Rheumatology News

This transcript has been edited for clarity.

How do you tell if a condition is caused by an infection?

It seems like an obvious question, right? In the post–van Leeuwenhoek era we can look at whatever part of the body is diseased under a microscope and see microbes – you know, the usual suspects.

Except when we can’t. And there are plenty of cases where we can’t: where the microbe is too small to be seen without more advanced imaging techniques, like with viruses; or when the pathogen is sparsely populated or hard to culture, like Mycobacterium.

Finding out that a condition is the result of an infection is not only an exercise for 19th century physicians. After all, it was 2008 when Barry Marshall and Robin Warren won their Nobel Prize for proving that stomach ulcers, long thought to be due to “stress,” were actually caused by a tiny microbe called Helicobacter pylori.

And this week, we are looking at a study which, once again, begins to suggest that a condition thought to be more or less random – cerebral amyloid angiopathy – may actually be the result of an infectious disease.

We’re talking about this paper, appearing in JAMA, which is just a great example of old-fashioned shoe-leather epidemiology. But let’s get up to speed on cerebral amyloid angiopathy (CAA) first.

CAA is characterized by the deposition of amyloid protein in the brain. While there are some genetic causes, they are quite rare, and most cases are thought to be idiopathic. Recent analyses suggest that somewhere between 5% and 7% of cognitively normal older adults have CAA, but the rate is much higher among those with intracerebral hemorrhage – brain bleeds. In fact, CAA is the second-most common cause of bleeding in the brain, second only to severe hypertension.

Most of the textbooks continue to describe CAA as a sporadic condition, but there have been some intriguing studies that suggest it may be transmissible. An article in Nature highlights cases that seemed to develop after the administration of cadaveric pituitary hormone.

Other studies have shown potential transmission via dura mater grafts and neurosurgical instruments. But despite those clues, no infectious organism has been identified. Some have suggested that the long latent period and difficulty of finding a responsible microbe points to a prion-like disease not yet known. But these studies are more or less case series. The new JAMA paper gives us, if not a smoking gun, a pretty decent set of fingerprints.

Here’s the idea: If CAA is caused by some infectious agent, it may be transmitted in the blood. We know that a decent percentage of people who have spontaneous brain bleeds have CAA. If those people donated blood in the past, maybe the people who received that blood would be at risk for brain bleeds too.

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy JAMA Internal Medicine

Dr. F. Perry Wilson is an associate professor of medicine and public health and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.
 

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

This transcript has been edited for clarity.

How do you tell if a condition is caused by an infection?

It seems like an obvious question, right? In the post–van Leeuwenhoek era we can look at whatever part of the body is diseased under a microscope and see microbes – you know, the usual suspects.

Except when we can’t. And there are plenty of cases where we can’t: where the microbe is too small to be seen without more advanced imaging techniques, like with viruses; or when the pathogen is sparsely populated or hard to culture, like Mycobacterium.

Finding out that a condition is the result of an infection is not only an exercise for 19th century physicians. After all, it was 2008 when Barry Marshall and Robin Warren won their Nobel Prize for proving that stomach ulcers, long thought to be due to “stress,” were actually caused by a tiny microbe called Helicobacter pylori.

And this week, we are looking at a study which, once again, begins to suggest that a condition thought to be more or less random – cerebral amyloid angiopathy – may actually be the result of an infectious disease.

We’re talking about this paper, appearing in JAMA, which is just a great example of old-fashioned shoe-leather epidemiology. But let’s get up to speed on cerebral amyloid angiopathy (CAA) first.

CAA is characterized by the deposition of amyloid protein in the brain. While there are some genetic causes, they are quite rare, and most cases are thought to be idiopathic. Recent analyses suggest that somewhere between 5% and 7% of cognitively normal older adults have CAA, but the rate is much higher among those with intracerebral hemorrhage – brain bleeds. In fact, CAA is the second-most common cause of bleeding in the brain, second only to severe hypertension.

Most of the textbooks continue to describe CAA as a sporadic condition, but there have been some intriguing studies that suggest it may be transmissible. An article in Nature highlights cases that seemed to develop after the administration of cadaveric pituitary hormone.

Other studies have shown potential transmission via dura mater grafts and neurosurgical instruments. But despite those clues, no infectious organism has been identified. Some have suggested that the long latent period and difficulty of finding a responsible microbe points to a prion-like disease not yet known. But these studies are more or less case series. The new JAMA paper gives us, if not a smoking gun, a pretty decent set of fingerprints.

Here’s the idea: If CAA is caused by some infectious agent, it may be transmitted in the blood. We know that a decent percentage of people who have spontaneous brain bleeds have CAA. If those people donated blood in the past, maybe the people who received that blood would be at risk for brain bleeds too.

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy JAMA Internal Medicine

Dr. F. Perry Wilson is an associate professor of medicine and public health and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.
 

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

This transcript has been edited for clarity.

How do you tell if a condition is caused by an infection?

It seems like an obvious question, right? In the post–van Leeuwenhoek era we can look at whatever part of the body is diseased under a microscope and see microbes – you know, the usual suspects.

Except when we can’t. And there are plenty of cases where we can’t: where the microbe is too small to be seen without more advanced imaging techniques, like with viruses; or when the pathogen is sparsely populated or hard to culture, like Mycobacterium.

Finding out that a condition is the result of an infection is not only an exercise for 19th century physicians. After all, it was 2008 when Barry Marshall and Robin Warren won their Nobel Prize for proving that stomach ulcers, long thought to be due to “stress,” were actually caused by a tiny microbe called Helicobacter pylori.

And this week, we are looking at a study which, once again, begins to suggest that a condition thought to be more or less random – cerebral amyloid angiopathy – may actually be the result of an infectious disease.

We’re talking about this paper, appearing in JAMA, which is just a great example of old-fashioned shoe-leather epidemiology. But let’s get up to speed on cerebral amyloid angiopathy (CAA) first.

CAA is characterized by the deposition of amyloid protein in the brain. While there are some genetic causes, they are quite rare, and most cases are thought to be idiopathic. Recent analyses suggest that somewhere between 5% and 7% of cognitively normal older adults have CAA, but the rate is much higher among those with intracerebral hemorrhage – brain bleeds. In fact, CAA is the second-most common cause of bleeding in the brain, second only to severe hypertension.

Most of the textbooks continue to describe CAA as a sporadic condition, but there have been some intriguing studies that suggest it may be transmissible. An article in Nature highlights cases that seemed to develop after the administration of cadaveric pituitary hormone.

Other studies have shown potential transmission via dura mater grafts and neurosurgical instruments. But despite those clues, no infectious organism has been identified. Some have suggested that the long latent period and difficulty of finding a responsible microbe points to a prion-like disease not yet known. But these studies are more or less case series. The new JAMA paper gives us, if not a smoking gun, a pretty decent set of fingerprints.

Here’s the idea: If CAA is caused by some infectious agent, it may be transmitted in the blood. We know that a decent percentage of people who have spontaneous brain bleeds have CAA. If those people donated blood in the past, maybe the people who received that blood would be at risk for brain bleeds too.

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy JAMA Internal Medicine

Dr. F. Perry Wilson is an associate professor of medicine and public health and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.
 

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

A single monthly injection of benralizumab (Fasenra) was noninferior to a series of three injections per month of mepolizumab (Nucala) for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA), based on data from 140 individuals.

The unpublished topline results of the phase 3 MANDARA study were shared in a press release from benralizumab’s manufacturer, AstraZeneca. More detailed findings are scheduled to be presented at a future medical meeting, according to the company.

EGPA, although rare, can damage multiple organs including the heart, lungs, gastrointestinal tract, skin, and nerves, and can be fatal if left untreated, but treatment options are limited, and mepolizumab, an anti-interleukin (IL)-5 monoclonal antibody, is the only currently approved treatment.

In the study, adults with EGPA were randomized to a single 30-mg subcutaneous injection of benralizumab or three separate 100-mg subcutaneous injections of mepolizumab once every 4 weeks. The primary endpoint was remission rates after 36 and 48 weeks of treatment. Remission was defined as a Birmingham Vasculitis Activity Score of 0 and use of 4 mg/day or less of oral corticosteroids.

At 36 weeks and 48 weeks, remission rates for benralizumab were noninferior to mepolizumab. According to Clinicaltrials.gov, the study is scheduled to last for 52 weeks to compare the remission rates with the two treatments, and collect data from an extension that allows each patient at least 1 year of treatment in an open-label format.

Benralizumab, also a monoclonal antibody, differs in action from mepolizumab by binding directly to the IL-5 receptor alpha on eosinophils.

“This trial demonstrates that a biologic medicine given in a single monthly injection could help patients achieve remission rates comparable to the current standard of care, adding to the importance of benralizumab as a potential treatment option for eosinophilic granulomatosis with polyangiitis,” Michael Wechsler, MD, principal investigator on the MANDARA study, said in the press release.

The safety and tolerability of benralizumab in the MANDARA study were consistent with drug’s known profile, according to the company.

Benralizumab is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the United States, the European Union, and Japan, among other countries, and for self-administration in the United States, the European Union, and other countries, according to the company.

Benralizumab also is in development for other eosinophilic diseases, including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome, and received an Orphan Drug Designation from the U.S. Food and Drug Administration in 2018, according to the company.
 

A single monthly injection of benralizumab (Fasenra) was noninferior to a series of three injections per month of mepolizumab (Nucala) for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA), based on data from 140 individuals.

The unpublished topline results of the phase 3 MANDARA study were shared in a press release from benralizumab’s manufacturer, AstraZeneca. More detailed findings are scheduled to be presented at a future medical meeting, according to the company.

EGPA, although rare, can damage multiple organs including the heart, lungs, gastrointestinal tract, skin, and nerves, and can be fatal if left untreated, but treatment options are limited, and mepolizumab, an anti-interleukin (IL)-5 monoclonal antibody, is the only currently approved treatment.

In the study, adults with EGPA were randomized to a single 30-mg subcutaneous injection of benralizumab or three separate 100-mg subcutaneous injections of mepolizumab once every 4 weeks. The primary endpoint was remission rates after 36 and 48 weeks of treatment. Remission was defined as a Birmingham Vasculitis Activity Score of 0 and use of 4 mg/day or less of oral corticosteroids.

At 36 weeks and 48 weeks, remission rates for benralizumab were noninferior to mepolizumab. According to Clinicaltrials.gov, the study is scheduled to last for 52 weeks to compare the remission rates with the two treatments, and collect data from an extension that allows each patient at least 1 year of treatment in an open-label format.

Benralizumab, also a monoclonal antibody, differs in action from mepolizumab by binding directly to the IL-5 receptor alpha on eosinophils.

“This trial demonstrates that a biologic medicine given in a single monthly injection could help patients achieve remission rates comparable to the current standard of care, adding to the importance of benralizumab as a potential treatment option for eosinophilic granulomatosis with polyangiitis,” Michael Wechsler, MD, principal investigator on the MANDARA study, said in the press release.

The safety and tolerability of benralizumab in the MANDARA study were consistent with drug’s known profile, according to the company.

Benralizumab is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the United States, the European Union, and Japan, among other countries, and for self-administration in the United States, the European Union, and other countries, according to the company.

Benralizumab also is in development for other eosinophilic diseases, including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome, and received an Orphan Drug Designation from the U.S. Food and Drug Administration in 2018, according to the company.
 

A single monthly injection of benralizumab (Fasenra) was noninferior to a series of three injections per month of mepolizumab (Nucala) for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA), based on data from 140 individuals.

The unpublished topline results of the phase 3 MANDARA study were shared in a press release from benralizumab’s manufacturer, AstraZeneca. More detailed findings are scheduled to be presented at a future medical meeting, according to the company.

EGPA, although rare, can damage multiple organs including the heart, lungs, gastrointestinal tract, skin, and nerves, and can be fatal if left untreated, but treatment options are limited, and mepolizumab, an anti-interleukin (IL)-5 monoclonal antibody, is the only currently approved treatment.

In the study, adults with EGPA were randomized to a single 30-mg subcutaneous injection of benralizumab or three separate 100-mg subcutaneous injections of mepolizumab once every 4 weeks. The primary endpoint was remission rates after 36 and 48 weeks of treatment. Remission was defined as a Birmingham Vasculitis Activity Score of 0 and use of 4 mg/day or less of oral corticosteroids.

At 36 weeks and 48 weeks, remission rates for benralizumab were noninferior to mepolizumab. According to Clinicaltrials.gov, the study is scheduled to last for 52 weeks to compare the remission rates with the two treatments, and collect data from an extension that allows each patient at least 1 year of treatment in an open-label format.

Benralizumab, also a monoclonal antibody, differs in action from mepolizumab by binding directly to the IL-5 receptor alpha on eosinophils.

“This trial demonstrates that a biologic medicine given in a single monthly injection could help patients achieve remission rates comparable to the current standard of care, adding to the importance of benralizumab as a potential treatment option for eosinophilic granulomatosis with polyangiitis,” Michael Wechsler, MD, principal investigator on the MANDARA study, said in the press release.

The safety and tolerability of benralizumab in the MANDARA study were consistent with drug’s known profile, according to the company.

Benralizumab is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the United States, the European Union, and Japan, among other countries, and for self-administration in the United States, the European Union, and other countries, according to the company.

Benralizumab also is in development for other eosinophilic diseases, including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome, and received an Orphan Drug Designation from the U.S. Food and Drug Administration in 2018, according to the company.
 

What happens to grief when those around you don’t understand it? Where does it go? How do you process it?

Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.

Here, we reflect as physicians on our own experiences and memories of this phenomenon.
 

Suzanne Cole, MD: ‘I didn’t feel the right to grieve’

During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.

Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.

But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.

To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
 

Don S. Dizon, MD: Working through tragedy

As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.

But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.

Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.

By the time help arrived, the patient was blue.

He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.

As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
 

A space for grieving: The Schwartz Center Rounds

Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.

Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.

More and more, though, we are being given opportunities to reflect on these sad moments.

The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.

During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.

As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.

Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.

Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.

As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.

We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.

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

What happens to grief when those around you don’t understand it? Where does it go? How do you process it?

Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.

Here, we reflect as physicians on our own experiences and memories of this phenomenon.
 

Suzanne Cole, MD: ‘I didn’t feel the right to grieve’

During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.

Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.

But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.

To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
 

Don S. Dizon, MD: Working through tragedy

As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.

But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.

Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.

By the time help arrived, the patient was blue.

He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.

As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
 

A space for grieving: The Schwartz Center Rounds

Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.

Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.

More and more, though, we are being given opportunities to reflect on these sad moments.

The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.

During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.

As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.

Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.

Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.

As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.

We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.

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

What happens to grief when those around you don’t understand it? Where does it go? How do you process it?

Disenfranchised grief, when someone or society more generally doesn’t see a loss as worthy of mourning, can deprive people of experiencing or processing their sadness. This grief, which may be triggered by the death of an ex-spouse, a pet, a failed adoption, can be painful and long-lasting.

Here, we reflect as physicians on our own experiences and memories of this phenomenon.
 

Suzanne Cole, MD: ‘I didn’t feel the right to grieve’

During the COVID-19 pandemic, my little sister unexpectedly died. Though she was not one of the nearly 7 million people who died of the virus, in 2021 she became another type of statistic: one of the 109,699 people in the United State who died from a drug overdose. Hers was from fentanyl laced with methamphetamines.

Her death unraveled me. I felt deep guilt that I could not pull her from the sweeping current that had wrenched her from mainstream society into the underbelly of sex work and toward the solace of mind-altering drugs.

But I did not feel the right to grieve for her as I have grieved for other loved ones who were not blamed for their exit from this world. My sister was living a sordid life on the fringes of society. My grief felt invalid, undeserved. Yet, in the eyes of other “upstanding citizens,” her life was not as worth grieving – or so I thought. I tucked my sorrow into a small corner of my soul so no one would see, and I carried on.

To this day, the shame I feel robbed me of the ability to freely talk about her or share the searing pain I feel. Tears still prick my eyes when I think of her, but I have become adept at swallowing them, shaking off the waves of grief as though nothing happened. Even now, I cannot shake the pervasive feeling that my silent tears don’t deserve to be wept.
 

Don S. Dizon, MD: Working through tragedy

As a medical student, I worked with an outpatient physician as part of a third-year rotation. When we met, the first thing that struck me was how disheveled he looked. His clothes were wrinkled, and his pants were baggy. He took cigarette breaks, which I found disturbing.

But I quickly came to admire him. Despite my first impression, he was the type of doctor I aspired to be. He didn’t need to look at a patient’s chart to recall who they were. He just knew them. He greeted patients warmly, asked about their family. He even remembered the special occasions his patients had mentioned since their past visit. He epitomized empathy and connectedness.

Spending one day in clinic brought to light the challenges of forming such bonds with patients. A man came into the cancer clinic reporting chest pain and was triaged to an exam room. Soon after, the patient was found unresponsive on the floor. Nurses were yelling for help, and the doctor ran in and started CPR while minutes ticked by waiting for an ambulance that could take him to the ED.

By the time help arrived, the patient was blue.

He had died in the clinic in the middle of the day, as the waiting room filled. After the body was taken away, the doctor went into the bathroom. About 20 minutes later, he came out, eyes bloodshot, and continued with the rest of his day, ensuring each patient was seen and cared for.

As a medical student, it hit me how hard it must be to see something so tragic like the end of a life and then continue with your day as if nothing had happened. This is an experience of grief I later came to know well after nearly 30 years treating patients with advanced cancers: compartmentalizing it and carrying on.
 

A space for grieving: The Schwartz Center Rounds

Disenfranchised grief, the grief that is hard to share and often seems wrong to feel in the first place, can be triggered in many situations. Losing a person others don’t believe deserve to be grieved, such as an abusive partner or someone who committed a crime; losing someone you cared for in a professional role; a loss experienced in a breakup or same-sex partnership, if that relationship was not accepted by one’s family; loss from infertility, miscarriage, stillbirth, or failed adoption; loss that may be taboo or stigmatized, such as deaths via suicide or abortion; and loss of a job, home, or possession that you treasure.

Many of us have had similar situations or will, and the feeling that no one understands the need to mourn can be paralyzing and alienating. In the early days, intense, crushing feelings can cause intrusive, distracting thoughts, and over time, that grief can linger and find a permanent place in our minds.

More and more, though, we are being given opportunities to reflect on these sad moments.

The Schwartz Rounds are an example of such an opportunity. In these rounds, we gather to talk about the experience of caring for people, not the science of medicine.

During one particularly powerful rounds, I spoke to my colleagues about my initial meeting with a patient who was very sick. I detailed the experience of telling her children and her at that initial consult how I thought she was dying and that I did not recommend therapy. I remember how they cried. And I remembered how powerless I felt.

As I recalled that memory during Schwartz Rounds, I could not stop from crying. The unfairness of being a physician meeting someone for the first time and having to tell them such bad news overwhelmed me.

Even more poignant, I had the chance to reconnect with this woman’s children, who were present that day, not as audience members but as participants. Their presence may have brought my emotions to the surface more strongly. In that moment, I could show them the feelings I had bottled up for the sake of professionalism. Ultimately, I felt relieved, freer somehow, as if this burden my soul was carrying had been lifted.

Although we are both grateful for forums like this, these opportunities to share and express the grief we may have hidden away are not as common as they should be.

As physicians, we may express grief by shedding tears at the bedside of a patient nearing the end of life or through the anxiety we feel when our patient suffers a severe reaction to treatment. But we tend to put it away, to go on with our day, because there are others to be seen and cared for and more work to be done. Somehow, we move forward, shedding tears in one room and celebrating victories in another.

We need to create more spaces to express and feel grief, so we don’t get lost in it. Because understanding how grief impacts us, as people and as providers, is one of the most important realizations we can make as we go about our time-honored profession as healers.

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute, director of medical oncology at Rhode Island Hospital, and a professor of medicine at Brown University, all in Providence. He reported conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol-Myers Squibb, and Kazia.

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

In a new salvo in the dispute over the wisdom of early “bridging” treatment with glucocorticoids in rheumatoid arthritis, Dutch researchers suggested in a new meta-analysis that the American College of Rheumatology guideline is too cautious.

The report, published in Annals of the Rheumatic Diseases, examined three randomized trials of bridging versus nonbridging. The findings “emphasize the benefits of bridging therapy and shows that bridgers are not using more glucocorticoids after their intended bridging period, compared with nonbridgers, during a 2-year follow-up,” study coauthor Sytske Anne Bergstra, PhD, a postdoctoral researcher at Leiden (the Netherlands) University Medical Center, said in an interview.

However, an American researcher who helped create the 2021 ACR guideline is unmoved by the new report. “This publication didn’t do anything to assuage my concerns,” Joel Kremer, MD, founder and president of the Corrona Research Foundation and professor of medicine emeritus at Albany (N.Y.) Medical College, said in an interview.

At issue is whether patients with early RA should be temporarily treated with glucocorticoids in order to provide rapid relief. The ACR’s 2021 guideline on the treatment of RA says short-term glucocorticoids should not be “systematically prescribed” but notes that they are still “frequently necessary to alleviate symptoms” before disease-modifying therapies are given. The guideline adds that “these recommendations were made in recognition of the frequent difficulty tapering glucocorticoids, leading to undesirable prolonged use and the increasing evidence of the negative impact of glucocorticoids on long-term patient outcomes, including risk for infection, osteoporosis, and cardiovascular disease, in RA and other rheumatic diseases.”

For its part, the European Alliance of Associations for Rheumatology’s 2022 recommendations state that short-term glucocorticoids “should be considered when initiating or changing [disease-modifying antirheumatic drugs], in different dose regimens and routes of administration, but should be tapered and discontinued as rapidly as clinically feasible.”

Members of the Dutch team behind the new meta-analysis have been supporters of “bridging” therapy. For the new report, they analyzed three studies, including one led by a member of the team. Each study had at least one arm that randomized patients with RA to glucocorticoid bridging. Patients also took disease-modifying antirheumatic drugs (DMARDs).

There were 252 patients in study arms that started with bridging (mean age, 52 years; 68% female) and 373 other patients (mean age, 53 years; 67% female).

The researchers found that glucocorticoid use was higher in the bridgers at 12 months (odds ratio, 3.27; 95% confidence interval, 1.06-10.08), but the excess risk at 18 months (OR, 1.60; 95% CI, 0.46-5.60) and 24 months (OR, 1.70; 95% CI, 0.58-4.97) dipped below statistical significance. Also, they reported that “bridgers improved more rapidly (P < .001) in the first 6 months and the bridgers required significantly fewer changes in DMARDs (incidence rate ratio, 0.59; 95% CI, 0.38-0.94).”

“Based on our results, combined with two earlier publications [here and here], we show that most patients included in clinical trials with protocolized tapering schedules are able to stop glucocorticoids after bridging,” Dr. Bergstra said. “We also confirm the well-known short-term clinical effects and show that patients using glucocorticoid bridging require fewer DMARD changes. For a re-evaluation of the ACR guideline, this evidence should be combined with the extensive evidence showing short- as well as long-term clinical benefits of glucocorticoid bridging but also with evidence on potential side effects at different doses.”

She added that “implementing predefined tapering protocols may help clinicians and patients to stop glucocorticoids after bridging.” As for limitations, “patients included in these trials may differ from patients in clinical practice. We cannot be sure whether these results can be generalized to the full patient population.”

Mitchel L. Zoler/MDedge News

Dr. Kremer, a coauthor of the ACR guideline, pointed out that the patients who took glucocorticoids early were much more likely to be on them at 12 months.

By definition, “bridging” is temporary, he said, a brief period to help patients tolerate RA until DMARDs kick in. But in the studies, many of the patients clearly took the drugs for extended periods of time. In those cases, “it not a bridge,” and the risk is that “you’re treating people with a lifelong disease with doses of glucocorticoids that have been shown in multiple studies to be dangerous.”

He added that, while the excess likelihood of these patients staying on the drugs at 18 or 24 months wasn’t deemed to be statistically significant in the meta-analysis, the confidence intervals were unusually wide. That raises questions about whether some of the patients actually stay on the drugs.

Dr. Kremer said it can still be appropriate to give glucocorticoids to patients in distress, although it’s crucial in those cases to take the patients off them as soon as possible. It’s best, though, to not prescribe them at all. “If you can avoid it,” he said, “definitely avoid it.”

The study was conducted without outside funding. Dr. Bergstra reported receiving grant funding from Pfizer, and some of the other study authors reported various relationships with industry. Dr. Kremer had no relevant disclosures.

In a new salvo in the dispute over the wisdom of early “bridging” treatment with glucocorticoids in rheumatoid arthritis, Dutch researchers suggested in a new meta-analysis that the American College of Rheumatology guideline is too cautious.

The report, published in Annals of the Rheumatic Diseases, examined three randomized trials of bridging versus nonbridging. The findings “emphasize the benefits of bridging therapy and shows that bridgers are not using more glucocorticoids after their intended bridging period, compared with nonbridgers, during a 2-year follow-up,” study coauthor Sytske Anne Bergstra, PhD, a postdoctoral researcher at Leiden (the Netherlands) University Medical Center, said in an interview.

However, an American researcher who helped create the 2021 ACR guideline is unmoved by the new report. “This publication didn’t do anything to assuage my concerns,” Joel Kremer, MD, founder and president of the Corrona Research Foundation and professor of medicine emeritus at Albany (N.Y.) Medical College, said in an interview.

At issue is whether patients with early RA should be temporarily treated with glucocorticoids in order to provide rapid relief. The ACR’s 2021 guideline on the treatment of RA says short-term glucocorticoids should not be “systematically prescribed” but notes that they are still “frequently necessary to alleviate symptoms” before disease-modifying therapies are given. The guideline adds that “these recommendations were made in recognition of the frequent difficulty tapering glucocorticoids, leading to undesirable prolonged use and the increasing evidence of the negative impact of glucocorticoids on long-term patient outcomes, including risk for infection, osteoporosis, and cardiovascular disease, in RA and other rheumatic diseases.”

For its part, the European Alliance of Associations for Rheumatology’s 2022 recommendations state that short-term glucocorticoids “should be considered when initiating or changing [disease-modifying antirheumatic drugs], in different dose regimens and routes of administration, but should be tapered and discontinued as rapidly as clinically feasible.”

Members of the Dutch team behind the new meta-analysis have been supporters of “bridging” therapy. For the new report, they analyzed three studies, including one led by a member of the team. Each study had at least one arm that randomized patients with RA to glucocorticoid bridging. Patients also took disease-modifying antirheumatic drugs (DMARDs).

There were 252 patients in study arms that started with bridging (mean age, 52 years; 68% female) and 373 other patients (mean age, 53 years; 67% female).

The researchers found that glucocorticoid use was higher in the bridgers at 12 months (odds ratio, 3.27; 95% confidence interval, 1.06-10.08), but the excess risk at 18 months (OR, 1.60; 95% CI, 0.46-5.60) and 24 months (OR, 1.70; 95% CI, 0.58-4.97) dipped below statistical significance. Also, they reported that “bridgers improved more rapidly (P < .001) in the first 6 months and the bridgers required significantly fewer changes in DMARDs (incidence rate ratio, 0.59; 95% CI, 0.38-0.94).”

“Based on our results, combined with two earlier publications [here and here], we show that most patients included in clinical trials with protocolized tapering schedules are able to stop glucocorticoids after bridging,” Dr. Bergstra said. “We also confirm the well-known short-term clinical effects and show that patients using glucocorticoid bridging require fewer DMARD changes. For a re-evaluation of the ACR guideline, this evidence should be combined with the extensive evidence showing short- as well as long-term clinical benefits of glucocorticoid bridging but also with evidence on potential side effects at different doses.”

She added that “implementing predefined tapering protocols may help clinicians and patients to stop glucocorticoids after bridging.” As for limitations, “patients included in these trials may differ from patients in clinical practice. We cannot be sure whether these results can be generalized to the full patient population.”

Mitchel L. Zoler/MDedge News

Dr. Kremer, a coauthor of the ACR guideline, pointed out that the patients who took glucocorticoids early were much more likely to be on them at 12 months.

By definition, “bridging” is temporary, he said, a brief period to help patients tolerate RA until DMARDs kick in. But in the studies, many of the patients clearly took the drugs for extended periods of time. In those cases, “it not a bridge,” and the risk is that “you’re treating people with a lifelong disease with doses of glucocorticoids that have been shown in multiple studies to be dangerous.”

He added that, while the excess likelihood of these patients staying on the drugs at 18 or 24 months wasn’t deemed to be statistically significant in the meta-analysis, the confidence intervals were unusually wide. That raises questions about whether some of the patients actually stay on the drugs.

Dr. Kremer said it can still be appropriate to give glucocorticoids to patients in distress, although it’s crucial in those cases to take the patients off them as soon as possible. It’s best, though, to not prescribe them at all. “If you can avoid it,” he said, “definitely avoid it.”

The study was conducted without outside funding. Dr. Bergstra reported receiving grant funding from Pfizer, and some of the other study authors reported various relationships with industry. Dr. Kremer had no relevant disclosures.

In a new salvo in the dispute over the wisdom of early “bridging” treatment with glucocorticoids in rheumatoid arthritis, Dutch researchers suggested in a new meta-analysis that the American College of Rheumatology guideline is too cautious.

The report, published in Annals of the Rheumatic Diseases, examined three randomized trials of bridging versus nonbridging. The findings “emphasize the benefits of bridging therapy and shows that bridgers are not using more glucocorticoids after their intended bridging period, compared with nonbridgers, during a 2-year follow-up,” study coauthor Sytske Anne Bergstra, PhD, a postdoctoral researcher at Leiden (the Netherlands) University Medical Center, said in an interview.

However, an American researcher who helped create the 2021 ACR guideline is unmoved by the new report. “This publication didn’t do anything to assuage my concerns,” Joel Kremer, MD, founder and president of the Corrona Research Foundation and professor of medicine emeritus at Albany (N.Y.) Medical College, said in an interview.

At issue is whether patients with early RA should be temporarily treated with glucocorticoids in order to provide rapid relief. The ACR’s 2021 guideline on the treatment of RA says short-term glucocorticoids should not be “systematically prescribed” but notes that they are still “frequently necessary to alleviate symptoms” before disease-modifying therapies are given. The guideline adds that “these recommendations were made in recognition of the frequent difficulty tapering glucocorticoids, leading to undesirable prolonged use and the increasing evidence of the negative impact of glucocorticoids on long-term patient outcomes, including risk for infection, osteoporosis, and cardiovascular disease, in RA and other rheumatic diseases.”

For its part, the European Alliance of Associations for Rheumatology’s 2022 recommendations state that short-term glucocorticoids “should be considered when initiating or changing [disease-modifying antirheumatic drugs], in different dose regimens and routes of administration, but should be tapered and discontinued as rapidly as clinically feasible.”

Members of the Dutch team behind the new meta-analysis have been supporters of “bridging” therapy. For the new report, they analyzed three studies, including one led by a member of the team. Each study had at least one arm that randomized patients with RA to glucocorticoid bridging. Patients also took disease-modifying antirheumatic drugs (DMARDs).

There were 252 patients in study arms that started with bridging (mean age, 52 years; 68% female) and 373 other patients (mean age, 53 years; 67% female).

The researchers found that glucocorticoid use was higher in the bridgers at 12 months (odds ratio, 3.27; 95% confidence interval, 1.06-10.08), but the excess risk at 18 months (OR, 1.60; 95% CI, 0.46-5.60) and 24 months (OR, 1.70; 95% CI, 0.58-4.97) dipped below statistical significance. Also, they reported that “bridgers improved more rapidly (P < .001) in the first 6 months and the bridgers required significantly fewer changes in DMARDs (incidence rate ratio, 0.59; 95% CI, 0.38-0.94).”

“Based on our results, combined with two earlier publications [here and here], we show that most patients included in clinical trials with protocolized tapering schedules are able to stop glucocorticoids after bridging,” Dr. Bergstra said. “We also confirm the well-known short-term clinical effects and show that patients using glucocorticoid bridging require fewer DMARD changes. For a re-evaluation of the ACR guideline, this evidence should be combined with the extensive evidence showing short- as well as long-term clinical benefits of glucocorticoid bridging but also with evidence on potential side effects at different doses.”

She added that “implementing predefined tapering protocols may help clinicians and patients to stop glucocorticoids after bridging.” As for limitations, “patients included in these trials may differ from patients in clinical practice. We cannot be sure whether these results can be generalized to the full patient population.”

Mitchel L. Zoler/MDedge News

Dr. Kremer, a coauthor of the ACR guideline, pointed out that the patients who took glucocorticoids early were much more likely to be on them at 12 months.

By definition, “bridging” is temporary, he said, a brief period to help patients tolerate RA until DMARDs kick in. But in the studies, many of the patients clearly took the drugs for extended periods of time. In those cases, “it not a bridge,” and the risk is that “you’re treating people with a lifelong disease with doses of glucocorticoids that have been shown in multiple studies to be dangerous.”

He added that, while the excess likelihood of these patients staying on the drugs at 18 or 24 months wasn’t deemed to be statistically significant in the meta-analysis, the confidence intervals were unusually wide. That raises questions about whether some of the patients actually stay on the drugs.

Dr. Kremer said it can still be appropriate to give glucocorticoids to patients in distress, although it’s crucial in those cases to take the patients off them as soon as possible. It’s best, though, to not prescribe them at all. “If you can avoid it,” he said, “definitely avoid it.”

The study was conducted without outside funding. Dr. Bergstra reported receiving grant funding from Pfizer, and some of the other study authors reported various relationships with industry. Dr. Kremer had no relevant disclosures.

A blood-level reference range of 750-1,200 ng/mL of hydroxychloroquine (HCQ) has been linked with 71% lower odds of active lupus, new research suggests.

AlexLMX/iStock/Getty Images

Researchers, led by Shivani Garg, MD, assistant professor of rheumatology at the University of Wisconsin–Madison, also found that maintaining levels within that range lowered the odds for flares by 26% over 9 months of follow-up.

The findings, published in Arthritis Care & Research, could help clinicians personalize HCQ doses to maximize efficacy for each patient.

UW Health

HCQ levels in whole blood and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were measured during a baseline visit and again during a routine follow-up visit.

Among 158 baseline patient visits, 19% of the patients had active lupus. Researchers longitudinally followed 42 patients using convenience sampling, and among those patients, 7 (17%) had flares at the follow-up visit.

Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center in Baltimore, called the findings that suggest upper and lower efficacy and safety boundaries “very important.”

The findings highlight that guidelines for dosing don’t match efficacy needs, said Dr. Petri, who was not involved with the study.

“HCQ dosing has been under threat by guidelines insisting that the dose should be < 5 mg/kg even though this does not correlate with efficacy,” she said. “Basically, if we dose too low, the patient loses efficacy. If we dose too high, the risk of retinopathy increases, so this paper hones down the sweet spot.”

A 2014 study identified a higher eye toxicity risk with HCQ doses > 5 mg/kg per day, and the American Academy of Ophthalmology followed with guidelines for HCQ retinopathy screening that recommended reducing HCQ to ≤ 5 mg/kg per day.

Dr. Petri said that the range Dr. Garg and colleagues identified corroborates findings in one of her team’s studies.

That paper showed that thrombotic events dropped by 69% in patients with average HCQ blood levels ≥ 1,068 ng/mL vs. those with levels < 648 ng/mL (relative risk, 0.31; 95% confidence interval, 0.11-0.86; P = .024).

Dr. Garg and colleagues write that current lupus treatment guidelines do not universally recommend blood level monitoring for HCQ “as different cut-points have been used to define therapeutic HCQ blood levels and an effective range of HCQ levels with upper and lower bounds for efficacy has not been extensively examined.”
 

When to start checking levels

Blood levels of HCQ can be checked for any patient, although 1-3 months after starting the medication may be best to get steady levels, Dr. Garg told this news organization.

Dr. Petri said that she recommends HCQ whole blood levels be checked routinely for maximum dosing efficacy “but also to identify patients who are missing so many doses that they are subtherapeutic.”

She noted that nonadherence is a major issue among patients with systemic lupus erythematosus, especially among those who are younger and newly diagnosed.

Dr. Garg and Dr. Petri both said that insurance does not automatically cover the costs of checking HCQ levels in the blood, which has been a consistent frustration in the field.

“Having more data validates the reason to do it,” Dr. Garg said.

She added that “HCQ blood levels are still not done routinely in all patients, and at times the test needs to be sent to outside laboratories.”
 

Importance for patients with CKD

Many patient factors can affect how the body absorbs HCQ, Dr. Garg said, so finding the right level that is safe and maximizes benefit individually is important.

The findings are particularly important for patients with chronic kidney disease (CKD) of stage 3 or higher, Dr. Garg said.

The authors write that because kidneys clear more than half of all HCQ, impaired kidney function could boost HCQ blood levels, risking toxicity.

“Our study found a sixfold higher odds of having supratherapeutic HCQ blood levels in patients with CKD stage ≥ 3,” they write.

Dr. Garg added that if blood levels cannot be analyzed in all patients, they could be prioritized in patients with CKD stage 3 or above because these patients are at “higher risk of being underdosed with arbitrary reductions in HCQ doses and carry higher risk of toxicity if HCQ doses are not adjusted.”

More research will uncover other high-risk groups who would benefit most from close monitoring of HCQ blood levels, she said.

The study was supported by an award from the University of Wisconsin–Madison, and by an award to the institution from the National Institutes of Health National Center for Advancing Translational Sciences. Dr. Garg and coauthors as well as Dr. Petri report no relevant financial relationships.

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

A blood-level reference range of 750-1,200 ng/mL of hydroxychloroquine (HCQ) has been linked with 71% lower odds of active lupus, new research suggests.

AlexLMX/iStock/Getty Images

Researchers, led by Shivani Garg, MD, assistant professor of rheumatology at the University of Wisconsin–Madison, also found that maintaining levels within that range lowered the odds for flares by 26% over 9 months of follow-up.

The findings, published in Arthritis Care & Research, could help clinicians personalize HCQ doses to maximize efficacy for each patient.

UW Health

HCQ levels in whole blood and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were measured during a baseline visit and again during a routine follow-up visit.

Among 158 baseline patient visits, 19% of the patients had active lupus. Researchers longitudinally followed 42 patients using convenience sampling, and among those patients, 7 (17%) had flares at the follow-up visit.

Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center in Baltimore, called the findings that suggest upper and lower efficacy and safety boundaries “very important.”

The findings highlight that guidelines for dosing don’t match efficacy needs, said Dr. Petri, who was not involved with the study.

“HCQ dosing has been under threat by guidelines insisting that the dose should be < 5 mg/kg even though this does not correlate with efficacy,” she said. “Basically, if we dose too low, the patient loses efficacy. If we dose too high, the risk of retinopathy increases, so this paper hones down the sweet spot.”

A 2014 study identified a higher eye toxicity risk with HCQ doses > 5 mg/kg per day, and the American Academy of Ophthalmology followed with guidelines for HCQ retinopathy screening that recommended reducing HCQ to ≤ 5 mg/kg per day.

Dr. Petri said that the range Dr. Garg and colleagues identified corroborates findings in one of her team’s studies.

That paper showed that thrombotic events dropped by 69% in patients with average HCQ blood levels ≥ 1,068 ng/mL vs. those with levels < 648 ng/mL (relative risk, 0.31; 95% confidence interval, 0.11-0.86; P = .024).

Dr. Garg and colleagues write that current lupus treatment guidelines do not universally recommend blood level monitoring for HCQ “as different cut-points have been used to define therapeutic HCQ blood levels and an effective range of HCQ levels with upper and lower bounds for efficacy has not been extensively examined.”
 

When to start checking levels

Blood levels of HCQ can be checked for any patient, although 1-3 months after starting the medication may be best to get steady levels, Dr. Garg told this news organization.

Dr. Petri said that she recommends HCQ whole blood levels be checked routinely for maximum dosing efficacy “but also to identify patients who are missing so many doses that they are subtherapeutic.”

She noted that nonadherence is a major issue among patients with systemic lupus erythematosus, especially among those who are younger and newly diagnosed.

Dr. Garg and Dr. Petri both said that insurance does not automatically cover the costs of checking HCQ levels in the blood, which has been a consistent frustration in the field.

“Having more data validates the reason to do it,” Dr. Garg said.

She added that “HCQ blood levels are still not done routinely in all patients, and at times the test needs to be sent to outside laboratories.”
 

Importance for patients with CKD

Many patient factors can affect how the body absorbs HCQ, Dr. Garg said, so finding the right level that is safe and maximizes benefit individually is important.

The findings are particularly important for patients with chronic kidney disease (CKD) of stage 3 or higher, Dr. Garg said.

The authors write that because kidneys clear more than half of all HCQ, impaired kidney function could boost HCQ blood levels, risking toxicity.

“Our study found a sixfold higher odds of having supratherapeutic HCQ blood levels in patients with CKD stage ≥ 3,” they write.

Dr. Garg added that if blood levels cannot be analyzed in all patients, they could be prioritized in patients with CKD stage 3 or above because these patients are at “higher risk of being underdosed with arbitrary reductions in HCQ doses and carry higher risk of toxicity if HCQ doses are not adjusted.”

More research will uncover other high-risk groups who would benefit most from close monitoring of HCQ blood levels, she said.

The study was supported by an award from the University of Wisconsin–Madison, and by an award to the institution from the National Institutes of Health National Center for Advancing Translational Sciences. Dr. Garg and coauthors as well as Dr. Petri report no relevant financial relationships.

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

A blood-level reference range of 750-1,200 ng/mL of hydroxychloroquine (HCQ) has been linked with 71% lower odds of active lupus, new research suggests.

AlexLMX/iStock/Getty Images

Researchers, led by Shivani Garg, MD, assistant professor of rheumatology at the University of Wisconsin–Madison, also found that maintaining levels within that range lowered the odds for flares by 26% over 9 months of follow-up.

The findings, published in Arthritis Care & Research, could help clinicians personalize HCQ doses to maximize efficacy for each patient.

UW Health

HCQ levels in whole blood and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were measured during a baseline visit and again during a routine follow-up visit.

Among 158 baseline patient visits, 19% of the patients had active lupus. Researchers longitudinally followed 42 patients using convenience sampling, and among those patients, 7 (17%) had flares at the follow-up visit.

Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center in Baltimore, called the findings that suggest upper and lower efficacy and safety boundaries “very important.”

The findings highlight that guidelines for dosing don’t match efficacy needs, said Dr. Petri, who was not involved with the study.

“HCQ dosing has been under threat by guidelines insisting that the dose should be < 5 mg/kg even though this does not correlate with efficacy,” she said. “Basically, if we dose too low, the patient loses efficacy. If we dose too high, the risk of retinopathy increases, so this paper hones down the sweet spot.”

A 2014 study identified a higher eye toxicity risk with HCQ doses > 5 mg/kg per day, and the American Academy of Ophthalmology followed with guidelines for HCQ retinopathy screening that recommended reducing HCQ to ≤ 5 mg/kg per day.

Dr. Petri said that the range Dr. Garg and colleagues identified corroborates findings in one of her team’s studies.

That paper showed that thrombotic events dropped by 69% in patients with average HCQ blood levels ≥ 1,068 ng/mL vs. those with levels < 648 ng/mL (relative risk, 0.31; 95% confidence interval, 0.11-0.86; P = .024).

Dr. Garg and colleagues write that current lupus treatment guidelines do not universally recommend blood level monitoring for HCQ “as different cut-points have been used to define therapeutic HCQ blood levels and an effective range of HCQ levels with upper and lower bounds for efficacy has not been extensively examined.”
 

When to start checking levels

Blood levels of HCQ can be checked for any patient, although 1-3 months after starting the medication may be best to get steady levels, Dr. Garg told this news organization.

Dr. Petri said that she recommends HCQ whole blood levels be checked routinely for maximum dosing efficacy “but also to identify patients who are missing so many doses that they are subtherapeutic.”

She noted that nonadherence is a major issue among patients with systemic lupus erythematosus, especially among those who are younger and newly diagnosed.

Dr. Garg and Dr. Petri both said that insurance does not automatically cover the costs of checking HCQ levels in the blood, which has been a consistent frustration in the field.

“Having more data validates the reason to do it,” Dr. Garg said.

She added that “HCQ blood levels are still not done routinely in all patients, and at times the test needs to be sent to outside laboratories.”
 

Importance for patients with CKD

Many patient factors can affect how the body absorbs HCQ, Dr. Garg said, so finding the right level that is safe and maximizes benefit individually is important.

The findings are particularly important for patients with chronic kidney disease (CKD) of stage 3 or higher, Dr. Garg said.

The authors write that because kidneys clear more than half of all HCQ, impaired kidney function could boost HCQ blood levels, risking toxicity.

“Our study found a sixfold higher odds of having supratherapeutic HCQ blood levels in patients with CKD stage ≥ 3,” they write.

Dr. Garg added that if blood levels cannot be analyzed in all patients, they could be prioritized in patients with CKD stage 3 or above because these patients are at “higher risk of being underdosed with arbitrary reductions in HCQ doses and carry higher risk of toxicity if HCQ doses are not adjusted.”

More research will uncover other high-risk groups who would benefit most from close monitoring of HCQ blood levels, she said.

The study was supported by an award from the University of Wisconsin–Madison, and by an award to the institution from the National Institutes of Health National Center for Advancing Translational Sciences. Dr. Garg and coauthors as well as Dr. Petri report no relevant financial relationships.

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

COVID vaccines will have a new formulation in 2023, according to a decision announced by the U.S. Food and Drug Administration, that will focus efforts on circulating variants. The move pushes last year’s bivalent vaccines out of circulation because they will no longer be authorized for use in the United States.

The updated mRNA vaccines for 2023-2024 are being revised to include a single component that corresponds to the Omicron variant XBB.1.5. Like the bivalents offered before, the new monovalents are being manufactured by Moderna and Pfizer.

The new vaccines are authorized for use in individuals age 6 months and older.  And the new options are being developed using a similar process as previous formulations, according to the FDA.
 

Targeting circulating variants

In recent studies, regulators point out the extent of neutralization observed by the updated vaccines against currently circulating viral variants causing COVID-19, including EG.5, BA.2.86, appears to be of a similar magnitude to the extent of neutralization observed with previous versions of the vaccines against corresponding prior variants.

“This suggests that the vaccines are a good match for protecting against the currently circulating COVID-19 variants,” according to the report.

Hundreds of millions of people in the United States have already received previously approved mRNA COVID vaccines, according to regulators who say the benefit-to-risk profile is well understood as they move forward with new formulations.

“Vaccination remains critical to public health and continued protection against serious consequences of COVID-19, including hospitalization and death,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement. “The public can be assured that these updated vaccines have met the agency’s rigorous scientific standards for safety, effectiveness, and manufacturing quality. We very much encourage those who are eligible to consider getting vaccinated.”
 

Timing the effort

On Sept. 12 the U.S. Centers for Disease Control and Prevention recommended that everyone 6 months and older get an updated COVID-19 vaccine. Updated vaccines from Pfizer-BioNTech and Moderna will be available later this week, according to the agency.

This article was updated 9/14/23.

A version of this article appeared on Medscape.com.

COVID vaccines will have a new formulation in 2023, according to a decision announced by the U.S. Food and Drug Administration, that will focus efforts on circulating variants. The move pushes last year’s bivalent vaccines out of circulation because they will no longer be authorized for use in the United States.

The updated mRNA vaccines for 2023-2024 are being revised to include a single component that corresponds to the Omicron variant XBB.1.5. Like the bivalents offered before, the new monovalents are being manufactured by Moderna and Pfizer.

The new vaccines are authorized for use in individuals age 6 months and older.  And the new options are being developed using a similar process as previous formulations, according to the FDA.
 

Targeting circulating variants

In recent studies, regulators point out the extent of neutralization observed by the updated vaccines against currently circulating viral variants causing COVID-19, including EG.5, BA.2.86, appears to be of a similar magnitude to the extent of neutralization observed with previous versions of the vaccines against corresponding prior variants.

“This suggests that the vaccines are a good match for protecting against the currently circulating COVID-19 variants,” according to the report.

Hundreds of millions of people in the United States have already received previously approved mRNA COVID vaccines, according to regulators who say the benefit-to-risk profile is well understood as they move forward with new formulations.

“Vaccination remains critical to public health and continued protection against serious consequences of COVID-19, including hospitalization and death,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement. “The public can be assured that these updated vaccines have met the agency’s rigorous scientific standards for safety, effectiveness, and manufacturing quality. We very much encourage those who are eligible to consider getting vaccinated.”
 

Timing the effort

On Sept. 12 the U.S. Centers for Disease Control and Prevention recommended that everyone 6 months and older get an updated COVID-19 vaccine. Updated vaccines from Pfizer-BioNTech and Moderna will be available later this week, according to the agency.

This article was updated 9/14/23.

A version of this article appeared on Medscape.com.

COVID vaccines will have a new formulation in 2023, according to a decision announced by the U.S. Food and Drug Administration, that will focus efforts on circulating variants. The move pushes last year’s bivalent vaccines out of circulation because they will no longer be authorized for use in the United States.

The updated mRNA vaccines for 2023-2024 are being revised to include a single component that corresponds to the Omicron variant XBB.1.5. Like the bivalents offered before, the new monovalents are being manufactured by Moderna and Pfizer.

The new vaccines are authorized for use in individuals age 6 months and older.  And the new options are being developed using a similar process as previous formulations, according to the FDA.
 

Targeting circulating variants

In recent studies, regulators point out the extent of neutralization observed by the updated vaccines against currently circulating viral variants causing COVID-19, including EG.5, BA.2.86, appears to be of a similar magnitude to the extent of neutralization observed with previous versions of the vaccines against corresponding prior variants.

“This suggests that the vaccines are a good match for protecting against the currently circulating COVID-19 variants,” according to the report.

Hundreds of millions of people in the United States have already received previously approved mRNA COVID vaccines, according to regulators who say the benefit-to-risk profile is well understood as they move forward with new formulations.

“Vaccination remains critical to public health and continued protection against serious consequences of COVID-19, including hospitalization and death,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement. “The public can be assured that these updated vaccines have met the agency’s rigorous scientific standards for safety, effectiveness, and manufacturing quality. We very much encourage those who are eligible to consider getting vaccinated.”
 

Timing the effort

On Sept. 12 the U.S. Centers for Disease Control and Prevention recommended that everyone 6 months and older get an updated COVID-19 vaccine. Updated vaccines from Pfizer-BioNTech and Moderna will be available later this week, according to the agency.

This article was updated 9/14/23.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with early psoriatic arthritis (PsA) were significantly more likely to have multiple comorbidities and cardiovascular risk factors than controls.

METHODOLOGY:

• The study population included 67 adults with early PsA and 61 healthy matched controls with mean ages of 47.9 years and 45 years, respectively.
• Early PsA was defined as symptom duration of less than 2 years; patients with conditions including active infection, malignancy, or other rheumatic or systemic disease were excluded.
• The researchers examined the prevalence of comorbidities and cardiovascular risk factors in treatment-naive, newly diagnosed patients with PsA at baseline and after 1 year.

TAKEAWAY:

• Adults with early PsA were significantly more likely to have two or more comorbidities and multiple cardiovascular risk factors at baseline, compared with healthy controls (odds ratios, 1.9 and 2.1, respectively).
• Dyslipidemia was the most prevalent comorbidity among patients with PsA and was more prevalent than in controls (64.2% vs. 39.3%; OR, 1.7).
• Obesity was more common in patients with PsA, compared with controls (40.3% vs. 18.3%, respectively), and more patients with PsA had cardiovascular disease at baseline than did controls (20.9% vs. 6.6%; OR, 3.2).
• Disease activity scores improved after 1 year, but the proportion of patients with comorbidities and CV risk factors remained stable.

IN PRACTICE:

The results support the early assessment of patients with PsA for comorbidities to inform treatment and suggest that comorbidities and CV risk factors are more than a consequence of long-term PsA and chronic systemic inflammation.

SOURCE:

The study was conducted by Alla Ishchenko, MD, and colleagues in the division of rheumatology at University Hospitals Leuven, Belgium. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The study was exploratory in nature, with a short follow-up period and a relatively small sample size.

DISCLOSURES:

Dr. Ishchenko disclosed support from PARTNER, an international fellowship program to study disease mechanisms in psoriatic arthritis, as well as grants from Lilly and from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

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

TOPLINE:

Patients with early psoriatic arthritis (PsA) were significantly more likely to have multiple comorbidities and cardiovascular risk factors than controls.

METHODOLOGY:

• The study population included 67 adults with early PsA and 61 healthy matched controls with mean ages of 47.9 years and 45 years, respectively.
• Early PsA was defined as symptom duration of less than 2 years; patients with conditions including active infection, malignancy, or other rheumatic or systemic disease were excluded.
• The researchers examined the prevalence of comorbidities and cardiovascular risk factors in treatment-naive, newly diagnosed patients with PsA at baseline and after 1 year.

TAKEAWAY:

• Adults with early PsA were significantly more likely to have two or more comorbidities and multiple cardiovascular risk factors at baseline, compared with healthy controls (odds ratios, 1.9 and 2.1, respectively).
• Dyslipidemia was the most prevalent comorbidity among patients with PsA and was more prevalent than in controls (64.2% vs. 39.3%; OR, 1.7).
• Obesity was more common in patients with PsA, compared with controls (40.3% vs. 18.3%, respectively), and more patients with PsA had cardiovascular disease at baseline than did controls (20.9% vs. 6.6%; OR, 3.2).
• Disease activity scores improved after 1 year, but the proportion of patients with comorbidities and CV risk factors remained stable.

IN PRACTICE:

The results support the early assessment of patients with PsA for comorbidities to inform treatment and suggest that comorbidities and CV risk factors are more than a consequence of long-term PsA and chronic systemic inflammation.

SOURCE:

The study was conducted by Alla Ishchenko, MD, and colleagues in the division of rheumatology at University Hospitals Leuven, Belgium. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The study was exploratory in nature, with a short follow-up period and a relatively small sample size.

DISCLOSURES:

Dr. Ishchenko disclosed support from PARTNER, an international fellowship program to study disease mechanisms in psoriatic arthritis, as well as grants from Lilly and from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

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

TOPLINE:

Patients with early psoriatic arthritis (PsA) were significantly more likely to have multiple comorbidities and cardiovascular risk factors than controls.

METHODOLOGY:

• The study population included 67 adults with early PsA and 61 healthy matched controls with mean ages of 47.9 years and 45 years, respectively.
• Early PsA was defined as symptom duration of less than 2 years; patients with conditions including active infection, malignancy, or other rheumatic or systemic disease were excluded.
• The researchers examined the prevalence of comorbidities and cardiovascular risk factors in treatment-naive, newly diagnosed patients with PsA at baseline and after 1 year.

TAKEAWAY:

• Adults with early PsA were significantly more likely to have two or more comorbidities and multiple cardiovascular risk factors at baseline, compared with healthy controls (odds ratios, 1.9 and 2.1, respectively).
• Dyslipidemia was the most prevalent comorbidity among patients with PsA and was more prevalent than in controls (64.2% vs. 39.3%; OR, 1.7).
• Obesity was more common in patients with PsA, compared with controls (40.3% vs. 18.3%, respectively), and more patients with PsA had cardiovascular disease at baseline than did controls (20.9% vs. 6.6%; OR, 3.2).
• Disease activity scores improved after 1 year, but the proportion of patients with comorbidities and CV risk factors remained stable.

IN PRACTICE:

The results support the early assessment of patients with PsA for comorbidities to inform treatment and suggest that comorbidities and CV risk factors are more than a consequence of long-term PsA and chronic systemic inflammation.

SOURCE:

The study was conducted by Alla Ishchenko, MD, and colleagues in the division of rheumatology at University Hospitals Leuven, Belgium. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The study was exploratory in nature, with a short follow-up period and a relatively small sample size.

DISCLOSURES:

Dr. Ishchenko disclosed support from PARTNER, an international fellowship program to study disease mechanisms in psoriatic arthritis, as well as grants from Lilly and from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

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

The use of colchicine prophylaxis during the process of up-titrating allopurinol slowly to reach target serum urate levels for patients with gout proved necessary to reduce the risk of flares in a randomized, double-blind, placebo-controlled noninferiority trial conducted by researchers in New Zealand.

Use of colchicine led to fewer flares during the first 6 months after initiating treatment with allopurinol, but when colchicine and placebo were stopped at 6 months, the number of flares rose, and there was no overall difference in the average number of flares between the placebo and colchicine groups over 12 months.

“Gout flares are common when starting urate-lowering therapy, although may be less frequent using the newer allopurinol ‘start-low, go-slow’ dose escalation strategy,” Lisa Stamp, MBChB, PhD, of the University of Otago, Christchurch, New Zealand, and colleagues write in Annals of the Rheumatic Diseases. “This study was undertaken to determine whether colchicine prophylaxis is required with the more gradual dose escalation of allopurinol to achieve target serum urate.”

The study was published online  in the BMJ.

The researchers randomly assigned 200 participants to receive colchicine 0.5 mg daily or placebo. At the same time, allopurinol 50 mg daily was initially given to those with an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2, and 100 mg daily was given to those with eGFR greater than or equal to 60 mL/min/1.73 m2; doses were increased monthly by 50 mg daily for those with eGFR less than 60 and by 100 mg daily for those with eGFR greater than or equal to 60 until the target urate level of less than 0.36 mmol/L (about < 6 mg/dL) was achieved. In total, 93% of patients were male, and 69% were White. Patients were enrolled from February 2019 through December 2021. The final study visit was in January 2023. Researchers tracked the mean number of patient-reported gout flares per month with a prespecified noninferiority margin of 0.12 gout flares/month. After the first 6 months, colchicine and placebo were stopped, and researchers continued to track outcomes up to month 12.

From baseline to 6 months, there were more gout flares per month in the placebo group (0.61) than in the colchicine group (0.35). From 6 to 12 months, there were more gout flares among patients who previously received colchicine, compared with those who received placebo. While 22.8% of patients in the colchicine group experienced flares at month 6, the following month – after stopping the drug – 41.2% experienced flares. For comparison, 30.8% of the placebo group experienced flares at month 6, and in month 7, 23.5% experienced flares. The spike in flares in the colchicine group began to decline after month 9.

Among the colchicine and placebo groups, reductions in serum urate at 6 and 12 months were similar, and mean serum urate levels declined below 0.36 mmol/L at 4 months and thereafter. Both groups reached a mean allopurinol dose of 280 mg/d at 6 months.

It is not clear what caused this rise in flares in the colchicine group, Stamp noted in an email to this news organization. Overall, there was no difference in the average number of gout flares between either group over the entire 12-month study period.

The study findings make a case for continuing colchicine prophylaxis considerably beyond the point at which the target urate serum level is reached, said Robert Terkeltaub, MD, professor emeritus of medicine in the division of rheumatology, allergy, and immunology at the University of California, San Diego. He was not involved with the research.

“The flare burden with this really conservative allopurinol dosing regimen is really stunning,” he said in an interview. Despite this “start low and go slow” strategy, flares remained a problem, he noted. “It argues that you need at least a year to get out of the woods and have a lower flare burden, even if colchicine prophylaxis is used for the first 6 months.”

The current standard of care in rheumatology for gout treatment includes flare prophylaxis when starting urate-lowering therapy. In daily practice, “this can (and often does) mean continuing flare prophylaxis for longer than the recommended minimum duration from [established] gout treatment guidelines for an individual patient,” explained Elizabeth R. Graef, DO, assistant professor of medicine at Boston University and a rheumatologist at Boston Medical Center.

There are many different factors to consider when determining a patient’s flare risk beyond serum urate levels and date of last flare, she noted. Flare severity, concurrent diuretic use, dose changes, tophus count, and additional health conditions such as diabetes can all contribute to individual patient outcomes.

“Gout is an erosive arthritis, and every time someone flares, there’s a risk of permanent erosive damage, so I tend to be more aggressive with prophylaxis,” she said.

The study was funded by the Health Research Council of New Zealand. Dr. Graef disclosed no relevant financial relationships. Dr. Terkeltaub consults for LG Chem, Fortress/Urica, Selecta Biosciences, Horizon Therapeutics, Atom Biosciences, Acquist Therapeutics, Generate Biomedicines, AstraZeneca, and Synlogic. Dr. Terkeltaub serves as the nonsalaried president of the Gout, Hyperuricemia, and Crystal-Associated Disease Network, which annually receives unrestricted arms-length grant support from pharma donors.

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

The use of colchicine prophylaxis during the process of up-titrating allopurinol slowly to reach target serum urate levels for patients with gout proved necessary to reduce the risk of flares in a randomized, double-blind, placebo-controlled noninferiority trial conducted by researchers in New Zealand.

Use of colchicine led to fewer flares during the first 6 months after initiating treatment with allopurinol, but when colchicine and placebo were stopped at 6 months, the number of flares rose, and there was no overall difference in the average number of flares between the placebo and colchicine groups over 12 months.

“Gout flares are common when starting urate-lowering therapy, although may be less frequent using the newer allopurinol ‘start-low, go-slow’ dose escalation strategy,” Lisa Stamp, MBChB, PhD, of the University of Otago, Christchurch, New Zealand, and colleagues write in Annals of the Rheumatic Diseases. “This study was undertaken to determine whether colchicine prophylaxis is required with the more gradual dose escalation of allopurinol to achieve target serum urate.”

The study was published online  in the BMJ.

The researchers randomly assigned 200 participants to receive colchicine 0.5 mg daily or placebo. At the same time, allopurinol 50 mg daily was initially given to those with an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2, and 100 mg daily was given to those with eGFR greater than or equal to 60 mL/min/1.73 m2; doses were increased monthly by 50 mg daily for those with eGFR less than 60 and by 100 mg daily for those with eGFR greater than or equal to 60 until the target urate level of less than 0.36 mmol/L (about < 6 mg/dL) was achieved. In total, 93% of patients were male, and 69% were White. Patients were enrolled from February 2019 through December 2021. The final study visit was in January 2023. Researchers tracked the mean number of patient-reported gout flares per month with a prespecified noninferiority margin of 0.12 gout flares/month. After the first 6 months, colchicine and placebo were stopped, and researchers continued to track outcomes up to month 12.

From baseline to 6 months, there were more gout flares per month in the placebo group (0.61) than in the colchicine group (0.35). From 6 to 12 months, there were more gout flares among patients who previously received colchicine, compared with those who received placebo. While 22.8% of patients in the colchicine group experienced flares at month 6, the following month – after stopping the drug – 41.2% experienced flares. For comparison, 30.8% of the placebo group experienced flares at month 6, and in month 7, 23.5% experienced flares. The spike in flares in the colchicine group began to decline after month 9.

Among the colchicine and placebo groups, reductions in serum urate at 6 and 12 months were similar, and mean serum urate levels declined below 0.36 mmol/L at 4 months and thereafter. Both groups reached a mean allopurinol dose of 280 mg/d at 6 months.

It is not clear what caused this rise in flares in the colchicine group, Stamp noted in an email to this news organization. Overall, there was no difference in the average number of gout flares between either group over the entire 12-month study period.

The study findings make a case for continuing colchicine prophylaxis considerably beyond the point at which the target urate serum level is reached, said Robert Terkeltaub, MD, professor emeritus of medicine in the division of rheumatology, allergy, and immunology at the University of California, San Diego. He was not involved with the research.

“The flare burden with this really conservative allopurinol dosing regimen is really stunning,” he said in an interview. Despite this “start low and go slow” strategy, flares remained a problem, he noted. “It argues that you need at least a year to get out of the woods and have a lower flare burden, even if colchicine prophylaxis is used for the first 6 months.”

The current standard of care in rheumatology for gout treatment includes flare prophylaxis when starting urate-lowering therapy. In daily practice, “this can (and often does) mean continuing flare prophylaxis for longer than the recommended minimum duration from [established] gout treatment guidelines for an individual patient,” explained Elizabeth R. Graef, DO, assistant professor of medicine at Boston University and a rheumatologist at Boston Medical Center.

There are many different factors to consider when determining a patient’s flare risk beyond serum urate levels and date of last flare, she noted. Flare severity, concurrent diuretic use, dose changes, tophus count, and additional health conditions such as diabetes can all contribute to individual patient outcomes.

“Gout is an erosive arthritis, and every time someone flares, there’s a risk of permanent erosive damage, so I tend to be more aggressive with prophylaxis,” she said.

The study was funded by the Health Research Council of New Zealand. Dr. Graef disclosed no relevant financial relationships. Dr. Terkeltaub consults for LG Chem, Fortress/Urica, Selecta Biosciences, Horizon Therapeutics, Atom Biosciences, Acquist Therapeutics, Generate Biomedicines, AstraZeneca, and Synlogic. Dr. Terkeltaub serves as the nonsalaried president of the Gout, Hyperuricemia, and Crystal-Associated Disease Network, which annually receives unrestricted arms-length grant support from pharma donors.

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

The use of colchicine prophylaxis during the process of up-titrating allopurinol slowly to reach target serum urate levels for patients with gout proved necessary to reduce the risk of flares in a randomized, double-blind, placebo-controlled noninferiority trial conducted by researchers in New Zealand.

Use of colchicine led to fewer flares during the first 6 months after initiating treatment with allopurinol, but when colchicine and placebo were stopped at 6 months, the number of flares rose, and there was no overall difference in the average number of flares between the placebo and colchicine groups over 12 months.

“Gout flares are common when starting urate-lowering therapy, although may be less frequent using the newer allopurinol ‘start-low, go-slow’ dose escalation strategy,” Lisa Stamp, MBChB, PhD, of the University of Otago, Christchurch, New Zealand, and colleagues write in Annals of the Rheumatic Diseases. “This study was undertaken to determine whether colchicine prophylaxis is required with the more gradual dose escalation of allopurinol to achieve target serum urate.”

The study was published online  in the BMJ.

The researchers randomly assigned 200 participants to receive colchicine 0.5 mg daily or placebo. At the same time, allopurinol 50 mg daily was initially given to those with an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2, and 100 mg daily was given to those with eGFR greater than or equal to 60 mL/min/1.73 m2; doses were increased monthly by 50 mg daily for those with eGFR less than 60 and by 100 mg daily for those with eGFR greater than or equal to 60 until the target urate level of less than 0.36 mmol/L (about < 6 mg/dL) was achieved. In total, 93% of patients were male, and 69% were White. Patients were enrolled from February 2019 through December 2021. The final study visit was in January 2023. Researchers tracked the mean number of patient-reported gout flares per month with a prespecified noninferiority margin of 0.12 gout flares/month. After the first 6 months, colchicine and placebo were stopped, and researchers continued to track outcomes up to month 12.

From baseline to 6 months, there were more gout flares per month in the placebo group (0.61) than in the colchicine group (0.35). From 6 to 12 months, there were more gout flares among patients who previously received colchicine, compared with those who received placebo. While 22.8% of patients in the colchicine group experienced flares at month 6, the following month – after stopping the drug – 41.2% experienced flares. For comparison, 30.8% of the placebo group experienced flares at month 6, and in month 7, 23.5% experienced flares. The spike in flares in the colchicine group began to decline after month 9.

Among the colchicine and placebo groups, reductions in serum urate at 6 and 12 months were similar, and mean serum urate levels declined below 0.36 mmol/L at 4 months and thereafter. Both groups reached a mean allopurinol dose of 280 mg/d at 6 months.

It is not clear what caused this rise in flares in the colchicine group, Stamp noted in an email to this news organization. Overall, there was no difference in the average number of gout flares between either group over the entire 12-month study period.

The study findings make a case for continuing colchicine prophylaxis considerably beyond the point at which the target urate serum level is reached, said Robert Terkeltaub, MD, professor emeritus of medicine in the division of rheumatology, allergy, and immunology at the University of California, San Diego. He was not involved with the research.

“The flare burden with this really conservative allopurinol dosing regimen is really stunning,” he said in an interview. Despite this “start low and go slow” strategy, flares remained a problem, he noted. “It argues that you need at least a year to get out of the woods and have a lower flare burden, even if colchicine prophylaxis is used for the first 6 months.”

The current standard of care in rheumatology for gout treatment includes flare prophylaxis when starting urate-lowering therapy. In daily practice, “this can (and often does) mean continuing flare prophylaxis for longer than the recommended minimum duration from [established] gout treatment guidelines for an individual patient,” explained Elizabeth R. Graef, DO, assistant professor of medicine at Boston University and a rheumatologist at Boston Medical Center.

There are many different factors to consider when determining a patient’s flare risk beyond serum urate levels and date of last flare, she noted. Flare severity, concurrent diuretic use, dose changes, tophus count, and additional health conditions such as diabetes can all contribute to individual patient outcomes.

“Gout is an erosive arthritis, and every time someone flares, there’s a risk of permanent erosive damage, so I tend to be more aggressive with prophylaxis,” she said.

The study was funded by the Health Research Council of New Zealand. Dr. Graef disclosed no relevant financial relationships. Dr. Terkeltaub consults for LG Chem, Fortress/Urica, Selecta Biosciences, Horizon Therapeutics, Atom Biosciences, Acquist Therapeutics, Generate Biomedicines, AstraZeneca, and Synlogic. Dr. Terkeltaub serves as the nonsalaried president of the Gout, Hyperuricemia, and Crystal-Associated Disease Network, which annually receives unrestricted arms-length grant support from pharma donors.

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

By the end of 2021, Anuj Peddada, MD, had hit a wall. He couldn’t sleep, couldn’t concentrate, erupted in anger, and felt isolated personally and professionally. To temper pandemic-driven pressures, the Colorado radiation oncologist took an 8-week stress management and resiliency course, but the feelings kept creeping back.

Still, Dr. Peddada, in his own private practice, pushed through, working 60-hour weeks and carrying the workload of two physicians. It wasn’t until he caught himself making uncharacteristic medical errors, including radiation planning for the wrong site, that he knew he needed help – and possibly a temporary break from medicine.

There was just one hitch: He was closing his private practice to start a new in-house job with Centura Health, the Colorado Springs hospital he’d contracted with for over 20 years.

Given the long-standing relationship – Dr. Peddada’s image graced some of the company’s marketing billboards – he expected Centura would understand when, on his doctor’s recommendation, he requested a short-term medical leave that would delay his start date by 1 month.

Instead, Centura abruptly rescinded the employment offer, leaving Dr. Peddada jobless and with no recourse but to sue.

“I was blindsided. The hospital had a physician resiliency program that claimed to encourage physicians to seek help, [so] I thought they would be completely supportive and understanding,” Dr. Peddada said.

He told this news organization that he was naive to have been so honest with the hospital he’d long served as a contractor, including the decade-plus he›d spent directing its radiation oncology department.

“It is exceedingly painful to see hospital leadership use me in their advertisement[s] ... trying to profit off my reputation and work after devastating my career.”

The lawsuit Dr. Peddada filed in July in Colorado federal district court may offer a rare glimpse of the potential career ramifications of seeking help for physician burnout. Despite employers’ oft-stated support for physician wellness, Dr. Peddada’s experience may serve as a cautionary tale for doctors who are open about their struggles.

Centura Health did not respond to requests for comment. In court documents, the health system’s attorneys asked for more time to respond to Dr. Peddada’s complaint.
 

A plea for help

In the complaint, Dr. Peddada and his attorneys claim that Centura violated the state’s Anti-Discrimination Act and the Americans with Disabilities Act (ADA) when it failed to offer reasonable accommodations after he began experiencing “physiological and psychological symptoms corresponding to burnout.”

Since 1999, Dr. Peddada had contracted exclusively with Centura to provide oncology services at its hospital, Penrose Cancer Center, and began covering a second Centura location in 2021. As medical director of Penrose’s radiation oncology department, he helped establish a community nurse navigator program and accounted for 75% of Centura’s radiation oncology referrals, according to the complaint.

But when his symptoms and fear for the safety of his patients became unbearable, Dr. Peddada requested an urgent evaluation from his primary care physician, who diagnosed him with “physician burnout” and recommended medical leave.

Shortly after presenting the leave request to Centura, rumors began circulating that he was having a “nervous breakdown,” the complaint noted. Dr. Peddada worried that perhaps his private health information was being shared with hospital employees.

After meeting with the hospital’s head of physician resiliency and agreeing to undergo a peer review evaluation by the Colorado Physician Health Program, which would decide the reinstatement timeline and if further therapy was necessary, Dr. Peddada was assured his leave would be approved.

Five days later, his job offer was revoked.

In an email from hospital leadership, the oncologist was informed that he had “declined employment” by failing to sign a revised employment contract sent to him 2 weeks prior when he was out of state on a preapproved vacation, according to the lawsuit.

The lawsuit alleges that Dr. Peddada was wrongfully discharged due to his disability after Centura “exploited [his] extensive patient base, referral network, and reputation to generate growth and profit.”

Colorado employment law attorney Deborah Yim, Esq., who is not involved in Peddada’s case, told this news organization that the ADA requires employers to provide reasonable accommodations for physical or mental impairments that substantially limit at least one major life activity, except when the request imposes an undue hardship on the employer.

“Depression and related mental health conditions would qualify, depending on the circumstances, and courts have certainly found them to be qualifying disabilities entitled to ADA protection in the past,” she said.

Not all employers are receptive to doctors’ needs, says the leadership team at Physicians Just Equity, an organization providing peer support to doctors experiencing workplace conflicts like discrimination and retaliation. They say that Dr. Peddada’s experience, where disclosing burnout results in being “ostracized, penalized, and ultimately ousted,” is the rule rather than the exception.

“Dr. Peddada’s case represents the unfortunate reality faced by many physicians in today’s clinical landscape,” the organization’s board of directors said in a written statement. “The imbalance of unreasonable professional demands, the lack of autonomy, moral injury, and disintegrating practice rewards is unsustainable for the medical professional.”

“Retaliation by employers after speaking up against this imbalance [and] requesting support and time to rejuvenate is a grave failure of health care systems that prioritize the business of delivering health care over the health, well-being, and satisfaction of their most valuable resource – the physician,” the board added in their statement.

Dr. Peddada has since closed his private practice and works as an independent contractor and consultant, his attorney, Iris Halpern, JD, said in an interview. She says Centura could have honored the accommodation request or suggested another option that met his needs, but “not only were they unsupportive, they terminated him.” 

Ms. Yim says the parties will have opportunities to reach a settlement and resolve the dispute as the case works through the court system. Otherwise, Dr. Peddada and Centura may eventually head to trial.
 

Current state of physician burnout

The state of physician burnout is certainly a concerning one. More than half (53%) of physicians responding to this year’s Medscape Physician Burnout & Depression Report said they are burned out. Nearly one-quarter reported feeling depressed. Some of the top reasons they cited were too many bureaucratic tasks (61%), too many work hours (37%), and lack of autonomy (31%).

A 2022 study by the Mayo Clinic found a substantial increase in physician burnout in the first 2 years of the pandemic, with doctors reporting rising emotional exhaustion and depersonalization.

Although burnout affects many physicians and is a priority focus of the National Academy of Medicine’s plan to restore workforce well-being, admitting it is often seen as taboo and can imperil a doctor’s career. In the Medscape report, for example, 39% of physicians said they would not even consider professional treatment for burnout, with many commenting that they would just deal with it themselves.

“Many physicians are frightened to take time out for self-care because [they] fear losing their job, being stigmatized, and potentially ending their careers,” said Dr. Peddada, adding that physicians are commonly asked questions about their mental health when applying for hospital privileges. He says this dynamic forces them to choose between getting help or ignoring their true feelings, leading to poor quality of care and patient safety risks.

Medical licensing boards probe physicians’ mental health, too. As part of its #FightingForDocs campaign, the American Medical Association hopes to remove the stigma around burnout and depression and advocates for licensing boards to revise questions that may discourage physicians from seeking assistance. The AMA recommends that physicians only disclose current physical or mental conditions affecting their ability to practice.

Pringl Miller, MD, founder and executive director of Physician Just Equity, told Medscape that improving physician wellness requires structural change.

“Physicians (who) experience burnout without the proper accommodations run the risk of personal harm, because most physicians will prioritize the health and well-being of their patients over themselves ... [resulting in] suboptimal and unsafe patient care,” she said.
 

Helping doctors regain a sense of purpose

One change involves reframing how the health care industry thinks about and approaches burnout, says Steven Siegel, MD, chief mental health and wellness officer with Keck Medicine of USC. He told this news organization that these discussions should enhance the physician’s sense of purpose. 

“Some people treat burnout as a concrete disorder like cancer, instead of saying, ‘I’m feeling exhausted, demoralized, and don’t enjoy my job anymore. What can we do to restore my enthusiasm for work?’ ”

Dr. Siegel recognizes that these issues existed before the pandemic and have only worsened as physicians feel less connected to and satisfied with their profession – a byproduct, he says, of the commercialization of medicine.

“We’ve moved from practices to systems, then from small to large systems, where it seems the path to survival is cutting costs and increasing margins, even among nonprofits.”
 

The road ahead

Making headway on these problems will take time. Last year, Keck Medicine received a $2 million grant to launch a 3-year randomized clinical trial to help reconnect physicians and other clinicians with their work. Dr. Siegel says the trial may serve as a national pilot program and will eventually grow to include 400 volunteers.

The trial will investigate the effectiveness of three possible interventions: (1) teaching people how to regulate their internal narratives and emotions through techniques like cognitive behavioral therapy and acceptance and commitment therapy; (2) providing customized EHR training to reduce the burden of navigating the system; and (3) allowing physicians to weigh in on workflow changes. 

“We put physicians on teams that make the decisions about workflows,” said Dr. Siegel. The arrangement can give people the agency they desire and help them understand why an idea might not be plausible, which enriches future suggestions and discussions, he says.

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

By the end of 2021, Anuj Peddada, MD, had hit a wall. He couldn’t sleep, couldn’t concentrate, erupted in anger, and felt isolated personally and professionally. To temper pandemic-driven pressures, the Colorado radiation oncologist took an 8-week stress management and resiliency course, but the feelings kept creeping back.

Still, Dr. Peddada, in his own private practice, pushed through, working 60-hour weeks and carrying the workload of two physicians. It wasn’t until he caught himself making uncharacteristic medical errors, including radiation planning for the wrong site, that he knew he needed help – and possibly a temporary break from medicine.

There was just one hitch: He was closing his private practice to start a new in-house job with Centura Health, the Colorado Springs hospital he’d contracted with for over 20 years.

Given the long-standing relationship – Dr. Peddada’s image graced some of the company’s marketing billboards – he expected Centura would understand when, on his doctor’s recommendation, he requested a short-term medical leave that would delay his start date by 1 month.

Instead, Centura abruptly rescinded the employment offer, leaving Dr. Peddada jobless and with no recourse but to sue.

“I was blindsided. The hospital had a physician resiliency program that claimed to encourage physicians to seek help, [so] I thought they would be completely supportive and understanding,” Dr. Peddada said.

He told this news organization that he was naive to have been so honest with the hospital he’d long served as a contractor, including the decade-plus he›d spent directing its radiation oncology department.

“It is exceedingly painful to see hospital leadership use me in their advertisement[s] ... trying to profit off my reputation and work after devastating my career.”

The lawsuit Dr. Peddada filed in July in Colorado federal district court may offer a rare glimpse of the potential career ramifications of seeking help for physician burnout. Despite employers’ oft-stated support for physician wellness, Dr. Peddada’s experience may serve as a cautionary tale for doctors who are open about their struggles.

Centura Health did not respond to requests for comment. In court documents, the health system’s attorneys asked for more time to respond to Dr. Peddada’s complaint.
 

A plea for help

In the complaint, Dr. Peddada and his attorneys claim that Centura violated the state’s Anti-Discrimination Act and the Americans with Disabilities Act (ADA) when it failed to offer reasonable accommodations after he began experiencing “physiological and psychological symptoms corresponding to burnout.”

Since 1999, Dr. Peddada had contracted exclusively with Centura to provide oncology services at its hospital, Penrose Cancer Center, and began covering a second Centura location in 2021. As medical director of Penrose’s radiation oncology department, he helped establish a community nurse navigator program and accounted for 75% of Centura’s radiation oncology referrals, according to the complaint.

But when his symptoms and fear for the safety of his patients became unbearable, Dr. Peddada requested an urgent evaluation from his primary care physician, who diagnosed him with “physician burnout” and recommended medical leave.

Shortly after presenting the leave request to Centura, rumors began circulating that he was having a “nervous breakdown,” the complaint noted. Dr. Peddada worried that perhaps his private health information was being shared with hospital employees.

After meeting with the hospital’s head of physician resiliency and agreeing to undergo a peer review evaluation by the Colorado Physician Health Program, which would decide the reinstatement timeline and if further therapy was necessary, Dr. Peddada was assured his leave would be approved.

Five days later, his job offer was revoked.

In an email from hospital leadership, the oncologist was informed that he had “declined employment” by failing to sign a revised employment contract sent to him 2 weeks prior when he was out of state on a preapproved vacation, according to the lawsuit.

The lawsuit alleges that Dr. Peddada was wrongfully discharged due to his disability after Centura “exploited [his] extensive patient base, referral network, and reputation to generate growth and profit.”

Colorado employment law attorney Deborah Yim, Esq., who is not involved in Peddada’s case, told this news organization that the ADA requires employers to provide reasonable accommodations for physical or mental impairments that substantially limit at least one major life activity, except when the request imposes an undue hardship on the employer.

“Depression and related mental health conditions would qualify, depending on the circumstances, and courts have certainly found them to be qualifying disabilities entitled to ADA protection in the past,” she said.

Not all employers are receptive to doctors’ needs, says the leadership team at Physicians Just Equity, an organization providing peer support to doctors experiencing workplace conflicts like discrimination and retaliation. They say that Dr. Peddada’s experience, where disclosing burnout results in being “ostracized, penalized, and ultimately ousted,” is the rule rather than the exception.

“Dr. Peddada’s case represents the unfortunate reality faced by many physicians in today’s clinical landscape,” the organization’s board of directors said in a written statement. “The imbalance of unreasonable professional demands, the lack of autonomy, moral injury, and disintegrating practice rewards is unsustainable for the medical professional.”

“Retaliation by employers after speaking up against this imbalance [and] requesting support and time to rejuvenate is a grave failure of health care systems that prioritize the business of delivering health care over the health, well-being, and satisfaction of their most valuable resource – the physician,” the board added in their statement.

Dr. Peddada has since closed his private practice and works as an independent contractor and consultant, his attorney, Iris Halpern, JD, said in an interview. She says Centura could have honored the accommodation request or suggested another option that met his needs, but “not only were they unsupportive, they terminated him.” 

Ms. Yim says the parties will have opportunities to reach a settlement and resolve the dispute as the case works through the court system. Otherwise, Dr. Peddada and Centura may eventually head to trial.
 

Current state of physician burnout

The state of physician burnout is certainly a concerning one. More than half (53%) of physicians responding to this year’s Medscape Physician Burnout & Depression Report said they are burned out. Nearly one-quarter reported feeling depressed. Some of the top reasons they cited were too many bureaucratic tasks (61%), too many work hours (37%), and lack of autonomy (31%).

A 2022 study by the Mayo Clinic found a substantial increase in physician burnout in the first 2 years of the pandemic, with doctors reporting rising emotional exhaustion and depersonalization.

Although burnout affects many physicians and is a priority focus of the National Academy of Medicine’s plan to restore workforce well-being, admitting it is often seen as taboo and can imperil a doctor’s career. In the Medscape report, for example, 39% of physicians said they would not even consider professional treatment for burnout, with many commenting that they would just deal with it themselves.

“Many physicians are frightened to take time out for self-care because [they] fear losing their job, being stigmatized, and potentially ending their careers,” said Dr. Peddada, adding that physicians are commonly asked questions about their mental health when applying for hospital privileges. He says this dynamic forces them to choose between getting help or ignoring their true feelings, leading to poor quality of care and patient safety risks.

Medical licensing boards probe physicians’ mental health, too. As part of its #FightingForDocs campaign, the American Medical Association hopes to remove the stigma around burnout and depression and advocates for licensing boards to revise questions that may discourage physicians from seeking assistance. The AMA recommends that physicians only disclose current physical or mental conditions affecting their ability to practice.

Pringl Miller, MD, founder and executive director of Physician Just Equity, told Medscape that improving physician wellness requires structural change.

“Physicians (who) experience burnout without the proper accommodations run the risk of personal harm, because most physicians will prioritize the health and well-being of their patients over themselves ... [resulting in] suboptimal and unsafe patient care,” she said.
 

Helping doctors regain a sense of purpose

One change involves reframing how the health care industry thinks about and approaches burnout, says Steven Siegel, MD, chief mental health and wellness officer with Keck Medicine of USC. He told this news organization that these discussions should enhance the physician’s sense of purpose. 

“Some people treat burnout as a concrete disorder like cancer, instead of saying, ‘I’m feeling exhausted, demoralized, and don’t enjoy my job anymore. What can we do to restore my enthusiasm for work?’ ”

Dr. Siegel recognizes that these issues existed before the pandemic and have only worsened as physicians feel less connected to and satisfied with their profession – a byproduct, he says, of the commercialization of medicine.

“We’ve moved from practices to systems, then from small to large systems, where it seems the path to survival is cutting costs and increasing margins, even among nonprofits.”
 

The road ahead

Making headway on these problems will take time. Last year, Keck Medicine received a $2 million grant to launch a 3-year randomized clinical trial to help reconnect physicians and other clinicians with their work. Dr. Siegel says the trial may serve as a national pilot program and will eventually grow to include 400 volunteers.

The trial will investigate the effectiveness of three possible interventions: (1) teaching people how to regulate their internal narratives and emotions through techniques like cognitive behavioral therapy and acceptance and commitment therapy; (2) providing customized EHR training to reduce the burden of navigating the system; and (3) allowing physicians to weigh in on workflow changes. 

“We put physicians on teams that make the decisions about workflows,” said Dr. Siegel. The arrangement can give people the agency they desire and help them understand why an idea might not be plausible, which enriches future suggestions and discussions, he says.

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

By the end of 2021, Anuj Peddada, MD, had hit a wall. He couldn’t sleep, couldn’t concentrate, erupted in anger, and felt isolated personally and professionally. To temper pandemic-driven pressures, the Colorado radiation oncologist took an 8-week stress management and resiliency course, but the feelings kept creeping back.

Still, Dr. Peddada, in his own private practice, pushed through, working 60-hour weeks and carrying the workload of two physicians. It wasn’t until he caught himself making uncharacteristic medical errors, including radiation planning for the wrong site, that he knew he needed help – and possibly a temporary break from medicine.

There was just one hitch: He was closing his private practice to start a new in-house job with Centura Health, the Colorado Springs hospital he’d contracted with for over 20 years.

Given the long-standing relationship – Dr. Peddada’s image graced some of the company’s marketing billboards – he expected Centura would understand when, on his doctor’s recommendation, he requested a short-term medical leave that would delay his start date by 1 month.

Instead, Centura abruptly rescinded the employment offer, leaving Dr. Peddada jobless and with no recourse but to sue.

“I was blindsided. The hospital had a physician resiliency program that claimed to encourage physicians to seek help, [so] I thought they would be completely supportive and understanding,” Dr. Peddada said.

He told this news organization that he was naive to have been so honest with the hospital he’d long served as a contractor, including the decade-plus he›d spent directing its radiation oncology department.

“It is exceedingly painful to see hospital leadership use me in their advertisement[s] ... trying to profit off my reputation and work after devastating my career.”

The lawsuit Dr. Peddada filed in July in Colorado federal district court may offer a rare glimpse of the potential career ramifications of seeking help for physician burnout. Despite employers’ oft-stated support for physician wellness, Dr. Peddada’s experience may serve as a cautionary tale for doctors who are open about their struggles.

Centura Health did not respond to requests for comment. In court documents, the health system’s attorneys asked for more time to respond to Dr. Peddada’s complaint.
 

A plea for help

In the complaint, Dr. Peddada and his attorneys claim that Centura violated the state’s Anti-Discrimination Act and the Americans with Disabilities Act (ADA) when it failed to offer reasonable accommodations after he began experiencing “physiological and psychological symptoms corresponding to burnout.”

Since 1999, Dr. Peddada had contracted exclusively with Centura to provide oncology services at its hospital, Penrose Cancer Center, and began covering a second Centura location in 2021. As medical director of Penrose’s radiation oncology department, he helped establish a community nurse navigator program and accounted for 75% of Centura’s radiation oncology referrals, according to the complaint.

But when his symptoms and fear for the safety of his patients became unbearable, Dr. Peddada requested an urgent evaluation from his primary care physician, who diagnosed him with “physician burnout” and recommended medical leave.

Shortly after presenting the leave request to Centura, rumors began circulating that he was having a “nervous breakdown,” the complaint noted. Dr. Peddada worried that perhaps his private health information was being shared with hospital employees.

After meeting with the hospital’s head of physician resiliency and agreeing to undergo a peer review evaluation by the Colorado Physician Health Program, which would decide the reinstatement timeline and if further therapy was necessary, Dr. Peddada was assured his leave would be approved.

Five days later, his job offer was revoked.

In an email from hospital leadership, the oncologist was informed that he had “declined employment” by failing to sign a revised employment contract sent to him 2 weeks prior when he was out of state on a preapproved vacation, according to the lawsuit.

The lawsuit alleges that Dr. Peddada was wrongfully discharged due to his disability after Centura “exploited [his] extensive patient base, referral network, and reputation to generate growth and profit.”

Colorado employment law attorney Deborah Yim, Esq., who is not involved in Peddada’s case, told this news organization that the ADA requires employers to provide reasonable accommodations for physical or mental impairments that substantially limit at least one major life activity, except when the request imposes an undue hardship on the employer.

“Depression and related mental health conditions would qualify, depending on the circumstances, and courts have certainly found them to be qualifying disabilities entitled to ADA protection in the past,” she said.

Not all employers are receptive to doctors’ needs, says the leadership team at Physicians Just Equity, an organization providing peer support to doctors experiencing workplace conflicts like discrimination and retaliation. They say that Dr. Peddada’s experience, where disclosing burnout results in being “ostracized, penalized, and ultimately ousted,” is the rule rather than the exception.

“Dr. Peddada’s case represents the unfortunate reality faced by many physicians in today’s clinical landscape,” the organization’s board of directors said in a written statement. “The imbalance of unreasonable professional demands, the lack of autonomy, moral injury, and disintegrating practice rewards is unsustainable for the medical professional.”

“Retaliation by employers after speaking up against this imbalance [and] requesting support and time to rejuvenate is a grave failure of health care systems that prioritize the business of delivering health care over the health, well-being, and satisfaction of their most valuable resource – the physician,” the board added in their statement.

Dr. Peddada has since closed his private practice and works as an independent contractor and consultant, his attorney, Iris Halpern, JD, said in an interview. She says Centura could have honored the accommodation request or suggested another option that met his needs, but “not only were they unsupportive, they terminated him.” 

Ms. Yim says the parties will have opportunities to reach a settlement and resolve the dispute as the case works through the court system. Otherwise, Dr. Peddada and Centura may eventually head to trial.
 

Current state of physician burnout

The state of physician burnout is certainly a concerning one. More than half (53%) of physicians responding to this year’s Medscape Physician Burnout & Depression Report said they are burned out. Nearly one-quarter reported feeling depressed. Some of the top reasons they cited were too many bureaucratic tasks (61%), too many work hours (37%), and lack of autonomy (31%).

A 2022 study by the Mayo Clinic found a substantial increase in physician burnout in the first 2 years of the pandemic, with doctors reporting rising emotional exhaustion and depersonalization.

Although burnout affects many physicians and is a priority focus of the National Academy of Medicine’s plan to restore workforce well-being, admitting it is often seen as taboo and can imperil a doctor’s career. In the Medscape report, for example, 39% of physicians said they would not even consider professional treatment for burnout, with many commenting that they would just deal with it themselves.

“Many physicians are frightened to take time out for self-care because [they] fear losing their job, being stigmatized, and potentially ending their careers,” said Dr. Peddada, adding that physicians are commonly asked questions about their mental health when applying for hospital privileges. He says this dynamic forces them to choose between getting help or ignoring their true feelings, leading to poor quality of care and patient safety risks.

Medical licensing boards probe physicians’ mental health, too. As part of its #FightingForDocs campaign, the American Medical Association hopes to remove the stigma around burnout and depression and advocates for licensing boards to revise questions that may discourage physicians from seeking assistance. The AMA recommends that physicians only disclose current physical or mental conditions affecting their ability to practice.

Pringl Miller, MD, founder and executive director of Physician Just Equity, told Medscape that improving physician wellness requires structural change.

“Physicians (who) experience burnout without the proper accommodations run the risk of personal harm, because most physicians will prioritize the health and well-being of their patients over themselves ... [resulting in] suboptimal and unsafe patient care,” she said.
 

Helping doctors regain a sense of purpose

One change involves reframing how the health care industry thinks about and approaches burnout, says Steven Siegel, MD, chief mental health and wellness officer with Keck Medicine of USC. He told this news organization that these discussions should enhance the physician’s sense of purpose. 

“Some people treat burnout as a concrete disorder like cancer, instead of saying, ‘I’m feeling exhausted, demoralized, and don’t enjoy my job anymore. What can we do to restore my enthusiasm for work?’ ”

Dr. Siegel recognizes that these issues existed before the pandemic and have only worsened as physicians feel less connected to and satisfied with their profession – a byproduct, he says, of the commercialization of medicine.

“We’ve moved from practices to systems, then from small to large systems, where it seems the path to survival is cutting costs and increasing margins, even among nonprofits.”
 

The road ahead

Making headway on these problems will take time. Last year, Keck Medicine received a $2 million grant to launch a 3-year randomized clinical trial to help reconnect physicians and other clinicians with their work. Dr. Siegel says the trial may serve as a national pilot program and will eventually grow to include 400 volunteers.

The trial will investigate the effectiveness of three possible interventions: (1) teaching people how to regulate their internal narratives and emotions through techniques like cognitive behavioral therapy and acceptance and commitment therapy; (2) providing customized EHR training to reduce the burden of navigating the system; and (3) allowing physicians to weigh in on workflow changes. 

“We put physicians on teams that make the decisions about workflows,” said Dr. Siegel. The arrangement can give people the agency they desire and help them understand why an idea might not be plausible, which enriches future suggestions and discussions, he says.

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

The Barbie movie is generating a lot of feelings, ranging from praise to vitriol. However one feels about the movie, let’s all pause and reflect for a moment on the fact that the number-one grossing film of 2023 is about our childhood doll trying to treat her anxiety disorder.

Eva Ritvo

“Life imitates art more than art imitates life.” So said Oscar Wilde in 1889.

When my adult daughter, a childhood Barbie enthusiast, asked me to see the film, we put on pink and went. Twice. Little did I know that it would stir up so many thoughts and feelings. The one I want to share is how blessed I feel at this moment in time to be a mental health care provider! No longer is mental health something to be whispered about at the water cooler; instead, even Barbie is suffering. And with all the controversy in the press about the movie, no one seems at all surprised by this storyline.

I was raised by two child psychiatrists and have been practicing as an adult psychiatrist since 1991. The start of the pandemic was the most difficult time of my career, as almost every patient was struggling simultaneously, as was I. Three long years later, we are gradually emerging from our shared trauma. How ironic, now with the opportunity to go back to work, I have elected to maintain the majority of my practice online from home. It seems that most patients and providers prefer this mode of treatment, with a full 90 percent of practitioners saying they are using a hybrid model.

As mental health professionals, we know that anywhere from 3% to 49% of those experiencing trauma will develop posttraumatic stress disorder (PTSD), and we have been trained to treat them.

But what happens when an entire global population is exposed simultaneously to trauma? Historians and social scientists refer to such events by many different names, such as: Singularity, Black Swan Event, and Tipping Point. These events are incredibly rare, and afterwards everything is different. These global traumas always lead to massive change.

I think we are at that tipping point. This is the singularity. This is our Black Swan Event. Within a 3-year span, we have experienced the following:

• A global traumatic event (COVID-19).
• A sudden and seemingly permanent shift from office to remote video meetings mostly from home.
• Upending of traditional fundamentals of the stock market as the game literally stopped in January 2021.
• Rapid and widespread availability of Artificial Intelligence.
• The first generation to be fully raised on the Internet and social media (Gen Z) is now entering the workforce.
• Ongoing war in Ukraine.

That’s already an overwhelming list, and I could go on, but let’s get back to Barbie’s anxiety disorder.

The awareness about and acceptance of mental health issues has never been higher. The access to treatment never greater. There are now more online therapy options than ever. Treatment options have dramatically expanded in recent years, from Transcranial Magnetic Stimulation (TMS) to ketamine centers and psychedelics, as well as more mainstream options such as dialectical behavior therapy (DBT), cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), and so many more.

What is particularly unique about this moment is the direct access to care. Self-help books abound with many making it to the New York Times bestseller list. YouTube is loaded with fantastic content on overcoming many mental health issues, although one should be careful with selecting reliable sources. Apps like HeadSpace and Calm are being downloaded by millions of people around the globe. Investors provided a record-breaking $1.5 billion to mental health startups in 2020 alone.

For most practitioners, our phones have been ringing off the hook since 2020. Applications to psychology, psychiatric residency, social work, and counseling degree programs are on the rise, with workforce shortages expected to continue for decades. Psychological expertise has been embraced by businesses especially for DEI (diversity, equity, and inclusion). Mental health experts are the most asked-for experts through media request services. Elite athletes are talking openly about bringing us on their teams.

In this unique moment, when everything seems set to transform into something else, it is time for mental health professionals to exert some agency and influence over where mental health will go from here. I think the next frontier for mental health specialists is to figure out how to speak collectively and help guide society.

Neil Howe, in his sweeping book “The Fourth Turning is Here,” says we have another 10 years in this “Millennial Crisis” phase. He calls this our “winter,” and it remains to be seen how we will emerge from our current challenges. I think we can make a difference.

If the Barbie movie is indeed a canary in the coal mine, I see positive trends ahead as we move past some of the societal and structural issues facing us, and work together to create a more open and egalitarian society. We must find creative solutions that will solve truly massive problems threatening our well-being and perhaps even our existence.

There has never been a better time to be (or become!) a mental health professional. I am so grateful to be able to continue to practice and share my thoughts with you here from my home office, and I hope you can take a break and see this movie, which is not only entertaining but also thought- and emotion-provoking.

Dr. Ritvo has almost 30 years’ experience in psychiatry and is currently practicing telemedicine. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She has no conflicts of interest.