Anecdotal reports have linked the vaccines against COVID-19 to the sudden loss of hearing in some people. But a new study has found no evidence for such a connection with any of the three approved shots. 

The analysis of data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Reporting System (VAERS) found that the incidence of sudden onset hearing loss was not elevated – and might even be a bit lower than expected – in the first few weeks after the injections.

“We’re not finding a signal,” said Eric J. Formeister, MD, a neurotology fellow at the Johns Hopkins University, Baltimore, and the first author of the U.S. study, which appeared Feb. 24 in JAMA Otolaryngology – Head and Neck Surgery.

Dr. Formeister and colleagues undertook the study in response to reports of hearing problems, including hearing loss and tinnitus, that occurred soon after COVID-19 vaccination.

They analyzed reports of sudden hearing loss, experienced within 21 days of vaccination, logged in VAERS. Anyone can report a potential event to the database, which does not require medical documentation in support of the adverse event. To minimize potential misdiagnoses, Dr. Formeister and colleagues reviewed only those reports that indicated that a doctor had diagnosed sudden hearing loss, leaving 555 cases (305 in women; mean age 54 years) between December 2020 and July 2021.

Dividing these reports by the total doses of vaccines administered in the United States during that period yielded an incidence rate of 0.6 cases of sudden hearing loss for every 100,000 people, Dr. Formeister and colleagues reported.

When the researchers divided all cases of hearing loss in the VAERS database (2,170) by the number of people who had received two doses of vaccine, the incidence rate increased to 28 per 100,000 people. For comparison, the authors reported, the incidence of sudden hearing loss within the United States population is between 11 and 77 per 100,000 people, depending on age.

“There was not an increase in cases of sudden [sensorineural] hearing loss associated with COVID-19 vaccination compared to previously published reports before the COVID-19 vaccination era,” study coauthor Elliott D. Kozin, MD, assistant professor of otolaryngology–head and neck surgery at Harvard Medical School, Boston, said in an interview.

Another reassuring sign: If hearing loss were linked to the vaccines, the researchers said, they would expect to see an increase in the number of complaints in lockstep with an increase in the number of doses administered. However, the opposite was true. “[T]he rate of reports per 100,000 doses decreased across the vaccination period, despite large concomitant increases in the absolute number of vaccine doses administered per week,” the researchers reported.

They also looked at case reports of 21 men and women who had experienced sudden hearing loss after having received COVID-19 vaccines, to see if they could discern any clinically relevant signs of people most likely to experience the adverse event. However, the group had a range of preexisting conditions and varying times after receiving a vaccine when their hearing loss occurred, leading Dr. Formeister’s team to conclude that they could find no clear markers of risk.

“When we examined patients across several institutions, there was no obvious pattern. The patient demographics and clinical findings were variable,” Dr. Kozin said. A provisional interpretation of this data, he added, is that no link exists between COVID-19 vaccination and predictable hearing deficits, although the analysis covered a small number of patients.

“Association does not necessarily imply a causal relationship,” said Michael Brenner, MD, FACS, associate professor of otolaryngology–head and neck surgery at the University of Michigan, Ann Arbor. Dr. Brenner, who was not involved in the study, said any hearing loss attributed to the COVID-19 vaccines could have had other causes besides the injections.

But a second study, also published in JAMA Otolaryngology – Head and Neck Surgery on Feb. 24, leaves open the possibility of a link. Researchers in Israel looked for increases in steroid prescriptions used to treat sudden hearing loss as vaccination with the Pfizer version of the shot became widespread in that country. Their conclusion: The vaccine might be associated with a slightly increased risk of sudden hearing loss, although if so, that risk is likely “very small” and the benefits of vaccination “outweigh its potential association” with the side effect.

Dr. Brenner agreed. “The evidence supports [the] clear public health benefit of COVID-19 vaccination, and the scale of those benefits dwarfs associations with hearing, which are of uncertain significance,” he said.

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

Anecdotal reports have linked the vaccines against COVID-19 to the sudden loss of hearing in some people. But a new study has found no evidence for such a connection with any of the three approved shots. 

The analysis of data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Reporting System (VAERS) found that the incidence of sudden onset hearing loss was not elevated – and might even be a bit lower than expected – in the first few weeks after the injections.

“We’re not finding a signal,” said Eric J. Formeister, MD, a neurotology fellow at the Johns Hopkins University, Baltimore, and the first author of the U.S. study, which appeared Feb. 24 in JAMA Otolaryngology – Head and Neck Surgery.

Dr. Formeister and colleagues undertook the study in response to reports of hearing problems, including hearing loss and tinnitus, that occurred soon after COVID-19 vaccination.

They analyzed reports of sudden hearing loss, experienced within 21 days of vaccination, logged in VAERS. Anyone can report a potential event to the database, which does not require medical documentation in support of the adverse event. To minimize potential misdiagnoses, Dr. Formeister and colleagues reviewed only those reports that indicated that a doctor had diagnosed sudden hearing loss, leaving 555 cases (305 in women; mean age 54 years) between December 2020 and July 2021.

Dividing these reports by the total doses of vaccines administered in the United States during that period yielded an incidence rate of 0.6 cases of sudden hearing loss for every 100,000 people, Dr. Formeister and colleagues reported.

When the researchers divided all cases of hearing loss in the VAERS database (2,170) by the number of people who had received two doses of vaccine, the incidence rate increased to 28 per 100,000 people. For comparison, the authors reported, the incidence of sudden hearing loss within the United States population is between 11 and 77 per 100,000 people, depending on age.

“There was not an increase in cases of sudden [sensorineural] hearing loss associated with COVID-19 vaccination compared to previously published reports before the COVID-19 vaccination era,” study coauthor Elliott D. Kozin, MD, assistant professor of otolaryngology–head and neck surgery at Harvard Medical School, Boston, said in an interview.

Another reassuring sign: If hearing loss were linked to the vaccines, the researchers said, they would expect to see an increase in the number of complaints in lockstep with an increase in the number of doses administered. However, the opposite was true. “[T]he rate of reports per 100,000 doses decreased across the vaccination period, despite large concomitant increases in the absolute number of vaccine doses administered per week,” the researchers reported.

They also looked at case reports of 21 men and women who had experienced sudden hearing loss after having received COVID-19 vaccines, to see if they could discern any clinically relevant signs of people most likely to experience the adverse event. However, the group had a range of preexisting conditions and varying times after receiving a vaccine when their hearing loss occurred, leading Dr. Formeister’s team to conclude that they could find no clear markers of risk.

“When we examined patients across several institutions, there was no obvious pattern. The patient demographics and clinical findings were variable,” Dr. Kozin said. A provisional interpretation of this data, he added, is that no link exists between COVID-19 vaccination and predictable hearing deficits, although the analysis covered a small number of patients.

“Association does not necessarily imply a causal relationship,” said Michael Brenner, MD, FACS, associate professor of otolaryngology–head and neck surgery at the University of Michigan, Ann Arbor. Dr. Brenner, who was not involved in the study, said any hearing loss attributed to the COVID-19 vaccines could have had other causes besides the injections.

But a second study, also published in JAMA Otolaryngology – Head and Neck Surgery on Feb. 24, leaves open the possibility of a link. Researchers in Israel looked for increases in steroid prescriptions used to treat sudden hearing loss as vaccination with the Pfizer version of the shot became widespread in that country. Their conclusion: The vaccine might be associated with a slightly increased risk of sudden hearing loss, although if so, that risk is likely “very small” and the benefits of vaccination “outweigh its potential association” with the side effect.

Dr. Brenner agreed. “The evidence supports [the] clear public health benefit of COVID-19 vaccination, and the scale of those benefits dwarfs associations with hearing, which are of uncertain significance,” he said.

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

Anecdotal reports have linked the vaccines against COVID-19 to the sudden loss of hearing in some people. But a new study has found no evidence for such a connection with any of the three approved shots. 

The analysis of data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Reporting System (VAERS) found that the incidence of sudden onset hearing loss was not elevated – and might even be a bit lower than expected – in the first few weeks after the injections.

“We’re not finding a signal,” said Eric J. Formeister, MD, a neurotology fellow at the Johns Hopkins University, Baltimore, and the first author of the U.S. study, which appeared Feb. 24 in JAMA Otolaryngology – Head and Neck Surgery.

Dr. Formeister and colleagues undertook the study in response to reports of hearing problems, including hearing loss and tinnitus, that occurred soon after COVID-19 vaccination.

They analyzed reports of sudden hearing loss, experienced within 21 days of vaccination, logged in VAERS. Anyone can report a potential event to the database, which does not require medical documentation in support of the adverse event. To minimize potential misdiagnoses, Dr. Formeister and colleagues reviewed only those reports that indicated that a doctor had diagnosed sudden hearing loss, leaving 555 cases (305 in women; mean age 54 years) between December 2020 and July 2021.

Dividing these reports by the total doses of vaccines administered in the United States during that period yielded an incidence rate of 0.6 cases of sudden hearing loss for every 100,000 people, Dr. Formeister and colleagues reported.

When the researchers divided all cases of hearing loss in the VAERS database (2,170) by the number of people who had received two doses of vaccine, the incidence rate increased to 28 per 100,000 people. For comparison, the authors reported, the incidence of sudden hearing loss within the United States population is between 11 and 77 per 100,000 people, depending on age.

“There was not an increase in cases of sudden [sensorineural] hearing loss associated with COVID-19 vaccination compared to previously published reports before the COVID-19 vaccination era,” study coauthor Elliott D. Kozin, MD, assistant professor of otolaryngology–head and neck surgery at Harvard Medical School, Boston, said in an interview.

Another reassuring sign: If hearing loss were linked to the vaccines, the researchers said, they would expect to see an increase in the number of complaints in lockstep with an increase in the number of doses administered. However, the opposite was true. “[T]he rate of reports per 100,000 doses decreased across the vaccination period, despite large concomitant increases in the absolute number of vaccine doses administered per week,” the researchers reported.

They also looked at case reports of 21 men and women who had experienced sudden hearing loss after having received COVID-19 vaccines, to see if they could discern any clinically relevant signs of people most likely to experience the adverse event. However, the group had a range of preexisting conditions and varying times after receiving a vaccine when their hearing loss occurred, leading Dr. Formeister’s team to conclude that they could find no clear markers of risk.

“When we examined patients across several institutions, there was no obvious pattern. The patient demographics and clinical findings were variable,” Dr. Kozin said. A provisional interpretation of this data, he added, is that no link exists between COVID-19 vaccination and predictable hearing deficits, although the analysis covered a small number of patients.

“Association does not necessarily imply a causal relationship,” said Michael Brenner, MD, FACS, associate professor of otolaryngology–head and neck surgery at the University of Michigan, Ann Arbor. Dr. Brenner, who was not involved in the study, said any hearing loss attributed to the COVID-19 vaccines could have had other causes besides the injections.

But a second study, also published in JAMA Otolaryngology – Head and Neck Surgery on Feb. 24, leaves open the possibility of a link. Researchers in Israel looked for increases in steroid prescriptions used to treat sudden hearing loss as vaccination with the Pfizer version of the shot became widespread in that country. Their conclusion: The vaccine might be associated with a slightly increased risk of sudden hearing loss, although if so, that risk is likely “very small” and the benefits of vaccination “outweigh its potential association” with the side effect.

Dr. Brenner agreed. “The evidence supports [the] clear public health benefit of COVID-19 vaccination, and the scale of those benefits dwarfs associations with hearing, which are of uncertain significance,” he said.

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

I have a secret. It’s one I think many physicians and nurses share. Sometimes, when I’m stretched too thin — overbooked, hungry, tired, fielding yet another appeal to an insurance company in the middle of a clinic day — I find myself momentarily resenting the patients on my schedule.

As soon as this happens, I feel immediate guilt. These are the worst moments of my day. Why the heck would I resent my patients? They’re the entire reason I’m there. I wouldn’t be a physician without patients to care for. I became a physician, and completed subspecialty training, to help patients. People.

Recently, I started thinking more about this emotion of resentment. What exactly is it, and where does it come from? Is what I’m feeling actually resentment? Or is it something else?

Two books I’ve recently read have helped me explore the complicated emotion of resentment and how it might play a role in burnout for both physicians and nurses.

First, Brené Brown’s most recent book, Atlas of the Heart: Mapping Meaningful Connection and the Language of Human Experience, provides a roadmap for 87 of our human emotions. (That’s right — 87!)

One emotion of the 87 that she shares has been a particular struggle for her has been our good old friend, resentment.

In her book, Dr Brown shares that she initially considered resentment to belong to the anger family of emotion. As I read this, I agreed. When I feel resentful, I associate that with feeling angry.

But she then writes about her discovery that resentment, in fact, belongs to the envy family. She explains how this discovery shook her world. I had to close the book for a moment at this point.

Wait a minute, I thought. If resentment is in the envy family, why do we (physicians) often find ourselves resenting patients who take up our time? What are we envious of?

I took some time to think about how this might be true. Could it be that I’m envious they have the time I don’t have? I want to have all the time in the world to answer their questions, but the reality is I don’t.

Or maybe it’s because sometimes I feel the patient is expecting me to offer them something more than is available. A cure when there might be none.

But is this actually true? Or is this my unrealistic expectation of myself?

Here’s how Brené Brown defines resentment in her book: “Resentment is the feeling of frustration, judgment, anger, ‘better than,’ and/or hidden envy related to perceived unfairness or injustice. It’s an emotion that we often experience when we fail to set boundaries or ask for what we need, or when expectations let us down because they were based on things we can’t control, like what other people think, what they feel, or how they’re going to react.”

Wow, I thought, Healthcare checks all of these boxes.

• Perceived unfairness of work schedules? Check.
• Perceived injustice? Of course — we see that in our dealings with insurance company denials every day.

But those are both extrinsic. What about the intrinsic factors she’s calling us out on here?

• Do we, as physicians, fail to set boundaries?
• Do we fail to ask for what we need?

Hard yes and yes. (Do we even know, as physicians, what our own boundaries are?)

And the last one:

• Do our expectations of how our clinic day will go let us down every day because they’re based on things we can’t control?

My brain had to repeat the critical parts of that: Expectations let us down when they’re based on things we can’t control.

But wait, my brain argued back; I’m the physician, I thought I was supposed to get to control things.

Next, the revelation: Could it be that a key to experiencing less resentment is accepting how much control we don’t have in a typical day?

And a corollary: How much does resentment factor into burnout? (To read more on my personal journey with burnout, see this piece).

It so happens that around this same time, I was reading another excellent book, Changing How We Think About Difficult Patients: A Guide for Physicians and Healthcare Professionals, by Joan Naidorf, DO.

Dr Naidorf is an emergency medicine physician of 30 years who wrote the book to “provid[e] insight and tools to manage our negative thoughts about difficult patients” and help “beleaguered colleagues…return to their benevolent guiding principles and find more enjoyment in their vitally important careers.”

As I read Dr Naidorf’s book, I thus did so with the mindset of wanting to further understand for myself where this specific emotion of resentment toward our “difficult” patients could come from and how to best understand it in order to get past it.

Dr. Naidorf writes, “Challenging patients will never stop appearing… You cannot change them or control them—the only person you can control is you.”

I wondered how much the resentment we might involuntarily feel at being asked to see a “difficult” patient has nothing to do with the patient but everything to do with it making us feel not in control of the situation.

Dr. Naidorf also writes, “Negative thoughts about challenging patients can cause, in otherwise capable clinicians, a sense of inadequacy and incompetence.”

Do we perhaps resent our challenging patients because of the negative thoughts they sometimes trigger in us? If so, how does this relate to envy, as Dr. Brown asserts resentment is tied to? Is it triggering us to feel inadequate?

“[Difficult patients] often make us question ourselves,” Dr. Naidorf writes, “and we need to feel comfortable with the answers.”

Again, the discrepancy between expectations and reality creates the negative emotion.

Or, as Dr. Naidorf writes, “What if you could stop judging others so harshly and accept them exactly as they are?”

Hmmm, I thought, then the cessation of harsh judgment and implementation of acceptance would have to apply to us too. The elusive concept of self-compassion.

Maybe the resentment/envy comes from us not allowing ourselves to behave in this way because to do so would allow too much vulnerability. Something most of us were conditioned to avoid to survive medical training.

Dr. Brown also writes about an “aha” moment she had in her struggle to understand resentment. “I’m not mad because you’re resting. I’m mad because I’m so bone tired and I want to rest. But, unlike you, I’m going to pretend that I don’t need to.”

I felt all too seen in that passage. Could it be my old nemesis, perfectionism, creeping its way back in? Is resentment the ugly stepsister to perfectionism?

Perhaps challenging patients can engender resentment because they make us feel like we’re not living up to our own unrealistic expectations. And in that case, we need to change our unrealistic expectations for ourselves.

Dr Naidorf’s book explores much more on the complex matter of what makes a “difficult” patient, but I chose to focus here only on the resentment piece as a tie-in to Dr. Brown’s book. I highly recommend both books for further reading to help physicians and nurses navigate the complex emotions our jobs can trigger.

Most importantly, recognizing that we have these transient negative emotions does not make us bad people or healthcare professionals. It only makes us human.

Dr. Lycette is medical director, Providence Oncology and Hematology Care Clinic, Seaside, Ore. She has disclosed having no relevant financial relationships.

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

I have a secret. It’s one I think many physicians and nurses share. Sometimes, when I’m stretched too thin — overbooked, hungry, tired, fielding yet another appeal to an insurance company in the middle of a clinic day — I find myself momentarily resenting the patients on my schedule.

As soon as this happens, I feel immediate guilt. These are the worst moments of my day. Why the heck would I resent my patients? They’re the entire reason I’m there. I wouldn’t be a physician without patients to care for. I became a physician, and completed subspecialty training, to help patients. People.

Recently, I started thinking more about this emotion of resentment. What exactly is it, and where does it come from? Is what I’m feeling actually resentment? Or is it something else?

Two books I’ve recently read have helped me explore the complicated emotion of resentment and how it might play a role in burnout for both physicians and nurses.

First, Brené Brown’s most recent book, Atlas of the Heart: Mapping Meaningful Connection and the Language of Human Experience, provides a roadmap for 87 of our human emotions. (That’s right — 87!)

One emotion of the 87 that she shares has been a particular struggle for her has been our good old friend, resentment.

In her book, Dr Brown shares that she initially considered resentment to belong to the anger family of emotion. As I read this, I agreed. When I feel resentful, I associate that with feeling angry.

But she then writes about her discovery that resentment, in fact, belongs to the envy family. She explains how this discovery shook her world. I had to close the book for a moment at this point.

Wait a minute, I thought. If resentment is in the envy family, why do we (physicians) often find ourselves resenting patients who take up our time? What are we envious of?

I took some time to think about how this might be true. Could it be that I’m envious they have the time I don’t have? I want to have all the time in the world to answer their questions, but the reality is I don’t.

Or maybe it’s because sometimes I feel the patient is expecting me to offer them something more than is available. A cure when there might be none.

But is this actually true? Or is this my unrealistic expectation of myself?

Here’s how Brené Brown defines resentment in her book: “Resentment is the feeling of frustration, judgment, anger, ‘better than,’ and/or hidden envy related to perceived unfairness or injustice. It’s an emotion that we often experience when we fail to set boundaries or ask for what we need, or when expectations let us down because they were based on things we can’t control, like what other people think, what they feel, or how they’re going to react.”

Wow, I thought, Healthcare checks all of these boxes.

• Perceived unfairness of work schedules? Check.
• Perceived injustice? Of course — we see that in our dealings with insurance company denials every day.

But those are both extrinsic. What about the intrinsic factors she’s calling us out on here?

• Do we, as physicians, fail to set boundaries?
• Do we fail to ask for what we need?

Hard yes and yes. (Do we even know, as physicians, what our own boundaries are?)

And the last one:

• Do our expectations of how our clinic day will go let us down every day because they’re based on things we can’t control?

My brain had to repeat the critical parts of that: Expectations let us down when they’re based on things we can’t control.

But wait, my brain argued back; I’m the physician, I thought I was supposed to get to control things.

Next, the revelation: Could it be that a key to experiencing less resentment is accepting how much control we don’t have in a typical day?

And a corollary: How much does resentment factor into burnout? (To read more on my personal journey with burnout, see this piece).

It so happens that around this same time, I was reading another excellent book, Changing How We Think About Difficult Patients: A Guide for Physicians and Healthcare Professionals, by Joan Naidorf, DO.

Dr Naidorf is an emergency medicine physician of 30 years who wrote the book to “provid[e] insight and tools to manage our negative thoughts about difficult patients” and help “beleaguered colleagues…return to their benevolent guiding principles and find more enjoyment in their vitally important careers.”

As I read Dr Naidorf’s book, I thus did so with the mindset of wanting to further understand for myself where this specific emotion of resentment toward our “difficult” patients could come from and how to best understand it in order to get past it.

Dr. Naidorf writes, “Challenging patients will never stop appearing… You cannot change them or control them—the only person you can control is you.”

I wondered how much the resentment we might involuntarily feel at being asked to see a “difficult” patient has nothing to do with the patient but everything to do with it making us feel not in control of the situation.

Dr. Naidorf also writes, “Negative thoughts about challenging patients can cause, in otherwise capable clinicians, a sense of inadequacy and incompetence.”

Do we perhaps resent our challenging patients because of the negative thoughts they sometimes trigger in us? If so, how does this relate to envy, as Dr. Brown asserts resentment is tied to? Is it triggering us to feel inadequate?

“[Difficult patients] often make us question ourselves,” Dr. Naidorf writes, “and we need to feel comfortable with the answers.”

Again, the discrepancy between expectations and reality creates the negative emotion.

Or, as Dr. Naidorf writes, “What if you could stop judging others so harshly and accept them exactly as they are?”

Hmmm, I thought, then the cessation of harsh judgment and implementation of acceptance would have to apply to us too. The elusive concept of self-compassion.

Maybe the resentment/envy comes from us not allowing ourselves to behave in this way because to do so would allow too much vulnerability. Something most of us were conditioned to avoid to survive medical training.

Dr. Brown also writes about an “aha” moment she had in her struggle to understand resentment. “I’m not mad because you’re resting. I’m mad because I’m so bone tired and I want to rest. But, unlike you, I’m going to pretend that I don’t need to.”

I felt all too seen in that passage. Could it be my old nemesis, perfectionism, creeping its way back in? Is resentment the ugly stepsister to perfectionism?

Perhaps challenging patients can engender resentment because they make us feel like we’re not living up to our own unrealistic expectations. And in that case, we need to change our unrealistic expectations for ourselves.

Dr Naidorf’s book explores much more on the complex matter of what makes a “difficult” patient, but I chose to focus here only on the resentment piece as a tie-in to Dr. Brown’s book. I highly recommend both books for further reading to help physicians and nurses navigate the complex emotions our jobs can trigger.

Most importantly, recognizing that we have these transient negative emotions does not make us bad people or healthcare professionals. It only makes us human.

Dr. Lycette is medical director, Providence Oncology and Hematology Care Clinic, Seaside, Ore. She has disclosed having no relevant financial relationships.

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

I have a secret. It’s one I think many physicians and nurses share. Sometimes, when I’m stretched too thin — overbooked, hungry, tired, fielding yet another appeal to an insurance company in the middle of a clinic day — I find myself momentarily resenting the patients on my schedule.

As soon as this happens, I feel immediate guilt. These are the worst moments of my day. Why the heck would I resent my patients? They’re the entire reason I’m there. I wouldn’t be a physician without patients to care for. I became a physician, and completed subspecialty training, to help patients. People.

Recently, I started thinking more about this emotion of resentment. What exactly is it, and where does it come from? Is what I’m feeling actually resentment? Or is it something else?

Two books I’ve recently read have helped me explore the complicated emotion of resentment and how it might play a role in burnout for both physicians and nurses.

First, Brené Brown’s most recent book, Atlas of the Heart: Mapping Meaningful Connection and the Language of Human Experience, provides a roadmap for 87 of our human emotions. (That’s right — 87!)

One emotion of the 87 that she shares has been a particular struggle for her has been our good old friend, resentment.

In her book, Dr Brown shares that she initially considered resentment to belong to the anger family of emotion. As I read this, I agreed. When I feel resentful, I associate that with feeling angry.

But she then writes about her discovery that resentment, in fact, belongs to the envy family. She explains how this discovery shook her world. I had to close the book for a moment at this point.

Wait a minute, I thought. If resentment is in the envy family, why do we (physicians) often find ourselves resenting patients who take up our time? What are we envious of?

I took some time to think about how this might be true. Could it be that I’m envious they have the time I don’t have? I want to have all the time in the world to answer their questions, but the reality is I don’t.

Or maybe it’s because sometimes I feel the patient is expecting me to offer them something more than is available. A cure when there might be none.

But is this actually true? Or is this my unrealistic expectation of myself?

Here’s how Brené Brown defines resentment in her book: “Resentment is the feeling of frustration, judgment, anger, ‘better than,’ and/or hidden envy related to perceived unfairness or injustice. It’s an emotion that we often experience when we fail to set boundaries or ask for what we need, or when expectations let us down because they were based on things we can’t control, like what other people think, what they feel, or how they’re going to react.”

Wow, I thought, Healthcare checks all of these boxes.

• Perceived unfairness of work schedules? Check.
• Perceived injustice? Of course — we see that in our dealings with insurance company denials every day.

But those are both extrinsic. What about the intrinsic factors she’s calling us out on here?

• Do we, as physicians, fail to set boundaries?
• Do we fail to ask for what we need?

Hard yes and yes. (Do we even know, as physicians, what our own boundaries are?)

And the last one:

• Do our expectations of how our clinic day will go let us down every day because they’re based on things we can’t control?

My brain had to repeat the critical parts of that: Expectations let us down when they’re based on things we can’t control.

But wait, my brain argued back; I’m the physician, I thought I was supposed to get to control things.

Next, the revelation: Could it be that a key to experiencing less resentment is accepting how much control we don’t have in a typical day?

And a corollary: How much does resentment factor into burnout? (To read more on my personal journey with burnout, see this piece).

It so happens that around this same time, I was reading another excellent book, Changing How We Think About Difficult Patients: A Guide for Physicians and Healthcare Professionals, by Joan Naidorf, DO.

Dr Naidorf is an emergency medicine physician of 30 years who wrote the book to “provid[e] insight and tools to manage our negative thoughts about difficult patients” and help “beleaguered colleagues…return to their benevolent guiding principles and find more enjoyment in their vitally important careers.”

As I read Dr Naidorf’s book, I thus did so with the mindset of wanting to further understand for myself where this specific emotion of resentment toward our “difficult” patients could come from and how to best understand it in order to get past it.

Dr. Naidorf writes, “Challenging patients will never stop appearing… You cannot change them or control them—the only person you can control is you.”

I wondered how much the resentment we might involuntarily feel at being asked to see a “difficult” patient has nothing to do with the patient but everything to do with it making us feel not in control of the situation.

Dr. Naidorf also writes, “Negative thoughts about challenging patients can cause, in otherwise capable clinicians, a sense of inadequacy and incompetence.”

Do we perhaps resent our challenging patients because of the negative thoughts they sometimes trigger in us? If so, how does this relate to envy, as Dr. Brown asserts resentment is tied to? Is it triggering us to feel inadequate?

“[Difficult patients] often make us question ourselves,” Dr. Naidorf writes, “and we need to feel comfortable with the answers.”

Again, the discrepancy between expectations and reality creates the negative emotion.

Or, as Dr. Naidorf writes, “What if you could stop judging others so harshly and accept them exactly as they are?”

Hmmm, I thought, then the cessation of harsh judgment and implementation of acceptance would have to apply to us too. The elusive concept of self-compassion.

Maybe the resentment/envy comes from us not allowing ourselves to behave in this way because to do so would allow too much vulnerability. Something most of us were conditioned to avoid to survive medical training.

Dr. Brown also writes about an “aha” moment she had in her struggle to understand resentment. “I’m not mad because you’re resting. I’m mad because I’m so bone tired and I want to rest. But, unlike you, I’m going to pretend that I don’t need to.”

I felt all too seen in that passage. Could it be my old nemesis, perfectionism, creeping its way back in? Is resentment the ugly stepsister to perfectionism?

Perhaps challenging patients can engender resentment because they make us feel like we’re not living up to our own unrealistic expectations. And in that case, we need to change our unrealistic expectations for ourselves.

Dr Naidorf’s book explores much more on the complex matter of what makes a “difficult” patient, but I chose to focus here only on the resentment piece as a tie-in to Dr. Brown’s book. I highly recommend both books for further reading to help physicians and nurses navigate the complex emotions our jobs can trigger.

Most importantly, recognizing that we have these transient negative emotions does not make us bad people or healthcare professionals. It only makes us human.

Dr. Lycette is medical director, Providence Oncology and Hematology Care Clinic, Seaside, Ore. She has disclosed having no relevant financial relationships.

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

What is the best test for the diagnosis of acute hepatitis A infection?

Continue to the answer...

The single best test for the diagnosis of acute hepatitis A infection is detection of immunoglobulin M (IgM)–specific antibody to the virus.

What is the best test for the diagnosis of acute hepatitis A infection?

Continue to the answer...

The single best test for the diagnosis of acute hepatitis A infection is detection of immunoglobulin M (IgM)–specific antibody to the virus.

What is the best test for the diagnosis of acute hepatitis A infection?

Continue to the answer...

The single best test for the diagnosis of acute hepatitis A infection is detection of immunoglobulin M (IgM)–specific antibody to the virus.

The Rome IV criteria assist physicians in diagnosing functional gastrointestinal disorders (FGID) such as irritable bowel syndrome (IBS), but the wide-ranging symptoms included don’t do a good job of distinguishing all disorders. The Rome Foundation has proposed changes to ROME IV, including reduction in the required duration and frequency of symptoms, and a greater focus on whether symptoms are bothersome.

In a review published in Gastroenterology, researchers suggest that these changes can improve the accuracy of IBS diagnoses. The researchers maintain that Rome IV identifies IBS patients with severe symptoms and a high burden of psychological comorbidity.

The review authors analyzed data from two previous studies. One was a cross-sectional survey of 1,375 self-reported IBS patients in the United Kingdom. When the researchers applied Rome IV criteria versus the earlier Rome III criteria, the proportion of patients identified as having IBS dropped from 79% to 59%. Those identified with IBS by Rome IV had more severe symptoms and worse psychological health. When the researchers applied the modified Rome IV criteria for IBS to the cross-sectional survey, they found that 92.5% met the criteria. Compared to those who did not meet the criteria for IBS by the modified standard, those who did were more likely to have anxiety (49.0% versus 37.3%; P = .001), somatization (47.5% vs. 28.4%; P < .001), and gastrointestinal symptom-specific anxiety (33.8% vs. 15.7%; P < .001). There were no differences in the frequency of depression or severe symptoms.

In a second study, the researchers collected prospective data on 577 consecutive UK patients who visited an IBS clinic. Compared to the reference definition of IBS of lower abdominal pain with altered stool form or frequency, the Rome IV criteria had a sensitivity of 82.4% and a specificity of 82.9%. The positive likelihood ratio was 4.82 (95% confidence interval, 3.30-7.28) and the negative likelihood ratio was 0.21 (95% CI, 0.17-0.16). When the researchers applied the modified Rome IV criteria, 90.6% of patients were identified as having IBS. Compared to the reference standard, the sensitivity of modified Rome IV was 99.1%, and the specificity was 42.7%. The positive LR was 1.73 (95% CI, 1.48-2.02) and the negative LR was 0.02 (95% CI, 0.01-0.06).

Although the new data are of use to specialists, primary care physicians are often only vaguely aware of the Rome criteria, according to John Wilkinson, MD, who was asked to comment on the study. “As important as diagnosing IBS may be, it’s just as important to recognize that the patient has a FGID and does not benefit from continued testing, but rather naming the condition, reassuring the patient, and working together for ongoing self-management using primarily traditional interventions with proven track records,” said Dr. Wilkinson, a consultant in family medicine at the Mayo Clinic, Rochester, Minn.

He noted that physicians may be reluctant to make a diagnosis of IBS, in part because of pushback from patients who may feel that an IBS diagnosis is inadequate. “People have heard of it, usually, and often in a kind of a negative context. ‘Isn’t that the thing where they say that it’s all in your head?’ So, both doctors and patients are [not] particularly happy with the diagnosis.”

Nevertheless, making a diagnosis helps patients begin to manage their condition through diet and lifestyle changes. “I think the most important thing is to not continue to do testing, but talk to people about what they have, and then kind of move on (to management),” said Dr. Wilkinson.

Patients often go through periods of good health, with occasional flareups that result in urgent or emergency care. Tests often return normal results. “So, they are told a variety of things: There’s nothing wrong with you or we can’t find an answer. And this goes on and on over the years, and then finally somebody says, ‘Well, we can’t find an answer, so it must be irritable bowel,’ which is completely unsatisfactory,” said Dr. Wilkinson.

He feels that there is often an over-emphasis on testing and that physicians too often regard IBS as a disease of exclusion. “If it meets some general criteria, and you’ve excluded a few things, you don’t need to do other tests. The diagnosis of exclusion is an idea that is commonly held by a lot of physicians in primary care,” he said.

Dr. Wilkinson called for physicians to become more comfortable making a diagnosis of IBS, “and then be comfortable working with patients and explaining that this is a real thing. It isn’t imaginary. There’s a lot we don’t understand about it. There are things you can do to treat it, but it’s not exactly the model that most people think of where I go to the doctor, do a blood test that confirms that that’s what it is, and then you cure it. It’s a lot of work to have the conversation and work with these patients.”

The authors concluded that the modified criteria, with increased sensitivity even with less specificity, were useful. “The high sensitivity seen with the modified criteria means if these are not met at the outset, then a final diagnosis of IBS is highly unlikely, and further investigation should be pursued.” Further research is required to confirm the results.

The authors and Dr. Wilkinson have no relevant financial disclosures.

The Rome IV criteria assist physicians in diagnosing functional gastrointestinal disorders (FGID) such as irritable bowel syndrome (IBS), but the wide-ranging symptoms included don’t do a good job of distinguishing all disorders. The Rome Foundation has proposed changes to ROME IV, including reduction in the required duration and frequency of symptoms, and a greater focus on whether symptoms are bothersome.

In a review published in Gastroenterology, researchers suggest that these changes can improve the accuracy of IBS diagnoses. The researchers maintain that Rome IV identifies IBS patients with severe symptoms and a high burden of psychological comorbidity.

The review authors analyzed data from two previous studies. One was a cross-sectional survey of 1,375 self-reported IBS patients in the United Kingdom. When the researchers applied Rome IV criteria versus the earlier Rome III criteria, the proportion of patients identified as having IBS dropped from 79% to 59%. Those identified with IBS by Rome IV had more severe symptoms and worse psychological health. When the researchers applied the modified Rome IV criteria for IBS to the cross-sectional survey, they found that 92.5% met the criteria. Compared to those who did not meet the criteria for IBS by the modified standard, those who did were more likely to have anxiety (49.0% versus 37.3%; P = .001), somatization (47.5% vs. 28.4%; P < .001), and gastrointestinal symptom-specific anxiety (33.8% vs. 15.7%; P < .001). There were no differences in the frequency of depression or severe symptoms.

In a second study, the researchers collected prospective data on 577 consecutive UK patients who visited an IBS clinic. Compared to the reference definition of IBS of lower abdominal pain with altered stool form or frequency, the Rome IV criteria had a sensitivity of 82.4% and a specificity of 82.9%. The positive likelihood ratio was 4.82 (95% confidence interval, 3.30-7.28) and the negative likelihood ratio was 0.21 (95% CI, 0.17-0.16). When the researchers applied the modified Rome IV criteria, 90.6% of patients were identified as having IBS. Compared to the reference standard, the sensitivity of modified Rome IV was 99.1%, and the specificity was 42.7%. The positive LR was 1.73 (95% CI, 1.48-2.02) and the negative LR was 0.02 (95% CI, 0.01-0.06).

Although the new data are of use to specialists, primary care physicians are often only vaguely aware of the Rome criteria, according to John Wilkinson, MD, who was asked to comment on the study. “As important as diagnosing IBS may be, it’s just as important to recognize that the patient has a FGID and does not benefit from continued testing, but rather naming the condition, reassuring the patient, and working together for ongoing self-management using primarily traditional interventions with proven track records,” said Dr. Wilkinson, a consultant in family medicine at the Mayo Clinic, Rochester, Minn.

He noted that physicians may be reluctant to make a diagnosis of IBS, in part because of pushback from patients who may feel that an IBS diagnosis is inadequate. “People have heard of it, usually, and often in a kind of a negative context. ‘Isn’t that the thing where they say that it’s all in your head?’ So, both doctors and patients are [not] particularly happy with the diagnosis.”

Nevertheless, making a diagnosis helps patients begin to manage their condition through diet and lifestyle changes. “I think the most important thing is to not continue to do testing, but talk to people about what they have, and then kind of move on (to management),” said Dr. Wilkinson.

Patients often go through periods of good health, with occasional flareups that result in urgent or emergency care. Tests often return normal results. “So, they are told a variety of things: There’s nothing wrong with you or we can’t find an answer. And this goes on and on over the years, and then finally somebody says, ‘Well, we can’t find an answer, so it must be irritable bowel,’ which is completely unsatisfactory,” said Dr. Wilkinson.

He feels that there is often an over-emphasis on testing and that physicians too often regard IBS as a disease of exclusion. “If it meets some general criteria, and you’ve excluded a few things, you don’t need to do other tests. The diagnosis of exclusion is an idea that is commonly held by a lot of physicians in primary care,” he said.

Dr. Wilkinson called for physicians to become more comfortable making a diagnosis of IBS, “and then be comfortable working with patients and explaining that this is a real thing. It isn’t imaginary. There’s a lot we don’t understand about it. There are things you can do to treat it, but it’s not exactly the model that most people think of where I go to the doctor, do a blood test that confirms that that’s what it is, and then you cure it. It’s a lot of work to have the conversation and work with these patients.”

The authors concluded that the modified criteria, with increased sensitivity even with less specificity, were useful. “The high sensitivity seen with the modified criteria means if these are not met at the outset, then a final diagnosis of IBS is highly unlikely, and further investigation should be pursued.” Further research is required to confirm the results.

The authors and Dr. Wilkinson have no relevant financial disclosures.

The Rome IV criteria assist physicians in diagnosing functional gastrointestinal disorders (FGID) such as irritable bowel syndrome (IBS), but the wide-ranging symptoms included don’t do a good job of distinguishing all disorders. The Rome Foundation has proposed changes to ROME IV, including reduction in the required duration and frequency of symptoms, and a greater focus on whether symptoms are bothersome.

In a review published in Gastroenterology, researchers suggest that these changes can improve the accuracy of IBS diagnoses. The researchers maintain that Rome IV identifies IBS patients with severe symptoms and a high burden of psychological comorbidity.

The review authors analyzed data from two previous studies. One was a cross-sectional survey of 1,375 self-reported IBS patients in the United Kingdom. When the researchers applied Rome IV criteria versus the earlier Rome III criteria, the proportion of patients identified as having IBS dropped from 79% to 59%. Those identified with IBS by Rome IV had more severe symptoms and worse psychological health. When the researchers applied the modified Rome IV criteria for IBS to the cross-sectional survey, they found that 92.5% met the criteria. Compared to those who did not meet the criteria for IBS by the modified standard, those who did were more likely to have anxiety (49.0% versus 37.3%; P = .001), somatization (47.5% vs. 28.4%; P < .001), and gastrointestinal symptom-specific anxiety (33.8% vs. 15.7%; P < .001). There were no differences in the frequency of depression or severe symptoms.

In a second study, the researchers collected prospective data on 577 consecutive UK patients who visited an IBS clinic. Compared to the reference definition of IBS of lower abdominal pain with altered stool form or frequency, the Rome IV criteria had a sensitivity of 82.4% and a specificity of 82.9%. The positive likelihood ratio was 4.82 (95% confidence interval, 3.30-7.28) and the negative likelihood ratio was 0.21 (95% CI, 0.17-0.16). When the researchers applied the modified Rome IV criteria, 90.6% of patients were identified as having IBS. Compared to the reference standard, the sensitivity of modified Rome IV was 99.1%, and the specificity was 42.7%. The positive LR was 1.73 (95% CI, 1.48-2.02) and the negative LR was 0.02 (95% CI, 0.01-0.06).

Although the new data are of use to specialists, primary care physicians are often only vaguely aware of the Rome criteria, according to John Wilkinson, MD, who was asked to comment on the study. “As important as diagnosing IBS may be, it’s just as important to recognize that the patient has a FGID and does not benefit from continued testing, but rather naming the condition, reassuring the patient, and working together for ongoing self-management using primarily traditional interventions with proven track records,” said Dr. Wilkinson, a consultant in family medicine at the Mayo Clinic, Rochester, Minn.

He noted that physicians may be reluctant to make a diagnosis of IBS, in part because of pushback from patients who may feel that an IBS diagnosis is inadequate. “People have heard of it, usually, and often in a kind of a negative context. ‘Isn’t that the thing where they say that it’s all in your head?’ So, both doctors and patients are [not] particularly happy with the diagnosis.”

Nevertheless, making a diagnosis helps patients begin to manage their condition through diet and lifestyle changes. “I think the most important thing is to not continue to do testing, but talk to people about what they have, and then kind of move on (to management),” said Dr. Wilkinson.

Patients often go through periods of good health, with occasional flareups that result in urgent or emergency care. Tests often return normal results. “So, they are told a variety of things: There’s nothing wrong with you or we can’t find an answer. And this goes on and on over the years, and then finally somebody says, ‘Well, we can’t find an answer, so it must be irritable bowel,’ which is completely unsatisfactory,” said Dr. Wilkinson.

He feels that there is often an over-emphasis on testing and that physicians too often regard IBS as a disease of exclusion. “If it meets some general criteria, and you’ve excluded a few things, you don’t need to do other tests. The diagnosis of exclusion is an idea that is commonly held by a lot of physicians in primary care,” he said.

Dr. Wilkinson called for physicians to become more comfortable making a diagnosis of IBS, “and then be comfortable working with patients and explaining that this is a real thing. It isn’t imaginary. There’s a lot we don’t understand about it. There are things you can do to treat it, but it’s not exactly the model that most people think of where I go to the doctor, do a blood test that confirms that that’s what it is, and then you cure it. It’s a lot of work to have the conversation and work with these patients.”

The authors concluded that the modified criteria, with increased sensitivity even with less specificity, were useful. “The high sensitivity seen with the modified criteria means if these are not met at the outset, then a final diagnosis of IBS is highly unlikely, and further investigation should be pursued.” Further research is required to confirm the results.

The authors and Dr. Wilkinson have no relevant financial disclosures.

Nasogastric tubes. Foley catheter kits. Hydrogel anti-burn bandages and transfusion bags. Heparin, atropine, tramadol.

These items are just a few of some two dozen critical medical supplies that physicians in Ukraine desperately need, according to Leo Wolansky, MD, a Ukrainian-American radiologist and president of the Ukrainian Medical Association of North America (UMANA).

Dr. Wolansky founded a teaching program with an organization called Friends of Radiology in Ukraine in 1996 and has been running courses for specialists there ever since. He last visited the country in 2019, before the COVID-19 pandemic, but has remained in contact with his medical colleagues by phone and email. Over the weekend of Feb. 26-27, UMANA held a fundraiser for Ukraine, raising more than $17,000.

This news organization spoke with Dr. Wolansky about the situation for his fellow physicians in the war-torn country.

Question: Where is your family from, and do you have relatives in the country now?

Dr. Wolansky: My family is from two different parts of Ukraine. My mother was from central Ukraine. Her father, Ivan Sharyj, was part of the students’ militia that fought at the famous battle of Kruty in 1918. Four hundred Ukrainian militia fought against 5,000 professional Russian soldiers and were massacred. He later wrote the first eye-witness account. Afterwards, he had the opportunity to flee Ukraine but chose to stay under a pseudonym. Eventually, during Stalin’s purges [1929-1933], the regime found him, arrested him, tortured him, and executed him. My mother was seven when she saw her father arrested, never to return home. My father was from Western Ukraine, which did not have a long history of Russian occupation. His mother’s family was very patriotic; her first cousin, Stepan Vytvytskyi, eventually became the president of Ukraine in exile from 1955-1964.

I have second and more distant cousins in Kyiv. My wife has first cousins in Western Ukraine. They and my doctor colleagues are suffering greatly but are ready to die for their freedom.

Question: The Russian invasion of Ukraine has put tremendous stress on the Ukrainian people, including the country’s medical professionals. How do doctors in these kinds of situations handle casualties they can’t prevent? How do they work around that sense that everything is out of their control?

Dr. Wolansky: A lot of infrastructural things are being disrupted; there are limitations that you wouldn’t normally encounter. Ukraine has been developing a lot of sophisticated medical technology, but it still has room to grow. Under these circumstances, when there are bombs going off and transportation is being disrupted, it creates very new and significant obstacles to surmount. It still has not risen to massive casualties, and we can just pray that it does not, but in times of war, a very different kind of medicine is practiced.

But remember, Ukraine has been at war since 2014, when Russia took Crimea and invaded the Eastern provinces. The doctors there are not unfamiliar with war injuries. At our conferences in Ukraine, I have seen radiological presentations of injuries sustained in war – gunshots, fractures, and amputations – as well as other kinds of traumatic injuries. You’re going for a kind of more emergent treatment: to transfuse, to maintain peoples’ blood pressure, put bandages on, sterilize and sanitize wounds to prevent infections. I imagine there will be many field hospitals set up between now and the next few weeks to deal with the acute injuries.

Question: Ukraine has struggled with high rates of HIV and multidrug-resistant tuberculosis, as well as a lack of resources for treating patients with mental illness. Meanwhile, the country has had more that 5 million cases of COVID-19 and an estimated 112,000 deaths from the disease. Are you concerned about an exacerbation of infection rates, including of COVID, particularly among refugees and those who become homeless?

Dr. Wolansky: Because COVID ran pretty rampant in Ukraine, I think that – at a high cost – there is a level of natural immunity in the population. And the weather is going to be getting warmer soon, and respiratory viruses are cyclic in nature, so I don’t know if that’s going to be a big complicating factor. However, people get sick all the time, and the prognosis for them is going to be much worse than it otherwise might be. If you have a heart attack, your chances were way better when the roads were clear and people weren’t shooting at you.

Right now, it’s very regional where the infrastructure is being destroyed. The West, where I used to go, is in much better shape than the East because it has not been the focus of Russian attacks. But Kyiv could turn into a very big humanitarian crisis very quickly if there’s no electricity, no water. All sorts of medical conditions could be greatly exacerbated, and some new health crises could arise from water contamination, bombs causing buildings to collapse, and other problems. Whatever the illness is, it’s going to be harder to take care of it.

Questions: Doctors Without Borders announced that it was suspending its operations in Ukraine because of the invasion – missions that included HIV care in Severodonetsk, tuberculosis care in Zhytomyr, and improving health care access in Donetsk in eastern Ukraine, according to the aid group. What do doctors in Ukraine need most acutely now, other than peace?

Dr. Wolansky: Obviously, money is valuable, and military protection, which would prevent additional damage to their infrastructure. One thing that bears mentioning. There’s been a fair amount of coverage of this, but I’ve witnessed it first-hand: The Ukrainian people are fiercely patriotic, and there’s really no way their spirit can be conquered. The USSR invaded Afghanistan, and after years of thinking they were in command, they left because they could no longer take the guerilla warfare and the constant sniper attacks. Ukraine’s population is many times larger than Afghanistan’s; there’s no way they can be subdued. And remember, the Ukrainian people have been free for 30 years – generations of young people have known no other way of life. They are not going to give that up.

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

Nasogastric tubes. Foley catheter kits. Hydrogel anti-burn bandages and transfusion bags. Heparin, atropine, tramadol.

These items are just a few of some two dozen critical medical supplies that physicians in Ukraine desperately need, according to Leo Wolansky, MD, a Ukrainian-American radiologist and president of the Ukrainian Medical Association of North America (UMANA).

Dr. Wolansky founded a teaching program with an organization called Friends of Radiology in Ukraine in 1996 and has been running courses for specialists there ever since. He last visited the country in 2019, before the COVID-19 pandemic, but has remained in contact with his medical colleagues by phone and email. Over the weekend of Feb. 26-27, UMANA held a fundraiser for Ukraine, raising more than $17,000.

This news organization spoke with Dr. Wolansky about the situation for his fellow physicians in the war-torn country.

Question: Where is your family from, and do you have relatives in the country now?

Dr. Wolansky: My family is from two different parts of Ukraine. My mother was from central Ukraine. Her father, Ivan Sharyj, was part of the students’ militia that fought at the famous battle of Kruty in 1918. Four hundred Ukrainian militia fought against 5,000 professional Russian soldiers and were massacred. He later wrote the first eye-witness account. Afterwards, he had the opportunity to flee Ukraine but chose to stay under a pseudonym. Eventually, during Stalin’s purges [1929-1933], the regime found him, arrested him, tortured him, and executed him. My mother was seven when she saw her father arrested, never to return home. My father was from Western Ukraine, which did not have a long history of Russian occupation. His mother’s family was very patriotic; her first cousin, Stepan Vytvytskyi, eventually became the president of Ukraine in exile from 1955-1964.

I have second and more distant cousins in Kyiv. My wife has first cousins in Western Ukraine. They and my doctor colleagues are suffering greatly but are ready to die for their freedom.

Question: The Russian invasion of Ukraine has put tremendous stress on the Ukrainian people, including the country’s medical professionals. How do doctors in these kinds of situations handle casualties they can’t prevent? How do they work around that sense that everything is out of their control?

Dr. Wolansky: A lot of infrastructural things are being disrupted; there are limitations that you wouldn’t normally encounter. Ukraine has been developing a lot of sophisticated medical technology, but it still has room to grow. Under these circumstances, when there are bombs going off and transportation is being disrupted, it creates very new and significant obstacles to surmount. It still has not risen to massive casualties, and we can just pray that it does not, but in times of war, a very different kind of medicine is practiced.

But remember, Ukraine has been at war since 2014, when Russia took Crimea and invaded the Eastern provinces. The doctors there are not unfamiliar with war injuries. At our conferences in Ukraine, I have seen radiological presentations of injuries sustained in war – gunshots, fractures, and amputations – as well as other kinds of traumatic injuries. You’re going for a kind of more emergent treatment: to transfuse, to maintain peoples’ blood pressure, put bandages on, sterilize and sanitize wounds to prevent infections. I imagine there will be many field hospitals set up between now and the next few weeks to deal with the acute injuries.

Question: Ukraine has struggled with high rates of HIV and multidrug-resistant tuberculosis, as well as a lack of resources for treating patients with mental illness. Meanwhile, the country has had more that 5 million cases of COVID-19 and an estimated 112,000 deaths from the disease. Are you concerned about an exacerbation of infection rates, including of COVID, particularly among refugees and those who become homeless?

Dr. Wolansky: Because COVID ran pretty rampant in Ukraine, I think that – at a high cost – there is a level of natural immunity in the population. And the weather is going to be getting warmer soon, and respiratory viruses are cyclic in nature, so I don’t know if that’s going to be a big complicating factor. However, people get sick all the time, and the prognosis for them is going to be much worse than it otherwise might be. If you have a heart attack, your chances were way better when the roads were clear and people weren’t shooting at you.

Right now, it’s very regional where the infrastructure is being destroyed. The West, where I used to go, is in much better shape than the East because it has not been the focus of Russian attacks. But Kyiv could turn into a very big humanitarian crisis very quickly if there’s no electricity, no water. All sorts of medical conditions could be greatly exacerbated, and some new health crises could arise from water contamination, bombs causing buildings to collapse, and other problems. Whatever the illness is, it’s going to be harder to take care of it.

Questions: Doctors Without Borders announced that it was suspending its operations in Ukraine because of the invasion – missions that included HIV care in Severodonetsk, tuberculosis care in Zhytomyr, and improving health care access in Donetsk in eastern Ukraine, according to the aid group. What do doctors in Ukraine need most acutely now, other than peace?

Dr. Wolansky: Obviously, money is valuable, and military protection, which would prevent additional damage to their infrastructure. One thing that bears mentioning. There’s been a fair amount of coverage of this, but I’ve witnessed it first-hand: The Ukrainian people are fiercely patriotic, and there’s really no way their spirit can be conquered. The USSR invaded Afghanistan, and after years of thinking they were in command, they left because they could no longer take the guerilla warfare and the constant sniper attacks. Ukraine’s population is many times larger than Afghanistan’s; there’s no way they can be subdued. And remember, the Ukrainian people have been free for 30 years – generations of young people have known no other way of life. They are not going to give that up.

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

Nasogastric tubes. Foley catheter kits. Hydrogel anti-burn bandages and transfusion bags. Heparin, atropine, tramadol.

These items are just a few of some two dozen critical medical supplies that physicians in Ukraine desperately need, according to Leo Wolansky, MD, a Ukrainian-American radiologist and president of the Ukrainian Medical Association of North America (UMANA).

Dr. Wolansky founded a teaching program with an organization called Friends of Radiology in Ukraine in 1996 and has been running courses for specialists there ever since. He last visited the country in 2019, before the COVID-19 pandemic, but has remained in contact with his medical colleagues by phone and email. Over the weekend of Feb. 26-27, UMANA held a fundraiser for Ukraine, raising more than $17,000.

This news organization spoke with Dr. Wolansky about the situation for his fellow physicians in the war-torn country.

Question: Where is your family from, and do you have relatives in the country now?

Dr. Wolansky: My family is from two different parts of Ukraine. My mother was from central Ukraine. Her father, Ivan Sharyj, was part of the students’ militia that fought at the famous battle of Kruty in 1918. Four hundred Ukrainian militia fought against 5,000 professional Russian soldiers and were massacred. He later wrote the first eye-witness account. Afterwards, he had the opportunity to flee Ukraine but chose to stay under a pseudonym. Eventually, during Stalin’s purges [1929-1933], the regime found him, arrested him, tortured him, and executed him. My mother was seven when she saw her father arrested, never to return home. My father was from Western Ukraine, which did not have a long history of Russian occupation. His mother’s family was very patriotic; her first cousin, Stepan Vytvytskyi, eventually became the president of Ukraine in exile from 1955-1964.

I have second and more distant cousins in Kyiv. My wife has first cousins in Western Ukraine. They and my doctor colleagues are suffering greatly but are ready to die for their freedom.

Question: The Russian invasion of Ukraine has put tremendous stress on the Ukrainian people, including the country’s medical professionals. How do doctors in these kinds of situations handle casualties they can’t prevent? How do they work around that sense that everything is out of their control?

Dr. Wolansky: A lot of infrastructural things are being disrupted; there are limitations that you wouldn’t normally encounter. Ukraine has been developing a lot of sophisticated medical technology, but it still has room to grow. Under these circumstances, when there are bombs going off and transportation is being disrupted, it creates very new and significant obstacles to surmount. It still has not risen to massive casualties, and we can just pray that it does not, but in times of war, a very different kind of medicine is practiced.

But remember, Ukraine has been at war since 2014, when Russia took Crimea and invaded the Eastern provinces. The doctors there are not unfamiliar with war injuries. At our conferences in Ukraine, I have seen radiological presentations of injuries sustained in war – gunshots, fractures, and amputations – as well as other kinds of traumatic injuries. You’re going for a kind of more emergent treatment: to transfuse, to maintain peoples’ blood pressure, put bandages on, sterilize and sanitize wounds to prevent infections. I imagine there will be many field hospitals set up between now and the next few weeks to deal with the acute injuries.

Question: Ukraine has struggled with high rates of HIV and multidrug-resistant tuberculosis, as well as a lack of resources for treating patients with mental illness. Meanwhile, the country has had more that 5 million cases of COVID-19 and an estimated 112,000 deaths from the disease. Are you concerned about an exacerbation of infection rates, including of COVID, particularly among refugees and those who become homeless?

Dr. Wolansky: Because COVID ran pretty rampant in Ukraine, I think that – at a high cost – there is a level of natural immunity in the population. And the weather is going to be getting warmer soon, and respiratory viruses are cyclic in nature, so I don’t know if that’s going to be a big complicating factor. However, people get sick all the time, and the prognosis for them is going to be much worse than it otherwise might be. If you have a heart attack, your chances were way better when the roads were clear and people weren’t shooting at you.

Right now, it’s very regional where the infrastructure is being destroyed. The West, where I used to go, is in much better shape than the East because it has not been the focus of Russian attacks. But Kyiv could turn into a very big humanitarian crisis very quickly if there’s no electricity, no water. All sorts of medical conditions could be greatly exacerbated, and some new health crises could arise from water contamination, bombs causing buildings to collapse, and other problems. Whatever the illness is, it’s going to be harder to take care of it.

Questions: Doctors Without Borders announced that it was suspending its operations in Ukraine because of the invasion – missions that included HIV care in Severodonetsk, tuberculosis care in Zhytomyr, and improving health care access in Donetsk in eastern Ukraine, according to the aid group. What do doctors in Ukraine need most acutely now, other than peace?

Dr. Wolansky: Obviously, money is valuable, and military protection, which would prevent additional damage to their infrastructure. One thing that bears mentioning. There’s been a fair amount of coverage of this, but I’ve witnessed it first-hand: The Ukrainian people are fiercely patriotic, and there’s really no way their spirit can be conquered. The USSR invaded Afghanistan, and after years of thinking they were in command, they left because they could no longer take the guerilla warfare and the constant sniper attacks. Ukraine’s population is many times larger than Afghanistan’s; there’s no way they can be subdued. And remember, the Ukrainian people have been free for 30 years – generations of young people have known no other way of life. They are not going to give that up.

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

About 5% of people who are eligible to receive lung cancer screening do not live close to a facility and have limited or no access to screening,a recent analysis shows.

That percentage, although quite small, still translates to more than 750,000 individuals who are eligible to receive lung cancer screening but live at least 40 miles from a facility.

Overall, a larger proportion of eligible individuals in rural areas had no access to a facility, but a greater number of people in urban areas had no access, especially at shorter distances.

Understanding access issues is important given that “lung cancer screening with low-dose computed tomography scanning (LDCT) reduces mortality among high-risk adults, ... [but] annual screening rates remain low,” write study authors Liora Sahar, PhD, of the American Cancer Society in Atlanta, and colleagues.

The study was published online Feb. 15 in the journal Cancer.

It expands on a previous report, which found that “less than 6% of those 55 to 79 years of age do not have access to registry screening facilities”.

The new analysis incorporates the most recent guidelines from the U.S. Preventive Services Task Force, which lowered the screening age to 50 years and compares access across urban and rural areas.

Dr. Sahar and colleagues calculated the distances from population centers to screening facilities and estimated the number of individuals living within different distances of those facilities – 10, 20, 40, 50, and 100 miles. Geographical subdivisions, or census tracts, were also classified along a spectrum of rural to urban.

The authors found that, overall, about 14.8 million people aged 50-80 years are eligible for lung cancer screening, and 5.1% of that population – or 753,038 individuals – do not live within 40 miles of a facility and have no access to screening.

The proportion of people affected by access issues varies by geographic location. For eligible people living 40 miles or more from a facility, almost 25% (n = 287,803) in rural counties had no access, compared with 1.6% (n = 195,120) in metropolitan areas.

At greater distances to facilities (50 and 100 miles), these proportions diminish. In rural counties, for instance, 16% of eligible individuals (n = 186,401) living 50 or more miles away and 2.8% (n = 33,504) living 100 or more miles away had no access to a facility.

Not surprisingly, across all distances, “there is a significantly higher percentage of rural residents who do not have access to facilities in comparison with those in urban settings,” the authors write. “There are fewer facilities in rural areas, so residents need to travel longer distances to reach a facility.”

Notably, however, distance to a facility was not necessarily the greatest barrier to screening. The authors found a greater number of eligible individuals living in or close to urban areas were not getting screening when facilities were 10 miles away – more than 2.8 million in metropolitan areas versus just over 1 million in rural areas.

“The total number of individuals with no access in urban areas exceeds that of rural individuals, particularly at shorter distances ... [which] reveals an additional underserved population.”

Identifying geographic areas with greater access issues can help researchers address barriers to screening and improve uptake. 

“Areas and local pockets with persistently low or no access across short and long distances should be considered for tailored interventions, such as implementing mobile units, repurposing existing imaging or health facilities, and adding appropriate navigation, radiology, and screening program staff to better support the communities,” the authors conclude.

The study was supported in part by the National Lung Cancer Roundtable. Coauthor Debra S. Dyer, MD, serves on the clinical advisory board for computer software company Imidex and on the GO2 Foundation scientific advisory board; she also serves as a consultant for Lung Ambition Alliance. Coauthor Ella A. Kazerooni, MD, reports past participation on the Bristol Myers Squibb Foundation advisory board. The other authors have disclosed no relevant financial relationships.

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

About 5% of people who are eligible to receive lung cancer screening do not live close to a facility and have limited or no access to screening,a recent analysis shows.

That percentage, although quite small, still translates to more than 750,000 individuals who are eligible to receive lung cancer screening but live at least 40 miles from a facility.

Overall, a larger proportion of eligible individuals in rural areas had no access to a facility, but a greater number of people in urban areas had no access, especially at shorter distances.

Understanding access issues is important given that “lung cancer screening with low-dose computed tomography scanning (LDCT) reduces mortality among high-risk adults, ... [but] annual screening rates remain low,” write study authors Liora Sahar, PhD, of the American Cancer Society in Atlanta, and colleagues.

The study was published online Feb. 15 in the journal Cancer.

It expands on a previous report, which found that “less than 6% of those 55 to 79 years of age do not have access to registry screening facilities”.

The new analysis incorporates the most recent guidelines from the U.S. Preventive Services Task Force, which lowered the screening age to 50 years and compares access across urban and rural areas.

Dr. Sahar and colleagues calculated the distances from population centers to screening facilities and estimated the number of individuals living within different distances of those facilities – 10, 20, 40, 50, and 100 miles. Geographical subdivisions, or census tracts, were also classified along a spectrum of rural to urban.

The authors found that, overall, about 14.8 million people aged 50-80 years are eligible for lung cancer screening, and 5.1% of that population – or 753,038 individuals – do not live within 40 miles of a facility and have no access to screening.

The proportion of people affected by access issues varies by geographic location. For eligible people living 40 miles or more from a facility, almost 25% (n = 287,803) in rural counties had no access, compared with 1.6% (n = 195,120) in metropolitan areas.

At greater distances to facilities (50 and 100 miles), these proportions diminish. In rural counties, for instance, 16% of eligible individuals (n = 186,401) living 50 or more miles away and 2.8% (n = 33,504) living 100 or more miles away had no access to a facility.

Not surprisingly, across all distances, “there is a significantly higher percentage of rural residents who do not have access to facilities in comparison with those in urban settings,” the authors write. “There are fewer facilities in rural areas, so residents need to travel longer distances to reach a facility.”

Notably, however, distance to a facility was not necessarily the greatest barrier to screening. The authors found a greater number of eligible individuals living in or close to urban areas were not getting screening when facilities were 10 miles away – more than 2.8 million in metropolitan areas versus just over 1 million in rural areas.

“The total number of individuals with no access in urban areas exceeds that of rural individuals, particularly at shorter distances ... [which] reveals an additional underserved population.”

Identifying geographic areas with greater access issues can help researchers address barriers to screening and improve uptake. 

“Areas and local pockets with persistently low or no access across short and long distances should be considered for tailored interventions, such as implementing mobile units, repurposing existing imaging or health facilities, and adding appropriate navigation, radiology, and screening program staff to better support the communities,” the authors conclude.

The study was supported in part by the National Lung Cancer Roundtable. Coauthor Debra S. Dyer, MD, serves on the clinical advisory board for computer software company Imidex and on the GO2 Foundation scientific advisory board; she also serves as a consultant for Lung Ambition Alliance. Coauthor Ella A. Kazerooni, MD, reports past participation on the Bristol Myers Squibb Foundation advisory board. The other authors have disclosed no relevant financial relationships.

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

About 5% of people who are eligible to receive lung cancer screening do not live close to a facility and have limited or no access to screening,a recent analysis shows.

That percentage, although quite small, still translates to more than 750,000 individuals who are eligible to receive lung cancer screening but live at least 40 miles from a facility.

Overall, a larger proportion of eligible individuals in rural areas had no access to a facility, but a greater number of people in urban areas had no access, especially at shorter distances.

Understanding access issues is important given that “lung cancer screening with low-dose computed tomography scanning (LDCT) reduces mortality among high-risk adults, ... [but] annual screening rates remain low,” write study authors Liora Sahar, PhD, of the American Cancer Society in Atlanta, and colleagues.

The study was published online Feb. 15 in the journal Cancer.

It expands on a previous report, which found that “less than 6% of those 55 to 79 years of age do not have access to registry screening facilities”.

The new analysis incorporates the most recent guidelines from the U.S. Preventive Services Task Force, which lowered the screening age to 50 years and compares access across urban and rural areas.

Dr. Sahar and colleagues calculated the distances from population centers to screening facilities and estimated the number of individuals living within different distances of those facilities – 10, 20, 40, 50, and 100 miles. Geographical subdivisions, or census tracts, were also classified along a spectrum of rural to urban.

The authors found that, overall, about 14.8 million people aged 50-80 years are eligible for lung cancer screening, and 5.1% of that population – or 753,038 individuals – do not live within 40 miles of a facility and have no access to screening.

The proportion of people affected by access issues varies by geographic location. For eligible people living 40 miles or more from a facility, almost 25% (n = 287,803) in rural counties had no access, compared with 1.6% (n = 195,120) in metropolitan areas.

At greater distances to facilities (50 and 100 miles), these proportions diminish. In rural counties, for instance, 16% of eligible individuals (n = 186,401) living 50 or more miles away and 2.8% (n = 33,504) living 100 or more miles away had no access to a facility.

Not surprisingly, across all distances, “there is a significantly higher percentage of rural residents who do not have access to facilities in comparison with those in urban settings,” the authors write. “There are fewer facilities in rural areas, so residents need to travel longer distances to reach a facility.”

Notably, however, distance to a facility was not necessarily the greatest barrier to screening. The authors found a greater number of eligible individuals living in or close to urban areas were not getting screening when facilities were 10 miles away – more than 2.8 million in metropolitan areas versus just over 1 million in rural areas.

“The total number of individuals with no access in urban areas exceeds that of rural individuals, particularly at shorter distances ... [which] reveals an additional underserved population.”

Identifying geographic areas with greater access issues can help researchers address barriers to screening and improve uptake. 

“Areas and local pockets with persistently low or no access across short and long distances should be considered for tailored interventions, such as implementing mobile units, repurposing existing imaging or health facilities, and adding appropriate navigation, radiology, and screening program staff to better support the communities,” the authors conclude.

The study was supported in part by the National Lung Cancer Roundtable. Coauthor Debra S. Dyer, MD, serves on the clinical advisory board for computer software company Imidex and on the GO2 Foundation scientific advisory board; she also serves as a consultant for Lung Ambition Alliance. Coauthor Ella A. Kazerooni, MD, reports past participation on the Bristol Myers Squibb Foundation advisory board. The other authors have disclosed no relevant financial relationships.

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

This study was published on Medrxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• in analyses of more than 100,000 women that used Mendelian randomization (MR) as a tool to reduce residual confounding.
• The MR analyses showed no significant association between ANM and breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.
• The clear lack of a causal effect of ANM on the outcomes of coronary heart disease and ischemic stroke in the MR analyses despite a strong inverse association seen in the observational data of this study (without MR) suggests residual confounding plays a substantial role in driving the observed outcomes.

Why this matters

• The authors said that, to their knowledge, this is the first study that has shown a causal association between older ANM and higher risk of postmenopausal lung cancer.
• This finding was directionally opposite to the significant protective effect of increased ANM documented in an observational analysis of roughly the same data as well as prior reports that did not use MR. This “notable inconsistency” suggests very substantial residual confounding without MR that could be driven by factors such as smoking, diet, and exercise.
• If these results are replicated in additional datasets, it would highlight a need for randomized, controlled trials of antiestrogen therapies in postmenopausal women for the prevention or treatment of lung cancer.

Study design

• The study included data from 106,853 postmenopausal women enrolled in the Women’s Health Initiative (WHI) and 95,464 women who were 37-73 years old included in the UK Biobank (UKB). Analyses for each outcome also included data from smaller numbers of women obtained from several additional datasets.
• The MR analysis used up to 55 single-nucleotide polymorphisms previously discovered through a genome-wide association study of about 70,000 women of European ancestry and independent of all datasets analyzed in the current study. The authors included all single-nucleotide polymorphisms with a consistent direction of effect on ANM.
• The MR analysis for lung cancer included 113,371 women from the two primary datasets and an additional 3012 women from six additional datasets.
• The MR analysis for bone fracture involved 113,239 women from the WHI and UKB only. The MR analysis for osteoporosis involved 137,080 women from the WHI, UKB, and one additional external dataset.

Key results

• Results from a meta-analysis of the MR results using data from the WHI, UKB, and the additional datasets showed ANM was causally associated with an increased risk of lung cancer by an odds ratio of 1.35 for each 5-year increase in ANM. In contrast, the adjusted observational analysis of data just from the WHI and UKB showed a significant 11% relative risk reduction in the incidence of lung cancer for each 5-year increase in ANM.
• The MR results also showed causally protective effects for fracture, with a 24% relative risk reduction, and for osteoporosis, with a 19% relative risk reduction for each 5-year increase in ANM.
• The MR analyses showed no significant association between AMN and outcome for breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.

Limitations

The main limitation of the MR study was the potential for inadequate power for assessing some outcomes despite the large overall size of the study cohort. Lack of adequate power may be responsible for some of the nonsignificant associations seen in the study, such as for breast and endometrial cancers, where substantial prior evidence has implicated increased risk through the effects of prolonged exposure to endogenous or exogenous estrogens.

The healthy cohort effect in the UKB is a known weakness of this dataset that may have limited the number of cases and generalizability of findings.

Osteoporosis and Alzheimer’s disease were self-reported.

The study only included participants of European ancestry because most subjects in most of the cohorts examined were White women and the applied MR instruments were found by genome-wide association studies run predominantly in White women. The authors said the causal effects of ANM need study in more diverse populations.
 

Disclosures

• The study received no commercial funding.
• None of the authors had disclosures.

This is a summary of a preprint research study, “Genetic evidence for causal relationships between age at natural menopause and the risk of aging-associated adverse health outcomes,” written by authors primarily based at Stanford University School of Medicine i

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

This study was published on Medrxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• in analyses of more than 100,000 women that used Mendelian randomization (MR) as a tool to reduce residual confounding.
• The MR analyses showed no significant association between ANM and breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.
• The clear lack of a causal effect of ANM on the outcomes of coronary heart disease and ischemic stroke in the MR analyses despite a strong inverse association seen in the observational data of this study (without MR) suggests residual confounding plays a substantial role in driving the observed outcomes.

Why this matters

• The authors said that, to their knowledge, this is the first study that has shown a causal association between older ANM and higher risk of postmenopausal lung cancer.
• This finding was directionally opposite to the significant protective effect of increased ANM documented in an observational analysis of roughly the same data as well as prior reports that did not use MR. This “notable inconsistency” suggests very substantial residual confounding without MR that could be driven by factors such as smoking, diet, and exercise.
• If these results are replicated in additional datasets, it would highlight a need for randomized, controlled trials of antiestrogen therapies in postmenopausal women for the prevention or treatment of lung cancer.

Study design

• The study included data from 106,853 postmenopausal women enrolled in the Women’s Health Initiative (WHI) and 95,464 women who were 37-73 years old included in the UK Biobank (UKB). Analyses for each outcome also included data from smaller numbers of women obtained from several additional datasets.
• The MR analysis used up to 55 single-nucleotide polymorphisms previously discovered through a genome-wide association study of about 70,000 women of European ancestry and independent of all datasets analyzed in the current study. The authors included all single-nucleotide polymorphisms with a consistent direction of effect on ANM.
• The MR analysis for lung cancer included 113,371 women from the two primary datasets and an additional 3012 women from six additional datasets.
• The MR analysis for bone fracture involved 113,239 women from the WHI and UKB only. The MR analysis for osteoporosis involved 137,080 women from the WHI, UKB, and one additional external dataset.

Key results

• Results from a meta-analysis of the MR results using data from the WHI, UKB, and the additional datasets showed ANM was causally associated with an increased risk of lung cancer by an odds ratio of 1.35 for each 5-year increase in ANM. In contrast, the adjusted observational analysis of data just from the WHI and UKB showed a significant 11% relative risk reduction in the incidence of lung cancer for each 5-year increase in ANM.
• The MR results also showed causally protective effects for fracture, with a 24% relative risk reduction, and for osteoporosis, with a 19% relative risk reduction for each 5-year increase in ANM.
• The MR analyses showed no significant association between AMN and outcome for breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.

Limitations

The main limitation of the MR study was the potential for inadequate power for assessing some outcomes despite the large overall size of the study cohort. Lack of adequate power may be responsible for some of the nonsignificant associations seen in the study, such as for breast and endometrial cancers, where substantial prior evidence has implicated increased risk through the effects of prolonged exposure to endogenous or exogenous estrogens.

The healthy cohort effect in the UKB is a known weakness of this dataset that may have limited the number of cases and generalizability of findings.

Osteoporosis and Alzheimer’s disease were self-reported.

The study only included participants of European ancestry because most subjects in most of the cohorts examined were White women and the applied MR instruments were found by genome-wide association studies run predominantly in White women. The authors said the causal effects of ANM need study in more diverse populations.
 

Disclosures

• The study received no commercial funding.
• None of the authors had disclosures.

This is a summary of a preprint research study, “Genetic evidence for causal relationships between age at natural menopause and the risk of aging-associated adverse health outcomes,” written by authors primarily based at Stanford University School of Medicine i

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

This study was published on Medrxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• in analyses of more than 100,000 women that used Mendelian randomization (MR) as a tool to reduce residual confounding.
• The MR analyses showed no significant association between ANM and breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.
• The clear lack of a causal effect of ANM on the outcomes of coronary heart disease and ischemic stroke in the MR analyses despite a strong inverse association seen in the observational data of this study (without MR) suggests residual confounding plays a substantial role in driving the observed outcomes.

Why this matters

• The authors said that, to their knowledge, this is the first study that has shown a causal association between older ANM and higher risk of postmenopausal lung cancer.
• This finding was directionally opposite to the significant protective effect of increased ANM documented in an observational analysis of roughly the same data as well as prior reports that did not use MR. This “notable inconsistency” suggests very substantial residual confounding without MR that could be driven by factors such as smoking, diet, and exercise.
• If these results are replicated in additional datasets, it would highlight a need for randomized, controlled trials of antiestrogen therapies in postmenopausal women for the prevention or treatment of lung cancer.

Study design

• The study included data from 106,853 postmenopausal women enrolled in the Women’s Health Initiative (WHI) and 95,464 women who were 37-73 years old included in the UK Biobank (UKB). Analyses for each outcome also included data from smaller numbers of women obtained from several additional datasets.
• The MR analysis used up to 55 single-nucleotide polymorphisms previously discovered through a genome-wide association study of about 70,000 women of European ancestry and independent of all datasets analyzed in the current study. The authors included all single-nucleotide polymorphisms with a consistent direction of effect on ANM.
• The MR analysis for lung cancer included 113,371 women from the two primary datasets and an additional 3012 women from six additional datasets.
• The MR analysis for bone fracture involved 113,239 women from the WHI and UKB only. The MR analysis for osteoporosis involved 137,080 women from the WHI, UKB, and one additional external dataset.

Key results

• Results from a meta-analysis of the MR results using data from the WHI, UKB, and the additional datasets showed ANM was causally associated with an increased risk of lung cancer by an odds ratio of 1.35 for each 5-year increase in ANM. In contrast, the adjusted observational analysis of data just from the WHI and UKB showed a significant 11% relative risk reduction in the incidence of lung cancer for each 5-year increase in ANM.
• The MR results also showed causally protective effects for fracture, with a 24% relative risk reduction, and for osteoporosis, with a 19% relative risk reduction for each 5-year increase in ANM.
• The MR analyses showed no significant association between AMN and outcome for breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.

Limitations

The main limitation of the MR study was the potential for inadequate power for assessing some outcomes despite the large overall size of the study cohort. Lack of adequate power may be responsible for some of the nonsignificant associations seen in the study, such as for breast and endometrial cancers, where substantial prior evidence has implicated increased risk through the effects of prolonged exposure to endogenous or exogenous estrogens.

The healthy cohort effect in the UKB is a known weakness of this dataset that may have limited the number of cases and generalizability of findings.

Osteoporosis and Alzheimer’s disease were self-reported.

The study only included participants of European ancestry because most subjects in most of the cohorts examined were White women and the applied MR instruments were found by genome-wide association studies run predominantly in White women. The authors said the causal effects of ANM need study in more diverse populations.
 

Disclosures

• The study received no commercial funding.
• None of the authors had disclosures.

This is a summary of a preprint research study, “Genetic evidence for causal relationships between age at natural menopause and the risk of aging-associated adverse health outcomes,” written by authors primarily based at Stanford University School of Medicine i

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

My office was open on Presidents Day this year. Granted, I’ve never closed for it.

We’re also open on Veteran’s Day, Columbus Day, and Martin Luther King Jr. Day.

Occasionally (usually MLK or Veteran’s days) we get a call from someone unhappy we’re open that day. Banks, government offices, and schools are closed, and they feel that, by not following suit, I’m insulting the memory of veterans and those who fought for civil rights.

Nothing could be farther from the truth. In fact, I don’t know any doctors’ offices that AREN’T open on those days.

Part of this is patient centered. When people need to see a doctor, they don’t want to wait too long. The emergency room isn’t where the majority of things should be handled. Besides, they’re already swamped with nonemergent cases.

Most practices work 8-5 on weekdays, and are booked out. Every additional weekday you’re closed only adds to the wait. So I try to be there enough days to care for people, but not enough so that I lose my sanity or family.

In my area, a fair number of my patients are schoolteachers, who work the same hours I do. So many of them come in on those days, and appreciate that I’m open when they’re off.

Another part is practical. In a small practice, cash flow is critical, and there are just so many days in a given year you can be closed without hurting your financial picture. So most practices are closed for the Big 6 (Memorial Day, Independence Day, Labor Day, Thanksgiving, Christmas, and New Years). Usually this also includes Black Friday and Christmas Eve. So a total of 8 days per year (in addition to vacations).

Unlike other businesses (such as stores and restaurants) most medical offices aren’t open on weekends and nights, so our entire revenue stream is dependent on weekdays from 8 to 5. In this day and age, with most practices running on razor-thin margins, every day off adds to the red line. I can’t take care of anyone if I can’t pay my rent and staff.

I mean no disrespect to anyone. Like other doctors I work hard to provide quality care to all. But the nature of medicine is such that we give up our own time to help others. So I try to be there for them as much as I can, without going overboard and at the same time keeping my small practice afloat.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

My office was open on Presidents Day this year. Granted, I’ve never closed for it.

We’re also open on Veteran’s Day, Columbus Day, and Martin Luther King Jr. Day.

Occasionally (usually MLK or Veteran’s days) we get a call from someone unhappy we’re open that day. Banks, government offices, and schools are closed, and they feel that, by not following suit, I’m insulting the memory of veterans and those who fought for civil rights.

Nothing could be farther from the truth. In fact, I don’t know any doctors’ offices that AREN’T open on those days.

Part of this is patient centered. When people need to see a doctor, they don’t want to wait too long. The emergency room isn’t where the majority of things should be handled. Besides, they’re already swamped with nonemergent cases.

Most practices work 8-5 on weekdays, and are booked out. Every additional weekday you’re closed only adds to the wait. So I try to be there enough days to care for people, but not enough so that I lose my sanity or family.

In my area, a fair number of my patients are schoolteachers, who work the same hours I do. So many of them come in on those days, and appreciate that I’m open when they’re off.

Another part is practical. In a small practice, cash flow is critical, and there are just so many days in a given year you can be closed without hurting your financial picture. So most practices are closed for the Big 6 (Memorial Day, Independence Day, Labor Day, Thanksgiving, Christmas, and New Years). Usually this also includes Black Friday and Christmas Eve. So a total of 8 days per year (in addition to vacations).

Unlike other businesses (such as stores and restaurants) most medical offices aren’t open on weekends and nights, so our entire revenue stream is dependent on weekdays from 8 to 5. In this day and age, with most practices running on razor-thin margins, every day off adds to the red line. I can’t take care of anyone if I can’t pay my rent and staff.

I mean no disrespect to anyone. Like other doctors I work hard to provide quality care to all. But the nature of medicine is such that we give up our own time to help others. So I try to be there for them as much as I can, without going overboard and at the same time keeping my small practice afloat.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

My office was open on Presidents Day this year. Granted, I’ve never closed for it.

We’re also open on Veteran’s Day, Columbus Day, and Martin Luther King Jr. Day.

Occasionally (usually MLK or Veteran’s days) we get a call from someone unhappy we’re open that day. Banks, government offices, and schools are closed, and they feel that, by not following suit, I’m insulting the memory of veterans and those who fought for civil rights.

Nothing could be farther from the truth. In fact, I don’t know any doctors’ offices that AREN’T open on those days.

Part of this is patient centered. When people need to see a doctor, they don’t want to wait too long. The emergency room isn’t where the majority of things should be handled. Besides, they’re already swamped with nonemergent cases.

Most practices work 8-5 on weekdays, and are booked out. Every additional weekday you’re closed only adds to the wait. So I try to be there enough days to care for people, but not enough so that I lose my sanity or family.

In my area, a fair number of my patients are schoolteachers, who work the same hours I do. So many of them come in on those days, and appreciate that I’m open when they’re off.

Another part is practical. In a small practice, cash flow is critical, and there are just so many days in a given year you can be closed without hurting your financial picture. So most practices are closed for the Big 6 (Memorial Day, Independence Day, Labor Day, Thanksgiving, Christmas, and New Years). Usually this also includes Black Friday and Christmas Eve. So a total of 8 days per year (in addition to vacations).

Unlike other businesses (such as stores and restaurants) most medical offices aren’t open on weekends and nights, so our entire revenue stream is dependent on weekdays from 8 to 5. In this day and age, with most practices running on razor-thin margins, every day off adds to the red line. I can’t take care of anyone if I can’t pay my rent and staff.

I mean no disrespect to anyone. Like other doctors I work hard to provide quality care to all. But the nature of medicine is such that we give up our own time to help others. So I try to be there for them as much as I can, without going overboard and at the same time keeping my small practice afloat.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). 
5.    Walscheid K et al. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15).

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). 
5.    Walscheid K et al. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15).

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). 
5.    Walscheid K et al. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).