease manifestation rather than a comorbidity,” Dr. Duarte-García said.

These are initial and very exploratory data, he stressed. “We have now moved on to modify the index.” Some of the changes that they have made were to incorporate the SLICC Damage Index Score and tighten up the list of ICD codes used.

No outside funding was received for either of the studies. Dr. Duarte García and Dr. Hocaoglu individually stated that they had no actual or potential conflicts of interest in relation to their presentations.

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

People with systemic lupus erythematosus (SLE) have a threefold greater likelihood of having up to five or more comorbidities in comparison with people in the general population, according to the results of two separate U.S. population-based studies.

The higher rate of comorbidities seen included many of those commonly reported before, such as cardiovascular and renal disease, but also some that may be less frequently associated with SLE, notably chronic obstructive pulmonary disease (COPD) and cardiac arrhythmias.

“In the past, the characterization of SLE comorbidities has relied on individual comorbidity assessment,” Alí Duarte García, MD, said at the 14th International Congress on Systemic Lupus Erythematosus, held together will the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“However, a patient-centric approach where a patient as a whole is seen and how many comorbidities they accrue has not been performed.” added Duarte García, who is a rheumatologist at the Mayo Clinic in Rochester, Minn.


 

Multiple conditions “overrepresented” in SLE patients

Dr. Duarte García reported the findings of one of the studies, both of which used data from the Rochester Epidemiology Project, a record-linkage system that collates clinical and hospital data from individuals who live in 19 counties in southeast Minnesota and eight counties in western Wisconsin; these patients have agreed to share their medical records for research.

The study population included 479 individuals diagnosed with SLE according to joint 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology criteria. These were matched by age, sex, race, and county to 479 individuals without SLE.

The mean age of the study population was 53 years, 82% were women, and 86% were White.

“We defined multimorbidity as those patients who have two or more comorbidities and substantial multimorbidity as those patients who have five or more comorbidities,” Dr. Duarte García explained.

A previously published list of 44 categories of comorbidities was used to classify the multimorbidity seen, and 27 of these were “overrepresented” in patients with SLE.

Patients with SLE averaged 5.3 comorbidities, whereas control study subjects had 2.9. Comparing SLE with non-SLE individuals, the odds ratio for having two or more comorbid conditions was 2.96, and for five or more comorbidities it was 3.06.

The highest odds ratio comparing SLE with non-SLE individuals was seen for pulmonary disorders (39.0).

Dr. Duarte García highlighted four comorbidities that occurred in SLE patients that were perhaps more unusual: congestive heart failure (OR, 13.3), valvular heart disease (OR, 4.2), cardiac arrhythmias (OR, 2.85), and COPD (OR, 2.7).

“Given the association of multimorbidity with poor outcomes, care delivery strategies to manage multimorbidity are needed in SLE,” Dr. Duarte García concluded.
 

Similar findings seen in cutaneous lupus

There is also an excess of comorbid conditions in people with cutaneous lupus erythematosus (CLE), Mehmet Hocaoglu, MD, said in reporting the findings of the second study.

Dr. Hocaoglu, an internal medicine resident at the University of Maryland Medical Center in Baltimore, and part of the same team of researchers as Dr. Duarte García, noted that in skin-related lupus the risk of multimorbidity was about doubled.

For this separate analysis, a total of 303 patients with cutaneous lupus had been matched to 303 controls from the general population. Odds ratios for having two or more or five or more comorbidities were a respective 2.27 and 1.65.

Among the comorbidities seen that were higher in those with cutaneous lupus than in the general population subjects were fibromyalgia, liver disease, hypertension, anemia, hypothyroidism, and COPD.

“Further research is definitely needed to identify if the driver of this multimorbidity in CLE patients is the disease itself or the treatments CLE patients are receiving or a multifactorial cause that is driving the disease association,” Dr. Hocaoglu said.
 

Comment and perspective

“Comorbidities that are not appropriate to the general population, compared to SLE,” seem to have been included in the overall SLE and the cutaneous lupus analyses, Raquel Faria, MD, suggested.

Dr. Faria, an internal medicine consultant at Unidade de Imunologia Clínica – Centro Hospitalar Universitário Porto (Portugal), chaired the poster discussion session in which the two studies had been presented.

She wondered if the researchers had analyzed the data while accounting for “the comorbidities that you knew are due to activity in lupus, like anemia?”

The number of patients with SLE who had pulmonary circulation disorders – 7.5% vs. 0.2% of the general population – also caught Dr. Faria’s attention.

That’s “a really huge number,” Dr. Faria pointed out, “I think it is pretty overrepresented.”

Dr. Duarte García acknowledged that they “took a very broad approach” in using a “very large comorbidity index.”

“What we were observing initially is precisely what you’re mentioning,” he responded to Dr. Faria.

“We were pulling patients who were having disease manifestation rather than a comorbidity,” Dr. Duarte-García said.

These are initial and very exploratory data, he stressed. “We have now moved on to modify the index.” Some of the changes that they have made were to incorporate the SLICC Damage Index Score and tighten up the list of ICD codes used.

No outside funding was received for either of the studies. Dr. Duarte García and Dr. Hocaoglu individually stated that they had no actual or potential conflicts of interest in relation to their presentations.

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

People with systemic lupus erythematosus (SLE) have a threefold greater likelihood of having up to five or more comorbidities in comparison with people in the general population, according to the results of two separate U.S. population-based studies.

The higher rate of comorbidities seen included many of those commonly reported before, such as cardiovascular and renal disease, but also some that may be less frequently associated with SLE, notably chronic obstructive pulmonary disease (COPD) and cardiac arrhythmias.

“In the past, the characterization of SLE comorbidities has relied on individual comorbidity assessment,” Alí Duarte García, MD, said at the 14th International Congress on Systemic Lupus Erythematosus, held together will the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“However, a patient-centric approach where a patient as a whole is seen and how many comorbidities they accrue has not been performed.” added Duarte García, who is a rheumatologist at the Mayo Clinic in Rochester, Minn.


 

Multiple conditions “overrepresented” in SLE patients

Dr. Duarte García reported the findings of one of the studies, both of which used data from the Rochester Epidemiology Project, a record-linkage system that collates clinical and hospital data from individuals who live in 19 counties in southeast Minnesota and eight counties in western Wisconsin; these patients have agreed to share their medical records for research.

The study population included 479 individuals diagnosed with SLE according to joint 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology criteria. These were matched by age, sex, race, and county to 479 individuals without SLE.

The mean age of the study population was 53 years, 82% were women, and 86% were White.

“We defined multimorbidity as those patients who have two or more comorbidities and substantial multimorbidity as those patients who have five or more comorbidities,” Dr. Duarte García explained.

A previously published list of 44 categories of comorbidities was used to classify the multimorbidity seen, and 27 of these were “overrepresented” in patients with SLE.

Patients with SLE averaged 5.3 comorbidities, whereas control study subjects had 2.9. Comparing SLE with non-SLE individuals, the odds ratio for having two or more comorbid conditions was 2.96, and for five or more comorbidities it was 3.06.

The highest odds ratio comparing SLE with non-SLE individuals was seen for pulmonary disorders (39.0).

Dr. Duarte García highlighted four comorbidities that occurred in SLE patients that were perhaps more unusual: congestive heart failure (OR, 13.3), valvular heart disease (OR, 4.2), cardiac arrhythmias (OR, 2.85), and COPD (OR, 2.7).

“Given the association of multimorbidity with poor outcomes, care delivery strategies to manage multimorbidity are needed in SLE,” Dr. Duarte García concluded.
 

Similar findings seen in cutaneous lupus

There is also an excess of comorbid conditions in people with cutaneous lupus erythematosus (CLE), Mehmet Hocaoglu, MD, said in reporting the findings of the second study.

Dr. Hocaoglu, an internal medicine resident at the University of Maryland Medical Center in Baltimore, and part of the same team of researchers as Dr. Duarte García, noted that in skin-related lupus the risk of multimorbidity was about doubled.

For this separate analysis, a total of 303 patients with cutaneous lupus had been matched to 303 controls from the general population. Odds ratios for having two or more or five or more comorbidities were a respective 2.27 and 1.65.

Among the comorbidities seen that were higher in those with cutaneous lupus than in the general population subjects were fibromyalgia, liver disease, hypertension, anemia, hypothyroidism, and COPD.

“Further research is definitely needed to identify if the driver of this multimorbidity in CLE patients is the disease itself or the treatments CLE patients are receiving or a multifactorial cause that is driving the disease association,” Dr. Hocaoglu said.
 

Comment and perspective

“Comorbidities that are not appropriate to the general population, compared to SLE,” seem to have been included in the overall SLE and the cutaneous lupus analyses, Raquel Faria, MD, suggested.

Dr. Faria, an internal medicine consultant at Unidade de Imunologia Clínica – Centro Hospitalar Universitário Porto (Portugal), chaired the poster discussion session in which the two studies had been presented.

She wondered if the researchers had analyzed the data while accounting for “the comorbidities that you knew are due to activity in lupus, like anemia?”

The number of patients with SLE who had pulmonary circulation disorders – 7.5% vs. 0.2% of the general population – also caught Dr. Faria’s attention.

That’s “a really huge number,” Dr. Faria pointed out, “I think it is pretty overrepresented.”

Dr. Duarte García acknowledged that they “took a very broad approach” in using a “very large comorbidity index.”

“What we were observing initially is precisely what you’re mentioning,” he responded to Dr. Faria.

“We were pulling patients who were having disease manifestation rather than a comorbidity,” Dr. Duarte-García said.

These are initial and very exploratory data, he stressed. “We have now moved on to modify the index.” Some of the changes that they have made were to incorporate the SLICC Damage Index Score and tighten up the list of ICD codes used.

No outside funding was received for either of the studies. Dr. Duarte García and Dr. Hocaoglu individually stated that they had no actual or potential conflicts of interest in relation to their presentations.

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

In June, Gerald Bock, MD, a dermatologist in central California, instituted a new office policy: He would not be seeing any more patients who remain unvaccinated against COVID-19 in his practice.

peterschreiber_media/iStock/Getty Images

“[It is] the height of self-centered and irresponsible behavior,” he told me. “People who come in unvaccinated, when vaccination is widely available, are stating that their personal preferences are more important than their health, and are more important than any risk that they may expose their friends and family to, and also to any risk they might present to my staff and me. We have gone to considerable effort and expense to diminish any risk that visiting our office might entail. I see no reason why we should tolerate this.”

Other doctors appear to be following in his footsteps. There is no question that physicians have the right to choose their patients, just as patients are free to choose their doctors, but is it ethical to treat unvaccinated patients differently than their vaccinated counterparts? That is a complicated question without a clear answer. In a statement on whether physicians can decline unvaccinated patients, the American Medical Association continues to maintain that “in general” a physician may not “ethically turn a patient away based solely on the individual’s infectious disease status,” but does concede that “the decision to accept or decline a patient must balance the urgency of the individual patient’s need; the risk the patient may pose to other patients in the physician’s practice; and the need for the physician and staff, to be available to provide care in the future.”

Medical ethics experts have offered varying opinions. Daniel Wikler, PhD, professor of ethics and population health at the Harvard School of Public Health, Boston, wrote in an op-ed in the Washington Post that “ignorance or other personal failing” should not be factors in the evaluation of patients for health care. He argues that “doctors and hospitals are not in the blame and punishment business. Nor should they be. That doctors treat sinners and responsible citizens alike is a noble tradition.”

Timothy Hoff, professor of management, healthcare systems, and health policy at Northeastern University, Boston, maintains that, in nonemergency situations, physicians are legally able to refuse patients for a variety of reasons, provided they are not doing so because of some aspect of the patient’s race, gender, sexuality, or religion. However, in the same Northeastern University news release,Robert Baginski, MD, the director of interdisciplinary affairs for the department of medical sciences at Northeastern, cautions that it is vital for health authorities to continue urging the public to get vaccinated, but not at the expense of care.

Arthur L. Caplan, PhD, the head of the division of medical ethics at New York University, said in a Medscape commentary, that the decision to refuse to see patients who can vaccinate, but choose not to, is justifiable. “If you’re trying to protect yourself, your staff, or other patients, I think you do have the right to not take on somebody who won’t vaccinate,” he writes. “This is somewhat similar to when pediatricians do not accept a family if they won’t give their kids the state-required shots to go to school. That’s been happening for many years now.

“I also think it is morally justified if they won’t take your advice,” he continues. “If they won’t follow what you think is the best healthcare for them [such as getting vaccinated], there’s not much point in building that relationship.”

The situation is different in ED and hospital settings, however. “It’s a little harder to use unvaccinated status when someone really is at death’s door,” Dr. Caplan pointed out. “When someone comes in very sick, or whatever the reason, I think we have to take care of them ethically, and legally we’re bound to get them stable in the emergency room. I do think different rules apply there.”

In the end, every private practitioner will have to make his or her own decision on this question. Dr. Bock feels he made the right one. “Since instituting the policy, we have written 55 refund checks for people who had paid for a series of cosmetic procedures. We have no idea how many people were deterred from making appointments. We’ve had several negative online reviews and one woman who wrote a letter to the Medical Board of California complaining that we were discriminating against her,” he said. He added, however, that “we’ve also had several patients who commented favorably about the policy. I have no regrets about instituting the policy, and would do it again.”

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].