MDedge Rheumatology

With the approval by the Food and Drug Administration of the calcineurin inhibitor voclosporin (Lupkynis) in January and belimumab (Benlysta) a month before that, clinicians now have new options for treating lupus nephritis in combination with a background immunosuppressive agent, such as mycophenolate mofetil.

But which combination should clinicians choose?

Brad Rovin, MD, a nephrologist with the Ohio State University Wexner Medical Center, Columbus, who worked on the phase 3 voclosprin trial, pointed to that drug’s fast reduction in proteinuria in a session of the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting. That effect on proteinuria is likely due to its effect on podocytes, special epithelial cells that cover the outside of capillaries in the kidney, he said.

These crucial cells have an elaborate cytoskeleton that is stabilized by the protein synaptopodin, which can be subject to harm from calcineurin. But because voclosporin blocks calcineurin, synaptopodin is protected, which consequently protects podocytes and the kidney, Dr. Rovin said.

“There’s a lot of data in the nephrology literature that suggests as you lose podocytes, you actually can develop glomerular sclerosis and loss of renal function,” he said. “In fact, if you lose a critical number of podocytes, then no matter what you do, the kidney is likely to progress to end-stage kidney disease.

“The way I think about it now is, what else do these drugs add? And this idea of preserving the histology of the kidney is really important, and this can be done with voclosporin,” Dr. Rovin said.

Belimumab is also hailed as an effective tool, particularly for the prevention of flares. In the trial leading to its approval), just under 16% of patients experienced a renal-related event or death over 2 years, compared with 28% of the group that received placebo. Those receiving belimumab had a 50% greater chance of reaching the primary efficacy renal response, which was defined as a ratio of urinary protein to creatinine of 0.7 or less, an estimated glomerular filtration rate that was no worse than 20% below the pre-flare value or at least 60 mL/min per 1.73 m², and no use of rescue therapy for treatment failure.

The endpoints in the belimumab lupus nephritis trial were “quite rigorous,” Richard A. Furie, MD, said in the same session at the meeting. Patients with class V lupus nephritis were included in the trial, although disease of this severity is known to be particularly difficult to treat, he noted.

“There’s little question that our patients with lupus nephritis will benefit from such a therapeutic approach” with belimumab and mycophenolate, said Dr. Furie, professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, in Hempstead, N.Y. “But regardless of which combination clinicians use, we are making advances, and that means better outcomes for our patients with lupus and lupus nephritis.”

Graciela Alarcon, MD, MPH, professor emeritus of medicine at the University of Alabama at Birmingham, who moderated the discussion, said there is no sure answer regarding the best choice for clinicians.

“As long as there’s no head-to-head comparison between the two new compounds, I don’t think that the question can be answered,” she said.

Indeed, the answer for many clinicians might be that for certain patients, dual therapy isn’t necessary, Dr. Furie said.

“The fundamental question, before we choose the second drug, is whether a second drug should be chosen,” he said. “There’s a lot of people in the community who are just sticking to the old-fashioned algorithm and that is just choosing one drug, like mycophenolate. ... Others might pick a second drug, but not until they see that mycophenolate is not doing an effective job.”

All agreed that the response rates are still not optimal for patients with lupus nephritis, even with these new combinations – they are still only in the 30%-40% range.

“We haven’t really boosted the response rate to where we want it to be, at least as measured by our current measurements and composite renal response,” Dr. Rovin said.

With voclosporin’s protective effects and belimumab’s flare prevention, the two could potentially be used together at some point, he suggested.

“I think these two drugs show us the possibility that we might use them together and get rid of the older drugs, and really minimize the older drugs and then use them on a longer-term basis to preserve kidney function, as well as keep the lupus in check,” he said.

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

With the approval by the Food and Drug Administration of the calcineurin inhibitor voclosporin (Lupkynis) in January and belimumab (Benlysta) a month before that, clinicians now have new options for treating lupus nephritis in combination with a background immunosuppressive agent, such as mycophenolate mofetil.

But which combination should clinicians choose?

Brad Rovin, MD, a nephrologist with the Ohio State University Wexner Medical Center, Columbus, who worked on the phase 3 voclosprin trial, pointed to that drug’s fast reduction in proteinuria in a session of the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting. That effect on proteinuria is likely due to its effect on podocytes, special epithelial cells that cover the outside of capillaries in the kidney, he said.

These crucial cells have an elaborate cytoskeleton that is stabilized by the protein synaptopodin, which can be subject to harm from calcineurin. But because voclosporin blocks calcineurin, synaptopodin is protected, which consequently protects podocytes and the kidney, Dr. Rovin said.

“There’s a lot of data in the nephrology literature that suggests as you lose podocytes, you actually can develop glomerular sclerosis and loss of renal function,” he said. “In fact, if you lose a critical number of podocytes, then no matter what you do, the kidney is likely to progress to end-stage kidney disease.

“The way I think about it now is, what else do these drugs add? And this idea of preserving the histology of the kidney is really important, and this can be done with voclosporin,” Dr. Rovin said.

Belimumab is also hailed as an effective tool, particularly for the prevention of flares. In the trial leading to its approval), just under 16% of patients experienced a renal-related event or death over 2 years, compared with 28% of the group that received placebo. Those receiving belimumab had a 50% greater chance of reaching the primary efficacy renal response, which was defined as a ratio of urinary protein to creatinine of 0.7 or less, an estimated glomerular filtration rate that was no worse than 20% below the pre-flare value or at least 60 mL/min per 1.73 m², and no use of rescue therapy for treatment failure.

The endpoints in the belimumab lupus nephritis trial were “quite rigorous,” Richard A. Furie, MD, said in the same session at the meeting. Patients with class V lupus nephritis were included in the trial, although disease of this severity is known to be particularly difficult to treat, he noted.

“There’s little question that our patients with lupus nephritis will benefit from such a therapeutic approach” with belimumab and mycophenolate, said Dr. Furie, professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, in Hempstead, N.Y. “But regardless of which combination clinicians use, we are making advances, and that means better outcomes for our patients with lupus and lupus nephritis.”

Graciela Alarcon, MD, MPH, professor emeritus of medicine at the University of Alabama at Birmingham, who moderated the discussion, said there is no sure answer regarding the best choice for clinicians.

“As long as there’s no head-to-head comparison between the two new compounds, I don’t think that the question can be answered,” she said.

Indeed, the answer for many clinicians might be that for certain patients, dual therapy isn’t necessary, Dr. Furie said.

“The fundamental question, before we choose the second drug, is whether a second drug should be chosen,” he said. “There’s a lot of people in the community who are just sticking to the old-fashioned algorithm and that is just choosing one drug, like mycophenolate. ... Others might pick a second drug, but not until they see that mycophenolate is not doing an effective job.”

All agreed that the response rates are still not optimal for patients with lupus nephritis, even with these new combinations – they are still only in the 30%-40% range.

“We haven’t really boosted the response rate to where we want it to be, at least as measured by our current measurements and composite renal response,” Dr. Rovin said.

With voclosporin’s protective effects and belimumab’s flare prevention, the two could potentially be used together at some point, he suggested.

“I think these two drugs show us the possibility that we might use them together and get rid of the older drugs, and really minimize the older drugs and then use them on a longer-term basis to preserve kidney function, as well as keep the lupus in check,” he said.

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

With the approval by the Food and Drug Administration of the calcineurin inhibitor voclosporin (Lupkynis) in January and belimumab (Benlysta) a month before that, clinicians now have new options for treating lupus nephritis in combination with a background immunosuppressive agent, such as mycophenolate mofetil.

But which combination should clinicians choose?

Brad Rovin, MD, a nephrologist with the Ohio State University Wexner Medical Center, Columbus, who worked on the phase 3 voclosprin trial, pointed to that drug’s fast reduction in proteinuria in a session of the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting. That effect on proteinuria is likely due to its effect on podocytes, special epithelial cells that cover the outside of capillaries in the kidney, he said.

These crucial cells have an elaborate cytoskeleton that is stabilized by the protein synaptopodin, which can be subject to harm from calcineurin. But because voclosporin blocks calcineurin, synaptopodin is protected, which consequently protects podocytes and the kidney, Dr. Rovin said.

“There’s a lot of data in the nephrology literature that suggests as you lose podocytes, you actually can develop glomerular sclerosis and loss of renal function,” he said. “In fact, if you lose a critical number of podocytes, then no matter what you do, the kidney is likely to progress to end-stage kidney disease.

“The way I think about it now is, what else do these drugs add? And this idea of preserving the histology of the kidney is really important, and this can be done with voclosporin,” Dr. Rovin said.

Belimumab is also hailed as an effective tool, particularly for the prevention of flares. In the trial leading to its approval), just under 16% of patients experienced a renal-related event or death over 2 years, compared with 28% of the group that received placebo. Those receiving belimumab had a 50% greater chance of reaching the primary efficacy renal response, which was defined as a ratio of urinary protein to creatinine of 0.7 or less, an estimated glomerular filtration rate that was no worse than 20% below the pre-flare value or at least 60 mL/min per 1.73 m², and no use of rescue therapy for treatment failure.

The endpoints in the belimumab lupus nephritis trial were “quite rigorous,” Richard A. Furie, MD, said in the same session at the meeting. Patients with class V lupus nephritis were included in the trial, although disease of this severity is known to be particularly difficult to treat, he noted.

“There’s little question that our patients with lupus nephritis will benefit from such a therapeutic approach” with belimumab and mycophenolate, said Dr. Furie, professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, in Hempstead, N.Y. “But regardless of which combination clinicians use, we are making advances, and that means better outcomes for our patients with lupus and lupus nephritis.”

Graciela Alarcon, MD, MPH, professor emeritus of medicine at the University of Alabama at Birmingham, who moderated the discussion, said there is no sure answer regarding the best choice for clinicians.

“As long as there’s no head-to-head comparison between the two new compounds, I don’t think that the question can be answered,” she said.

Indeed, the answer for many clinicians might be that for certain patients, dual therapy isn’t necessary, Dr. Furie said.

“The fundamental question, before we choose the second drug, is whether a second drug should be chosen,” he said. “There’s a lot of people in the community who are just sticking to the old-fashioned algorithm and that is just choosing one drug, like mycophenolate. ... Others might pick a second drug, but not until they see that mycophenolate is not doing an effective job.”

All agreed that the response rates are still not optimal for patients with lupus nephritis, even with these new combinations – they are still only in the 30%-40% range.

“We haven’t really boosted the response rate to where we want it to be, at least as measured by our current measurements and composite renal response,” Dr. Rovin said.

With voclosporin’s protective effects and belimumab’s flare prevention, the two could potentially be used together at some point, he suggested.

“I think these two drugs show us the possibility that we might use them together and get rid of the older drugs, and really minimize the older drugs and then use them on a longer-term basis to preserve kidney function, as well as keep the lupus in check,” he said.

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

Thanks to the rollout of the COVID-19 vaccines, more than just flowers were blooming this past spring. People came out of lockdown like bears emerging from hibernation, making plans to reunite with friends and loved ones they hadn’t seen in months. But with the tremendous surge in cases brought by the Delta variant, this summer has been anything but sunny and carefree. Case counts have once more reached prevaccination levels. In a repeat of last summer, people are canceling travel plans, and the lead-up to the new school year has become fraught and stressful.

“This whiplash is causing people to feel a variety of emotions: disappointment, uncertainty, anxiety, possibly anger and frustration,” says Vaile Wright, Ph.D., senior director of health care innovation at the American Psychological Association. “When it seemed like there was a light at the end of the tunnel, and we have the tools to overcome [the virus], and we’re not really using them, it can be hard for people to understand.”
 

The importance of hope

For decades, researchers have been digging into the crucial role hopefulness plays in mental health. The vaccine rollout, earlier than anticipated, provided a much needed burst of hope after months of bad news.

“It was a feeling of almost euphoria in June: ‘We’re going to see everybody!’” says Rachel Goldenberg, a rabbi in Jackson Heights, NY. “We have a theme for our High Holidays, and this year’s is very hopeful: Sow in tears, reap in joy. It felt like the sowing in tears part was behind us, and we were looking forward to reaping in joy. Slowly but surely, with Delta, everything has turned upside down.”

For Roxanne Hawn, a writer in Golden, Colo., vaccination offered a glimpse of something like normal life.

“I wore cute clothes. I stopped and got takeout for lunch. I bought myself flowers. I even had a little uplifting soundtrack for that time of hope and relief,” she says. “With the Delta variant, it feels like that window of normalcy closed quickly.”

Having that little bit of hope dashed can wear down even the sturdiest spirits, says Marissa King, PhD, author of “Social Chemistry: Decoding the Elements of Human Connection”.

“There was a moment when we were able to reconnect, to experience joy and the hope of being able to revitalize relationships,” she says. “The loss of that hope and the fear of being isolated again is causing so much distress.”
 

A new kind of loneliness

When the pandemic started, mom of three Julie Schwietert Collazo formed a WhatsApp group with several friends who were taking lockdown seriously. They got each other through months of isolation and celebrated the idea of reopening. Then Ms. Collazo’s oldest got COVID, just 5 weeks before her 12th birthday, and their family went back into quarantine. Her moms’ group is no longer on the same page about precautions.

“Last year we were doing it together, and it made it feel a bit easier,” she says. “As things started to normalize, everybody started thinking and moving in different directions. It feels like we’re not working through the same issues collectively like before.”

Dr. King says the feeling Ms. Collazo describes is quite common these days.

“A profound sense of loneliness comes from feeling like you’re the only one,” she says. “There’s such disagreement about the best path forward, it can feel lonely just because you think differently.”
 

An epidemic of anxiety

As the Delta variant drives case numbers back up again, worries increase as well.

“Is this ever going to end?” asks Ms. Collazo. “Is this our new reality, constantly having to order our lives around COVID?”

This uneasiness affects our well-being.

The National Center for Health Statistics and the Census Bureau have monitored the nation’s mental health via the ongoing Household Pulse Survey during the pandemic. It asks participants about their symptoms of either anxiety or depression. Throughout, more people have reported feeling anxious than depressed.

Anxiety peaked around Thanksgiving and Christmas, with nearly 38% of people reporting symptoms. The first vaccines began to roll out around that time, and anxiety levels steadily went down through the spring and early summer, dipping below 25% in late June. But those numbers have begun to creep back up – the most recent data, which goes through Aug. 2, found 27% of Americans reporting symptoms of anxiety.

“Nervous is the new normal,” says Vivian Pender, MD, president of the American Psychiatric Association. “Uncertainty makes people feel anxious.”
 

Empathy vs. anger

The way politics play into basic measures like mask-wearing and vaccination adds its own layer of stress. Physical altercations have resulted: In Los Angeles, a participant was stabbed at an antivaccination protest. At an Austin, Tex., elementary school, angry parents physically and verbally assaulted teachers who wore masks. Things have gotten so heated, the Department of Homeland Security issued a National Terrorism Advisory System bulletin last week. It warns that extremists could use new COVID-driven public health restrictions as an excuse to commit domestic terrorism.

Anger goes in the opposite direction, too, with people who’ve been following recommended procedures becoming increasingly fed up with those who flout them. Those intense emotions may not lead to violence, but they do make it harder for us to feel secure.

“It’s a public health crisis, and it’s turned into something different. When we get into us/them situations, we start to lose empathy. Empathy is important to identify solutions and work together as a community,” says Dr. Wright. “That’s what sparks the anger: the sense of ‘You aren’t doing what you’re supposed to be doing.’”
 

How to cope

Loneliness, anxiety, and anger may be swirling all around you right now. But that doesn’t make you powerless to boost your mental health. These suggestions may help:

• Trust your gut. If your community is reopening faster than feels comfortable to you, do whatever makes your family feel safe. “Ask yourself how you’re feeling, and use your feelings to guide your decisions,” says Dr. Pender. “Get more information, then follow the science.”
• Stop judging yourself. If you’re feeling lonely or mourning the losses COVID has brought, don’t fight it, says Wright. “Let it be an emotion that comes and goes, and try to find ways to feel connected to other people.”
• Practice self-care. It may sound simplistic, but eating healthy foods, exercising, and getting a good night’s sleep can all contribute to a more positive 
• Try to ease anxiety. Meditation, calming self-talk, and soothing music can all lift your spirits. Or try diaphragmatic breathing: Breathe in for 5 seconds, hold for 2, and breathe out for 5. Even squeezing a stress ball can give you a tangible sense of 
• Take action. Both Rabbi Goldenberg and Ms. Collazo, who runs a nonprofit that works to reunite immigrant families, say helping their community helps them feel better. “To sing and lead Shabbat services, even on Zoom, to see the faces of my people, it’s very healing,” says Rabbi Goldenberg. One small thing you can do: If you have family or friends who are hesitant about vaccination, Dr. Wright suggests having gentle conversations to convince them. “You can be way more influential than a celebrity,” she says.
• Remember you’re not alone. Whether you’re physically isolated from others or just feel like nobody else is following the same protocols as you, there are ways to feel connected. “Reach out to people you’ve been close with in the past, but you may have lost touch,” says Dr. King. “It gives you an opportunity to rekindle joy. Particularly in this moment, when a lot of people are so afraid, it’s easier to reach out to those you already know than try to meet new people.” Dr. King’s research has found it takes as few as two close connections to make people feel supported.
• Stay in the present. Instead of stressing over what’s already happened or worrying about what might still come, just think about today. “We’ve learned a lot about the coronavirus, and we’re still learning more,” says Dr. Wright. “We don’t know what the future looks like, but it won’t be like this forever.”

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

Thanks to the rollout of the COVID-19 vaccines, more than just flowers were blooming this past spring. People came out of lockdown like bears emerging from hibernation, making plans to reunite with friends and loved ones they hadn’t seen in months. But with the tremendous surge in cases brought by the Delta variant, this summer has been anything but sunny and carefree. Case counts have once more reached prevaccination levels. In a repeat of last summer, people are canceling travel plans, and the lead-up to the new school year has become fraught and stressful.

“This whiplash is causing people to feel a variety of emotions: disappointment, uncertainty, anxiety, possibly anger and frustration,” says Vaile Wright, Ph.D., senior director of health care innovation at the American Psychological Association. “When it seemed like there was a light at the end of the tunnel, and we have the tools to overcome [the virus], and we’re not really using them, it can be hard for people to understand.”
 

The importance of hope

For decades, researchers have been digging into the crucial role hopefulness plays in mental health. The vaccine rollout, earlier than anticipated, provided a much needed burst of hope after months of bad news.

“It was a feeling of almost euphoria in June: ‘We’re going to see everybody!’” says Rachel Goldenberg, a rabbi in Jackson Heights, NY. “We have a theme for our High Holidays, and this year’s is very hopeful: Sow in tears, reap in joy. It felt like the sowing in tears part was behind us, and we were looking forward to reaping in joy. Slowly but surely, with Delta, everything has turned upside down.”

For Roxanne Hawn, a writer in Golden, Colo., vaccination offered a glimpse of something like normal life.

“I wore cute clothes. I stopped and got takeout for lunch. I bought myself flowers. I even had a little uplifting soundtrack for that time of hope and relief,” she says. “With the Delta variant, it feels like that window of normalcy closed quickly.”

Having that little bit of hope dashed can wear down even the sturdiest spirits, says Marissa King, PhD, author of “Social Chemistry: Decoding the Elements of Human Connection”.

“There was a moment when we were able to reconnect, to experience joy and the hope of being able to revitalize relationships,” she says. “The loss of that hope and the fear of being isolated again is causing so much distress.”
 

A new kind of loneliness

When the pandemic started, mom of three Julie Schwietert Collazo formed a WhatsApp group with several friends who were taking lockdown seriously. They got each other through months of isolation and celebrated the idea of reopening. Then Ms. Collazo’s oldest got COVID, just 5 weeks before her 12th birthday, and their family went back into quarantine. Her moms’ group is no longer on the same page about precautions.

“Last year we were doing it together, and it made it feel a bit easier,” she says. “As things started to normalize, everybody started thinking and moving in different directions. It feels like we’re not working through the same issues collectively like before.”

Dr. King says the feeling Ms. Collazo describes is quite common these days.

“A profound sense of loneliness comes from feeling like you’re the only one,” she says. “There’s such disagreement about the best path forward, it can feel lonely just because you think differently.”
 

An epidemic of anxiety

As the Delta variant drives case numbers back up again, worries increase as well.

“Is this ever going to end?” asks Ms. Collazo. “Is this our new reality, constantly having to order our lives around COVID?”

This uneasiness affects our well-being.

The National Center for Health Statistics and the Census Bureau have monitored the nation’s mental health via the ongoing Household Pulse Survey during the pandemic. It asks participants about their symptoms of either anxiety or depression. Throughout, more people have reported feeling anxious than depressed.

Anxiety peaked around Thanksgiving and Christmas, with nearly 38% of people reporting symptoms. The first vaccines began to roll out around that time, and anxiety levels steadily went down through the spring and early summer, dipping below 25% in late June. But those numbers have begun to creep back up – the most recent data, which goes through Aug. 2, found 27% of Americans reporting symptoms of anxiety.

“Nervous is the new normal,” says Vivian Pender, MD, president of the American Psychiatric Association. “Uncertainty makes people feel anxious.”
 

Empathy vs. anger

The way politics play into basic measures like mask-wearing and vaccination adds its own layer of stress. Physical altercations have resulted: In Los Angeles, a participant was stabbed at an antivaccination protest. At an Austin, Tex., elementary school, angry parents physically and verbally assaulted teachers who wore masks. Things have gotten so heated, the Department of Homeland Security issued a National Terrorism Advisory System bulletin last week. It warns that extremists could use new COVID-driven public health restrictions as an excuse to commit domestic terrorism.

Anger goes in the opposite direction, too, with people who’ve been following recommended procedures becoming increasingly fed up with those who flout them. Those intense emotions may not lead to violence, but they do make it harder for us to feel secure.

“It’s a public health crisis, and it’s turned into something different. When we get into us/them situations, we start to lose empathy. Empathy is important to identify solutions and work together as a community,” says Dr. Wright. “That’s what sparks the anger: the sense of ‘You aren’t doing what you’re supposed to be doing.’”
 

How to cope

Loneliness, anxiety, and anger may be swirling all around you right now. But that doesn’t make you powerless to boost your mental health. These suggestions may help:

• Trust your gut. If your community is reopening faster than feels comfortable to you, do whatever makes your family feel safe. “Ask yourself how you’re feeling, and use your feelings to guide your decisions,” says Dr. Pender. “Get more information, then follow the science.”
• Stop judging yourself. If you’re feeling lonely or mourning the losses COVID has brought, don’t fight it, says Wright. “Let it be an emotion that comes and goes, and try to find ways to feel connected to other people.”
• Practice self-care. It may sound simplistic, but eating healthy foods, exercising, and getting a good night’s sleep can all contribute to a more positive 
• Try to ease anxiety. Meditation, calming self-talk, and soothing music can all lift your spirits. Or try diaphragmatic breathing: Breathe in for 5 seconds, hold for 2, and breathe out for 5. Even squeezing a stress ball can give you a tangible sense of 
• Take action. Both Rabbi Goldenberg and Ms. Collazo, who runs a nonprofit that works to reunite immigrant families, say helping their community helps them feel better. “To sing and lead Shabbat services, even on Zoom, to see the faces of my people, it’s very healing,” says Rabbi Goldenberg. One small thing you can do: If you have family or friends who are hesitant about vaccination, Dr. Wright suggests having gentle conversations to convince them. “You can be way more influential than a celebrity,” she says.
• Remember you’re not alone. Whether you’re physically isolated from others or just feel like nobody else is following the same protocols as you, there are ways to feel connected. “Reach out to people you’ve been close with in the past, but you may have lost touch,” says Dr. King. “It gives you an opportunity to rekindle joy. Particularly in this moment, when a lot of people are so afraid, it’s easier to reach out to those you already know than try to meet new people.” Dr. King’s research has found it takes as few as two close connections to make people feel supported.
• Stay in the present. Instead of stressing over what’s already happened or worrying about what might still come, just think about today. “We’ve learned a lot about the coronavirus, and we’re still learning more,” says Dr. Wright. “We don’t know what the future looks like, but it won’t be like this forever.”

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

Thanks to the rollout of the COVID-19 vaccines, more than just flowers were blooming this past spring. People came out of lockdown like bears emerging from hibernation, making plans to reunite with friends and loved ones they hadn’t seen in months. But with the tremendous surge in cases brought by the Delta variant, this summer has been anything but sunny and carefree. Case counts have once more reached prevaccination levels. In a repeat of last summer, people are canceling travel plans, and the lead-up to the new school year has become fraught and stressful.

“This whiplash is causing people to feel a variety of emotions: disappointment, uncertainty, anxiety, possibly anger and frustration,” says Vaile Wright, Ph.D., senior director of health care innovation at the American Psychological Association. “When it seemed like there was a light at the end of the tunnel, and we have the tools to overcome [the virus], and we’re not really using them, it can be hard for people to understand.”
 

The importance of hope

For decades, researchers have been digging into the crucial role hopefulness plays in mental health. The vaccine rollout, earlier than anticipated, provided a much needed burst of hope after months of bad news.

“It was a feeling of almost euphoria in June: ‘We’re going to see everybody!’” says Rachel Goldenberg, a rabbi in Jackson Heights, NY. “We have a theme for our High Holidays, and this year’s is very hopeful: Sow in tears, reap in joy. It felt like the sowing in tears part was behind us, and we were looking forward to reaping in joy. Slowly but surely, with Delta, everything has turned upside down.”

For Roxanne Hawn, a writer in Golden, Colo., vaccination offered a glimpse of something like normal life.

“I wore cute clothes. I stopped and got takeout for lunch. I bought myself flowers. I even had a little uplifting soundtrack for that time of hope and relief,” she says. “With the Delta variant, it feels like that window of normalcy closed quickly.”

Having that little bit of hope dashed can wear down even the sturdiest spirits, says Marissa King, PhD, author of “Social Chemistry: Decoding the Elements of Human Connection”.

“There was a moment when we were able to reconnect, to experience joy and the hope of being able to revitalize relationships,” she says. “The loss of that hope and the fear of being isolated again is causing so much distress.”
 

A new kind of loneliness

When the pandemic started, mom of three Julie Schwietert Collazo formed a WhatsApp group with several friends who were taking lockdown seriously. They got each other through months of isolation and celebrated the idea of reopening. Then Ms. Collazo’s oldest got COVID, just 5 weeks before her 12th birthday, and their family went back into quarantine. Her moms’ group is no longer on the same page about precautions.

“Last year we were doing it together, and it made it feel a bit easier,” she says. “As things started to normalize, everybody started thinking and moving in different directions. It feels like we’re not working through the same issues collectively like before.”

Dr. King says the feeling Ms. Collazo describes is quite common these days.

“A profound sense of loneliness comes from feeling like you’re the only one,” she says. “There’s such disagreement about the best path forward, it can feel lonely just because you think differently.”
 

An epidemic of anxiety

As the Delta variant drives case numbers back up again, worries increase as well.

“Is this ever going to end?” asks Ms. Collazo. “Is this our new reality, constantly having to order our lives around COVID?”

This uneasiness affects our well-being.

The National Center for Health Statistics and the Census Bureau have monitored the nation’s mental health via the ongoing Household Pulse Survey during the pandemic. It asks participants about their symptoms of either anxiety or depression. Throughout, more people have reported feeling anxious than depressed.

Anxiety peaked around Thanksgiving and Christmas, with nearly 38% of people reporting symptoms. The first vaccines began to roll out around that time, and anxiety levels steadily went down through the spring and early summer, dipping below 25% in late June. But those numbers have begun to creep back up – the most recent data, which goes through Aug. 2, found 27% of Americans reporting symptoms of anxiety.

“Nervous is the new normal,” says Vivian Pender, MD, president of the American Psychiatric Association. “Uncertainty makes people feel anxious.”
 

Empathy vs. anger

The way politics play into basic measures like mask-wearing and vaccination adds its own layer of stress. Physical altercations have resulted: In Los Angeles, a participant was stabbed at an antivaccination protest. At an Austin, Tex., elementary school, angry parents physically and verbally assaulted teachers who wore masks. Things have gotten so heated, the Department of Homeland Security issued a National Terrorism Advisory System bulletin last week. It warns that extremists could use new COVID-driven public health restrictions as an excuse to commit domestic terrorism.

Anger goes in the opposite direction, too, with people who’ve been following recommended procedures becoming increasingly fed up with those who flout them. Those intense emotions may not lead to violence, but they do make it harder for us to feel secure.

“It’s a public health crisis, and it’s turned into something different. When we get into us/them situations, we start to lose empathy. Empathy is important to identify solutions and work together as a community,” says Dr. Wright. “That’s what sparks the anger: the sense of ‘You aren’t doing what you’re supposed to be doing.’”
 

How to cope

Loneliness, anxiety, and anger may be swirling all around you right now. But that doesn’t make you powerless to boost your mental health. These suggestions may help:

• Trust your gut. If your community is reopening faster than feels comfortable to you, do whatever makes your family feel safe. “Ask yourself how you’re feeling, and use your feelings to guide your decisions,” says Dr. Pender. “Get more information, then follow the science.”
• Stop judging yourself. If you’re feeling lonely or mourning the losses COVID has brought, don’t fight it, says Wright. “Let it be an emotion that comes and goes, and try to find ways to feel connected to other people.”
• Practice self-care. It may sound simplistic, but eating healthy foods, exercising, and getting a good night’s sleep can all contribute to a more positive 
• Try to ease anxiety. Meditation, calming self-talk, and soothing music can all lift your spirits. Or try diaphragmatic breathing: Breathe in for 5 seconds, hold for 2, and breathe out for 5. Even squeezing a stress ball can give you a tangible sense of 
• Take action. Both Rabbi Goldenberg and Ms. Collazo, who runs a nonprofit that works to reunite immigrant families, say helping their community helps them feel better. “To sing and lead Shabbat services, even on Zoom, to see the faces of my people, it’s very healing,” says Rabbi Goldenberg. One small thing you can do: If you have family or friends who are hesitant about vaccination, Dr. Wright suggests having gentle conversations to convince them. “You can be way more influential than a celebrity,” she says.
• Remember you’re not alone. Whether you’re physically isolated from others or just feel like nobody else is following the same protocols as you, there are ways to feel connected. “Reach out to people you’ve been close with in the past, but you may have lost touch,” says Dr. King. “It gives you an opportunity to rekindle joy. Particularly in this moment, when a lot of people are so afraid, it’s easier to reach out to those you already know than try to meet new people.” Dr. King’s research has found it takes as few as two close connections to make people feel supported.
• Stay in the present. Instead of stressing over what’s already happened or worrying about what might still come, just think about today. “We’ve learned a lot about the coronavirus, and we’re still learning more,” says Dr. Wright. “We don’t know what the future looks like, but it won’t be like this forever.”

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

One essential back-to-school item for children this fall is a face mask – the Centers for Disease Control and Prevention and the American Academy of Pediatrics both recommend them – but finding one that’s actually protective for a child is not a straightforward task, as many parents can attest. 

There’s little in the way of official guidance or research to inform evidence-based recommendations on what type of face masks works best for children. 

Search for children’s face masks on Amazon and you’ll run into a smorgasbord of options: masks with three, four, or five layers, different designs, and different materials. There’s one company selling a mask it calls an m95 model, a term the company devised. 

It’s almost impossible to verify many of the claims being made by the manufacturers, or to know if they will fit your child’s face until you order some, which can get expensive.

But it’s worth looking for a good mask.  A large study of more than 1 million people being conducted online by Facebook and Carnegie Mellon University found that students who wore face masks in school had a reduced risk for testing positive for the virus and getting sick with COVID-19 symptoms. The study was published in June in the journal Science.
 

Delta more contagious

The Delta variant of the new coronavirus is much more contagious than previous versions of the virus. Studies have shown that infected people carry 1,000 times more virus in their noses and throats than with the viruses that circulated last winter and spring. They shed more viral particles into the air when they talk or yell or sing, making this COVID-19–causing virus much more transmissible than in the past.

What that means, says Kimberly Prather, PhD, an aerosol scientist and distinguished professor at the Scripps Institution of Oceanography in La Jolla, California, is that if it once took about 15 minutes of proximity to an infected person to catch the infection, that window of risk is now much shorter.

“If you believe the 15-minute magical number, now if you take 1,000 times the viral load, basically in 1 second you could inhale that same amount of virus. So it’s gone from 15 minutes to 1 second,” Dr. Prather said in an online seminar on school safety she helped to organize. 
 

A better mask

What that means is that we need to upgrade our face masks, switching away from ill-fitting fabric masks, which can offer varying degrees of protection depending on the number of layers and type of fabric that’s used, to more highly protective surgical masks or better yet, N95 respirators, which provide the highest level of filtration.

That’s harder to do for children, who have much smaller faces.

Any masks that gapes around the edges isn’t going to work well, no matter how well it filters.

“N95s are not made to fit kids. They do not come in kid sizes, so I do not recommend N95s for kids,” said Linsey Marr, an environmental engineer at Virginia Tech, who tests face masks in her lab.

Ms. Marr says parents need to consider the attributes masks in this order of priority: 

Comfort: “If your kid won’t wear it, it’s not helping at all,” she said.

Fit: “Leaks around the sides are like having a hole in your mask and aerosols carrying the virus can get right through,” Ms. Marr said.

Filtration: How well the mask blocks small particles.

One option to improve fit is to layer a fabric mask over a surgical mask. The fabric mask helps to hold the edges of the surgical mask more tightly to a person’s face.  The surgical mask creates better filtration.

Ms. Marr said KN94 or KN95 masks, which are being manufactured in China and Korea, are good choices. They offer nearly the same degree of filtration as an N95, and they fit closely to the face, to minimize leaks.
 

Check for counterfeits

The KN94 and KN95 masks for children are widely available, but Ms. Marr said parents do need to watch out for counterfeits, which don’t perform as well.

The National Institute for Occupational Safety and Health gives examples of counterfeit products here.

There’s also a type of cloth mask that has a built-in, edge-to-edge filter layer that is made for children.

“Some of these filter out more than 99% of particles and those can be very effective, if they fit well,” Ms. Marr said.

She has compiled and publicly posted a list of her recommendations for masks for children.

There’s also a new standard for face masks. It’s called ASTM F3502-21, and it’s published by an international organization that sets voluntary standards for thousands of products. To claim that a mask meets this standard, a manufacturer has to have its mask tested and demonstrate that it provides a certain level of filtration and breathability.

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

One essential back-to-school item for children this fall is a face mask – the Centers for Disease Control and Prevention and the American Academy of Pediatrics both recommend them – but finding one that’s actually protective for a child is not a straightforward task, as many parents can attest. 

There’s little in the way of official guidance or research to inform evidence-based recommendations on what type of face masks works best for children. 

Search for children’s face masks on Amazon and you’ll run into a smorgasbord of options: masks with three, four, or five layers, different designs, and different materials. There’s one company selling a mask it calls an m95 model, a term the company devised. 

It’s almost impossible to verify many of the claims being made by the manufacturers, or to know if they will fit your child’s face until you order some, which can get expensive.

But it’s worth looking for a good mask.  A large study of more than 1 million people being conducted online by Facebook and Carnegie Mellon University found that students who wore face masks in school had a reduced risk for testing positive for the virus and getting sick with COVID-19 symptoms. The study was published in June in the journal Science.
 

Delta more contagious

The Delta variant of the new coronavirus is much more contagious than previous versions of the virus. Studies have shown that infected people carry 1,000 times more virus in their noses and throats than with the viruses that circulated last winter and spring. They shed more viral particles into the air when they talk or yell or sing, making this COVID-19–causing virus much more transmissible than in the past.

What that means, says Kimberly Prather, PhD, an aerosol scientist and distinguished professor at the Scripps Institution of Oceanography in La Jolla, California, is that if it once took about 15 minutes of proximity to an infected person to catch the infection, that window of risk is now much shorter.

“If you believe the 15-minute magical number, now if you take 1,000 times the viral load, basically in 1 second you could inhale that same amount of virus. So it’s gone from 15 minutes to 1 second,” Dr. Prather said in an online seminar on school safety she helped to organize. 
 

A better mask

What that means is that we need to upgrade our face masks, switching away from ill-fitting fabric masks, which can offer varying degrees of protection depending on the number of layers and type of fabric that’s used, to more highly protective surgical masks or better yet, N95 respirators, which provide the highest level of filtration.

That’s harder to do for children, who have much smaller faces.

Any masks that gapes around the edges isn’t going to work well, no matter how well it filters.

“N95s are not made to fit kids. They do not come in kid sizes, so I do not recommend N95s for kids,” said Linsey Marr, an environmental engineer at Virginia Tech, who tests face masks in her lab.

Ms. Marr says parents need to consider the attributes masks in this order of priority: 

Comfort: “If your kid won’t wear it, it’s not helping at all,” she said.

Fit: “Leaks around the sides are like having a hole in your mask and aerosols carrying the virus can get right through,” Ms. Marr said.

Filtration: How well the mask blocks small particles.

One option to improve fit is to layer a fabric mask over a surgical mask. The fabric mask helps to hold the edges of the surgical mask more tightly to a person’s face.  The surgical mask creates better filtration.

Ms. Marr said KN94 or KN95 masks, which are being manufactured in China and Korea, are good choices. They offer nearly the same degree of filtration as an N95, and they fit closely to the face, to minimize leaks.
 

Check for counterfeits

The KN94 and KN95 masks for children are widely available, but Ms. Marr said parents do need to watch out for counterfeits, which don’t perform as well.

The National Institute for Occupational Safety and Health gives examples of counterfeit products here.

There’s also a type of cloth mask that has a built-in, edge-to-edge filter layer that is made for children.

“Some of these filter out more than 99% of particles and those can be very effective, if they fit well,” Ms. Marr said.

She has compiled and publicly posted a list of her recommendations for masks for children.

There’s also a new standard for face masks. It’s called ASTM F3502-21, and it’s published by an international organization that sets voluntary standards for thousands of products. To claim that a mask meets this standard, a manufacturer has to have its mask tested and demonstrate that it provides a certain level of filtration and breathability.

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

One essential back-to-school item for children this fall is a face mask – the Centers for Disease Control and Prevention and the American Academy of Pediatrics both recommend them – but finding one that’s actually protective for a child is not a straightforward task, as many parents can attest. 

There’s little in the way of official guidance or research to inform evidence-based recommendations on what type of face masks works best for children. 

Search for children’s face masks on Amazon and you’ll run into a smorgasbord of options: masks with three, four, or five layers, different designs, and different materials. There’s one company selling a mask it calls an m95 model, a term the company devised. 

It’s almost impossible to verify many of the claims being made by the manufacturers, or to know if they will fit your child’s face until you order some, which can get expensive.

But it’s worth looking for a good mask.  A large study of more than 1 million people being conducted online by Facebook and Carnegie Mellon University found that students who wore face masks in school had a reduced risk for testing positive for the virus and getting sick with COVID-19 symptoms. The study was published in June in the journal Science.
 

Delta more contagious

The Delta variant of the new coronavirus is much more contagious than previous versions of the virus. Studies have shown that infected people carry 1,000 times more virus in their noses and throats than with the viruses that circulated last winter and spring. They shed more viral particles into the air when they talk or yell or sing, making this COVID-19–causing virus much more transmissible than in the past.

What that means, says Kimberly Prather, PhD, an aerosol scientist and distinguished professor at the Scripps Institution of Oceanography in La Jolla, California, is that if it once took about 15 minutes of proximity to an infected person to catch the infection, that window of risk is now much shorter.

“If you believe the 15-minute magical number, now if you take 1,000 times the viral load, basically in 1 second you could inhale that same amount of virus. So it’s gone from 15 minutes to 1 second,” Dr. Prather said in an online seminar on school safety she helped to organize. 
 

A better mask

What that means is that we need to upgrade our face masks, switching away from ill-fitting fabric masks, which can offer varying degrees of protection depending on the number of layers and type of fabric that’s used, to more highly protective surgical masks or better yet, N95 respirators, which provide the highest level of filtration.

That’s harder to do for children, who have much smaller faces.

Any masks that gapes around the edges isn’t going to work well, no matter how well it filters.

“N95s are not made to fit kids. They do not come in kid sizes, so I do not recommend N95s for kids,” said Linsey Marr, an environmental engineer at Virginia Tech, who tests face masks in her lab.

Ms. Marr says parents need to consider the attributes masks in this order of priority: 

Comfort: “If your kid won’t wear it, it’s not helping at all,” she said.

Fit: “Leaks around the sides are like having a hole in your mask and aerosols carrying the virus can get right through,” Ms. Marr said.

Filtration: How well the mask blocks small particles.

One option to improve fit is to layer a fabric mask over a surgical mask. The fabric mask helps to hold the edges of the surgical mask more tightly to a person’s face.  The surgical mask creates better filtration.

Ms. Marr said KN94 or KN95 masks, which are being manufactured in China and Korea, are good choices. They offer nearly the same degree of filtration as an N95, and they fit closely to the face, to minimize leaks.
 

Check for counterfeits

The KN94 and KN95 masks for children are widely available, but Ms. Marr said parents do need to watch out for counterfeits, which don’t perform as well.

The National Institute for Occupational Safety and Health gives examples of counterfeit products here.

There’s also a type of cloth mask that has a built-in, edge-to-edge filter layer that is made for children.

“Some of these filter out more than 99% of particles and those can be very effective, if they fit well,” Ms. Marr said.

She has compiled and publicly posted a list of her recommendations for masks for children.

There’s also a new standard for face masks. It’s called ASTM F3502-21, and it’s published by an international organization that sets voluntary standards for thousands of products. To claim that a mask meets this standard, a manufacturer has to have its mask tested and demonstrate that it provides a certain level of filtration and breathability.

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

Childhood exposure to parental smoking appears to greatly boost the risk of confirmed cases of rheumatoid arthritis in adult women, although the overall rate is small, a new study reports. The findings, published Aug. 18, 2021, in Arthritis & Rheumatology, follows other evidence that early second-hand smoke exposure can trigger lifelong damage to the immune system.

pmphoto/iStockphoto.com

“We estimated that there is 75% increased risk of adult seropositive RA due to the direct impact of childhood parental smoking,” said study lead author and Brigham & Women’s Hospital epidemiologist Kazuki Yoshida, MD, ScD, referring to an adjusted analysis conducted in the study. “Passive smoking is likely harmful throughout an individual’s life course regarding rheumatoid arthritis but potentially more harmful during the childhood period.”

The researchers launched the study to fill an evidence gap, Dr. Yoshida said in an interview. “Active smoking is a well-established risk factor for RA. However, studies on passive smoking’s impact on RA are sparse, and few studies had a well-characterized cohort of participants with comprehensive data of passive smoking during life course – in utero exposure, childhood exposure, adult exposure – and chart review–adjudicated RA outcomes.”

The study authors retrospectively tracked 90,923 subjects who joined the Nurses’ Health Study II in 1989 when they were aged 25-42. At the study’s start, the average age of subjects was 34.5, 93% were White, and 98% were premenopausal. Almost two-thirds had never smoked themselves, and 65% said their parents had smoked during their childhoods.

Of the subjects, the researchers found that 532 were identified as having RA over a median follow-up period of 27.7 years. Two-thirds of those cases (n = 352) were confirmed as seropositive by clinical testing.

The study linked maternal smoking during pregnancy to confirmed RA in adulthood via a confounder-adjusted analysis (hazard ratio, 1.25; 95% confidence interval, 1.03-1.52), but the connection vanished after researchers adjusted their statistics to reflect possible influences by later exposures to smoke.

After adjustment for confounders, the study linked childhood exposure to parental smoking to a 41% in increase in risk of confirmed adulthood RA (HR, 1.41; 95% CI, 1.08-1.83). A controlled direct effect analysis boosted the excess risk to 75% (HR, 1.75; 95% CI, 1.03-2.98).

This analysis reveals that “childhood parental smoking seems to be associated with adult rheumatoid arthritis beyond what is explained by the fact that childhood passive smoking can promote personal smoking uptake, a known risk factor for rheumatoid arthritis,” Dr. Yoshida said.

The overall rate of RA in the study population – roughly 0.6% – aligns with risk levels in the general population, he said. As a result, “the absolute risk increase may not be extremely high. But the concept that early life exposure may affect immunological health later in life is important.”

Potential pathophysiological mechanisms

Why might parental smoking boost the risk of RA? Exposure to secondhand smoke may irritate the lungs and cause abnormal proteins to form, Dr. Yoshida said. “The immune system produces antibodies in an attempt to attack such abnormal proteins. This immune reaction can spread to other body sites and attack normal tissues, including the joints.”

In addition, “smoking increases the risk of infections, which could in turn increase the risk of RA. Smoking is also known to result in epigenetic changes which could trigger RA in susceptible people,” University of California, San Francisco, autoimmune disease epidemiologist Milena A. Gianfrancesco, PhD, MPH, said in an interview. She cowrote a commentary accompanying the new study.

Other studies have linked smoking exposure to autoimmune disorders. Earlier this year, researchers who tracked 79,806 French women reported at the EULAR 2021 annual meeting that they found a link between exposure to second-hand smoking during childhood or adulthood and higher rates of RA.

Dr. Yoshida and colleagues noted their study’s limitations, including the inability to track cases of RA in subjects up to the age when they entered the nurses research project. Also, only one questionnaire over the entire period of the Nurses’ Health Study II asks subjects about whether they were exposed to secondhand smoke as adults.

The study also says nothing about whether a similar risk exists for males, and the nurse subjects are overwhelmingly White.

Still, Dr. Gianfrancesco praised the study and said it relies on extensive data and strong statistical methods. “The findings are important because they drive home the importance of reducing cigarette smoke exposure to reduce risk of disease,” she said. “They highlight the need to not only focus on one’s personal smoking habits, but also other sources of secondhand smoke exposure.”

She added that children with a family history of RA or other autoimmune diseases are especially vulnerable to the effects of secondhand smoke because they may be more susceptible to developing the diseases themselves. “Rheumatologists and other health care providers should be sure to discuss the risks of smoking with their patients, as well as the risk of secondhand smoke,” she said. “And parents should keep their children away from secondhand smoke in the home or other environments in which smoke is prevalent, such as the home of another caregiver or a workplace if the child accompanies their parent to work.”

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, and the National Institutes of Health. The study and commentary authors, including Dr. Yoshida and Dr. Gianfrancesco, reported having no relevant disclosures.

Childhood exposure to parental smoking appears to greatly boost the risk of confirmed cases of rheumatoid arthritis in adult women, although the overall rate is small, a new study reports. The findings, published Aug. 18, 2021, in Arthritis & Rheumatology, follows other evidence that early second-hand smoke exposure can trigger lifelong damage to the immune system.

pmphoto/iStockphoto.com

“We estimated that there is 75% increased risk of adult seropositive RA due to the direct impact of childhood parental smoking,” said study lead author and Brigham & Women’s Hospital epidemiologist Kazuki Yoshida, MD, ScD, referring to an adjusted analysis conducted in the study. “Passive smoking is likely harmful throughout an individual’s life course regarding rheumatoid arthritis but potentially more harmful during the childhood period.”

The researchers launched the study to fill an evidence gap, Dr. Yoshida said in an interview. “Active smoking is a well-established risk factor for RA. However, studies on passive smoking’s impact on RA are sparse, and few studies had a well-characterized cohort of participants with comprehensive data of passive smoking during life course – in utero exposure, childhood exposure, adult exposure – and chart review–adjudicated RA outcomes.”

The study authors retrospectively tracked 90,923 subjects who joined the Nurses’ Health Study II in 1989 when they were aged 25-42. At the study’s start, the average age of subjects was 34.5, 93% were White, and 98% were premenopausal. Almost two-thirds had never smoked themselves, and 65% said their parents had smoked during their childhoods.

Of the subjects, the researchers found that 532 were identified as having RA over a median follow-up period of 27.7 years. Two-thirds of those cases (n = 352) were confirmed as seropositive by clinical testing.

The study linked maternal smoking during pregnancy to confirmed RA in adulthood via a confounder-adjusted analysis (hazard ratio, 1.25; 95% confidence interval, 1.03-1.52), but the connection vanished after researchers adjusted their statistics to reflect possible influences by later exposures to smoke.

After adjustment for confounders, the study linked childhood exposure to parental smoking to a 41% in increase in risk of confirmed adulthood RA (HR, 1.41; 95% CI, 1.08-1.83). A controlled direct effect analysis boosted the excess risk to 75% (HR, 1.75; 95% CI, 1.03-2.98).

This analysis reveals that “childhood parental smoking seems to be associated with adult rheumatoid arthritis beyond what is explained by the fact that childhood passive smoking can promote personal smoking uptake, a known risk factor for rheumatoid arthritis,” Dr. Yoshida said.

The overall rate of RA in the study population – roughly 0.6% – aligns with risk levels in the general population, he said. As a result, “the absolute risk increase may not be extremely high. But the concept that early life exposure may affect immunological health later in life is important.”

Potential pathophysiological mechanisms

Why might parental smoking boost the risk of RA? Exposure to secondhand smoke may irritate the lungs and cause abnormal proteins to form, Dr. Yoshida said. “The immune system produces antibodies in an attempt to attack such abnormal proteins. This immune reaction can spread to other body sites and attack normal tissues, including the joints.”

In addition, “smoking increases the risk of infections, which could in turn increase the risk of RA. Smoking is also known to result in epigenetic changes which could trigger RA in susceptible people,” University of California, San Francisco, autoimmune disease epidemiologist Milena A. Gianfrancesco, PhD, MPH, said in an interview. She cowrote a commentary accompanying the new study.

Other studies have linked smoking exposure to autoimmune disorders. Earlier this year, researchers who tracked 79,806 French women reported at the EULAR 2021 annual meeting that they found a link between exposure to second-hand smoking during childhood or adulthood and higher rates of RA.

Dr. Yoshida and colleagues noted their study’s limitations, including the inability to track cases of RA in subjects up to the age when they entered the nurses research project. Also, only one questionnaire over the entire period of the Nurses’ Health Study II asks subjects about whether they were exposed to secondhand smoke as adults.

The study also says nothing about whether a similar risk exists for males, and the nurse subjects are overwhelmingly White.

Still, Dr. Gianfrancesco praised the study and said it relies on extensive data and strong statistical methods. “The findings are important because they drive home the importance of reducing cigarette smoke exposure to reduce risk of disease,” she said. “They highlight the need to not only focus on one’s personal smoking habits, but also other sources of secondhand smoke exposure.”

She added that children with a family history of RA or other autoimmune diseases are especially vulnerable to the effects of secondhand smoke because they may be more susceptible to developing the diseases themselves. “Rheumatologists and other health care providers should be sure to discuss the risks of smoking with their patients, as well as the risk of secondhand smoke,” she said. “And parents should keep their children away from secondhand smoke in the home or other environments in which smoke is prevalent, such as the home of another caregiver or a workplace if the child accompanies their parent to work.”

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, and the National Institutes of Health. The study and commentary authors, including Dr. Yoshida and Dr. Gianfrancesco, reported having no relevant disclosures.

Childhood exposure to parental smoking appears to greatly boost the risk of confirmed cases of rheumatoid arthritis in adult women, although the overall rate is small, a new study reports. The findings, published Aug. 18, 2021, in Arthritis & Rheumatology, follows other evidence that early second-hand smoke exposure can trigger lifelong damage to the immune system.

pmphoto/iStockphoto.com

“We estimated that there is 75% increased risk of adult seropositive RA due to the direct impact of childhood parental smoking,” said study lead author and Brigham & Women’s Hospital epidemiologist Kazuki Yoshida, MD, ScD, referring to an adjusted analysis conducted in the study. “Passive smoking is likely harmful throughout an individual’s life course regarding rheumatoid arthritis but potentially more harmful during the childhood period.”

The researchers launched the study to fill an evidence gap, Dr. Yoshida said in an interview. “Active smoking is a well-established risk factor for RA. However, studies on passive smoking’s impact on RA are sparse, and few studies had a well-characterized cohort of participants with comprehensive data of passive smoking during life course – in utero exposure, childhood exposure, adult exposure – and chart review–adjudicated RA outcomes.”

The study authors retrospectively tracked 90,923 subjects who joined the Nurses’ Health Study II in 1989 when they were aged 25-42. At the study’s start, the average age of subjects was 34.5, 93% were White, and 98% were premenopausal. Almost two-thirds had never smoked themselves, and 65% said their parents had smoked during their childhoods.

Of the subjects, the researchers found that 532 were identified as having RA over a median follow-up period of 27.7 years. Two-thirds of those cases (n = 352) were confirmed as seropositive by clinical testing.

The study linked maternal smoking during pregnancy to confirmed RA in adulthood via a confounder-adjusted analysis (hazard ratio, 1.25; 95% confidence interval, 1.03-1.52), but the connection vanished after researchers adjusted their statistics to reflect possible influences by later exposures to smoke.

After adjustment for confounders, the study linked childhood exposure to parental smoking to a 41% in increase in risk of confirmed adulthood RA (HR, 1.41; 95% CI, 1.08-1.83). A controlled direct effect analysis boosted the excess risk to 75% (HR, 1.75; 95% CI, 1.03-2.98).

This analysis reveals that “childhood parental smoking seems to be associated with adult rheumatoid arthritis beyond what is explained by the fact that childhood passive smoking can promote personal smoking uptake, a known risk factor for rheumatoid arthritis,” Dr. Yoshida said.

The overall rate of RA in the study population – roughly 0.6% – aligns with risk levels in the general population, he said. As a result, “the absolute risk increase may not be extremely high. But the concept that early life exposure may affect immunological health later in life is important.”

Potential pathophysiological mechanisms

Why might parental smoking boost the risk of RA? Exposure to secondhand smoke may irritate the lungs and cause abnormal proteins to form, Dr. Yoshida said. “The immune system produces antibodies in an attempt to attack such abnormal proteins. This immune reaction can spread to other body sites and attack normal tissues, including the joints.”

In addition, “smoking increases the risk of infections, which could in turn increase the risk of RA. Smoking is also known to result in epigenetic changes which could trigger RA in susceptible people,” University of California, San Francisco, autoimmune disease epidemiologist Milena A. Gianfrancesco, PhD, MPH, said in an interview. She cowrote a commentary accompanying the new study.

Other studies have linked smoking exposure to autoimmune disorders. Earlier this year, researchers who tracked 79,806 French women reported at the EULAR 2021 annual meeting that they found a link between exposure to second-hand smoking during childhood or adulthood and higher rates of RA.

Dr. Yoshida and colleagues noted their study’s limitations, including the inability to track cases of RA in subjects up to the age when they entered the nurses research project. Also, only one questionnaire over the entire period of the Nurses’ Health Study II asks subjects about whether they were exposed to secondhand smoke as adults.

The study also says nothing about whether a similar risk exists for males, and the nurse subjects are overwhelmingly White.

Still, Dr. Gianfrancesco praised the study and said it relies on extensive data and strong statistical methods. “The findings are important because they drive home the importance of reducing cigarette smoke exposure to reduce risk of disease,” she said. “They highlight the need to not only focus on one’s personal smoking habits, but also other sources of secondhand smoke exposure.”

She added that children with a family history of RA or other autoimmune diseases are especially vulnerable to the effects of secondhand smoke because they may be more susceptible to developing the diseases themselves. “Rheumatologists and other health care providers should be sure to discuss the risks of smoking with their patients, as well as the risk of secondhand smoke,” she said. “And parents should keep their children away from secondhand smoke in the home or other environments in which smoke is prevalent, such as the home of another caregiver or a workplace if the child accompanies their parent to work.”

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, and the National Institutes of Health. The study and commentary authors, including Dr. Yoshida and Dr. Gianfrancesco, reported having no relevant disclosures.

New efforts – including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively – are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass – experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise – is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Dr. Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Dr. Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, was recently found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Dr. Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem – by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests – would be a big step, the panelists said. Dr. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Dr. Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Dr. Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Dr. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Dr. Brance has disclosed no relevant financial relationships.

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

New efforts – including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively – are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass – experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise – is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Dr. Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Dr. Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, was recently found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Dr. Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem – by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests – would be a big step, the panelists said. Dr. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Dr. Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Dr. Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Dr. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Dr. Brance has disclosed no relevant financial relationships.

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

New efforts – including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively – are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass – experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise – is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Dr. Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Dr. Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, was recently found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Dr. Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem – by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests – would be a big step, the panelists said. Dr. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Dr. Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Dr. Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Dr. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Dr. Brance has disclosed no relevant financial relationships.

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

With worldwide supplies of tocilizumab dwindling as the COVID-19 pandemic rages on, a shortage of the agent will persist “for at least the next several weeks,” according to Genentech, the Roche unit that manufactures tocilizumab under the trade name Actemra IV.

The World Health Organization and Unitaid have called on Genentech to guarantee equitable distribution of the biologic agent globally and to ease up on technology transfer restrictions to make the treatment more accessible.

At this point, supplies of tocilizumab for subcutaneous use to treat rheumatoid arthritis and its other approved indications for inflammatory conditions aren’t as dire, but Genentech is watching them as well, the company says.

In June, the Food and Drug Administration issued an emergency use authorization for intravenous tocilizumab for hospitalized COVID-19 patients. Since then, it has been included in the WHO Therapeutics and COVID-19: living guideline. And on the same day Genentech and Roche reported the tocilizumab shortage, the European Medicines Agency posted a statement that it had started evaluating RoActemra, the European brand name for tocilizumab, for hospitalized COVID-19 patients.

The FDA authorization has caused an unprecedented run on supplies for the biologic agent, which is FDA approved to treat RA, giant cell arteritis, systemic sclerosis–associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome. 
 

Depleted stocks

In the United States, stocks of the 200- and 400-mg units were unavailable, according to an FDA update in mid-August on its website, and the 80-mg/4-mL unit is available by drop ship only. Supplies of 80-mg units were expected to be depleted by the end of the third week in August, Genentech said in a press release.

The company expects to resupply stocks by the end of August. “However,” the Genentech statement added, “if the pandemic continues to spread at its current pace, we anticipate additional periods of stockout in the weeks and months ahead.”

For patients with RA or other approved indications taking the subcutaneous formulation – pens and prefilled syringes – supplies continue to be available, but, the company added, “the supply situation continues to evolve.” The subcutaneous formulations aren’t authorized for use in COVID-19 patients. However, the American Society of Health-System Pharmacists’ website lists the 162-mg/0.9-mL prefilled syringe as one of the products affected by the shortage.

In a separate statement, Roche said that demand for tocilizumab increased 300% in developing countries over prepandemic orders, and that U.S. demand spiked more than 400% in the first 2 weeks of August.

Roche laid out four reasons for the shortage: global manufacturing capacity limits; raw material shortages; the overall complex process of manufacturing biologic agents; and “the dynamically evolving nature of the pandemic.”

The Roche statement noted the company ramped up manufacturing of tocilizumab more than 100% over prepandemic capacity.

With regard to issues WHO and Unitaid raised in their statement, Roche stated that about 60% of its COVID-19 supplies have gone to developing countries, and that Roche and partner Chugai – both of whom hold tocilizumab-related patents – won’t assert any patents over its use for COVID-19 in low- and middle-income countries (LMICs) during the pandemic.

“Roche is in the midst of discussions with WHO and we are committed to support access in LMICs as much as we can,” a Roche spokesperson said in an interview.

Blair Solow, MD, chair of the American College of Rheumatology’s government affairs committee, said the organization supports the equitable distribution of tocilizumab. “We will work to ensure that our patients continue to have access to the medications they need,” she said. “We will continue to engage with the FDA and others to address shortages and ensure patient access to critical therapies.”

The ACR said that any health care professionals having difficulty getting tocilizumab IV or any other COVID-19-related issues can contact the organization at [email protected].

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

With worldwide supplies of tocilizumab dwindling as the COVID-19 pandemic rages on, a shortage of the agent will persist “for at least the next several weeks,” according to Genentech, the Roche unit that manufactures tocilizumab under the trade name Actemra IV.

The World Health Organization and Unitaid have called on Genentech to guarantee equitable distribution of the biologic agent globally and to ease up on technology transfer restrictions to make the treatment more accessible.

At this point, supplies of tocilizumab for subcutaneous use to treat rheumatoid arthritis and its other approved indications for inflammatory conditions aren’t as dire, but Genentech is watching them as well, the company says.

In June, the Food and Drug Administration issued an emergency use authorization for intravenous tocilizumab for hospitalized COVID-19 patients. Since then, it has been included in the WHO Therapeutics and COVID-19: living guideline. And on the same day Genentech and Roche reported the tocilizumab shortage, the European Medicines Agency posted a statement that it had started evaluating RoActemra, the European brand name for tocilizumab, for hospitalized COVID-19 patients.

The FDA authorization has caused an unprecedented run on supplies for the biologic agent, which is FDA approved to treat RA, giant cell arteritis, systemic sclerosis–associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome. 
 

Depleted stocks

In the United States, stocks of the 200- and 400-mg units were unavailable, according to an FDA update in mid-August on its website, and the 80-mg/4-mL unit is available by drop ship only. Supplies of 80-mg units were expected to be depleted by the end of the third week in August, Genentech said in a press release.

The company expects to resupply stocks by the end of August. “However,” the Genentech statement added, “if the pandemic continues to spread at its current pace, we anticipate additional periods of stockout in the weeks and months ahead.”

For patients with RA or other approved indications taking the subcutaneous formulation – pens and prefilled syringes – supplies continue to be available, but, the company added, “the supply situation continues to evolve.” The subcutaneous formulations aren’t authorized for use in COVID-19 patients. However, the American Society of Health-System Pharmacists’ website lists the 162-mg/0.9-mL prefilled syringe as one of the products affected by the shortage.

In a separate statement, Roche said that demand for tocilizumab increased 300% in developing countries over prepandemic orders, and that U.S. demand spiked more than 400% in the first 2 weeks of August.

Roche laid out four reasons for the shortage: global manufacturing capacity limits; raw material shortages; the overall complex process of manufacturing biologic agents; and “the dynamically evolving nature of the pandemic.”

The Roche statement noted the company ramped up manufacturing of tocilizumab more than 100% over prepandemic capacity.

With regard to issues WHO and Unitaid raised in their statement, Roche stated that about 60% of its COVID-19 supplies have gone to developing countries, and that Roche and partner Chugai – both of whom hold tocilizumab-related patents – won’t assert any patents over its use for COVID-19 in low- and middle-income countries (LMICs) during the pandemic.

“Roche is in the midst of discussions with WHO and we are committed to support access in LMICs as much as we can,” a Roche spokesperson said in an interview.

Blair Solow, MD, chair of the American College of Rheumatology’s government affairs committee, said the organization supports the equitable distribution of tocilizumab. “We will work to ensure that our patients continue to have access to the medications they need,” she said. “We will continue to engage with the FDA and others to address shortages and ensure patient access to critical therapies.”

The ACR said that any health care professionals having difficulty getting tocilizumab IV or any other COVID-19-related issues can contact the organization at [email protected].

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

With worldwide supplies of tocilizumab dwindling as the COVID-19 pandemic rages on, a shortage of the agent will persist “for at least the next several weeks,” according to Genentech, the Roche unit that manufactures tocilizumab under the trade name Actemra IV.

The World Health Organization and Unitaid have called on Genentech to guarantee equitable distribution of the biologic agent globally and to ease up on technology transfer restrictions to make the treatment more accessible.

At this point, supplies of tocilizumab for subcutaneous use to treat rheumatoid arthritis and its other approved indications for inflammatory conditions aren’t as dire, but Genentech is watching them as well, the company says.

In June, the Food and Drug Administration issued an emergency use authorization for intravenous tocilizumab for hospitalized COVID-19 patients. Since then, it has been included in the WHO Therapeutics and COVID-19: living guideline. And on the same day Genentech and Roche reported the tocilizumab shortage, the European Medicines Agency posted a statement that it had started evaluating RoActemra, the European brand name for tocilizumab, for hospitalized COVID-19 patients.

The FDA authorization has caused an unprecedented run on supplies for the biologic agent, which is FDA approved to treat RA, giant cell arteritis, systemic sclerosis–associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome. 
 

Depleted stocks

In the United States, stocks of the 200- and 400-mg units were unavailable, according to an FDA update in mid-August on its website, and the 80-mg/4-mL unit is available by drop ship only. Supplies of 80-mg units were expected to be depleted by the end of the third week in August, Genentech said in a press release.

The company expects to resupply stocks by the end of August. “However,” the Genentech statement added, “if the pandemic continues to spread at its current pace, we anticipate additional periods of stockout in the weeks and months ahead.”

For patients with RA or other approved indications taking the subcutaneous formulation – pens and prefilled syringes – supplies continue to be available, but, the company added, “the supply situation continues to evolve.” The subcutaneous formulations aren’t authorized for use in COVID-19 patients. However, the American Society of Health-System Pharmacists’ website lists the 162-mg/0.9-mL prefilled syringe as one of the products affected by the shortage.

In a separate statement, Roche said that demand for tocilizumab increased 300% in developing countries over prepandemic orders, and that U.S. demand spiked more than 400% in the first 2 weeks of August.

Roche laid out four reasons for the shortage: global manufacturing capacity limits; raw material shortages; the overall complex process of manufacturing biologic agents; and “the dynamically evolving nature of the pandemic.”

The Roche statement noted the company ramped up manufacturing of tocilizumab more than 100% over prepandemic capacity.

With regard to issues WHO and Unitaid raised in their statement, Roche stated that about 60% of its COVID-19 supplies have gone to developing countries, and that Roche and partner Chugai – both of whom hold tocilizumab-related patents – won’t assert any patents over its use for COVID-19 in low- and middle-income countries (LMICs) during the pandemic.

“Roche is in the midst of discussions with WHO and we are committed to support access in LMICs as much as we can,” a Roche spokesperson said in an interview.

Blair Solow, MD, chair of the American College of Rheumatology’s government affairs committee, said the organization supports the equitable distribution of tocilizumab. “We will work to ensure that our patients continue to have access to the medications they need,” she said. “We will continue to engage with the FDA and others to address shortages and ensure patient access to critical therapies.”

The ACR said that any health care professionals having difficulty getting tocilizumab IV or any other COVID-19-related issues can contact the organization at [email protected].

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

Following the White House administration’s announcement to start booster COVID-19 vaccinations for American adults in September, experts weighed in on the evidence for choosing an 8-month cutoff, how breakthrough infections figure in, and why calling one mRNA vaccine better than the other could be misleading.

Timing came up more than once at the Aug. 18 White House briefing announcing the booster plans. Reporters asked about the start time of Sept. 20 and people waiting at least 8 months after their second mRNA vaccine dose to get a booster.

Anthony Fauci, MD, chief medical adviser to the president and director of the National Institute of Allergy and Infectious Diseases, explained that late September gives the United States time to set up the logistics.

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, added that 8 months is in part based on data from Israel and other countries on the waning of vaccine effectiveness over time.

“It is possible that 8 [months] is associated with the amount of time that we’ve been able to follow large groups of people, especially those who are 65 and older,” Julie Swann, PhD, said during a subsequent media briefing sponsored by Newswise on Aug. 18. “I know that Pfizer has said that they think a booster sometime between 6 and 12 months would be reasonable.”

Dr. Swann supported the administration’s booster shots plan. She said it is important “that we continue to get people the full amount of protection if it’s recommended by CDC and ACIP [Advisory Committee on Immunization Practices] that would come from a booster shot.” Dr. Swann is department head and A. Doug Allison Distinguished Professor at North Carolina State University and an adjunct professor in the joint department of biomedical engineering at the University of North Carolina at Chapel Hill. 
 

Rising importance of breakthrough cases

Also on Aug. 18, news emerged that breakthrough cases are on the rise in seven U.S. states, likely because of the Delta variant.

These SARS-CoV-2 infections among the fully vaccinated account for 20% of cases in six of the seven states cited in a New York Times report, for example. Researchers also suggested that hospitalization and deaths associated with breakthrough cases could be higher than previously appreciated.

“It is expected that over time we will see more cases of Delta variant infections among vaccinated people. This points toward the need for booster vaccines and/or eventual modifications to the vaccine to capture new variants in the future,” Juan Wisnivesky, MD, DrPH, chief of the division of general internal medicine at Mount Sinai Health System in New York City, said during the briefing.
 

Vaccine comparisons unfair?

Following the release of a Mayo Clinic study reporting lower effectiveness of the Pfizer mRNA vaccine at 42% versus 76% for the Moderna product, some people started asking if one vaccine was better than the other.

“To begin with, the vaccines are not being compared side-by-side,” Dr. Wisnivesky said. “So we only know the effectiveness of each vaccine versus placebo, but we don’t know one versus the other.”

He added that different study designs, different populations, and other factors make direct comparisons difficult.

More evidence will be needed, Dr. Wisnivesky said, before public health officials can recommend that someone who received one mRNA vaccine switch to another for their booster shot.
 

Layering protections

Continuing to recommend masks is essential, Dr. Swann added. “With this Delta variant, it does appear that the possibility of reinfection or of a disease case breaking through vaccination can occur. So that makes it even more important to consider using nonpharmaceutical interventions while we continue to vaccinate people.”

Wearing or not wearing a mask is one of the behaviors that drive the transmission of disease, Dr. Swann said.

“What we saw across the board is that many people really wanted to go back to normal as much as they could. And we went back to normal a little bit too soon, especially given this new version of the virus that was circulating,” she said.
 

In poll, most favor boosters

A recent poll conducted by Medscape indicates that a majority of vaccinated physicians and nurses are ready and willing to take a COVID-19 booster vaccine. For example, 93% of 943 doctors and 87% of 1,680 nurses who responded want booster shots, either immediately or when they are authorized and recommended.

Among 510 WebMD readers responding to a similar poll, 82% indicated they wanted a booster shot.
 

A challenging task lies ahead

According to CDC data, as of Aug. 18, 2021, almost 169 million Americans are fully vaccinated, including the one-shot Johnson & Johnson adenovirus vaccine.

“I think it will be a challenge to get everyone who is fully vaccinated to come in for that booster,” Dr. Swann said.

Logistically speaking, Dr. Swann explained that many sites that were open for initial vaccinations, including drive-up locations and 24/7 vaccination sites, are no longer operating.

“We might see that rollout look a little bit differently. You might be able to go to your pharmacy or go to your primary care physician,” she said.

“But we may not see as many weekend events so it is going to be easier to get some people a booster than others.

“One interesting thing will also be whether a booster is effective in actually preventing you from giving a disease to someone else,” Dr. Swann said. “That could make a difference as well, because that might play into whether companies, hospitals, universities, or others require a booster.”

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

Following the White House administration’s announcement to start booster COVID-19 vaccinations for American adults in September, experts weighed in on the evidence for choosing an 8-month cutoff, how breakthrough infections figure in, and why calling one mRNA vaccine better than the other could be misleading.

Timing came up more than once at the Aug. 18 White House briefing announcing the booster plans. Reporters asked about the start time of Sept. 20 and people waiting at least 8 months after their second mRNA vaccine dose to get a booster.

Anthony Fauci, MD, chief medical adviser to the president and director of the National Institute of Allergy and Infectious Diseases, explained that late September gives the United States time to set up the logistics.

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, added that 8 months is in part based on data from Israel and other countries on the waning of vaccine effectiveness over time.

“It is possible that 8 [months] is associated with the amount of time that we’ve been able to follow large groups of people, especially those who are 65 and older,” Julie Swann, PhD, said during a subsequent media briefing sponsored by Newswise on Aug. 18. “I know that Pfizer has said that they think a booster sometime between 6 and 12 months would be reasonable.”

Dr. Swann supported the administration’s booster shots plan. She said it is important “that we continue to get people the full amount of protection if it’s recommended by CDC and ACIP [Advisory Committee on Immunization Practices] that would come from a booster shot.” Dr. Swann is department head and A. Doug Allison Distinguished Professor at North Carolina State University and an adjunct professor in the joint department of biomedical engineering at the University of North Carolina at Chapel Hill. 
 

Rising importance of breakthrough cases

Also on Aug. 18, news emerged that breakthrough cases are on the rise in seven U.S. states, likely because of the Delta variant.

These SARS-CoV-2 infections among the fully vaccinated account for 20% of cases in six of the seven states cited in a New York Times report, for example. Researchers also suggested that hospitalization and deaths associated with breakthrough cases could be higher than previously appreciated.

“It is expected that over time we will see more cases of Delta variant infections among vaccinated people. This points toward the need for booster vaccines and/or eventual modifications to the vaccine to capture new variants in the future,” Juan Wisnivesky, MD, DrPH, chief of the division of general internal medicine at Mount Sinai Health System in New York City, said during the briefing.
 

Vaccine comparisons unfair?

Following the release of a Mayo Clinic study reporting lower effectiveness of the Pfizer mRNA vaccine at 42% versus 76% for the Moderna product, some people started asking if one vaccine was better than the other.

“To begin with, the vaccines are not being compared side-by-side,” Dr. Wisnivesky said. “So we only know the effectiveness of each vaccine versus placebo, but we don’t know one versus the other.”

He added that different study designs, different populations, and other factors make direct comparisons difficult.

More evidence will be needed, Dr. Wisnivesky said, before public health officials can recommend that someone who received one mRNA vaccine switch to another for their booster shot.
 

Layering protections

Continuing to recommend masks is essential, Dr. Swann added. “With this Delta variant, it does appear that the possibility of reinfection or of a disease case breaking through vaccination can occur. So that makes it even more important to consider using nonpharmaceutical interventions while we continue to vaccinate people.”

Wearing or not wearing a mask is one of the behaviors that drive the transmission of disease, Dr. Swann said.

“What we saw across the board is that many people really wanted to go back to normal as much as they could. And we went back to normal a little bit too soon, especially given this new version of the virus that was circulating,” she said.
 

In poll, most favor boosters

A recent poll conducted by Medscape indicates that a majority of vaccinated physicians and nurses are ready and willing to take a COVID-19 booster vaccine. For example, 93% of 943 doctors and 87% of 1,680 nurses who responded want booster shots, either immediately or when they are authorized and recommended.

Among 510 WebMD readers responding to a similar poll, 82% indicated they wanted a booster shot.
 

A challenging task lies ahead

According to CDC data, as of Aug. 18, 2021, almost 169 million Americans are fully vaccinated, including the one-shot Johnson & Johnson adenovirus vaccine.

“I think it will be a challenge to get everyone who is fully vaccinated to come in for that booster,” Dr. Swann said.

Logistically speaking, Dr. Swann explained that many sites that were open for initial vaccinations, including drive-up locations and 24/7 vaccination sites, are no longer operating.

“We might see that rollout look a little bit differently. You might be able to go to your pharmacy or go to your primary care physician,” she said.

“But we may not see as many weekend events so it is going to be easier to get some people a booster than others.

“One interesting thing will also be whether a booster is effective in actually preventing you from giving a disease to someone else,” Dr. Swann said. “That could make a difference as well, because that might play into whether companies, hospitals, universities, or others require a booster.”

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

Following the White House administration’s announcement to start booster COVID-19 vaccinations for American adults in September, experts weighed in on the evidence for choosing an 8-month cutoff, how breakthrough infections figure in, and why calling one mRNA vaccine better than the other could be misleading.

Timing came up more than once at the Aug. 18 White House briefing announcing the booster plans. Reporters asked about the start time of Sept. 20 and people waiting at least 8 months after their second mRNA vaccine dose to get a booster.

Anthony Fauci, MD, chief medical adviser to the president and director of the National Institute of Allergy and Infectious Diseases, explained that late September gives the United States time to set up the logistics.

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, added that 8 months is in part based on data from Israel and other countries on the waning of vaccine effectiveness over time.

“It is possible that 8 [months] is associated with the amount of time that we’ve been able to follow large groups of people, especially those who are 65 and older,” Julie Swann, PhD, said during a subsequent media briefing sponsored by Newswise on Aug. 18. “I know that Pfizer has said that they think a booster sometime between 6 and 12 months would be reasonable.”

Dr. Swann supported the administration’s booster shots plan. She said it is important “that we continue to get people the full amount of protection if it’s recommended by CDC and ACIP [Advisory Committee on Immunization Practices] that would come from a booster shot.” Dr. Swann is department head and A. Doug Allison Distinguished Professor at North Carolina State University and an adjunct professor in the joint department of biomedical engineering at the University of North Carolina at Chapel Hill. 
 

Rising importance of breakthrough cases

Also on Aug. 18, news emerged that breakthrough cases are on the rise in seven U.S. states, likely because of the Delta variant.

These SARS-CoV-2 infections among the fully vaccinated account for 20% of cases in six of the seven states cited in a New York Times report, for example. Researchers also suggested that hospitalization and deaths associated with breakthrough cases could be higher than previously appreciated.

“It is expected that over time we will see more cases of Delta variant infections among vaccinated people. This points toward the need for booster vaccines and/or eventual modifications to the vaccine to capture new variants in the future,” Juan Wisnivesky, MD, DrPH, chief of the division of general internal medicine at Mount Sinai Health System in New York City, said during the briefing.
 

Vaccine comparisons unfair?

Following the release of a Mayo Clinic study reporting lower effectiveness of the Pfizer mRNA vaccine at 42% versus 76% for the Moderna product, some people started asking if one vaccine was better than the other.

“To begin with, the vaccines are not being compared side-by-side,” Dr. Wisnivesky said. “So we only know the effectiveness of each vaccine versus placebo, but we don’t know one versus the other.”

He added that different study designs, different populations, and other factors make direct comparisons difficult.

More evidence will be needed, Dr. Wisnivesky said, before public health officials can recommend that someone who received one mRNA vaccine switch to another for their booster shot.
 

Layering protections

Continuing to recommend masks is essential, Dr. Swann added. “With this Delta variant, it does appear that the possibility of reinfection or of a disease case breaking through vaccination can occur. So that makes it even more important to consider using nonpharmaceutical interventions while we continue to vaccinate people.”

Wearing or not wearing a mask is one of the behaviors that drive the transmission of disease, Dr. Swann said.

“What we saw across the board is that many people really wanted to go back to normal as much as they could. And we went back to normal a little bit too soon, especially given this new version of the virus that was circulating,” she said.
 

In poll, most favor boosters

A recent poll conducted by Medscape indicates that a majority of vaccinated physicians and nurses are ready and willing to take a COVID-19 booster vaccine. For example, 93% of 943 doctors and 87% of 1,680 nurses who responded want booster shots, either immediately or when they are authorized and recommended.

Among 510 WebMD readers responding to a similar poll, 82% indicated they wanted a booster shot.
 

A challenging task lies ahead

According to CDC data, as of Aug. 18, 2021, almost 169 million Americans are fully vaccinated, including the one-shot Johnson & Johnson adenovirus vaccine.

“I think it will be a challenge to get everyone who is fully vaccinated to come in for that booster,” Dr. Swann said.

Logistically speaking, Dr. Swann explained that many sites that were open for initial vaccinations, including drive-up locations and 24/7 vaccination sites, are no longer operating.

“We might see that rollout look a little bit differently. You might be able to go to your pharmacy or go to your primary care physician,” she said.

“But we may not see as many weekend events so it is going to be easier to get some people a booster than others.

“One interesting thing will also be whether a booster is effective in actually preventing you from giving a disease to someone else,” Dr. Swann said. “That could make a difference as well, because that might play into whether companies, hospitals, universities, or others require a booster.”

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

Older patients with knee osteoarthritis (OA) who underwent lengthy diet and exercise interventions reported less pain and maintained some weight loss years after the program ended, according to a new study published in Arthritis Care & Research.

AlexRaths/Getty Images

“These data imply that clinicians who treat people with knee osteoarthritis have a variety of nonpharmacologic options that preserve clinically important effects 3.5 years after the treatments end,” wrote lead author Stephen P. Messier, PhD, professor and director of the J.B. Snow Biomechanics Laboratory at Wake Forest University, Winston-Salem, N.C.

The study involved patients with overweight or obesity aged 55 years or older who were previously enrolled in the 1.5-year Intensive Diet and Exercise for Arthritis (IDEA) trial.

“You have to remember, this is 3.5 years after the IDEA trial ended,” Dr. Messier said in an interview. “There was no contact with them for that entire time; you’d expect, based on the literature, that they’d revert back to where they were before they entered the trial. And certainly, there was some regression, there was some weight regain, but the important part of the study is that, even after 3.5 years, and even with some weight regain, there were some clinically important effects that lasted.”

“What we feel now is that if we can somehow prepare people better for that time after they finish a weight loss intervention, from a psychological standpoint, it will make a real difference,” he added. “We are very good at helping people have the confidence to lose weight. But having the confidence to lose weight is totally different than having confidence to maintain weight loss. If we can give folks an intervention that has a psychological component, hopefully we can increase their confidence to maintain the weight loss that they attained.”
 

Study details

Of the 184 participants who were contacted for a follow-up visit, 94 consented to participate, 67% of whom were females and 88% of whom were White. A total of 27 participants had completed the diet and exercise intervention, and another 35 completed the diet-only and 32 exercise-only interventions.

In the 3.5-year period between the IDEA trial’s end and follow-up, body weight increased by 5.9 kg in the diet and exercise group (P < .0001) and by 3.1 kg in the diet-only group (P = .0006) but decreased in the exercise-only group by 1.0 kg (P = .25). However, from baseline to 5-year follow-up, all groups saw a reduction in body weight. Mean weight loss was –3.7 kg for the diet and exercise group (P = .0007), –5.8 kg for the diet group (P < .0001), and –2.9 kg for the exercise group (P = .003). Body mass index also decreased in all groups: by –1.2 kg/m2 in the diet and exercise group (P = .001), by –2.0 kg/m² in the diet group (P < .0001), and by –1.0 kg/m² in the exercise group (P = .004).

Pain – as measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score – was reduced in all groups across 5-year follow-up: –1.2 (P = .03) for the diet and exercise group, –1.5 (P = .001) for the diet-only group, and –1.6 (P = .0008) for the exercise-only group. WOMAC function also significantly improved relative to baseline by 6.2 (P = .0001) in the diet and exercise group, by 6.1 (P < .0001) in the diet group, and by 3.7 (P = .01) in the exercise-only group.
 

Finding time to advise on weight loss, exercise

“If exercise and weight loss were easy, this country wouldn’t be in the state we’re in,” Tuhina Neogi, MD, PhD, of Boston University said in an interview. “Shared decision-making and personalized medicine are important; unfortunately, for the majority of physicians – particularly primary care physicians, where a good deal of OA management is undertaken – they don’t have a lot of time in their 20 minutes with a patient who has OA to counsel individuals toward a healthy weight and physical activity program when they’re also addressing common comorbidities seen in OA such as diabetes and heart disease.

“But as we know,” she added, “when you do address weight loss and physical activity, it has wide-ranging health benefits. This study provides support for utilizing formal diet and exercise programs to achieve important and durable benefits for people with OA.”

Dr. Neogi did note one of the study’s acknowledged limitations: Only slightly more than half of the contacted participants returned for follow-up. Though the authors stated that the individuals who returned were representative of both the pool of potential participants and the IDEA cohort as a whole, “we don’t want to make too many inferences when you don’t have the whole study population available,” she said. “The people who have agreed to come back 3.5 years later for follow-up testing, maybe they are a little more health conscious, more resilient. Those people might be systematically different than the people who [did not return], even though most of the factors were not statistically different between the groups.

“Whatever positive attributes they may have, though, we need to understand more about them,” she added. “We need to know how they maintained the benefits they had 3.5 years prior. That kind of understanding is important to inform long-term strategies in OA management.”

Dr. Messier highlighted a related, ongoing study he’s leading in which more than 800 overweight patients in North Carolina who suffer from knee pain are being led through diet and exercise interventions in a community setting. The goal is to replicate the IDEA results outside of a clinical trial setting and show skeptical physicians that diet and exercise can be enacted and maintained in this subset of patients.

“I think we know how effective weight loss is, especially when combined with exercise, in reducing pain, improving function, improving quality of life in these patients,” he said. “The next step is to allow them to maintain those benefits for a long period of time after the intervention ends.”

The study was supported by grants from the National Institutes of Health and by General Nutrition Centers. Its authors reported no potential conflicts of interest.

Older patients with knee osteoarthritis (OA) who underwent lengthy diet and exercise interventions reported less pain and maintained some weight loss years after the program ended, according to a new study published in Arthritis Care & Research.

AlexRaths/Getty Images

“These data imply that clinicians who treat people with knee osteoarthritis have a variety of nonpharmacologic options that preserve clinically important effects 3.5 years after the treatments end,” wrote lead author Stephen P. Messier, PhD, professor and director of the J.B. Snow Biomechanics Laboratory at Wake Forest University, Winston-Salem, N.C.

The study involved patients with overweight or obesity aged 55 years or older who were previously enrolled in the 1.5-year Intensive Diet and Exercise for Arthritis (IDEA) trial.

“You have to remember, this is 3.5 years after the IDEA trial ended,” Dr. Messier said in an interview. “There was no contact with them for that entire time; you’d expect, based on the literature, that they’d revert back to where they were before they entered the trial. And certainly, there was some regression, there was some weight regain, but the important part of the study is that, even after 3.5 years, and even with some weight regain, there were some clinically important effects that lasted.”

“What we feel now is that if we can somehow prepare people better for that time after they finish a weight loss intervention, from a psychological standpoint, it will make a real difference,” he added. “We are very good at helping people have the confidence to lose weight. But having the confidence to lose weight is totally different than having confidence to maintain weight loss. If we can give folks an intervention that has a psychological component, hopefully we can increase their confidence to maintain the weight loss that they attained.”
 

Study details

Of the 184 participants who were contacted for a follow-up visit, 94 consented to participate, 67% of whom were females and 88% of whom were White. A total of 27 participants had completed the diet and exercise intervention, and another 35 completed the diet-only and 32 exercise-only interventions.

In the 3.5-year period between the IDEA trial’s end and follow-up, body weight increased by 5.9 kg in the diet and exercise group (P < .0001) and by 3.1 kg in the diet-only group (P = .0006) but decreased in the exercise-only group by 1.0 kg (P = .25). However, from baseline to 5-year follow-up, all groups saw a reduction in body weight. Mean weight loss was –3.7 kg for the diet and exercise group (P = .0007), –5.8 kg for the diet group (P < .0001), and –2.9 kg for the exercise group (P = .003). Body mass index also decreased in all groups: by –1.2 kg/m2 in the diet and exercise group (P = .001), by –2.0 kg/m² in the diet group (P < .0001), and by –1.0 kg/m² in the exercise group (P = .004).

Pain – as measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score – was reduced in all groups across 5-year follow-up: –1.2 (P = .03) for the diet and exercise group, –1.5 (P = .001) for the diet-only group, and –1.6 (P = .0008) for the exercise-only group. WOMAC function also significantly improved relative to baseline by 6.2 (P = .0001) in the diet and exercise group, by 6.1 (P < .0001) in the diet group, and by 3.7 (P = .01) in the exercise-only group.
 

Finding time to advise on weight loss, exercise

“If exercise and weight loss were easy, this country wouldn’t be in the state we’re in,” Tuhina Neogi, MD, PhD, of Boston University said in an interview. “Shared decision-making and personalized medicine are important; unfortunately, for the majority of physicians – particularly primary care physicians, where a good deal of OA management is undertaken – they don’t have a lot of time in their 20 minutes with a patient who has OA to counsel individuals toward a healthy weight and physical activity program when they’re also addressing common comorbidities seen in OA such as diabetes and heart disease.

“But as we know,” she added, “when you do address weight loss and physical activity, it has wide-ranging health benefits. This study provides support for utilizing formal diet and exercise programs to achieve important and durable benefits for people with OA.”

Dr. Neogi did note one of the study’s acknowledged limitations: Only slightly more than half of the contacted participants returned for follow-up. Though the authors stated that the individuals who returned were representative of both the pool of potential participants and the IDEA cohort as a whole, “we don’t want to make too many inferences when you don’t have the whole study population available,” she said. “The people who have agreed to come back 3.5 years later for follow-up testing, maybe they are a little more health conscious, more resilient. Those people might be systematically different than the people who [did not return], even though most of the factors were not statistically different between the groups.

“Whatever positive attributes they may have, though, we need to understand more about them,” she added. “We need to know how they maintained the benefits they had 3.5 years prior. That kind of understanding is important to inform long-term strategies in OA management.”

Dr. Messier highlighted a related, ongoing study he’s leading in which more than 800 overweight patients in North Carolina who suffer from knee pain are being led through diet and exercise interventions in a community setting. The goal is to replicate the IDEA results outside of a clinical trial setting and show skeptical physicians that diet and exercise can be enacted and maintained in this subset of patients.

“I think we know how effective weight loss is, especially when combined with exercise, in reducing pain, improving function, improving quality of life in these patients,” he said. “The next step is to allow them to maintain those benefits for a long period of time after the intervention ends.”

The study was supported by grants from the National Institutes of Health and by General Nutrition Centers. Its authors reported no potential conflicts of interest.

Older patients with knee osteoarthritis (OA) who underwent lengthy diet and exercise interventions reported less pain and maintained some weight loss years after the program ended, according to a new study published in Arthritis Care & Research.

AlexRaths/Getty Images

“These data imply that clinicians who treat people with knee osteoarthritis have a variety of nonpharmacologic options that preserve clinically important effects 3.5 years after the treatments end,” wrote lead author Stephen P. Messier, PhD, professor and director of the J.B. Snow Biomechanics Laboratory at Wake Forest University, Winston-Salem, N.C.

The study involved patients with overweight or obesity aged 55 years or older who were previously enrolled in the 1.5-year Intensive Diet and Exercise for Arthritis (IDEA) trial.

“You have to remember, this is 3.5 years after the IDEA trial ended,” Dr. Messier said in an interview. “There was no contact with them for that entire time; you’d expect, based on the literature, that they’d revert back to where they were before they entered the trial. And certainly, there was some regression, there was some weight regain, but the important part of the study is that, even after 3.5 years, and even with some weight regain, there were some clinically important effects that lasted.”

“What we feel now is that if we can somehow prepare people better for that time after they finish a weight loss intervention, from a psychological standpoint, it will make a real difference,” he added. “We are very good at helping people have the confidence to lose weight. But having the confidence to lose weight is totally different than having confidence to maintain weight loss. If we can give folks an intervention that has a psychological component, hopefully we can increase their confidence to maintain the weight loss that they attained.”
 

Study details

Of the 184 participants who were contacted for a follow-up visit, 94 consented to participate, 67% of whom were females and 88% of whom were White. A total of 27 participants had completed the diet and exercise intervention, and another 35 completed the diet-only and 32 exercise-only interventions.

In the 3.5-year period between the IDEA trial’s end and follow-up, body weight increased by 5.9 kg in the diet and exercise group (P < .0001) and by 3.1 kg in the diet-only group (P = .0006) but decreased in the exercise-only group by 1.0 kg (P = .25). However, from baseline to 5-year follow-up, all groups saw a reduction in body weight. Mean weight loss was –3.7 kg for the diet and exercise group (P = .0007), –5.8 kg for the diet group (P < .0001), and –2.9 kg for the exercise group (P = .003). Body mass index also decreased in all groups: by –1.2 kg/m2 in the diet and exercise group (P = .001), by –2.0 kg/m² in the diet group (P < .0001), and by –1.0 kg/m² in the exercise group (P = .004).

Pain – as measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score – was reduced in all groups across 5-year follow-up: –1.2 (P = .03) for the diet and exercise group, –1.5 (P = .001) for the diet-only group, and –1.6 (P = .0008) for the exercise-only group. WOMAC function also significantly improved relative to baseline by 6.2 (P = .0001) in the diet and exercise group, by 6.1 (P < .0001) in the diet group, and by 3.7 (P = .01) in the exercise-only group.
 

Finding time to advise on weight loss, exercise

“If exercise and weight loss were easy, this country wouldn’t be in the state we’re in,” Tuhina Neogi, MD, PhD, of Boston University said in an interview. “Shared decision-making and personalized medicine are important; unfortunately, for the majority of physicians – particularly primary care physicians, where a good deal of OA management is undertaken – they don’t have a lot of time in their 20 minutes with a patient who has OA to counsel individuals toward a healthy weight and physical activity program when they’re also addressing common comorbidities seen in OA such as diabetes and heart disease.

“But as we know,” she added, “when you do address weight loss and physical activity, it has wide-ranging health benefits. This study provides support for utilizing formal diet and exercise programs to achieve important and durable benefits for people with OA.”

Dr. Neogi did note one of the study’s acknowledged limitations: Only slightly more than half of the contacted participants returned for follow-up. Though the authors stated that the individuals who returned were representative of both the pool of potential participants and the IDEA cohort as a whole, “we don’t want to make too many inferences when you don’t have the whole study population available,” she said. “The people who have agreed to come back 3.5 years later for follow-up testing, maybe they are a little more health conscious, more resilient. Those people might be systematically different than the people who [did not return], even though most of the factors were not statistically different between the groups.

“Whatever positive attributes they may have, though, we need to understand more about them,” she added. “We need to know how they maintained the benefits they had 3.5 years prior. That kind of understanding is important to inform long-term strategies in OA management.”

Dr. Messier highlighted a related, ongoing study he’s leading in which more than 800 overweight patients in North Carolina who suffer from knee pain are being led through diet and exercise interventions in a community setting. The goal is to replicate the IDEA results outside of a clinical trial setting and show skeptical physicians that diet and exercise can be enacted and maintained in this subset of patients.

“I think we know how effective weight loss is, especially when combined with exercise, in reducing pain, improving function, improving quality of life in these patients,” he said. “The next step is to allow them to maintain those benefits for a long period of time after the intervention ends.”

The study was supported by grants from the National Institutes of Health and by General Nutrition Centers. Its authors reported no potential conflicts of interest.

Drink to your health?

Whether you drink or not, most of us can agree that liquor is not the first thing that comes to mind when looking to make health improvements. But researchers have found a small exception in something traditional.

Xvision/Moment

We’ve added buckwheat to pancakes, bread, and other baked goodies we made during the height of quarantine, but it’s also used to create a traditional liquor in some East Asian countries, where it is used medicinally.

Investigators have found that extracts in the Tartary buckwheat used to make the liquor induce autophagy, a process cells go through to remove proteins that are damaged or not needed anymore – sort of like a cellular spring cleaning.

To test this, the researchers treated liver and skin cells with Tartary buckwheat extract and looked to see how the cells responded with fluorescent markers. The results were clear.

“Treating cells with the extract stimulated the formation of autophagosomes, specialized cellular structures that carry out autophagy, and altered the location of proteins involved in regulating autophagy,” said senior author Takeshi Noda of Osaka (Japan) University.

Looking deeper, the researchers found that quercetin, a component of the buckwheat extract, had the same autophagic effect. And both the buckwheat and the quercetin gave the green light for liver cells to induce aggrephagy, the process of cleaning up protein aggregates.

Those protein aggregates in liver cells are closely linked to alcoholic liver disease, suggesting that quercetin could be a game changer in its treatment. In other words, liquor could help fix the problem that liquor started. Go figure.
 

From hospital bills to X-rated

Ralph Puglisi was an accounting manager for the University Medical Service Association (UMSA), a nonprofit that supports the massive University of South Florida health system. The association took in over $300 million in revenue in the 2019-2020 fiscal year, which is a rather large sum of money, but we’ll glide over the ethics of a “nonprofit” making a few hundred million for now.

wakila/Getty Images

Mr. Puglisi was in very close proximity to the money, generated from patient care, and he pled guilty to stealing it using UMSA credit cards. Now, that wouldn’t be LOTME worthy on its own, but what elevates this above garden-variety embezzlement is how the intrepid Mr. Puglisi chose to spend the millions he stole from the university health system: Adult entertainment.

And before you ask, he didn’t spend $11.5 million on something most people so inclined can find for free with judicious Google searches. What Mr. Puglisi actually did was invest in a website providing adult content through individual user profiles, one of which is believed to belong to his stepson’s fiancée, which brings a whole new level of sleaze to this enterprise. Over the course of 2 years, he visited her profile 2,800 times, an amount some might view as excessive.

While the vast majority of the embezzled money went to the adult website, Mr. Puglisi also used thousands of UMSA dollars to pay for travel, household improvements, rent, the works. Almost $44,000 was spent at a resort sometimes known as the happiest place on earth.

Then there’s Mr. Puglisi’s wife. Oh yes, this guy is married. He poured over $600,000 into a company he and his wife owned, which is a lot, but how much do you think went to the woman he married? Probably quite a bit. Go ahead, try to think of a number. It’s not like it was his money.

Did you guess $100 went into his wife’s PayPal account? No? Clearly you don’t understand the criminal mind. His stepson’s fiancée got millions, and his wife got a hundred. Now there are some priorities.
 

Step 1: Sit at desk. Step 2: Get in shape

Being a physician is not really a desk job, but doctors must spend a fair share of their time sitting, yes? Dealing with recalcitrant EHRs or talking on the phone to insurers or PBMs? If you are one of these physicians, or if you have patients who spend a lot of time sitting at their desks and might need to get a bit of exercise, then we’ve got a multitasking tip for you.

Mohamed Hassan/pxhere

It came to us via one of our favorite websites, Sad and Useless. It’s the site that declares itself “the most depressive humor site on the Internet” and they’re offering up the “12 Best Exercises To Do At Your Desk.” It may not sound like much, but we think that the gang at Dunder-Mifflin would approve. And besides, who couldn’t stand to burn a few calories without having to leave the chair?

We won’t spoil your fun by going through all 12 – each one comes with step-by-step instructions and a helpful illustration or GIF – but here are just a few:

• Bending over backwards: “Agree to do something you don’t want to do. Spend twice as long as expected doing that thing. Hate yourself.”
• Fake laughter: “Hear a joke that isn’t even remotely funny. Open your mouth and make laughing sounds.”
• Bang your head: Feel the “pointlessness of your job overwhelm you” and then “bring your head forcefully down to your desk.”

Now, we here at LOTME are, of course [Bang!], highly skilled, professional wordsmithing humorists [Bang!], so when we tell you that this is a great workout [Bang!] … that this is a great workout [Bang!] … it’s great … uggh.

Wooooo. Feel the burn.
 

One order of mosquitoes, extra Crispr

What would it be like to have a barbecue in your backyard on a humid summer night and not get eaten alive by mosquitoes? If you’re like us, you probably thought you’d never see that day.

©TacioPhilip/Thinkstock

Mosquitoes cause itchy bites, but, more importantly, they can carry dengue, malaria, yellow fever, and Zika virus. New research shows that protection from these diseases may be possible with use of the Crispr-Cas9 gene-editing tool, which could make humans invisible to mosquitoes by taking away their light-sensing abilities and, thus, their ability to find us.

“The better we understand how they sense the human, the better we can control the mosquito in an eco-friendly manner,” Yinpeng Zhan, a postdoctoral researcher at the University of California, Santa Barbara, and the study’s lead author, told the New York Times.

After studying the mosquitoes and figuring out their hunting patterns, the researchers found that mosquitoes are attracted to dark spots more than white spots and used this to their advantage. After knocking out two of the proteins that mosquitoes need for vision – via Crispr – the little suckers could not distinguish the difference between the white and dark spots.

We’re sure mosquitoes don’t mean any harm – they’re just trying to survive and reproduce like any other species – but thanks to this new tool, gone might be the days of having to douse yourself in bug spray that smells like a mix of chemicals and melon.

Drink to your health?

Whether you drink or not, most of us can agree that liquor is not the first thing that comes to mind when looking to make health improvements. But researchers have found a small exception in something traditional.

Xvision/Moment

We’ve added buckwheat to pancakes, bread, and other baked goodies we made during the height of quarantine, but it’s also used to create a traditional liquor in some East Asian countries, where it is used medicinally.

Investigators have found that extracts in the Tartary buckwheat used to make the liquor induce autophagy, a process cells go through to remove proteins that are damaged or not needed anymore – sort of like a cellular spring cleaning.

To test this, the researchers treated liver and skin cells with Tartary buckwheat extract and looked to see how the cells responded with fluorescent markers. The results were clear.

“Treating cells with the extract stimulated the formation of autophagosomes, specialized cellular structures that carry out autophagy, and altered the location of proteins involved in regulating autophagy,” said senior author Takeshi Noda of Osaka (Japan) University.

Looking deeper, the researchers found that quercetin, a component of the buckwheat extract, had the same autophagic effect. And both the buckwheat and the quercetin gave the green light for liver cells to induce aggrephagy, the process of cleaning up protein aggregates.

Those protein aggregates in liver cells are closely linked to alcoholic liver disease, suggesting that quercetin could be a game changer in its treatment. In other words, liquor could help fix the problem that liquor started. Go figure.
 

From hospital bills to X-rated

Ralph Puglisi was an accounting manager for the University Medical Service Association (UMSA), a nonprofit that supports the massive University of South Florida health system. The association took in over $300 million in revenue in the 2019-2020 fiscal year, which is a rather large sum of money, but we’ll glide over the ethics of a “nonprofit” making a few hundred million for now.

wakila/Getty Images

Mr. Puglisi was in very close proximity to the money, generated from patient care, and he pled guilty to stealing it using UMSA credit cards. Now, that wouldn’t be LOTME worthy on its own, but what elevates this above garden-variety embezzlement is how the intrepid Mr. Puglisi chose to spend the millions he stole from the university health system: Adult entertainment.

And before you ask, he didn’t spend $11.5 million on something most people so inclined can find for free with judicious Google searches. What Mr. Puglisi actually did was invest in a website providing adult content through individual user profiles, one of which is believed to belong to his stepson’s fiancée, which brings a whole new level of sleaze to this enterprise. Over the course of 2 years, he visited her profile 2,800 times, an amount some might view as excessive.

While the vast majority of the embezzled money went to the adult website, Mr. Puglisi also used thousands of UMSA dollars to pay for travel, household improvements, rent, the works. Almost $44,000 was spent at a resort sometimes known as the happiest place on earth.

Then there’s Mr. Puglisi’s wife. Oh yes, this guy is married. He poured over $600,000 into a company he and his wife owned, which is a lot, but how much do you think went to the woman he married? Probably quite a bit. Go ahead, try to think of a number. It’s not like it was his money.

Did you guess $100 went into his wife’s PayPal account? No? Clearly you don’t understand the criminal mind. His stepson’s fiancée got millions, and his wife got a hundred. Now there are some priorities.
 

Step 1: Sit at desk. Step 2: Get in shape

Being a physician is not really a desk job, but doctors must spend a fair share of their time sitting, yes? Dealing with recalcitrant EHRs or talking on the phone to insurers or PBMs? If you are one of these physicians, or if you have patients who spend a lot of time sitting at their desks and might need to get a bit of exercise, then we’ve got a multitasking tip for you.

Mohamed Hassan/pxhere

It came to us via one of our favorite websites, Sad and Useless. It’s the site that declares itself “the most depressive humor site on the Internet” and they’re offering up the “12 Best Exercises To Do At Your Desk.” It may not sound like much, but we think that the gang at Dunder-Mifflin would approve. And besides, who couldn’t stand to burn a few calories without having to leave the chair?

We won’t spoil your fun by going through all 12 – each one comes with step-by-step instructions and a helpful illustration or GIF – but here are just a few:

• Bending over backwards: “Agree to do something you don’t want to do. Spend twice as long as expected doing that thing. Hate yourself.”
• Fake laughter: “Hear a joke that isn’t even remotely funny. Open your mouth and make laughing sounds.”
• Bang your head: Feel the “pointlessness of your job overwhelm you” and then “bring your head forcefully down to your desk.”

Now, we here at LOTME are, of course [Bang!], highly skilled, professional wordsmithing humorists [Bang!], so when we tell you that this is a great workout [Bang!] … that this is a great workout [Bang!] … it’s great … uggh.

Wooooo. Feel the burn.
 

One order of mosquitoes, extra Crispr

What would it be like to have a barbecue in your backyard on a humid summer night and not get eaten alive by mosquitoes? If you’re like us, you probably thought you’d never see that day.

©TacioPhilip/Thinkstock

Mosquitoes cause itchy bites, but, more importantly, they can carry dengue, malaria, yellow fever, and Zika virus. New research shows that protection from these diseases may be possible with use of the Crispr-Cas9 gene-editing tool, which could make humans invisible to mosquitoes by taking away their light-sensing abilities and, thus, their ability to find us.

“The better we understand how they sense the human, the better we can control the mosquito in an eco-friendly manner,” Yinpeng Zhan, a postdoctoral researcher at the University of California, Santa Barbara, and the study’s lead author, told the New York Times.

After studying the mosquitoes and figuring out their hunting patterns, the researchers found that mosquitoes are attracted to dark spots more than white spots and used this to their advantage. After knocking out two of the proteins that mosquitoes need for vision – via Crispr – the little suckers could not distinguish the difference between the white and dark spots.

We’re sure mosquitoes don’t mean any harm – they’re just trying to survive and reproduce like any other species – but thanks to this new tool, gone might be the days of having to douse yourself in bug spray that smells like a mix of chemicals and melon.

Drink to your health?

Whether you drink or not, most of us can agree that liquor is not the first thing that comes to mind when looking to make health improvements. But researchers have found a small exception in something traditional.

Xvision/Moment

We’ve added buckwheat to pancakes, bread, and other baked goodies we made during the height of quarantine, but it’s also used to create a traditional liquor in some East Asian countries, where it is used medicinally.

Investigators have found that extracts in the Tartary buckwheat used to make the liquor induce autophagy, a process cells go through to remove proteins that are damaged or not needed anymore – sort of like a cellular spring cleaning.

To test this, the researchers treated liver and skin cells with Tartary buckwheat extract and looked to see how the cells responded with fluorescent markers. The results were clear.

“Treating cells with the extract stimulated the formation of autophagosomes, specialized cellular structures that carry out autophagy, and altered the location of proteins involved in regulating autophagy,” said senior author Takeshi Noda of Osaka (Japan) University.

Looking deeper, the researchers found that quercetin, a component of the buckwheat extract, had the same autophagic effect. And both the buckwheat and the quercetin gave the green light for liver cells to induce aggrephagy, the process of cleaning up protein aggregates.

Those protein aggregates in liver cells are closely linked to alcoholic liver disease, suggesting that quercetin could be a game changer in its treatment. In other words, liquor could help fix the problem that liquor started. Go figure.
 

From hospital bills to X-rated

Ralph Puglisi was an accounting manager for the University Medical Service Association (UMSA), a nonprofit that supports the massive University of South Florida health system. The association took in over $300 million in revenue in the 2019-2020 fiscal year, which is a rather large sum of money, but we’ll glide over the ethics of a “nonprofit” making a few hundred million for now.

wakila/Getty Images

Mr. Puglisi was in very close proximity to the money, generated from patient care, and he pled guilty to stealing it using UMSA credit cards. Now, that wouldn’t be LOTME worthy on its own, but what elevates this above garden-variety embezzlement is how the intrepid Mr. Puglisi chose to spend the millions he stole from the university health system: Adult entertainment.

And before you ask, he didn’t spend $11.5 million on something most people so inclined can find for free with judicious Google searches. What Mr. Puglisi actually did was invest in a website providing adult content through individual user profiles, one of which is believed to belong to his stepson’s fiancée, which brings a whole new level of sleaze to this enterprise. Over the course of 2 years, he visited her profile 2,800 times, an amount some might view as excessive.

While the vast majority of the embezzled money went to the adult website, Mr. Puglisi also used thousands of UMSA dollars to pay for travel, household improvements, rent, the works. Almost $44,000 was spent at a resort sometimes known as the happiest place on earth.

Then there’s Mr. Puglisi’s wife. Oh yes, this guy is married. He poured over $600,000 into a company he and his wife owned, which is a lot, but how much do you think went to the woman he married? Probably quite a bit. Go ahead, try to think of a number. It’s not like it was his money.

Did you guess $100 went into his wife’s PayPal account? No? Clearly you don’t understand the criminal mind. His stepson’s fiancée got millions, and his wife got a hundred. Now there are some priorities.
 

Step 1: Sit at desk. Step 2: Get in shape

Being a physician is not really a desk job, but doctors must spend a fair share of their time sitting, yes? Dealing with recalcitrant EHRs or talking on the phone to insurers or PBMs? If you are one of these physicians, or if you have patients who spend a lot of time sitting at their desks and might need to get a bit of exercise, then we’ve got a multitasking tip for you.

Mohamed Hassan/pxhere

It came to us via one of our favorite websites, Sad and Useless. It’s the site that declares itself “the most depressive humor site on the Internet” and they’re offering up the “12 Best Exercises To Do At Your Desk.” It may not sound like much, but we think that the gang at Dunder-Mifflin would approve. And besides, who couldn’t stand to burn a few calories without having to leave the chair?

We won’t spoil your fun by going through all 12 – each one comes with step-by-step instructions and a helpful illustration or GIF – but here are just a few:

• Bending over backwards: “Agree to do something you don’t want to do. Spend twice as long as expected doing that thing. Hate yourself.”
• Fake laughter: “Hear a joke that isn’t even remotely funny. Open your mouth and make laughing sounds.”
• Bang your head: Feel the “pointlessness of your job overwhelm you” and then “bring your head forcefully down to your desk.”

Now, we here at LOTME are, of course [Bang!], highly skilled, professional wordsmithing humorists [Bang!], so when we tell you that this is a great workout [Bang!] … that this is a great workout [Bang!] … it’s great … uggh.

Wooooo. Feel the burn.
 

One order of mosquitoes, extra Crispr

What would it be like to have a barbecue in your backyard on a humid summer night and not get eaten alive by mosquitoes? If you’re like us, you probably thought you’d never see that day.

©TacioPhilip/Thinkstock

Mosquitoes cause itchy bites, but, more importantly, they can carry dengue, malaria, yellow fever, and Zika virus. New research shows that protection from these diseases may be possible with use of the Crispr-Cas9 gene-editing tool, which could make humans invisible to mosquitoes by taking away their light-sensing abilities and, thus, their ability to find us.

“The better we understand how they sense the human, the better we can control the mosquito in an eco-friendly manner,” Yinpeng Zhan, a postdoctoral researcher at the University of California, Santa Barbara, and the study’s lead author, told the New York Times.

After studying the mosquitoes and figuring out their hunting patterns, the researchers found that mosquitoes are attracted to dark spots more than white spots and used this to their advantage. After knocking out two of the proteins that mosquitoes need for vision – via Crispr – the little suckers could not distinguish the difference between the white and dark spots.

We’re sure mosquitoes don’t mean any harm – they’re just trying to survive and reproduce like any other species – but thanks to this new tool, gone might be the days of having to douse yourself in bug spray that smells like a mix of chemicals and melon.

A 64-year-old White woman with very few medical problems complains of bug bites. She had seen no bugs and had no visible bites. There is no rash. “So what bit me?” she asked, pulling her mask down for emphasis. How should I know? I thought, but didn’t say. She and I have been through this many times.

Before I could respond, she filled the pause with her usual complaints including how hard it is to get an appointment with me and how every appointment with me is a waste of her time. Ignoring the contradistinction of her charges, I took some satisfaction realizing she has just given me a topic to write about: The hateful patient.

Hateful patients are not diagnostic dilemmas, they are the patients whose name on your schedule evokes fury. They are frustrating, troublesome, rude, sometimes racist, misogynistic, depressing, hopeless, and disheartening. They call you, email you, and come to see you just to annoy you (so it seems). And they’re everywhere. According to one study, nearly one in six are “difficult patients.” It feels like more lately because the vaccine has brought haters back into clinic, just to get us.

But hateful patients aren’t new. In 1978, James E. Groves, MD, a Harvard psychiatrist, wrote a now-classic New England Journal of Medicine article about them called: Taking Care of the Hateful Patient. Even Osler, back in 1889, covered these patients in his lecture to University of Pennsylvania students, advising us to “deal gently with this deliciously credulous old human nature in which we work ... restrain your indignation.” But like much of Osler’s advice, it is easier said than done.

Dr. Groves is more helpful, and presents a model to understand them. Difficult patients, as we’d now call them, fall into four stereotypes: dependent clingers, entitled demanders, manipulative help-rejectors, and self-destructive deniers. It’s Dr. Groves’s bottom line I found insightful. He says that, when patients create negative feelings in us, we’re more likely to make errors. He then gives sound advice: Set firm boundaries and learn to counter the countertransference these patients provoke. Don’t disavow or discharge, Dr. Groves advises, redirect these emotions to motivate you to dig deeper. There you’ll find clinical data that will facilitate understanding and enable better patient management. Yes, easier said.

In addition to Dr. Groves’s analysis of how we harm these patients, I’d add that these disagreeable, malingering patients also harm us doctors. The hangover from a difficult patient encounter can linger for several appointments later or, worse, carryover to home. And now with patient emails proliferating, demanding patients behave as if we have an inexhaustible ability to engage them. We don’t. Many physicians are struggling to care at all; their low empathy battery warnings are blinking red, less than 1% remaining.

What is toxic to us doctors is the maelstrom of cognitive dissonance these patients create in us. Have you ever felt relief to learn a difficult patient has “finally” died? How could we think such a thing?! Didn’t we choose medicine instead of Wall Street because we care about people? But manipulative patients can make us care less. We even use secret language with each other to protect ourselves from them, those GOMERs (get out of my emergency room), bouncebacks, patients with status dramaticus, and those ornery FTDs (failure to die). Save yourself, we say to each other, this patient will kill you.

Caring for my somatizing 64-year-old patient has been difficult, but writing this has helped me reframe our interaction. Unsurprisingly, at the end of her failed visit she asked when she could see me again. “I need to schedule now because I have to find a neighbor to watch my dogs. It takes two buses to come here and I can’t take them with me.” Ah, there’s the clinical data Dr. Groves said I’d find – she’s not here to hurt me, she’s here because I’m all she’s got. At least for this difficult patient, I have a plan. At the bottom of my note I type “RTC 3 mo.”

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

A 64-year-old White woman with very few medical problems complains of bug bites. She had seen no bugs and had no visible bites. There is no rash. “So what bit me?” she asked, pulling her mask down for emphasis. How should I know? I thought, but didn’t say. She and I have been through this many times.

Before I could respond, she filled the pause with her usual complaints including how hard it is to get an appointment with me and how every appointment with me is a waste of her time. Ignoring the contradistinction of her charges, I took some satisfaction realizing she has just given me a topic to write about: The hateful patient.

Hateful patients are not diagnostic dilemmas, they are the patients whose name on your schedule evokes fury. They are frustrating, troublesome, rude, sometimes racist, misogynistic, depressing, hopeless, and disheartening. They call you, email you, and come to see you just to annoy you (so it seems). And they’re everywhere. According to one study, nearly one in six are “difficult patients.” It feels like more lately because the vaccine has brought haters back into clinic, just to get us.

But hateful patients aren’t new. In 1978, James E. Groves, MD, a Harvard psychiatrist, wrote a now-classic New England Journal of Medicine article about them called: Taking Care of the Hateful Patient. Even Osler, back in 1889, covered these patients in his lecture to University of Pennsylvania students, advising us to “deal gently with this deliciously credulous old human nature in which we work ... restrain your indignation.” But like much of Osler’s advice, it is easier said than done.

Dr. Groves is more helpful, and presents a model to understand them. Difficult patients, as we’d now call them, fall into four stereotypes: dependent clingers, entitled demanders, manipulative help-rejectors, and self-destructive deniers. It’s Dr. Groves’s bottom line I found insightful. He says that, when patients create negative feelings in us, we’re more likely to make errors. He then gives sound advice: Set firm boundaries and learn to counter the countertransference these patients provoke. Don’t disavow or discharge, Dr. Groves advises, redirect these emotions to motivate you to dig deeper. There you’ll find clinical data that will facilitate understanding and enable better patient management. Yes, easier said.

In addition to Dr. Groves’s analysis of how we harm these patients, I’d add that these disagreeable, malingering patients also harm us doctors. The hangover from a difficult patient encounter can linger for several appointments later or, worse, carryover to home. And now with patient emails proliferating, demanding patients behave as if we have an inexhaustible ability to engage them. We don’t. Many physicians are struggling to care at all; their low empathy battery warnings are blinking red, less than 1% remaining.

What is toxic to us doctors is the maelstrom of cognitive dissonance these patients create in us. Have you ever felt relief to learn a difficult patient has “finally” died? How could we think such a thing?! Didn’t we choose medicine instead of Wall Street because we care about people? But manipulative patients can make us care less. We even use secret language with each other to protect ourselves from them, those GOMERs (get out of my emergency room), bouncebacks, patients with status dramaticus, and those ornery FTDs (failure to die). Save yourself, we say to each other, this patient will kill you.

Caring for my somatizing 64-year-old patient has been difficult, but writing this has helped me reframe our interaction. Unsurprisingly, at the end of her failed visit she asked when she could see me again. “I need to schedule now because I have to find a neighbor to watch my dogs. It takes two buses to come here and I can’t take them with me.” Ah, there’s the clinical data Dr. Groves said I’d find – she’s not here to hurt me, she’s here because I’m all she’s got. At least for this difficult patient, I have a plan. At the bottom of my note I type “RTC 3 mo.”

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

A 64-year-old White woman with very few medical problems complains of bug bites. She had seen no bugs and had no visible bites. There is no rash. “So what bit me?” she asked, pulling her mask down for emphasis. How should I know? I thought, but didn’t say. She and I have been through this many times.

Before I could respond, she filled the pause with her usual complaints including how hard it is to get an appointment with me and how every appointment with me is a waste of her time. Ignoring the contradistinction of her charges, I took some satisfaction realizing she has just given me a topic to write about: The hateful patient.

Hateful patients are not diagnostic dilemmas, they are the patients whose name on your schedule evokes fury. They are frustrating, troublesome, rude, sometimes racist, misogynistic, depressing, hopeless, and disheartening. They call you, email you, and come to see you just to annoy you (so it seems). And they’re everywhere. According to one study, nearly one in six are “difficult patients.” It feels like more lately because the vaccine has brought haters back into clinic, just to get us.

But hateful patients aren’t new. In 1978, James E. Groves, MD, a Harvard psychiatrist, wrote a now-classic New England Journal of Medicine article about them called: Taking Care of the Hateful Patient. Even Osler, back in 1889, covered these patients in his lecture to University of Pennsylvania students, advising us to “deal gently with this deliciously credulous old human nature in which we work ... restrain your indignation.” But like much of Osler’s advice, it is easier said than done.

Dr. Groves is more helpful, and presents a model to understand them. Difficult patients, as we’d now call them, fall into four stereotypes: dependent clingers, entitled demanders, manipulative help-rejectors, and self-destructive deniers. It’s Dr. Groves’s bottom line I found insightful. He says that, when patients create negative feelings in us, we’re more likely to make errors. He then gives sound advice: Set firm boundaries and learn to counter the countertransference these patients provoke. Don’t disavow or discharge, Dr. Groves advises, redirect these emotions to motivate you to dig deeper. There you’ll find clinical data that will facilitate understanding and enable better patient management. Yes, easier said.

In addition to Dr. Groves’s analysis of how we harm these patients, I’d add that these disagreeable, malingering patients also harm us doctors. The hangover from a difficult patient encounter can linger for several appointments later or, worse, carryover to home. And now with patient emails proliferating, demanding patients behave as if we have an inexhaustible ability to engage them. We don’t. Many physicians are struggling to care at all; their low empathy battery warnings are blinking red, less than 1% remaining.

What is toxic to us doctors is the maelstrom of cognitive dissonance these patients create in us. Have you ever felt relief to learn a difficult patient has “finally” died? How could we think such a thing?! Didn’t we choose medicine instead of Wall Street because we care about people? But manipulative patients can make us care less. We even use secret language with each other to protect ourselves from them, those GOMERs (get out of my emergency room), bouncebacks, patients with status dramaticus, and those ornery FTDs (failure to die). Save yourself, we say to each other, this patient will kill you.

Caring for my somatizing 64-year-old patient has been difficult, but writing this has helped me reframe our interaction. Unsurprisingly, at the end of her failed visit she asked when she could see me again. “I need to schedule now because I have to find a neighbor to watch my dogs. It takes two buses to come here and I can’t take them with me.” Ah, there’s the clinical data Dr. Groves said I’d find – she’s not here to hurt me, she’s here because I’m all she’s got. At least for this difficult patient, I have a plan. At the bottom of my note I type “RTC 3 mo.”

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