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Who’s in charge here? Rheumatologists battle local Medicare policies threatening access, practice sustainability

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Rheumatologists who administer medications in their office for Medicare patients, specifically those that are infused, have in recent years encountered problems providing certain medication formulations as well as coding and billing for their administration. In attempting to resolve these issues, rheumatologists and their professional organizations have found themselves caught in a morass of Medicare agency “ping-pong,” where it is unclear who the decision makers are.

The private health care insurers that process medical claims for Medicare beneficiaries, called A/B Medicare Administrative Contractors or more commonly known as MACs, are the operational intermediary between the Centers for Medicare & Medicaid Services’ fee-for-service program and the physicians enrolled in it. The country is divided into 12 sections, each with a MAC that has jurisdiction over that area. Among other things, the MACs establish local coverage and payment policies based on their understanding of CMS’ rules, regulations, and the Medicare statute, and therein lies the problem: When a physician has a question on a policy or decision that was made by a MAC, it is very difficult to determine the origins of the issue and who can address the problem. It’s a lot of “running in circles” between the MACs and CMS headquarters, hoping that someone will take the time to listen to your concern, but more importantly, work toward resolving the problem.

Dr. Madelaine Feldman

Who can address problems?

Meaningful, solutions-driven engagement with the MACs and CMS has become frustrating for physicians and advocacy organizations attempting to address a host of problems. The two issues alluded to above include the Self-Administered Drug Exclusion List (SAD List), which excludes certain Part B medication formulations from coverage under certain conditions and the “down coding” of certain infusion administration codes when specific drugs are delivered. These problems are compounded by the curtailment of physician stakeholder input via Contractor Advisory Committees (CACs). Each state has its own CAC, but the CAC meetings have been restructured as a result of the 21st Century Cures Act, and ultimately eradicated the involvement of these physician advisers in policy development at the local level.

This has left many of rheumatology representatives to the CACs demoralized and generally unhappy about certain decisions being made without their input. There is also inconsistency in terms of coverage and payment policies throughout the country. For example, in one MAC jurisdiction, a certain medication may be on the SAD List and excluded from Part B coverage, meaning beneficiary access is only available through Part D (and assuming they can afford it), while in an adjacent MAC jurisdiction, both formulations are covered.

The Coalition of State Rheumatology Organizations, along with the American College of Rheumatology and other specialty groups, is attempting to address these issues from many different angles. There is not enough space to explain the nuances of local coverage policy development, but the timeline below highlights the long and winding road that we have travelled to resolve these issues.

  • February 2021: CSRO meets with CMS’ Coverage and Analysis Group (CAG) to raise concerns about ustekinumab (Stelara) and its inclusion on the SAD List.
  • April 2021: CSRO follows up with CMS’ CAG on SAD List concerns in a letter.
  • May 2021: Most MACs issue or revise local coverage articles, or “billing and coding” articles, that down code the administration of certain biologic medications, with some expanding the list of biologic medications subject to the policy, prompting a strong response from CSRO.
  • September 2021: CSRO meets with multijurisdictional MAC Contract Medical Director (CMD) work group to discuss down coding, SAD List, and physician/CAC engagement.
  • October 2021: At the suggestion of the CMDs, CSRO re-engages with CMS’ CAG to raise concerns about down-coding policies and physician/CAC engagement, and continue the SAD List discussion.
  • November 2021: CSRO is connected with CMS’ “payment ombudsman” on down coding and the SAD List.
  • January 2022: CSRO signs on to multispecialty coalition effort aimed at improving local coverage and payment policy and restoring the importance of the CAC.
  • February 2022: CSRO participates in CMS CAG meeting with multispecialty coalition, raising concerns about the down-coding and SAD List policies.
  • March/April 2022: Through its coalition partner, the Alliance of Specialty Medicine, CSRO meets with the principal deputy CMS administrator and raises awareness to these issues.
  • May 2022: CSRO participates in follow-up discussion with CMS’ CAG as part of multispecialty coalition, reiterating concerns about the down coding and SAD List policies. With the assistance of the CMS’ Office of the Administrator, CSRO meets with CMS’ Center for Program Integrity to seek a “pause” in down-coding policies for certain biologic medications.
  • June 2022: CMS notifies CSRO of a “temporary pause” in medical review while the agency reviews various manuals and policies to determine the appropriate steps forward. To assist the agency, CSRO works with practices to develop a resource that CMS can use to establish criteria for determining when a medication warrants use of complex drug administration codes. CSRO re-engages with multijurisdictional MAC CMD workgroup to continue discussions on SAD List.
  • July 2022: CSRO meets with new multijurisdictional MAC CMD workgroup focused on improving the process for developing local coverage and payment policy.

Our dialogue with CMS leadership and staff continues. In the most recent communication, staff in the CMS administrator’s office informed us that the issue is complicated and crosses several different parts of the agency, and they are still determining next steps.



The rheumatology community’s journey toward solving the challenges facing practices and patients is emblematic of the communication problem between provider groups and the CMS-MAC establishment. While we understand this is how bureaucracy works, it is not to the benefit of Medicare beneficiaries to have a system that is so difficult to navigate, even by the best of the regulatory gurus. This is not an indictment of any specific group but a call to action on the part of the government and their contractors to create a clear, transparent path to getting answers when we have a problem.

And by the way, we do have another meeting with yet another CMS “center” regarding the SAD List in August.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is president of the CSRO, past chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

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Rheumatologists who administer medications in their office for Medicare patients, specifically those that are infused, have in recent years encountered problems providing certain medication formulations as well as coding and billing for their administration. In attempting to resolve these issues, rheumatologists and their professional organizations have found themselves caught in a morass of Medicare agency “ping-pong,” where it is unclear who the decision makers are.

The private health care insurers that process medical claims for Medicare beneficiaries, called A/B Medicare Administrative Contractors or more commonly known as MACs, are the operational intermediary between the Centers for Medicare & Medicaid Services’ fee-for-service program and the physicians enrolled in it. The country is divided into 12 sections, each with a MAC that has jurisdiction over that area. Among other things, the MACs establish local coverage and payment policies based on their understanding of CMS’ rules, regulations, and the Medicare statute, and therein lies the problem: When a physician has a question on a policy or decision that was made by a MAC, it is very difficult to determine the origins of the issue and who can address the problem. It’s a lot of “running in circles” between the MACs and CMS headquarters, hoping that someone will take the time to listen to your concern, but more importantly, work toward resolving the problem.

Dr. Madelaine Feldman

Who can address problems?

Meaningful, solutions-driven engagement with the MACs and CMS has become frustrating for physicians and advocacy organizations attempting to address a host of problems. The two issues alluded to above include the Self-Administered Drug Exclusion List (SAD List), which excludes certain Part B medication formulations from coverage under certain conditions and the “down coding” of certain infusion administration codes when specific drugs are delivered. These problems are compounded by the curtailment of physician stakeholder input via Contractor Advisory Committees (CACs). Each state has its own CAC, but the CAC meetings have been restructured as a result of the 21st Century Cures Act, and ultimately eradicated the involvement of these physician advisers in policy development at the local level.

This has left many of rheumatology representatives to the CACs demoralized and generally unhappy about certain decisions being made without their input. There is also inconsistency in terms of coverage and payment policies throughout the country. For example, in one MAC jurisdiction, a certain medication may be on the SAD List and excluded from Part B coverage, meaning beneficiary access is only available through Part D (and assuming they can afford it), while in an adjacent MAC jurisdiction, both formulations are covered.

The Coalition of State Rheumatology Organizations, along with the American College of Rheumatology and other specialty groups, is attempting to address these issues from many different angles. There is not enough space to explain the nuances of local coverage policy development, but the timeline below highlights the long and winding road that we have travelled to resolve these issues.

  • February 2021: CSRO meets with CMS’ Coverage and Analysis Group (CAG) to raise concerns about ustekinumab (Stelara) and its inclusion on the SAD List.
  • April 2021: CSRO follows up with CMS’ CAG on SAD List concerns in a letter.
  • May 2021: Most MACs issue or revise local coverage articles, or “billing and coding” articles, that down code the administration of certain biologic medications, with some expanding the list of biologic medications subject to the policy, prompting a strong response from CSRO.
  • September 2021: CSRO meets with multijurisdictional MAC Contract Medical Director (CMD) work group to discuss down coding, SAD List, and physician/CAC engagement.
  • October 2021: At the suggestion of the CMDs, CSRO re-engages with CMS’ CAG to raise concerns about down-coding policies and physician/CAC engagement, and continue the SAD List discussion.
  • November 2021: CSRO is connected with CMS’ “payment ombudsman” on down coding and the SAD List.
  • January 2022: CSRO signs on to multispecialty coalition effort aimed at improving local coverage and payment policy and restoring the importance of the CAC.
  • February 2022: CSRO participates in CMS CAG meeting with multispecialty coalition, raising concerns about the down-coding and SAD List policies.
  • March/April 2022: Through its coalition partner, the Alliance of Specialty Medicine, CSRO meets with the principal deputy CMS administrator and raises awareness to these issues.
  • May 2022: CSRO participates in follow-up discussion with CMS’ CAG as part of multispecialty coalition, reiterating concerns about the down coding and SAD List policies. With the assistance of the CMS’ Office of the Administrator, CSRO meets with CMS’ Center for Program Integrity to seek a “pause” in down-coding policies for certain biologic medications.
  • June 2022: CMS notifies CSRO of a “temporary pause” in medical review while the agency reviews various manuals and policies to determine the appropriate steps forward. To assist the agency, CSRO works with practices to develop a resource that CMS can use to establish criteria for determining when a medication warrants use of complex drug administration codes. CSRO re-engages with multijurisdictional MAC CMD workgroup to continue discussions on SAD List.
  • July 2022: CSRO meets with new multijurisdictional MAC CMD workgroup focused on improving the process for developing local coverage and payment policy.

Our dialogue with CMS leadership and staff continues. In the most recent communication, staff in the CMS administrator’s office informed us that the issue is complicated and crosses several different parts of the agency, and they are still determining next steps.



The rheumatology community’s journey toward solving the challenges facing practices and patients is emblematic of the communication problem between provider groups and the CMS-MAC establishment. While we understand this is how bureaucracy works, it is not to the benefit of Medicare beneficiaries to have a system that is so difficult to navigate, even by the best of the regulatory gurus. This is not an indictment of any specific group but a call to action on the part of the government and their contractors to create a clear, transparent path to getting answers when we have a problem.

And by the way, we do have another meeting with yet another CMS “center” regarding the SAD List in August.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is president of the CSRO, past chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

Rheumatologists who administer medications in their office for Medicare patients, specifically those that are infused, have in recent years encountered problems providing certain medication formulations as well as coding and billing for their administration. In attempting to resolve these issues, rheumatologists and their professional organizations have found themselves caught in a morass of Medicare agency “ping-pong,” where it is unclear who the decision makers are.

The private health care insurers that process medical claims for Medicare beneficiaries, called A/B Medicare Administrative Contractors or more commonly known as MACs, are the operational intermediary between the Centers for Medicare & Medicaid Services’ fee-for-service program and the physicians enrolled in it. The country is divided into 12 sections, each with a MAC that has jurisdiction over that area. Among other things, the MACs establish local coverage and payment policies based on their understanding of CMS’ rules, regulations, and the Medicare statute, and therein lies the problem: When a physician has a question on a policy or decision that was made by a MAC, it is very difficult to determine the origins of the issue and who can address the problem. It’s a lot of “running in circles” between the MACs and CMS headquarters, hoping that someone will take the time to listen to your concern, but more importantly, work toward resolving the problem.

Dr. Madelaine Feldman

Who can address problems?

Meaningful, solutions-driven engagement with the MACs and CMS has become frustrating for physicians and advocacy organizations attempting to address a host of problems. The two issues alluded to above include the Self-Administered Drug Exclusion List (SAD List), which excludes certain Part B medication formulations from coverage under certain conditions and the “down coding” of certain infusion administration codes when specific drugs are delivered. These problems are compounded by the curtailment of physician stakeholder input via Contractor Advisory Committees (CACs). Each state has its own CAC, but the CAC meetings have been restructured as a result of the 21st Century Cures Act, and ultimately eradicated the involvement of these physician advisers in policy development at the local level.

This has left many of rheumatology representatives to the CACs demoralized and generally unhappy about certain decisions being made without their input. There is also inconsistency in terms of coverage and payment policies throughout the country. For example, in one MAC jurisdiction, a certain medication may be on the SAD List and excluded from Part B coverage, meaning beneficiary access is only available through Part D (and assuming they can afford it), while in an adjacent MAC jurisdiction, both formulations are covered.

The Coalition of State Rheumatology Organizations, along with the American College of Rheumatology and other specialty groups, is attempting to address these issues from many different angles. There is not enough space to explain the nuances of local coverage policy development, but the timeline below highlights the long and winding road that we have travelled to resolve these issues.

  • February 2021: CSRO meets with CMS’ Coverage and Analysis Group (CAG) to raise concerns about ustekinumab (Stelara) and its inclusion on the SAD List.
  • April 2021: CSRO follows up with CMS’ CAG on SAD List concerns in a letter.
  • May 2021: Most MACs issue or revise local coverage articles, or “billing and coding” articles, that down code the administration of certain biologic medications, with some expanding the list of biologic medications subject to the policy, prompting a strong response from CSRO.
  • September 2021: CSRO meets with multijurisdictional MAC Contract Medical Director (CMD) work group to discuss down coding, SAD List, and physician/CAC engagement.
  • October 2021: At the suggestion of the CMDs, CSRO re-engages with CMS’ CAG to raise concerns about down-coding policies and physician/CAC engagement, and continue the SAD List discussion.
  • November 2021: CSRO is connected with CMS’ “payment ombudsman” on down coding and the SAD List.
  • January 2022: CSRO signs on to multispecialty coalition effort aimed at improving local coverage and payment policy and restoring the importance of the CAC.
  • February 2022: CSRO participates in CMS CAG meeting with multispecialty coalition, raising concerns about the down-coding and SAD List policies.
  • March/April 2022: Through its coalition partner, the Alliance of Specialty Medicine, CSRO meets with the principal deputy CMS administrator and raises awareness to these issues.
  • May 2022: CSRO participates in follow-up discussion with CMS’ CAG as part of multispecialty coalition, reiterating concerns about the down coding and SAD List policies. With the assistance of the CMS’ Office of the Administrator, CSRO meets with CMS’ Center for Program Integrity to seek a “pause” in down-coding policies for certain biologic medications.
  • June 2022: CMS notifies CSRO of a “temporary pause” in medical review while the agency reviews various manuals and policies to determine the appropriate steps forward. To assist the agency, CSRO works with practices to develop a resource that CMS can use to establish criteria for determining when a medication warrants use of complex drug administration codes. CSRO re-engages with multijurisdictional MAC CMD workgroup to continue discussions on SAD List.
  • July 2022: CSRO meets with new multijurisdictional MAC CMD workgroup focused on improving the process for developing local coverage and payment policy.

Our dialogue with CMS leadership and staff continues. In the most recent communication, staff in the CMS administrator’s office informed us that the issue is complicated and crosses several different parts of the agency, and they are still determining next steps.



The rheumatology community’s journey toward solving the challenges facing practices and patients is emblematic of the communication problem between provider groups and the CMS-MAC establishment. While we understand this is how bureaucracy works, it is not to the benefit of Medicare beneficiaries to have a system that is so difficult to navigate, even by the best of the regulatory gurus. This is not an indictment of any specific group but a call to action on the part of the government and their contractors to create a clear, transparent path to getting answers when we have a problem.

And by the way, we do have another meeting with yet another CMS “center” regarding the SAD List in August.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is president of the CSRO, past chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

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Biden tests positive for COVID-19: White House

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President Joe Biden has tested positive for COVID-19, the White House announced today.

Biden, 79, is experiencing “very mild” symptoms, White House Press Secretary Karine Jean-Pierre said in a statement. The president is fully vaccinated and has been boosted twice and has started taking the antiviral Paxlovid since testing positive, Ms. Jean-Pierre said.

President Biden plans to isolate at the White House and “will continue to carry out all of his duties fully during that time,” the statement said.

“He has been in contact with members of the White House staff by phone this morning, and will participate in his planned meetings at the White House this morning via phone and Zoom from the residence.”

President Biden will return to in-person work after he tests negative.

This is a developing story. Please check back for updates. A version of this article first appeared on WebMD.com .

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President Joe Biden has tested positive for COVID-19, the White House announced today.

Biden, 79, is experiencing “very mild” symptoms, White House Press Secretary Karine Jean-Pierre said in a statement. The president is fully vaccinated and has been boosted twice and has started taking the antiviral Paxlovid since testing positive, Ms. Jean-Pierre said.

President Biden plans to isolate at the White House and “will continue to carry out all of his duties fully during that time,” the statement said.

“He has been in contact with members of the White House staff by phone this morning, and will participate in his planned meetings at the White House this morning via phone and Zoom from the residence.”

President Biden will return to in-person work after he tests negative.

This is a developing story. Please check back for updates. A version of this article first appeared on WebMD.com .

President Joe Biden has tested positive for COVID-19, the White House announced today.

Biden, 79, is experiencing “very mild” symptoms, White House Press Secretary Karine Jean-Pierre said in a statement. The president is fully vaccinated and has been boosted twice and has started taking the antiviral Paxlovid since testing positive, Ms. Jean-Pierre said.

President Biden plans to isolate at the White House and “will continue to carry out all of his duties fully during that time,” the statement said.

“He has been in contact with members of the White House staff by phone this morning, and will participate in his planned meetings at the White House this morning via phone and Zoom from the residence.”

President Biden will return to in-person work after he tests negative.

This is a developing story. Please check back for updates. A version of this article first appeared on WebMD.com .

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Job market for physicians, advanced practitioners rebounds after COVID-19 slump: Report

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After a year of uncertainty and decline because of the COVID-19 pandemic, demand for clinicians has rebounded – and the job market for new physicians and advanced practitioners is back to normal, or more accurately “the new normal,” according to a recently released report from Merritt Hawkins, the physician search division of AMN Healthcare.

The study is based on an analysis of job search and consulting assignments that the firm conducted on behalf of its health care organization clients from April 1, 2021, to March 31, 2022.

“Search engagements were down a little over 30% in 2020, but by the end of 2021, everything started spiking dramatically to the point of where we were at a 34-year high,” Michael Belkin, divisional vice president with Merritt Hawkins, told this news organization. “The pendulum has gone all the way back. People are more interested in going out and seeing their physicians.”

Demand for physicians was suppressed during the peak of the pandemic, as many hospitals curtailed elective procedures and many patients refrained from entering a medical facility. A large backlog of patients needing care subsequently developed.

This, combined with an aging population and widespread chronic medical conditions, has caused a strong surge in demand for physicians and advanced practitioners, according to the report.

In addition to the volume of searches increasing, physician starting salaries have rebounded from the COVID-19 downturn.

Average starting salaries of 14 physician specialties tracked in 2021/2022 increased, while only 3 decreased. Orthopedic surgeons were offered an average of $565,000 to start, exclusive of signing bonuses and other incentives, up from $546,000 the previous year. Urologists were offered an average of $510,000 to start, up from $497,000; gastroenterologists were offered $474,000, up from $453,000; while radiologists were offered $455,000, up from $401,000.

Similarly, a recent Medscape study based on responses from more than 13,000 U.S. physicians across 29 specialties found that income for all physician specialists increased, with otolaryngologists, gastroenterologists, and dermatologists experiencing the greatest gains.
 

A new reality

While the job market for physicians and advanced practitioners has seemingly recovered, there are many differences between today’s working environment for clinicians and what existed during the pandemic.

First, specialists are now stepping into the spotlight, a position that primary care clinicians previously held. The majority of Merritt Hawkins’ search engagements (64%) in 2021/2022 were for physician specialists, including cardiologists, gastroenterologists, orthopedic surgeons, neurologists, oncologists, and others. Only 17% of the search engagements were for primary care physicians, down from 18% in 2020/2021 and 20% in 2019/2020.

“We’ve seen specialties bounce back faster. Of course, you’ve got the aging population; you’ve got people that want that specialized care,” Mr. Belkin said.

Advanced practitioners also are playing a more significant role in the postpandemic word. In fact, 19% of Merritt Hawkins’ search engagements were for advanced practitioners, including nurse practitioners (NPs), physician assistants, and certified registered nurse anesthetists, up from 18% the previous year and just 13% the year prior to that, indicating growing demand for nonphysician providers.

NPs, in fact, topped the list of most requested search engagements, underscoring a shift from traditional physician office-based primary care delivery settings toward “convenient care” settings such as urgent care centers and retail clinics that are largely staffed by NPs and other advanced practitioners.

Advanced practitioners are taking on more responsibility for primary care simply because there is a large number of these professionals ready to take on the challenge.

The health care industry was “not able to produce enough primary care physicians over the last decade. So advanced practitioners, I believe, have slowly started to work alongside those primary care physicians. In a lot of areas such as your retail space, your CVS, your Walmart, your Walgreens, your standalone urgent cares, they’ve stepped up,” Mr. Belkin said.

Advanced practitioners also are providing the convenience that consumers are increasingly demanding.

“We are a society that wants things immediately ... but it’s still a challenge to schedule an appointment with a physician. However, it’s less of a challenge to get into a retail clinic or an urgent care center or to schedule something through telehealth,” Mr. Belkin noted.
 

 

 

More than just money

With the job market strong, the challenge for health care organizations is to create competitive recruiting packages. Sure enough, 92% of candidates were offered signing bonuses in 2021/2022 compared with just 61% in 2020/2021.

The financial incentives, however, might not be enough. In this environment, health care organizations need to go beyond simply offering competitive salaries to new recruits. For example, clinicians are seeking flexibility, as many potential hires are seeking remote positions. In fact, 18% of radiology search engagements were for teleradiologists, while 15% of its search engagements for psychiatrists were for telepsychiatrists in 2021/2022.

“Right now, quality of life is a very important factor. It’s work-life balance. It’s sensitivity to the stresses that we just experienced over the last 2.5 years,” Mr. Belkin concluded. “There’s more sensitivity around the culture of the organizations. What’s the leadership like? How did the organization handle the pandemic? How do they respond?”

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

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After a year of uncertainty and decline because of the COVID-19 pandemic, demand for clinicians has rebounded – and the job market for new physicians and advanced practitioners is back to normal, or more accurately “the new normal,” according to a recently released report from Merritt Hawkins, the physician search division of AMN Healthcare.

The study is based on an analysis of job search and consulting assignments that the firm conducted on behalf of its health care organization clients from April 1, 2021, to March 31, 2022.

“Search engagements were down a little over 30% in 2020, but by the end of 2021, everything started spiking dramatically to the point of where we were at a 34-year high,” Michael Belkin, divisional vice president with Merritt Hawkins, told this news organization. “The pendulum has gone all the way back. People are more interested in going out and seeing their physicians.”

Demand for physicians was suppressed during the peak of the pandemic, as many hospitals curtailed elective procedures and many patients refrained from entering a medical facility. A large backlog of patients needing care subsequently developed.

This, combined with an aging population and widespread chronic medical conditions, has caused a strong surge in demand for physicians and advanced practitioners, according to the report.

In addition to the volume of searches increasing, physician starting salaries have rebounded from the COVID-19 downturn.

Average starting salaries of 14 physician specialties tracked in 2021/2022 increased, while only 3 decreased. Orthopedic surgeons were offered an average of $565,000 to start, exclusive of signing bonuses and other incentives, up from $546,000 the previous year. Urologists were offered an average of $510,000 to start, up from $497,000; gastroenterologists were offered $474,000, up from $453,000; while radiologists were offered $455,000, up from $401,000.

Similarly, a recent Medscape study based on responses from more than 13,000 U.S. physicians across 29 specialties found that income for all physician specialists increased, with otolaryngologists, gastroenterologists, and dermatologists experiencing the greatest gains.
 

A new reality

While the job market for physicians and advanced practitioners has seemingly recovered, there are many differences between today’s working environment for clinicians and what existed during the pandemic.

First, specialists are now stepping into the spotlight, a position that primary care clinicians previously held. The majority of Merritt Hawkins’ search engagements (64%) in 2021/2022 were for physician specialists, including cardiologists, gastroenterologists, orthopedic surgeons, neurologists, oncologists, and others. Only 17% of the search engagements were for primary care physicians, down from 18% in 2020/2021 and 20% in 2019/2020.

“We’ve seen specialties bounce back faster. Of course, you’ve got the aging population; you’ve got people that want that specialized care,” Mr. Belkin said.

Advanced practitioners also are playing a more significant role in the postpandemic word. In fact, 19% of Merritt Hawkins’ search engagements were for advanced practitioners, including nurse practitioners (NPs), physician assistants, and certified registered nurse anesthetists, up from 18% the previous year and just 13% the year prior to that, indicating growing demand for nonphysician providers.

NPs, in fact, topped the list of most requested search engagements, underscoring a shift from traditional physician office-based primary care delivery settings toward “convenient care” settings such as urgent care centers and retail clinics that are largely staffed by NPs and other advanced practitioners.

Advanced practitioners are taking on more responsibility for primary care simply because there is a large number of these professionals ready to take on the challenge.

The health care industry was “not able to produce enough primary care physicians over the last decade. So advanced practitioners, I believe, have slowly started to work alongside those primary care physicians. In a lot of areas such as your retail space, your CVS, your Walmart, your Walgreens, your standalone urgent cares, they’ve stepped up,” Mr. Belkin said.

Advanced practitioners also are providing the convenience that consumers are increasingly demanding.

“We are a society that wants things immediately ... but it’s still a challenge to schedule an appointment with a physician. However, it’s less of a challenge to get into a retail clinic or an urgent care center or to schedule something through telehealth,” Mr. Belkin noted.
 

 

 

More than just money

With the job market strong, the challenge for health care organizations is to create competitive recruiting packages. Sure enough, 92% of candidates were offered signing bonuses in 2021/2022 compared with just 61% in 2020/2021.

The financial incentives, however, might not be enough. In this environment, health care organizations need to go beyond simply offering competitive salaries to new recruits. For example, clinicians are seeking flexibility, as many potential hires are seeking remote positions. In fact, 18% of radiology search engagements were for teleradiologists, while 15% of its search engagements for psychiatrists were for telepsychiatrists in 2021/2022.

“Right now, quality of life is a very important factor. It’s work-life balance. It’s sensitivity to the stresses that we just experienced over the last 2.5 years,” Mr. Belkin concluded. “There’s more sensitivity around the culture of the organizations. What’s the leadership like? How did the organization handle the pandemic? How do they respond?”

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

After a year of uncertainty and decline because of the COVID-19 pandemic, demand for clinicians has rebounded – and the job market for new physicians and advanced practitioners is back to normal, or more accurately “the new normal,” according to a recently released report from Merritt Hawkins, the physician search division of AMN Healthcare.

The study is based on an analysis of job search and consulting assignments that the firm conducted on behalf of its health care organization clients from April 1, 2021, to March 31, 2022.

“Search engagements were down a little over 30% in 2020, but by the end of 2021, everything started spiking dramatically to the point of where we were at a 34-year high,” Michael Belkin, divisional vice president with Merritt Hawkins, told this news organization. “The pendulum has gone all the way back. People are more interested in going out and seeing their physicians.”

Demand for physicians was suppressed during the peak of the pandemic, as many hospitals curtailed elective procedures and many patients refrained from entering a medical facility. A large backlog of patients needing care subsequently developed.

This, combined with an aging population and widespread chronic medical conditions, has caused a strong surge in demand for physicians and advanced practitioners, according to the report.

In addition to the volume of searches increasing, physician starting salaries have rebounded from the COVID-19 downturn.

Average starting salaries of 14 physician specialties tracked in 2021/2022 increased, while only 3 decreased. Orthopedic surgeons were offered an average of $565,000 to start, exclusive of signing bonuses and other incentives, up from $546,000 the previous year. Urologists were offered an average of $510,000 to start, up from $497,000; gastroenterologists were offered $474,000, up from $453,000; while radiologists were offered $455,000, up from $401,000.

Similarly, a recent Medscape study based on responses from more than 13,000 U.S. physicians across 29 specialties found that income for all physician specialists increased, with otolaryngologists, gastroenterologists, and dermatologists experiencing the greatest gains.
 

A new reality

While the job market for physicians and advanced practitioners has seemingly recovered, there are many differences between today’s working environment for clinicians and what existed during the pandemic.

First, specialists are now stepping into the spotlight, a position that primary care clinicians previously held. The majority of Merritt Hawkins’ search engagements (64%) in 2021/2022 were for physician specialists, including cardiologists, gastroenterologists, orthopedic surgeons, neurologists, oncologists, and others. Only 17% of the search engagements were for primary care physicians, down from 18% in 2020/2021 and 20% in 2019/2020.

“We’ve seen specialties bounce back faster. Of course, you’ve got the aging population; you’ve got people that want that specialized care,” Mr. Belkin said.

Advanced practitioners also are playing a more significant role in the postpandemic word. In fact, 19% of Merritt Hawkins’ search engagements were for advanced practitioners, including nurse practitioners (NPs), physician assistants, and certified registered nurse anesthetists, up from 18% the previous year and just 13% the year prior to that, indicating growing demand for nonphysician providers.

NPs, in fact, topped the list of most requested search engagements, underscoring a shift from traditional physician office-based primary care delivery settings toward “convenient care” settings such as urgent care centers and retail clinics that are largely staffed by NPs and other advanced practitioners.

Advanced practitioners are taking on more responsibility for primary care simply because there is a large number of these professionals ready to take on the challenge.

The health care industry was “not able to produce enough primary care physicians over the last decade. So advanced practitioners, I believe, have slowly started to work alongside those primary care physicians. In a lot of areas such as your retail space, your CVS, your Walmart, your Walgreens, your standalone urgent cares, they’ve stepped up,” Mr. Belkin said.

Advanced practitioners also are providing the convenience that consumers are increasingly demanding.

“We are a society that wants things immediately ... but it’s still a challenge to schedule an appointment with a physician. However, it’s less of a challenge to get into a retail clinic or an urgent care center or to schedule something through telehealth,” Mr. Belkin noted.
 

 

 

More than just money

With the job market strong, the challenge for health care organizations is to create competitive recruiting packages. Sure enough, 92% of candidates were offered signing bonuses in 2021/2022 compared with just 61% in 2020/2021.

The financial incentives, however, might not be enough. In this environment, health care organizations need to go beyond simply offering competitive salaries to new recruits. For example, clinicians are seeking flexibility, as many potential hires are seeking remote positions. In fact, 18% of radiology search engagements were for teleradiologists, while 15% of its search engagements for psychiatrists were for telepsychiatrists in 2021/2022.

“Right now, quality of life is a very important factor. It’s work-life balance. It’s sensitivity to the stresses that we just experienced over the last 2.5 years,” Mr. Belkin concluded. “There’s more sensitivity around the culture of the organizations. What’s the leadership like? How did the organization handle the pandemic? How do they respond?”

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

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What are your weaknesses?

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In a video posted to TikTok by the comedian Will Flanary, MD, better known to his followers as Dr. Glaucomflecken, he imitates a neurosurgical residency interview. With glasses perched on the bridge of his nose, Dr. Glaucomflecken poses as the attending, asking: “What are your weaknesses?”

The residency applicant answers without hesitation: “My physiological need for sleep.” “What are your strengths?” The resident replies with the hard, steely stare of the determined and uninitiated: “My desire to eliminate my physiological need for sleep.”

If you follow Dr. Glaucomflecken on Twitter, you might know the skit I’m referencing. For many physicians and physicians-in-training, what makes the satire successful is its reflection of reality.

Many things have changed in medicine since his time, but the tired trope of the sleepless surgeon hangs on. Undaunted, I spent my second and third year of medical school accumulating accolades, conducting research, and connecting with mentors with the singular goal of joining the surgical ranks.

Midway through my third year, I completed a month-long surgical subinternship designed to give students a taste of what life would look like as an intern. I loved the operating room; it felt like the difference between being on dry land and being underwater. There were fewer distractions – your patient in the spotlight while everything else receded to the shadows.

However, as the month wore on, something stronger took hold. I couldn’t keep my eyes open in the darkened operating rooms and had to decline stools, fearing that I would fall asleep if I sat down.

On early morning prerounds, it’s 4:50 a.m. when I glance at the clock and pull back the curtain, already apologizing. My patient rolls over, flashing a wry smile. “Do you ever go home?” I’ve seen residents respond to this exact question in various ways. I live here. Yes. No. Soon. Not enough. My partner doesn’t think so.

There are days and, yes, years when we are led to believe this is what we live for: to be constantly available to our patients. It feels like a hollow victory when the patient, 2 days out from a total colectomy, begins to worry about your personal life. I ask her how she slept (not enough), any fevers (no), vomiting (no), urinating (I pause – she has a catheter).

My favorite part of these early morning rounds is the pause in my scripted litany of questions to listen to heart and lungs. It never fails to feel sacred: Patients become so quiet and still that I can’t help but think they have faith in me. Without prompting, she slides the back of her hospital gown forward like a curtain, already taking deep breaths so I can hear her lungs.

I look outside. The streetlights are still on, and from the seventh-floor window, I can watch staff making their way through the sliding double-doors, just beyond the yellowed pools of streetlight. I smile. I love medicine. I’m so tired.

For many in medicine, we are treated, and thus behave, as though our ability to manipulate physiology should also apply within the borders of our bodies: commanding less sleep, food, or bathroom breaks.

It places health care workers solidly in the realm of superhuman, living beyond one’s corporeal needs. The pandemic only heightened this misappropriation – adding hero and setting out a pedestal for health care workers to make their ungainly ascent. This kind of unsolicited admiration implicitly implies inhumanness, an otherness.

What would it look like if we started treating ourselves less like physicians and more like patients? I wish I was offering a solution, but really this is just a story. Maybe it’s not more sleep you need but something just as critical to the delicate physiologic and psychological scales of well-being.

To students rising through the ranks of medical training, identify what it is you need early and often. I can count on one hand how many physicians I’ve seen take a lunch break – even 10 minutes. Embrace hard work and self-preservation equally. My hope is that if enough of us take this path, it just might become a matter of course.

Dr. Meffert is a resident in the department of emergency medicine, MedStar Georgetown University Hospital, Washington Hospital Center, Washington. Dr. Meffert disclosed no relevant financial relationships.

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

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In a video posted to TikTok by the comedian Will Flanary, MD, better known to his followers as Dr. Glaucomflecken, he imitates a neurosurgical residency interview. With glasses perched on the bridge of his nose, Dr. Glaucomflecken poses as the attending, asking: “What are your weaknesses?”

The residency applicant answers without hesitation: “My physiological need for sleep.” “What are your strengths?” The resident replies with the hard, steely stare of the determined and uninitiated: “My desire to eliminate my physiological need for sleep.”

If you follow Dr. Glaucomflecken on Twitter, you might know the skit I’m referencing. For many physicians and physicians-in-training, what makes the satire successful is its reflection of reality.

Many things have changed in medicine since his time, but the tired trope of the sleepless surgeon hangs on. Undaunted, I spent my second and third year of medical school accumulating accolades, conducting research, and connecting with mentors with the singular goal of joining the surgical ranks.

Midway through my third year, I completed a month-long surgical subinternship designed to give students a taste of what life would look like as an intern. I loved the operating room; it felt like the difference between being on dry land and being underwater. There were fewer distractions – your patient in the spotlight while everything else receded to the shadows.

However, as the month wore on, something stronger took hold. I couldn’t keep my eyes open in the darkened operating rooms and had to decline stools, fearing that I would fall asleep if I sat down.

On early morning prerounds, it’s 4:50 a.m. when I glance at the clock and pull back the curtain, already apologizing. My patient rolls over, flashing a wry smile. “Do you ever go home?” I’ve seen residents respond to this exact question in various ways. I live here. Yes. No. Soon. Not enough. My partner doesn’t think so.

There are days and, yes, years when we are led to believe this is what we live for: to be constantly available to our patients. It feels like a hollow victory when the patient, 2 days out from a total colectomy, begins to worry about your personal life. I ask her how she slept (not enough), any fevers (no), vomiting (no), urinating (I pause – she has a catheter).

My favorite part of these early morning rounds is the pause in my scripted litany of questions to listen to heart and lungs. It never fails to feel sacred: Patients become so quiet and still that I can’t help but think they have faith in me. Without prompting, she slides the back of her hospital gown forward like a curtain, already taking deep breaths so I can hear her lungs.

I look outside. The streetlights are still on, and from the seventh-floor window, I can watch staff making their way through the sliding double-doors, just beyond the yellowed pools of streetlight. I smile. I love medicine. I’m so tired.

For many in medicine, we are treated, and thus behave, as though our ability to manipulate physiology should also apply within the borders of our bodies: commanding less sleep, food, or bathroom breaks.

It places health care workers solidly in the realm of superhuman, living beyond one’s corporeal needs. The pandemic only heightened this misappropriation – adding hero and setting out a pedestal for health care workers to make their ungainly ascent. This kind of unsolicited admiration implicitly implies inhumanness, an otherness.

What would it look like if we started treating ourselves less like physicians and more like patients? I wish I was offering a solution, but really this is just a story. Maybe it’s not more sleep you need but something just as critical to the delicate physiologic and psychological scales of well-being.

To students rising through the ranks of medical training, identify what it is you need early and often. I can count on one hand how many physicians I’ve seen take a lunch break – even 10 minutes. Embrace hard work and self-preservation equally. My hope is that if enough of us take this path, it just might become a matter of course.

Dr. Meffert is a resident in the department of emergency medicine, MedStar Georgetown University Hospital, Washington Hospital Center, Washington. Dr. Meffert disclosed no relevant financial relationships.

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

In a video posted to TikTok by the comedian Will Flanary, MD, better known to his followers as Dr. Glaucomflecken, he imitates a neurosurgical residency interview. With glasses perched on the bridge of his nose, Dr. Glaucomflecken poses as the attending, asking: “What are your weaknesses?”

The residency applicant answers without hesitation: “My physiological need for sleep.” “What are your strengths?” The resident replies with the hard, steely stare of the determined and uninitiated: “My desire to eliminate my physiological need for sleep.”

If you follow Dr. Glaucomflecken on Twitter, you might know the skit I’m referencing. For many physicians and physicians-in-training, what makes the satire successful is its reflection of reality.

Many things have changed in medicine since his time, but the tired trope of the sleepless surgeon hangs on. Undaunted, I spent my second and third year of medical school accumulating accolades, conducting research, and connecting with mentors with the singular goal of joining the surgical ranks.

Midway through my third year, I completed a month-long surgical subinternship designed to give students a taste of what life would look like as an intern. I loved the operating room; it felt like the difference between being on dry land and being underwater. There were fewer distractions – your patient in the spotlight while everything else receded to the shadows.

However, as the month wore on, something stronger took hold. I couldn’t keep my eyes open in the darkened operating rooms and had to decline stools, fearing that I would fall asleep if I sat down.

On early morning prerounds, it’s 4:50 a.m. when I glance at the clock and pull back the curtain, already apologizing. My patient rolls over, flashing a wry smile. “Do you ever go home?” I’ve seen residents respond to this exact question in various ways. I live here. Yes. No. Soon. Not enough. My partner doesn’t think so.

There are days and, yes, years when we are led to believe this is what we live for: to be constantly available to our patients. It feels like a hollow victory when the patient, 2 days out from a total colectomy, begins to worry about your personal life. I ask her how she slept (not enough), any fevers (no), vomiting (no), urinating (I pause – she has a catheter).

My favorite part of these early morning rounds is the pause in my scripted litany of questions to listen to heart and lungs. It never fails to feel sacred: Patients become so quiet and still that I can’t help but think they have faith in me. Without prompting, she slides the back of her hospital gown forward like a curtain, already taking deep breaths so I can hear her lungs.

I look outside. The streetlights are still on, and from the seventh-floor window, I can watch staff making their way through the sliding double-doors, just beyond the yellowed pools of streetlight. I smile. I love medicine. I’m so tired.

For many in medicine, we are treated, and thus behave, as though our ability to manipulate physiology should also apply within the borders of our bodies: commanding less sleep, food, or bathroom breaks.

It places health care workers solidly in the realm of superhuman, living beyond one’s corporeal needs. The pandemic only heightened this misappropriation – adding hero and setting out a pedestal for health care workers to make their ungainly ascent. This kind of unsolicited admiration implicitly implies inhumanness, an otherness.

What would it look like if we started treating ourselves less like physicians and more like patients? I wish I was offering a solution, but really this is just a story. Maybe it’s not more sleep you need but something just as critical to the delicate physiologic and psychological scales of well-being.

To students rising through the ranks of medical training, identify what it is you need early and often. I can count on one hand how many physicians I’ve seen take a lunch break – even 10 minutes. Embrace hard work and self-preservation equally. My hope is that if enough of us take this path, it just might become a matter of course.

Dr. Meffert is a resident in the department of emergency medicine, MedStar Georgetown University Hospital, Washington Hospital Center, Washington. Dr. Meffert disclosed no relevant financial relationships.

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

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Charcoal could be the cure for the common high-fat diet

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Charcoal won’t let high-fat diet weigh you down

Do you want to be the funniest person alive? Of course you do. It’s really simple too, just one joke can make you the greatest comedian of all time. All you have to do is go camping and cook food over a roaring campfire. When someone drops food into the fire (which they always will), get ready. Once they fish out the offending food, which is almost certainly coated in hot coals, tell them: “Ah, eat it anyway. A little texture never hurt!” Trust us, most hilarious and original gag of all time.

But before your hapless friend brushes off his hot dog and forces a laugh, consider this: Japanese researchers have found that a charcoal supplement can prevent weight gain in mice consuming a high-fat diet. Charcoal is actually quite the helpful substance, and not just for grilling. It’s been used as medicine for hundreds of years and even today is used as a treatment for drug overdose and excess gas and flatulence.

PxHere

The study involved two groups of mice: One was fed a normal diet, the other a high-fat diet. After 12 weeks, the high-fat diet mice had gained weight. At that point, edible activated charcoal was added to their diet. From that point, weight gain was similar between the two groups, and the amount of bile acid, cholesterol, triglyceride, and fatty acid excreted by the high-fat mice increased by two to four times.

The researchers supported the notion that consuming an activated charcoal supplement before or while eating fatty food could prevent weight gain from said fatty food. Which works out well for the classic American barbecue, which is traditionally both high in fat and charcoal. All you have to do is buy some extra charcoal briquettes to pass around and munch on with your friends. Now that’s a party we can get behind.
 

There’s awake, and then there’s neurologically awake

Time to toss another urban legend onto the trash heap of history. Say goodbye to the benefits of uninterrupted sleep. It’s a fraud, a fake, a myth, a hit or myth, a swing and a myth, an old wives’ tale. You can stuff it and put it on a shelf next to Bigfoot, the Slender Man, and Twinkies.

JackF/thinkstockphotos.com

We all thought we needed 8 hours of uninterrupted sleep every night, but guess who we forgot to tell? Our brains. They’ve been doing exactly the opposite all along, laughing at us the whole time. Smug SOBs.

To straighten out this mess, let’s bring in a scientist, Celia Kjaerby of the Center for Translational Neuromedicine at the University of Copenhagen: “You may think that sleep is a constant state that you are in, and then you wake up. But there is a lot more to sleep than meets the eye. We have learned that noradrenaline causes you to wake up more than 100 times a night. And that is during perfectly normal sleep.”

Those 100 or so sleep interruptions are so brief that we don’t even notice, but they are very important, according to a study conducted at the university. Those tiny little wake-up calls are “the essence for the part of sleep that makes us wake up rested and which enables us to remember what we learned the day before. ... The very short awakenings are created by waves of norepinephrine [and they] reset the brain so that it is ready to store memory when you dive back into sleep,” lead author Maiken Nedergaard, MD, explained.

The investigators compared the level of noradrenaline in sleeping mice with their electrical activity and found that the hormone constantly increased and decreased in a wavelike pattern. A high level meant that the animal was neurologically awake. Deeper valleys between the high points meant better sleep, and the mice with the “highest number of deep noradrenaline valleys were also the ones with the best memory,” the team said in their written statement.

Not just the best memory, they said, but “super memory.” That, of course, was enough to get the attention of Marvel Comics, so the next Disney superhero blockbuster will feature Nocturna, the queen of the night. Her power? Never forgets. Her archnemesis? The Insomniac. Her catchphrase? “Let me sleep on it.”

 

Words can hurt, literally

Growing up, we’re sure you heard the “sticks and stones” rhyme. Maybe you’ve even recited it once or twice to defend yourself. Well, forget it, because words can hurt and your brain knows it.

PxHere

In a new study published in Frontiers in Communication, Marijn Struiksma, PhD, of Utrecht University, and colleagues incorporated the use of electroencephalography (EEG) and skin conductance on 79 women to see how words (specifically insults) actually affect the human body.

Each subject was asked to read three different types of statements: an insult, a compliment, and something factual but neutral. Half of the statements contained the subject’s name and half used somebody else’s. The participants were told that these statements were collected from three men.

Nobody interacted with each other, and the setting was completely clinical, yet the results were unmistakable. The EEG showed an effect in P2 amplitude with repetitive insults, no matter who it was about. Even though the insults weren’t real and the participants were aware of it, the brain still recognized them as hurtful, coming across as “mini slaps in the face,” Dr. Struiksma noted in a written statement.

The researchers noted that more needs to be done to better understand the long-term effects that insults can have and create a deeper understanding between words and emotion, but studying the effects of insults in a real-life setting is ethically tricky. This study is a start.

So, yeah, sticks and stones can break your bones, but words will actually hurt you.

This article was updated 7/21/22.

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Charcoal won’t let high-fat diet weigh you down

Do you want to be the funniest person alive? Of course you do. It’s really simple too, just one joke can make you the greatest comedian of all time. All you have to do is go camping and cook food over a roaring campfire. When someone drops food into the fire (which they always will), get ready. Once they fish out the offending food, which is almost certainly coated in hot coals, tell them: “Ah, eat it anyway. A little texture never hurt!” Trust us, most hilarious and original gag of all time.

But before your hapless friend brushes off his hot dog and forces a laugh, consider this: Japanese researchers have found that a charcoal supplement can prevent weight gain in mice consuming a high-fat diet. Charcoal is actually quite the helpful substance, and not just for grilling. It’s been used as medicine for hundreds of years and even today is used as a treatment for drug overdose and excess gas and flatulence.

PxHere

The study involved two groups of mice: One was fed a normal diet, the other a high-fat diet. After 12 weeks, the high-fat diet mice had gained weight. At that point, edible activated charcoal was added to their diet. From that point, weight gain was similar between the two groups, and the amount of bile acid, cholesterol, triglyceride, and fatty acid excreted by the high-fat mice increased by two to four times.

The researchers supported the notion that consuming an activated charcoal supplement before or while eating fatty food could prevent weight gain from said fatty food. Which works out well for the classic American barbecue, which is traditionally both high in fat and charcoal. All you have to do is buy some extra charcoal briquettes to pass around and munch on with your friends. Now that’s a party we can get behind.
 

There’s awake, and then there’s neurologically awake

Time to toss another urban legend onto the trash heap of history. Say goodbye to the benefits of uninterrupted sleep. It’s a fraud, a fake, a myth, a hit or myth, a swing and a myth, an old wives’ tale. You can stuff it and put it on a shelf next to Bigfoot, the Slender Man, and Twinkies.

JackF/thinkstockphotos.com

We all thought we needed 8 hours of uninterrupted sleep every night, but guess who we forgot to tell? Our brains. They’ve been doing exactly the opposite all along, laughing at us the whole time. Smug SOBs.

To straighten out this mess, let’s bring in a scientist, Celia Kjaerby of the Center for Translational Neuromedicine at the University of Copenhagen: “You may think that sleep is a constant state that you are in, and then you wake up. But there is a lot more to sleep than meets the eye. We have learned that noradrenaline causes you to wake up more than 100 times a night. And that is during perfectly normal sleep.”

Those 100 or so sleep interruptions are so brief that we don’t even notice, but they are very important, according to a study conducted at the university. Those tiny little wake-up calls are “the essence for the part of sleep that makes us wake up rested and which enables us to remember what we learned the day before. ... The very short awakenings are created by waves of norepinephrine [and they] reset the brain so that it is ready to store memory when you dive back into sleep,” lead author Maiken Nedergaard, MD, explained.

The investigators compared the level of noradrenaline in sleeping mice with their electrical activity and found that the hormone constantly increased and decreased in a wavelike pattern. A high level meant that the animal was neurologically awake. Deeper valleys between the high points meant better sleep, and the mice with the “highest number of deep noradrenaline valleys were also the ones with the best memory,” the team said in their written statement.

Not just the best memory, they said, but “super memory.” That, of course, was enough to get the attention of Marvel Comics, so the next Disney superhero blockbuster will feature Nocturna, the queen of the night. Her power? Never forgets. Her archnemesis? The Insomniac. Her catchphrase? “Let me sleep on it.”

 

Words can hurt, literally

Growing up, we’re sure you heard the “sticks and stones” rhyme. Maybe you’ve even recited it once or twice to defend yourself. Well, forget it, because words can hurt and your brain knows it.

PxHere

In a new study published in Frontiers in Communication, Marijn Struiksma, PhD, of Utrecht University, and colleagues incorporated the use of electroencephalography (EEG) and skin conductance on 79 women to see how words (specifically insults) actually affect the human body.

Each subject was asked to read three different types of statements: an insult, a compliment, and something factual but neutral. Half of the statements contained the subject’s name and half used somebody else’s. The participants were told that these statements were collected from three men.

Nobody interacted with each other, and the setting was completely clinical, yet the results were unmistakable. The EEG showed an effect in P2 amplitude with repetitive insults, no matter who it was about. Even though the insults weren’t real and the participants were aware of it, the brain still recognized them as hurtful, coming across as “mini slaps in the face,” Dr. Struiksma noted in a written statement.

The researchers noted that more needs to be done to better understand the long-term effects that insults can have and create a deeper understanding between words and emotion, but studying the effects of insults in a real-life setting is ethically tricky. This study is a start.

So, yeah, sticks and stones can break your bones, but words will actually hurt you.

This article was updated 7/21/22.

 

Charcoal won’t let high-fat diet weigh you down

Do you want to be the funniest person alive? Of course you do. It’s really simple too, just one joke can make you the greatest comedian of all time. All you have to do is go camping and cook food over a roaring campfire. When someone drops food into the fire (which they always will), get ready. Once they fish out the offending food, which is almost certainly coated in hot coals, tell them: “Ah, eat it anyway. A little texture never hurt!” Trust us, most hilarious and original gag of all time.

But before your hapless friend brushes off his hot dog and forces a laugh, consider this: Japanese researchers have found that a charcoal supplement can prevent weight gain in mice consuming a high-fat diet. Charcoal is actually quite the helpful substance, and not just for grilling. It’s been used as medicine for hundreds of years and even today is used as a treatment for drug overdose and excess gas and flatulence.

PxHere

The study involved two groups of mice: One was fed a normal diet, the other a high-fat diet. After 12 weeks, the high-fat diet mice had gained weight. At that point, edible activated charcoal was added to their diet. From that point, weight gain was similar between the two groups, and the amount of bile acid, cholesterol, triglyceride, and fatty acid excreted by the high-fat mice increased by two to four times.

The researchers supported the notion that consuming an activated charcoal supplement before or while eating fatty food could prevent weight gain from said fatty food. Which works out well for the classic American barbecue, which is traditionally both high in fat and charcoal. All you have to do is buy some extra charcoal briquettes to pass around and munch on with your friends. Now that’s a party we can get behind.
 

There’s awake, and then there’s neurologically awake

Time to toss another urban legend onto the trash heap of history. Say goodbye to the benefits of uninterrupted sleep. It’s a fraud, a fake, a myth, a hit or myth, a swing and a myth, an old wives’ tale. You can stuff it and put it on a shelf next to Bigfoot, the Slender Man, and Twinkies.

JackF/thinkstockphotos.com

We all thought we needed 8 hours of uninterrupted sleep every night, but guess who we forgot to tell? Our brains. They’ve been doing exactly the opposite all along, laughing at us the whole time. Smug SOBs.

To straighten out this mess, let’s bring in a scientist, Celia Kjaerby of the Center for Translational Neuromedicine at the University of Copenhagen: “You may think that sleep is a constant state that you are in, and then you wake up. But there is a lot more to sleep than meets the eye. We have learned that noradrenaline causes you to wake up more than 100 times a night. And that is during perfectly normal sleep.”

Those 100 or so sleep interruptions are so brief that we don’t even notice, but they are very important, according to a study conducted at the university. Those tiny little wake-up calls are “the essence for the part of sleep that makes us wake up rested and which enables us to remember what we learned the day before. ... The very short awakenings are created by waves of norepinephrine [and they] reset the brain so that it is ready to store memory when you dive back into sleep,” lead author Maiken Nedergaard, MD, explained.

The investigators compared the level of noradrenaline in sleeping mice with their electrical activity and found that the hormone constantly increased and decreased in a wavelike pattern. A high level meant that the animal was neurologically awake. Deeper valleys between the high points meant better sleep, and the mice with the “highest number of deep noradrenaline valleys were also the ones with the best memory,” the team said in their written statement.

Not just the best memory, they said, but “super memory.” That, of course, was enough to get the attention of Marvel Comics, so the next Disney superhero blockbuster will feature Nocturna, the queen of the night. Her power? Never forgets. Her archnemesis? The Insomniac. Her catchphrase? “Let me sleep on it.”

 

Words can hurt, literally

Growing up, we’re sure you heard the “sticks and stones” rhyme. Maybe you’ve even recited it once or twice to defend yourself. Well, forget it, because words can hurt and your brain knows it.

PxHere

In a new study published in Frontiers in Communication, Marijn Struiksma, PhD, of Utrecht University, and colleagues incorporated the use of electroencephalography (EEG) and skin conductance on 79 women to see how words (specifically insults) actually affect the human body.

Each subject was asked to read three different types of statements: an insult, a compliment, and something factual but neutral. Half of the statements contained the subject’s name and half used somebody else’s. The participants were told that these statements were collected from three men.

Nobody interacted with each other, and the setting was completely clinical, yet the results were unmistakable. The EEG showed an effect in P2 amplitude with repetitive insults, no matter who it was about. Even though the insults weren’t real and the participants were aware of it, the brain still recognized them as hurtful, coming across as “mini slaps in the face,” Dr. Struiksma noted in a written statement.

The researchers noted that more needs to be done to better understand the long-term effects that insults can have and create a deeper understanding between words and emotion, but studying the effects of insults in a real-life setting is ethically tricky. This study is a start.

So, yeah, sticks and stones can break your bones, but words will actually hurt you.

This article was updated 7/21/22.

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‘I shall harm’

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I was quite sure I had multiple sclerosis when I was a medical student. I first noticed symptoms during my neurology rotation. All the signs were there: Fatigue that was getting worse in the North Carolina heat (Uhthoff sign!). A tingle running down my neck (Lhermitte sign!). Blurry vision late at night while studying pathways in Lange Neurology. “Didn’t cousin Amy have MS?” I asked my Mom. I started researching which medical specialties didn’t require dexterity. My left eyelid began twitching and didn’t stop until I rotated to ob.gyn.

Dr. Jeffrey Benabio

Fortunately, it was not multiple sclerosis I had, but rather nosophobia, also known as Medical Student’s Disease. The combination of intense study of symptoms, spotty knowledge of diagnoses, and grade anxiety makes nosophobia common in med students. Despite its name, it doesn’t afflict only doctors. Patients often come to us convinced they have a disease but without reason. So unshakable is their belief that multiple visits are often required to disabuse them of their self-diagnosis. I sometimes have to remind myself to appear concerned even when a “melanoma” is a freckle so small I can barely see it with a dermatoscope. Or a “genital wart” is a hair follicle that looks exactly like the hundreds on the patient’s scrotum. Tougher though, are the treatment-avoiders: patients whose imagined side effects lead them to stop or refuse treatment.

I recently saw a middle-aged man with erythroderma so severe he looked like a ghillie suit of scale. He had a lifelong history of atopic dermatitis and a 2-year history of avoiding treatments. At some point, he tried all the usual remedies: cyclosporine, methotrexate, azathioprine, light therapy, boxes of topicals. The last treatment had been dupilumab, which he tried for a few weeks. “Why did you stop that one?” I asked. The injections were making him go blind, he explained. “Not blurry? Blind?” I asked. Yes, he could not see at all after each injection. Perhaps he might have dry eyes or keratitis? Sure. But blindness? It seemed an unreasonable concern. Further discussion revealed that intolerance to medication side effects was why he had stopped all his other treatments.

Nocebo, from the Latin “I shall harm,” is the dark counterpart to the placebo. Patients experience imagined, or even real, adverse effects because they believe the treatment is causing them harm. This is true even though that treatment might not be having any unwanted physiologic effect. Statins are a good example. Studies have shown that most patient-reported side effects of statins are in fact nocebo effects rather than a result of pharmacologic causes.

Yet, many patients on statins report muscle pain or other concerns as unbearable. As a consequence, some patients who might have benefited from statins might be missing out on the protective gains. Nocebo effects are exacerbated by a common bias that causes deeper regret when bad outcomes result from an action taken as compared with bad outcomes that occurred from not taking action. It’s frustrating when there’s a standard of care treatment, but our patient can’t get past their fear of harm to try it.

Despite my recommendations, my eczema patient insisted on continuing his nontreatment rather than take any risks with treatments for now. There are ways I might help, but I expect it will require additional visits to build trust. Today, the best I can do is to understand and respect him. At least he doesn’t think he has a genital wart – I’m not sure how I’d treat it if he did.

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].

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I was quite sure I had multiple sclerosis when I was a medical student. I first noticed symptoms during my neurology rotation. All the signs were there: Fatigue that was getting worse in the North Carolina heat (Uhthoff sign!). A tingle running down my neck (Lhermitte sign!). Blurry vision late at night while studying pathways in Lange Neurology. “Didn’t cousin Amy have MS?” I asked my Mom. I started researching which medical specialties didn’t require dexterity. My left eyelid began twitching and didn’t stop until I rotated to ob.gyn.

Dr. Jeffrey Benabio

Fortunately, it was not multiple sclerosis I had, but rather nosophobia, also known as Medical Student’s Disease. The combination of intense study of symptoms, spotty knowledge of diagnoses, and grade anxiety makes nosophobia common in med students. Despite its name, it doesn’t afflict only doctors. Patients often come to us convinced they have a disease but without reason. So unshakable is their belief that multiple visits are often required to disabuse them of their self-diagnosis. I sometimes have to remind myself to appear concerned even when a “melanoma” is a freckle so small I can barely see it with a dermatoscope. Or a “genital wart” is a hair follicle that looks exactly like the hundreds on the patient’s scrotum. Tougher though, are the treatment-avoiders: patients whose imagined side effects lead them to stop or refuse treatment.

I recently saw a middle-aged man with erythroderma so severe he looked like a ghillie suit of scale. He had a lifelong history of atopic dermatitis and a 2-year history of avoiding treatments. At some point, he tried all the usual remedies: cyclosporine, methotrexate, azathioprine, light therapy, boxes of topicals. The last treatment had been dupilumab, which he tried for a few weeks. “Why did you stop that one?” I asked. The injections were making him go blind, he explained. “Not blurry? Blind?” I asked. Yes, he could not see at all after each injection. Perhaps he might have dry eyes or keratitis? Sure. But blindness? It seemed an unreasonable concern. Further discussion revealed that intolerance to medication side effects was why he had stopped all his other treatments.

Nocebo, from the Latin “I shall harm,” is the dark counterpart to the placebo. Patients experience imagined, or even real, adverse effects because they believe the treatment is causing them harm. This is true even though that treatment might not be having any unwanted physiologic effect. Statins are a good example. Studies have shown that most patient-reported side effects of statins are in fact nocebo effects rather than a result of pharmacologic causes.

Yet, many patients on statins report muscle pain or other concerns as unbearable. As a consequence, some patients who might have benefited from statins might be missing out on the protective gains. Nocebo effects are exacerbated by a common bias that causes deeper regret when bad outcomes result from an action taken as compared with bad outcomes that occurred from not taking action. It’s frustrating when there’s a standard of care treatment, but our patient can’t get past their fear of harm to try it.

Despite my recommendations, my eczema patient insisted on continuing his nontreatment rather than take any risks with treatments for now. There are ways I might help, but I expect it will require additional visits to build trust. Today, the best I can do is to understand and respect him. At least he doesn’t think he has a genital wart – I’m not sure how I’d treat it if he did.

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].

I was quite sure I had multiple sclerosis when I was a medical student. I first noticed symptoms during my neurology rotation. All the signs were there: Fatigue that was getting worse in the North Carolina heat (Uhthoff sign!). A tingle running down my neck (Lhermitte sign!). Blurry vision late at night while studying pathways in Lange Neurology. “Didn’t cousin Amy have MS?” I asked my Mom. I started researching which medical specialties didn’t require dexterity. My left eyelid began twitching and didn’t stop until I rotated to ob.gyn.

Dr. Jeffrey Benabio

Fortunately, it was not multiple sclerosis I had, but rather nosophobia, also known as Medical Student’s Disease. The combination of intense study of symptoms, spotty knowledge of diagnoses, and grade anxiety makes nosophobia common in med students. Despite its name, it doesn’t afflict only doctors. Patients often come to us convinced they have a disease but without reason. So unshakable is their belief that multiple visits are often required to disabuse them of their self-diagnosis. I sometimes have to remind myself to appear concerned even when a “melanoma” is a freckle so small I can barely see it with a dermatoscope. Or a “genital wart” is a hair follicle that looks exactly like the hundreds on the patient’s scrotum. Tougher though, are the treatment-avoiders: patients whose imagined side effects lead them to stop or refuse treatment.

I recently saw a middle-aged man with erythroderma so severe he looked like a ghillie suit of scale. He had a lifelong history of atopic dermatitis and a 2-year history of avoiding treatments. At some point, he tried all the usual remedies: cyclosporine, methotrexate, azathioprine, light therapy, boxes of topicals. The last treatment had been dupilumab, which he tried for a few weeks. “Why did you stop that one?” I asked. The injections were making him go blind, he explained. “Not blurry? Blind?” I asked. Yes, he could not see at all after each injection. Perhaps he might have dry eyes or keratitis? Sure. But blindness? It seemed an unreasonable concern. Further discussion revealed that intolerance to medication side effects was why he had stopped all his other treatments.

Nocebo, from the Latin “I shall harm,” is the dark counterpart to the placebo. Patients experience imagined, or even real, adverse effects because they believe the treatment is causing them harm. This is true even though that treatment might not be having any unwanted physiologic effect. Statins are a good example. Studies have shown that most patient-reported side effects of statins are in fact nocebo effects rather than a result of pharmacologic causes.

Yet, many patients on statins report muscle pain or other concerns as unbearable. As a consequence, some patients who might have benefited from statins might be missing out on the protective gains. Nocebo effects are exacerbated by a common bias that causes deeper regret when bad outcomes result from an action taken as compared with bad outcomes that occurred from not taking action. It’s frustrating when there’s a standard of care treatment, but our patient can’t get past their fear of harm to try it.

Despite my recommendations, my eczema patient insisted on continuing his nontreatment rather than take any risks with treatments for now. There are ways I might help, but I expect it will require additional visits to build trust. Today, the best I can do is to understand and respect him. At least he doesn’t think he has a genital wart – I’m not sure how I’d treat it if he did.

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].

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NAFLD strongly correlated with psoriasis, PsA; risk linked to severity

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Patients with chronic plaque psoriasis face a nearly twofold increased risk of nonalcoholic fatty liver disease (NAFLD), and the risk climbs higher in those with more severe skin involvement – and probably in those with psoriatic arthritis (PsA) as well, according to a systematic review and meta-analysis presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“Our findings imply that psoriatic patients should be screened with an ultrasonographic exam in cases where there are metabolic features that are associated with NAFLD,” reported Francesco Bellinato, MD, a researcher in the section of dermatology and venereology, University of Verona (Italy).

Dr. Francesco Belinato


The data are strong. Of 76 nonduplicate publications found in the literature, the 11 observational studies included in the meta-analysis met stringent criteria, including a diagnosis of psoriasis and PsA based on objective criteria, NAFLD confirmed with liver biopsy or imaging, and odds rates calculated with 95% confidence intervals.

From these 11 studies, aggregate data were available for 249,333 psoriatic patients, of which 49% had NAFLD, and 1,491,402 were healthy controls. Among the controls, 36% had NAFLD. Four of the studies were from North America, four from Europe, and three from Asia.



In the pooled data, the risk of NAFLD among those with psoriasis relative to healthy controls fell just short of a twofold increase (odds ratio, 1.96; 95% CI, 1.70-2.26; P < .001). When stratified by studies that confirmed NAFLD by biopsy relative to ultrasonography, there was no significant heterogeneity.

Eight of the studies included an analysis of relative risk in the context of skin lesion severity defined by Psoriasis Area and Severity Index (PASI) score. Relative to those without NAFLD, psoriatic patients with NAFLD had a significant greater mean PASI score on a pooled weighted mean difference analysis (OR, 3.93; 95% CI, 2.01-5.84; P < .0001).

courtesy Dr. Francesco Belinato
NAFLD is readily detectable in psoriasis patients on ultrasonography as exemplified by this sonogram of a patient recently evaluated by Dr. Belinato.

For PsA relative to no PsA in the five studies that compared risk between these two groups, the risk of NAFLD was again nearly twofold higher. This fell short of conventional definition of statistical significance, but it was associated with a strong trend (OR, 1.83; 95% CI, 0.98-3.43; P = .06).

The risk of NAFLD among patients with psoriasis was not found to vary significantly when assessed by univariable meta-regressions across numerous characteristics, such as sex and body mass index.

In one of the largest of the observational studies included in the meta-analysis by Alexis Ogdie, MD, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, and colleagues, data were analyzed in more than 1.5 million patients, which included 54,251 patients with rheumatoid arthritis. While the hazard ratio of NAFLD was increased for both psoriasis (HR, 2.23) and PsA (HR, 2.11), it was not elevated in those with RA (HR, 0.96).


Risk by severity, possible mechanisms


This study also included an analysis of NAFLD risk according to psoriasis severity. While risk was still significant among those with mild disease (HR, 1.18; 95% CI, 1.07-1.30), it was almost twofold greater in those with moderate to severe psoriasis (HR, 2.23; 95% CI, 1.73-2.87).

Dr. Bellinato conceded that the mechanisms underlying the association between psoriasis and NAFLD are unknown, but he said “metaflammation” is suspected.

“The secretion of proinflammatory, prothrombotic, and oxidative stress mediators in both psoriatic skin and adipose tissue might act systemically and promote insulin resistance and other metabolic derangements that promote the development and progression of NAFLD,” Dr. Bellinato explained.

He thinks that noninvasive screening methods, such as currently used methods to calculate fibrosis score, might be useful for evaluating patients with psoriasis for NAFLD and referring them to a hepatologist when appropriate.

Given the strong association with NAFLD, Dr. Bellinato suggested that “the findings of this meta-analysis pave the way for novel, large, prospective, and histologically based studies.”

Courtesy Dr. Joel M. Gelfand
Dr. Joel M. Gelfand

The association between psoriasis and NAFLD is clinically relevant, agreed Joel M. Gelfand, MD, vice-chair of clinical research and medical director of the clinical studies unit, department of dermatology, University of Pennsylvania, Philadelphia.

“It is not clear if psoriasis causes fatty liver disease or vice versa, but clinicians should be aware of this association,” he said in an interview. Dr. Gelfand was a coauthor of the study by Dr. Ogdie and colleagues and led another more recent population-based study that implicated methotrexate as a factor in psoriasis-related hepatotoxicity.

If NAFLD is identified in a patient with psoriasis, treatments are limited, but Dr. Gelfand suggested that patients should be made aware of the risk. “Clinicians should encourage patients with psoriasis to take measures to protect their liver, such as avoiding drinking alcohol to excess and trying to maintain a healthy body weight,” he said.

Dr. Bellinato reported no conflicts of interest. Dr. Gelfand has financial relationships with more than 10 pharmaceutical companies, including those that make therapies for psoriasis.

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Patients with chronic plaque psoriasis face a nearly twofold increased risk of nonalcoholic fatty liver disease (NAFLD), and the risk climbs higher in those with more severe skin involvement – and probably in those with psoriatic arthritis (PsA) as well, according to a systematic review and meta-analysis presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“Our findings imply that psoriatic patients should be screened with an ultrasonographic exam in cases where there are metabolic features that are associated with NAFLD,” reported Francesco Bellinato, MD, a researcher in the section of dermatology and venereology, University of Verona (Italy).

Dr. Francesco Belinato


The data are strong. Of 76 nonduplicate publications found in the literature, the 11 observational studies included in the meta-analysis met stringent criteria, including a diagnosis of psoriasis and PsA based on objective criteria, NAFLD confirmed with liver biopsy or imaging, and odds rates calculated with 95% confidence intervals.

From these 11 studies, aggregate data were available for 249,333 psoriatic patients, of which 49% had NAFLD, and 1,491,402 were healthy controls. Among the controls, 36% had NAFLD. Four of the studies were from North America, four from Europe, and three from Asia.



In the pooled data, the risk of NAFLD among those with psoriasis relative to healthy controls fell just short of a twofold increase (odds ratio, 1.96; 95% CI, 1.70-2.26; P < .001). When stratified by studies that confirmed NAFLD by biopsy relative to ultrasonography, there was no significant heterogeneity.

Eight of the studies included an analysis of relative risk in the context of skin lesion severity defined by Psoriasis Area and Severity Index (PASI) score. Relative to those without NAFLD, psoriatic patients with NAFLD had a significant greater mean PASI score on a pooled weighted mean difference analysis (OR, 3.93; 95% CI, 2.01-5.84; P < .0001).

courtesy Dr. Francesco Belinato
NAFLD is readily detectable in psoriasis patients on ultrasonography as exemplified by this sonogram of a patient recently evaluated by Dr. Belinato.

For PsA relative to no PsA in the five studies that compared risk between these two groups, the risk of NAFLD was again nearly twofold higher. This fell short of conventional definition of statistical significance, but it was associated with a strong trend (OR, 1.83; 95% CI, 0.98-3.43; P = .06).

The risk of NAFLD among patients with psoriasis was not found to vary significantly when assessed by univariable meta-regressions across numerous characteristics, such as sex and body mass index.

In one of the largest of the observational studies included in the meta-analysis by Alexis Ogdie, MD, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, and colleagues, data were analyzed in more than 1.5 million patients, which included 54,251 patients with rheumatoid arthritis. While the hazard ratio of NAFLD was increased for both psoriasis (HR, 2.23) and PsA (HR, 2.11), it was not elevated in those with RA (HR, 0.96).


Risk by severity, possible mechanisms


This study also included an analysis of NAFLD risk according to psoriasis severity. While risk was still significant among those with mild disease (HR, 1.18; 95% CI, 1.07-1.30), it was almost twofold greater in those with moderate to severe psoriasis (HR, 2.23; 95% CI, 1.73-2.87).

Dr. Bellinato conceded that the mechanisms underlying the association between psoriasis and NAFLD are unknown, but he said “metaflammation” is suspected.

“The secretion of proinflammatory, prothrombotic, and oxidative stress mediators in both psoriatic skin and adipose tissue might act systemically and promote insulin resistance and other metabolic derangements that promote the development and progression of NAFLD,” Dr. Bellinato explained.

He thinks that noninvasive screening methods, such as currently used methods to calculate fibrosis score, might be useful for evaluating patients with psoriasis for NAFLD and referring them to a hepatologist when appropriate.

Given the strong association with NAFLD, Dr. Bellinato suggested that “the findings of this meta-analysis pave the way for novel, large, prospective, and histologically based studies.”

Courtesy Dr. Joel M. Gelfand
Dr. Joel M. Gelfand

The association between psoriasis and NAFLD is clinically relevant, agreed Joel M. Gelfand, MD, vice-chair of clinical research and medical director of the clinical studies unit, department of dermatology, University of Pennsylvania, Philadelphia.

“It is not clear if psoriasis causes fatty liver disease or vice versa, but clinicians should be aware of this association,” he said in an interview. Dr. Gelfand was a coauthor of the study by Dr. Ogdie and colleagues and led another more recent population-based study that implicated methotrexate as a factor in psoriasis-related hepatotoxicity.

If NAFLD is identified in a patient with psoriasis, treatments are limited, but Dr. Gelfand suggested that patients should be made aware of the risk. “Clinicians should encourage patients with psoriasis to take measures to protect their liver, such as avoiding drinking alcohol to excess and trying to maintain a healthy body weight,” he said.

Dr. Bellinato reported no conflicts of interest. Dr. Gelfand has financial relationships with more than 10 pharmaceutical companies, including those that make therapies for psoriasis.

Patients with chronic plaque psoriasis face a nearly twofold increased risk of nonalcoholic fatty liver disease (NAFLD), and the risk climbs higher in those with more severe skin involvement – and probably in those with psoriatic arthritis (PsA) as well, according to a systematic review and meta-analysis presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“Our findings imply that psoriatic patients should be screened with an ultrasonographic exam in cases where there are metabolic features that are associated with NAFLD,” reported Francesco Bellinato, MD, a researcher in the section of dermatology and venereology, University of Verona (Italy).

Dr. Francesco Belinato


The data are strong. Of 76 nonduplicate publications found in the literature, the 11 observational studies included in the meta-analysis met stringent criteria, including a diagnosis of psoriasis and PsA based on objective criteria, NAFLD confirmed with liver biopsy or imaging, and odds rates calculated with 95% confidence intervals.

From these 11 studies, aggregate data were available for 249,333 psoriatic patients, of which 49% had NAFLD, and 1,491,402 were healthy controls. Among the controls, 36% had NAFLD. Four of the studies were from North America, four from Europe, and three from Asia.



In the pooled data, the risk of NAFLD among those with psoriasis relative to healthy controls fell just short of a twofold increase (odds ratio, 1.96; 95% CI, 1.70-2.26; P < .001). When stratified by studies that confirmed NAFLD by biopsy relative to ultrasonography, there was no significant heterogeneity.

Eight of the studies included an analysis of relative risk in the context of skin lesion severity defined by Psoriasis Area and Severity Index (PASI) score. Relative to those without NAFLD, psoriatic patients with NAFLD had a significant greater mean PASI score on a pooled weighted mean difference analysis (OR, 3.93; 95% CI, 2.01-5.84; P < .0001).

courtesy Dr. Francesco Belinato
NAFLD is readily detectable in psoriasis patients on ultrasonography as exemplified by this sonogram of a patient recently evaluated by Dr. Belinato.

For PsA relative to no PsA in the five studies that compared risk between these two groups, the risk of NAFLD was again nearly twofold higher. This fell short of conventional definition of statistical significance, but it was associated with a strong trend (OR, 1.83; 95% CI, 0.98-3.43; P = .06).

The risk of NAFLD among patients with psoriasis was not found to vary significantly when assessed by univariable meta-regressions across numerous characteristics, such as sex and body mass index.

In one of the largest of the observational studies included in the meta-analysis by Alexis Ogdie, MD, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, and colleagues, data were analyzed in more than 1.5 million patients, which included 54,251 patients with rheumatoid arthritis. While the hazard ratio of NAFLD was increased for both psoriasis (HR, 2.23) and PsA (HR, 2.11), it was not elevated in those with RA (HR, 0.96).


Risk by severity, possible mechanisms


This study also included an analysis of NAFLD risk according to psoriasis severity. While risk was still significant among those with mild disease (HR, 1.18; 95% CI, 1.07-1.30), it was almost twofold greater in those with moderate to severe psoriasis (HR, 2.23; 95% CI, 1.73-2.87).

Dr. Bellinato conceded that the mechanisms underlying the association between psoriasis and NAFLD are unknown, but he said “metaflammation” is suspected.

“The secretion of proinflammatory, prothrombotic, and oxidative stress mediators in both psoriatic skin and adipose tissue might act systemically and promote insulin resistance and other metabolic derangements that promote the development and progression of NAFLD,” Dr. Bellinato explained.

He thinks that noninvasive screening methods, such as currently used methods to calculate fibrosis score, might be useful for evaluating patients with psoriasis for NAFLD and referring them to a hepatologist when appropriate.

Given the strong association with NAFLD, Dr. Bellinato suggested that “the findings of this meta-analysis pave the way for novel, large, prospective, and histologically based studies.”

Courtesy Dr. Joel M. Gelfand
Dr. Joel M. Gelfand

The association between psoriasis and NAFLD is clinically relevant, agreed Joel M. Gelfand, MD, vice-chair of clinical research and medical director of the clinical studies unit, department of dermatology, University of Pennsylvania, Philadelphia.

“It is not clear if psoriasis causes fatty liver disease or vice versa, but clinicians should be aware of this association,” he said in an interview. Dr. Gelfand was a coauthor of the study by Dr. Ogdie and colleagues and led another more recent population-based study that implicated methotrexate as a factor in psoriasis-related hepatotoxicity.

If NAFLD is identified in a patient with psoriasis, treatments are limited, but Dr. Gelfand suggested that patients should be made aware of the risk. “Clinicians should encourage patients with psoriasis to take measures to protect their liver, such as avoiding drinking alcohol to excess and trying to maintain a healthy body weight,” he said.

Dr. Bellinato reported no conflicts of interest. Dr. Gelfand has financial relationships with more than 10 pharmaceutical companies, including those that make therapies for psoriasis.

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Methotrexate’s impact on COVID-19 vaccination: New insights made

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Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.



“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Dr. Jeffrey A. Sparks


“Although this finding adds to the evidence base to support interruption of methotrexate after vaccination, a shared decision process is needed to weigh the possible benefit of optimizing protection from COVID-19 and the possible risk of underlying disease flare,” they added.

Dr. Sara K. Tedeschi


Dr. Abhishek and colleagues assessed 254 patients with immune-mediated inflammatory disease from dermatology and rheumatology clinics across 26 hospitals in the United Kingdom. Participants had been diagnosed with systemic lupus erythematosus, rheumatoid arthritis, atopic dermatitis, polymyalgia rheumatica, axial spondyloarthritis, and psoriasis without or with arthritis. They had also been taking up to 25 mg of methotrexate per week for 3 months or longer and had received two doses of either the Pfizer/BioNTech BNT162b2 vaccine or AstraZeneca/Oxford viral vector vaccine. The booster dose was most often the Pfizer BNT162b2 vaccine (82%). The patients’ mean age was 59 years, with females comprising 61% of the cohort. Participants were randomly assigned 1:1 to either group.

Investigators performing laboratory analysis were masked to cohort assignment, and clinical research staff, data analysts, participants, and researchers were unmasked.

The elevated antibody response of patients who suspended methotrexate was the same across different kinds of immune-mediated inflammatory disease, primary vaccination platform, SARS-CoV-2 infection history, and age.

Notably, no intervention-associated adverse events were reported, the study team noted.

The conclusions that could be drawn from the booster-dose study were limited by the trial’s modest cohort size, the small number of patients in exploratory subgroup analyses, a lack of information about differences in prescription drug behavior, and early termination’s effect on the researchers’ ability to identify differences between subgroups and in secondary outcomes, the authors noted.

Other limitations included a lack of generalizability to patients with active disease who couldn’t stop therapy and were not included in the investigation, and participants were not blinded to what group they were in, the researchers said.
 
 

 

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

Dr. Kevin Winthrop

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Dr. Anu Sreekanth

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.



The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

 

 

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

Dr. Ines Colmegna

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

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Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.



“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Dr. Jeffrey A. Sparks


“Although this finding adds to the evidence base to support interruption of methotrexate after vaccination, a shared decision process is needed to weigh the possible benefit of optimizing protection from COVID-19 and the possible risk of underlying disease flare,” they added.

Dr. Sara K. Tedeschi


Dr. Abhishek and colleagues assessed 254 patients with immune-mediated inflammatory disease from dermatology and rheumatology clinics across 26 hospitals in the United Kingdom. Participants had been diagnosed with systemic lupus erythematosus, rheumatoid arthritis, atopic dermatitis, polymyalgia rheumatica, axial spondyloarthritis, and psoriasis without or with arthritis. They had also been taking up to 25 mg of methotrexate per week for 3 months or longer and had received two doses of either the Pfizer/BioNTech BNT162b2 vaccine or AstraZeneca/Oxford viral vector vaccine. The booster dose was most often the Pfizer BNT162b2 vaccine (82%). The patients’ mean age was 59 years, with females comprising 61% of the cohort. Participants were randomly assigned 1:1 to either group.

Investigators performing laboratory analysis were masked to cohort assignment, and clinical research staff, data analysts, participants, and researchers were unmasked.

The elevated antibody response of patients who suspended methotrexate was the same across different kinds of immune-mediated inflammatory disease, primary vaccination platform, SARS-CoV-2 infection history, and age.

Notably, no intervention-associated adverse events were reported, the study team noted.

The conclusions that could be drawn from the booster-dose study were limited by the trial’s modest cohort size, the small number of patients in exploratory subgroup analyses, a lack of information about differences in prescription drug behavior, and early termination’s effect on the researchers’ ability to identify differences between subgroups and in secondary outcomes, the authors noted.

Other limitations included a lack of generalizability to patients with active disease who couldn’t stop therapy and were not included in the investigation, and participants were not blinded to what group they were in, the researchers said.
 
 

 

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

Dr. Kevin Winthrop

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Dr. Anu Sreekanth

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.



The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

 

 

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

Dr. Ines Colmegna

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.



“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Dr. Jeffrey A. Sparks


“Although this finding adds to the evidence base to support interruption of methotrexate after vaccination, a shared decision process is needed to weigh the possible benefit of optimizing protection from COVID-19 and the possible risk of underlying disease flare,” they added.

Dr. Sara K. Tedeschi


Dr. Abhishek and colleagues assessed 254 patients with immune-mediated inflammatory disease from dermatology and rheumatology clinics across 26 hospitals in the United Kingdom. Participants had been diagnosed with systemic lupus erythematosus, rheumatoid arthritis, atopic dermatitis, polymyalgia rheumatica, axial spondyloarthritis, and psoriasis without or with arthritis. They had also been taking up to 25 mg of methotrexate per week for 3 months or longer and had received two doses of either the Pfizer/BioNTech BNT162b2 vaccine or AstraZeneca/Oxford viral vector vaccine. The booster dose was most often the Pfizer BNT162b2 vaccine (82%). The patients’ mean age was 59 years, with females comprising 61% of the cohort. Participants were randomly assigned 1:1 to either group.

Investigators performing laboratory analysis were masked to cohort assignment, and clinical research staff, data analysts, participants, and researchers were unmasked.

The elevated antibody response of patients who suspended methotrexate was the same across different kinds of immune-mediated inflammatory disease, primary vaccination platform, SARS-CoV-2 infection history, and age.

Notably, no intervention-associated adverse events were reported, the study team noted.

The conclusions that could be drawn from the booster-dose study were limited by the trial’s modest cohort size, the small number of patients in exploratory subgroup analyses, a lack of information about differences in prescription drug behavior, and early termination’s effect on the researchers’ ability to identify differences between subgroups and in secondary outcomes, the authors noted.

Other limitations included a lack of generalizability to patients with active disease who couldn’t stop therapy and were not included in the investigation, and participants were not blinded to what group they were in, the researchers said.
 
 

 

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

Dr. Kevin Winthrop

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Dr. Anu Sreekanth

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.



The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

 

 

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

Dr. Ines Colmegna

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

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Think of pediatric morphea as a systemic, chronic disease, expert advises

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– In the opinion of Elena Pope, MD, MSc, it’s time to think of morphea in children as a systemic, chronic condition with associated extracutaneous manifestations and the potential for relapse.

“There is no correlation between the extent and activity of skin lesions and the presence, severity, and activity of extracutaneous manifestations,” Dr. Pope, professor of pediatrics at the University of Toronto and division head of pediatric dermatology at the Hospital for Sick Children in Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “Treatment needs to be tailored to the extent of cutaneous manifestations, and I think we need to be aware of and address the impact on patients’ quality of life,” she added. There is also a need for more research “on targeted and better-tolerated therapies to put a stop to the progression of disease.”

Congenital morphea is a form of localized scleroderma that presents at birth but can be confused with port wine stain. Results from a multicenter retrospective review of 25 cases conducted by Dr. Pope and colleagues found that the median age at diagnosis was 2.9 years and 76% had linear-type lesions. In addition, 48% had extracutaneous involvement (all of these patients had linear morphea), most commonly of the central nervous system.

“It’s important to realize these lesions may become active over time,” Dr. Pope said. “In my experience, there are two different courses. Either you have innocuous lesions when the patients are born and they may become active around 3-4 years of age, or you have early intrauterine involvement, with lesions inactive at birth but with potential for significant damage in utero.”

She cautioned against treating a suspected port wine stain lesion with laser until congenital morphea is ruled out. “I’m aware of at least one lawsuit of a child where someone used a laser in a child who had progression with significant sclerosis,” she said. “The parents assumed it was the use of the laser that led to the progression, not the actual disease.”

Extracutaneous manifestations are common in morphea patients. A multicenter study of 750 patients with juvenile scleroderma found that 22% had extracutaneous manifestations. Almost half of patients (47%) had arthritis, but 17% had neurologic findings such as seizures and headaches, 9% had vascular manifestations, and 8% had uveitis. Subsequent studies found that neurological disease affects between 11% and 19% of cases, especially in those involving the head and neck.



“There is a wide range of manifestations from headache and neuropsychiatric changes to brain atrophy, seizures, and CNS cavernoma,” Dr. Pope said. “There also can be orthodental involvement such as malocclusion. It’s important to do a brain MRI, eye exam for uveitis, and don’t forget the orthodental assessment.”

She recalled a 10-year-old boy who presented to the Hospital for Sick Children with tissue loss on the forehead and eyebrow and eyelashes. He had no other congenital morphea symptoms and the MRI was normal, but the eye exam revealed uveitis. “It’s important to remember that uveitis is asymptomatic, so unless you look for it, you’re not going to find it,” she said.

According to unpublished data in 42 congenital morphea patients with lesions limited to the head and neck, who underwent MRI imaging at the Hospital for Sick Children, 57% had CNS changes that were ipsilateral in 68% of cases. “White matter changes were the most common, and to our surprise, there were patients who had progressive CNS disease, including CNS vasculitis, new lesions, and enhancement of prior stable lesions,” Dr. Pope said.

She recalled the case of an 8-year-old boy who presented to the hospital with intractable seizures. Upon completion of the MRI, one of the radiologists noted that the imaging showed subtle thinning of the forehead, and he was referred to Dr. Pope and colleagues for assessment. In the span of 4 years, despite aggressive treatment, the boy’s CNS disease progressed. “There was more enhancement, more tissue loss, his seizures are very hard to control, and he has many neurodevelopmental changes,” she recalled. “What I learned from this case is that skin activity does not correlate with imaging. Don’t assume that just because the skin is burnt out that the CNS will be the same. Also, the extent of skin disease does not predict involvement or progression of the CNS.”

Linear lesions on the lower extremities are a harbinger of orthopedic complications, which can occur in about half of patients. Joint contractures in this subset of patients are seen in about 81% of cases, while other sequelae can include arthritis, limb atrophy, leg-leg discrepancy, and angular deformity. “About 14% of patients require intervention,” Dr. Pope said. “In terms of working those patients up, you need to do an MRI and assess the extent of muscle and fascial involvement. Early physiotherapy and an orthopedic evaluation are also recommended.”

As for possible markers of morphea, antinuclear antibody is positive in 22%-68% of cases and correlates with disease severity, extracutaneous manifestations, and disease flare-up. Antihistone antibodies (AHA) are positive in about 47% of cases, “and that tends to correlate with the extent of skin and muscle involvement,” Dr. Pope said. “Anti–double-stranded DNA correlates with extent of disease, but the only known biomarker to date that correlates with disease activity is CXCL9/10. This has been documented in the skin as well as in the blood. So, this marker may help us determine if the patient needs to be treated or not.”



Treatments

For treatment of active localized disease, topical medications are helpful in some cases. Options include topical steroids, calcipotriol with or without betamethasone, imiquimod, and tacrolimus. “In my experience the combination of calcipotriol with betamethasone is best,” she said. “It really shuts down the activity fairly soon, and you can scale down to calcipotriol alone. I don’t find imiquimod very helpful for active lesions, although it has a role for inactive lesions.”

For patients with linear or generalized/mixed disease, “the combination of methotrexate and corticosteroids or methotrexate alone is probably the way to go,” Dr. Pope said. “The addition of steroids really depends on where the lesion is and how worried you are about other problems.”

According to the best available literature, 88% of patients should respond to treatment with methotrexate (MTX) and/or steroids within 3-6 months, and 74% within 3 months. “If they don’t, you have to wonder if the patient’s taking the medication, or you need to think about other alternative treatments,” she said. “Complete remission is possible in most of the patients, and the longer you treat the more you will see that. On average, most of us treat patients for about 3 years, but there are treatment failures as well. This can occur in up to 16% of patients.”

As for second-line treatment agents for congenital morphea, clinicians often turn to mycophenolate mofetil (MMF). Results from a retrospective longitudinal study of juvenile localized scleroderma patients found that after a mean of 9 years 91% of patients on MMF and 100% of patients on MTX had inactive disease. “There were no differences in relapse rates, although MMF seems to have a more sustained long-term effect and overall is better tolerated,” said Dr. Pope, who was not involved with the study. “However, it’s more immunosuppressive than MTX, which is important, especially in the era of COVID-19. You also need to think about the potential for more hematological suppression with MMF use.” If standard therapy fails, there is anecdotal data supporting the use of abatacept (which suppresses the T-cell activity in affected patients), tofacitinib (which inhibits transforming growth factor–beta), or dupilumab (which inhibits interleukin-4).

Dr. Pope emphasized the effect congenital morphea has on quality of life. Remarks from patients with facial morphea and their parents who participated in a focus group on the topic organized by the Hospital for Sick Children included, “You just want to stay inside because you are afraid of what people will say,” “They laugh at her. They make fun of her, and it’s terrible,” and “MTX makes me feel weird. I would throw up, feel dizzy.”

“You have to take that into consideration, because we cannot make the treatment worse than the disease,” Dr. Pope said. “There are many domains where patients could be affected, including skin symptoms, physical functioning, body image and social support, side effects of medication, and presence of extracutaneous manifestations. Predictors of poor quality of life include female sex and involvement of hands and feet.”

Dr. Pope disclosed that she has received grants/research support from AbbVie, Centocor, and Amgen. She has also received consulting fees from AbbVie, Sanofi, Novartis, Boehringer-Ingelheim, Phoenix, Amryt Pharma, and Timber Pharmaceuticals.

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– In the opinion of Elena Pope, MD, MSc, it’s time to think of morphea in children as a systemic, chronic condition with associated extracutaneous manifestations and the potential for relapse.

“There is no correlation between the extent and activity of skin lesions and the presence, severity, and activity of extracutaneous manifestations,” Dr. Pope, professor of pediatrics at the University of Toronto and division head of pediatric dermatology at the Hospital for Sick Children in Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “Treatment needs to be tailored to the extent of cutaneous manifestations, and I think we need to be aware of and address the impact on patients’ quality of life,” she added. There is also a need for more research “on targeted and better-tolerated therapies to put a stop to the progression of disease.”

Congenital morphea is a form of localized scleroderma that presents at birth but can be confused with port wine stain. Results from a multicenter retrospective review of 25 cases conducted by Dr. Pope and colleagues found that the median age at diagnosis was 2.9 years and 76% had linear-type lesions. In addition, 48% had extracutaneous involvement (all of these patients had linear morphea), most commonly of the central nervous system.

“It’s important to realize these lesions may become active over time,” Dr. Pope said. “In my experience, there are two different courses. Either you have innocuous lesions when the patients are born and they may become active around 3-4 years of age, or you have early intrauterine involvement, with lesions inactive at birth but with potential for significant damage in utero.”

She cautioned against treating a suspected port wine stain lesion with laser until congenital morphea is ruled out. “I’m aware of at least one lawsuit of a child where someone used a laser in a child who had progression with significant sclerosis,” she said. “The parents assumed it was the use of the laser that led to the progression, not the actual disease.”

Extracutaneous manifestations are common in morphea patients. A multicenter study of 750 patients with juvenile scleroderma found that 22% had extracutaneous manifestations. Almost half of patients (47%) had arthritis, but 17% had neurologic findings such as seizures and headaches, 9% had vascular manifestations, and 8% had uveitis. Subsequent studies found that neurological disease affects between 11% and 19% of cases, especially in those involving the head and neck.



“There is a wide range of manifestations from headache and neuropsychiatric changes to brain atrophy, seizures, and CNS cavernoma,” Dr. Pope said. “There also can be orthodental involvement such as malocclusion. It’s important to do a brain MRI, eye exam for uveitis, and don’t forget the orthodental assessment.”

She recalled a 10-year-old boy who presented to the Hospital for Sick Children with tissue loss on the forehead and eyebrow and eyelashes. He had no other congenital morphea symptoms and the MRI was normal, but the eye exam revealed uveitis. “It’s important to remember that uveitis is asymptomatic, so unless you look for it, you’re not going to find it,” she said.

According to unpublished data in 42 congenital morphea patients with lesions limited to the head and neck, who underwent MRI imaging at the Hospital for Sick Children, 57% had CNS changes that were ipsilateral in 68% of cases. “White matter changes were the most common, and to our surprise, there were patients who had progressive CNS disease, including CNS vasculitis, new lesions, and enhancement of prior stable lesions,” Dr. Pope said.

She recalled the case of an 8-year-old boy who presented to the hospital with intractable seizures. Upon completion of the MRI, one of the radiologists noted that the imaging showed subtle thinning of the forehead, and he was referred to Dr. Pope and colleagues for assessment. In the span of 4 years, despite aggressive treatment, the boy’s CNS disease progressed. “There was more enhancement, more tissue loss, his seizures are very hard to control, and he has many neurodevelopmental changes,” she recalled. “What I learned from this case is that skin activity does not correlate with imaging. Don’t assume that just because the skin is burnt out that the CNS will be the same. Also, the extent of skin disease does not predict involvement or progression of the CNS.”

Linear lesions on the lower extremities are a harbinger of orthopedic complications, which can occur in about half of patients. Joint contractures in this subset of patients are seen in about 81% of cases, while other sequelae can include arthritis, limb atrophy, leg-leg discrepancy, and angular deformity. “About 14% of patients require intervention,” Dr. Pope said. “In terms of working those patients up, you need to do an MRI and assess the extent of muscle and fascial involvement. Early physiotherapy and an orthopedic evaluation are also recommended.”

As for possible markers of morphea, antinuclear antibody is positive in 22%-68% of cases and correlates with disease severity, extracutaneous manifestations, and disease flare-up. Antihistone antibodies (AHA) are positive in about 47% of cases, “and that tends to correlate with the extent of skin and muscle involvement,” Dr. Pope said. “Anti–double-stranded DNA correlates with extent of disease, but the only known biomarker to date that correlates with disease activity is CXCL9/10. This has been documented in the skin as well as in the blood. So, this marker may help us determine if the patient needs to be treated or not.”



Treatments

For treatment of active localized disease, topical medications are helpful in some cases. Options include topical steroids, calcipotriol with or without betamethasone, imiquimod, and tacrolimus. “In my experience the combination of calcipotriol with betamethasone is best,” she said. “It really shuts down the activity fairly soon, and you can scale down to calcipotriol alone. I don’t find imiquimod very helpful for active lesions, although it has a role for inactive lesions.”

For patients with linear or generalized/mixed disease, “the combination of methotrexate and corticosteroids or methotrexate alone is probably the way to go,” Dr. Pope said. “The addition of steroids really depends on where the lesion is and how worried you are about other problems.”

According to the best available literature, 88% of patients should respond to treatment with methotrexate (MTX) and/or steroids within 3-6 months, and 74% within 3 months. “If they don’t, you have to wonder if the patient’s taking the medication, or you need to think about other alternative treatments,” she said. “Complete remission is possible in most of the patients, and the longer you treat the more you will see that. On average, most of us treat patients for about 3 years, but there are treatment failures as well. This can occur in up to 16% of patients.”

As for second-line treatment agents for congenital morphea, clinicians often turn to mycophenolate mofetil (MMF). Results from a retrospective longitudinal study of juvenile localized scleroderma patients found that after a mean of 9 years 91% of patients on MMF and 100% of patients on MTX had inactive disease. “There were no differences in relapse rates, although MMF seems to have a more sustained long-term effect and overall is better tolerated,” said Dr. Pope, who was not involved with the study. “However, it’s more immunosuppressive than MTX, which is important, especially in the era of COVID-19. You also need to think about the potential for more hematological suppression with MMF use.” If standard therapy fails, there is anecdotal data supporting the use of abatacept (which suppresses the T-cell activity in affected patients), tofacitinib (which inhibits transforming growth factor–beta), or dupilumab (which inhibits interleukin-4).

Dr. Pope emphasized the effect congenital morphea has on quality of life. Remarks from patients with facial morphea and their parents who participated in a focus group on the topic organized by the Hospital for Sick Children included, “You just want to stay inside because you are afraid of what people will say,” “They laugh at her. They make fun of her, and it’s terrible,” and “MTX makes me feel weird. I would throw up, feel dizzy.”

“You have to take that into consideration, because we cannot make the treatment worse than the disease,” Dr. Pope said. “There are many domains where patients could be affected, including skin symptoms, physical functioning, body image and social support, side effects of medication, and presence of extracutaneous manifestations. Predictors of poor quality of life include female sex and involvement of hands and feet.”

Dr. Pope disclosed that she has received grants/research support from AbbVie, Centocor, and Amgen. She has also received consulting fees from AbbVie, Sanofi, Novartis, Boehringer-Ingelheim, Phoenix, Amryt Pharma, and Timber Pharmaceuticals.

– In the opinion of Elena Pope, MD, MSc, it’s time to think of morphea in children as a systemic, chronic condition with associated extracutaneous manifestations and the potential for relapse.

“There is no correlation between the extent and activity of skin lesions and the presence, severity, and activity of extracutaneous manifestations,” Dr. Pope, professor of pediatrics at the University of Toronto and division head of pediatric dermatology at the Hospital for Sick Children in Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “Treatment needs to be tailored to the extent of cutaneous manifestations, and I think we need to be aware of and address the impact on patients’ quality of life,” she added. There is also a need for more research “on targeted and better-tolerated therapies to put a stop to the progression of disease.”

Congenital morphea is a form of localized scleroderma that presents at birth but can be confused with port wine stain. Results from a multicenter retrospective review of 25 cases conducted by Dr. Pope and colleagues found that the median age at diagnosis was 2.9 years and 76% had linear-type lesions. In addition, 48% had extracutaneous involvement (all of these patients had linear morphea), most commonly of the central nervous system.

“It’s important to realize these lesions may become active over time,” Dr. Pope said. “In my experience, there are two different courses. Either you have innocuous lesions when the patients are born and they may become active around 3-4 years of age, or you have early intrauterine involvement, with lesions inactive at birth but with potential for significant damage in utero.”

She cautioned against treating a suspected port wine stain lesion with laser until congenital morphea is ruled out. “I’m aware of at least one lawsuit of a child where someone used a laser in a child who had progression with significant sclerosis,” she said. “The parents assumed it was the use of the laser that led to the progression, not the actual disease.”

Extracutaneous manifestations are common in morphea patients. A multicenter study of 750 patients with juvenile scleroderma found that 22% had extracutaneous manifestations. Almost half of patients (47%) had arthritis, but 17% had neurologic findings such as seizures and headaches, 9% had vascular manifestations, and 8% had uveitis. Subsequent studies found that neurological disease affects between 11% and 19% of cases, especially in those involving the head and neck.



“There is a wide range of manifestations from headache and neuropsychiatric changes to brain atrophy, seizures, and CNS cavernoma,” Dr. Pope said. “There also can be orthodental involvement such as malocclusion. It’s important to do a brain MRI, eye exam for uveitis, and don’t forget the orthodental assessment.”

She recalled a 10-year-old boy who presented to the Hospital for Sick Children with tissue loss on the forehead and eyebrow and eyelashes. He had no other congenital morphea symptoms and the MRI was normal, but the eye exam revealed uveitis. “It’s important to remember that uveitis is asymptomatic, so unless you look for it, you’re not going to find it,” she said.

According to unpublished data in 42 congenital morphea patients with lesions limited to the head and neck, who underwent MRI imaging at the Hospital for Sick Children, 57% had CNS changes that were ipsilateral in 68% of cases. “White matter changes were the most common, and to our surprise, there were patients who had progressive CNS disease, including CNS vasculitis, new lesions, and enhancement of prior stable lesions,” Dr. Pope said.

She recalled the case of an 8-year-old boy who presented to the hospital with intractable seizures. Upon completion of the MRI, one of the radiologists noted that the imaging showed subtle thinning of the forehead, and he was referred to Dr. Pope and colleagues for assessment. In the span of 4 years, despite aggressive treatment, the boy’s CNS disease progressed. “There was more enhancement, more tissue loss, his seizures are very hard to control, and he has many neurodevelopmental changes,” she recalled. “What I learned from this case is that skin activity does not correlate with imaging. Don’t assume that just because the skin is burnt out that the CNS will be the same. Also, the extent of skin disease does not predict involvement or progression of the CNS.”

Linear lesions on the lower extremities are a harbinger of orthopedic complications, which can occur in about half of patients. Joint contractures in this subset of patients are seen in about 81% of cases, while other sequelae can include arthritis, limb atrophy, leg-leg discrepancy, and angular deformity. “About 14% of patients require intervention,” Dr. Pope said. “In terms of working those patients up, you need to do an MRI and assess the extent of muscle and fascial involvement. Early physiotherapy and an orthopedic evaluation are also recommended.”

As for possible markers of morphea, antinuclear antibody is positive in 22%-68% of cases and correlates with disease severity, extracutaneous manifestations, and disease flare-up. Antihistone antibodies (AHA) are positive in about 47% of cases, “and that tends to correlate with the extent of skin and muscle involvement,” Dr. Pope said. “Anti–double-stranded DNA correlates with extent of disease, but the only known biomarker to date that correlates with disease activity is CXCL9/10. This has been documented in the skin as well as in the blood. So, this marker may help us determine if the patient needs to be treated or not.”



Treatments

For treatment of active localized disease, topical medications are helpful in some cases. Options include topical steroids, calcipotriol with or without betamethasone, imiquimod, and tacrolimus. “In my experience the combination of calcipotriol with betamethasone is best,” she said. “It really shuts down the activity fairly soon, and you can scale down to calcipotriol alone. I don’t find imiquimod very helpful for active lesions, although it has a role for inactive lesions.”

For patients with linear or generalized/mixed disease, “the combination of methotrexate and corticosteroids or methotrexate alone is probably the way to go,” Dr. Pope said. “The addition of steroids really depends on where the lesion is and how worried you are about other problems.”

According to the best available literature, 88% of patients should respond to treatment with methotrexate (MTX) and/or steroids within 3-6 months, and 74% within 3 months. “If they don’t, you have to wonder if the patient’s taking the medication, or you need to think about other alternative treatments,” she said. “Complete remission is possible in most of the patients, and the longer you treat the more you will see that. On average, most of us treat patients for about 3 years, but there are treatment failures as well. This can occur in up to 16% of patients.”

As for second-line treatment agents for congenital morphea, clinicians often turn to mycophenolate mofetil (MMF). Results from a retrospective longitudinal study of juvenile localized scleroderma patients found that after a mean of 9 years 91% of patients on MMF and 100% of patients on MTX had inactive disease. “There were no differences in relapse rates, although MMF seems to have a more sustained long-term effect and overall is better tolerated,” said Dr. Pope, who was not involved with the study. “However, it’s more immunosuppressive than MTX, which is important, especially in the era of COVID-19. You also need to think about the potential for more hematological suppression with MMF use.” If standard therapy fails, there is anecdotal data supporting the use of abatacept (which suppresses the T-cell activity in affected patients), tofacitinib (which inhibits transforming growth factor–beta), or dupilumab (which inhibits interleukin-4).

Dr. Pope emphasized the effect congenital morphea has on quality of life. Remarks from patients with facial morphea and their parents who participated in a focus group on the topic organized by the Hospital for Sick Children included, “You just want to stay inside because you are afraid of what people will say,” “They laugh at her. They make fun of her, and it’s terrible,” and “MTX makes me feel weird. I would throw up, feel dizzy.”

“You have to take that into consideration, because we cannot make the treatment worse than the disease,” Dr. Pope said. “There are many domains where patients could be affected, including skin symptoms, physical functioning, body image and social support, side effects of medication, and presence of extracutaneous manifestations. Predictors of poor quality of life include female sex and involvement of hands and feet.”

Dr. Pope disclosed that she has received grants/research support from AbbVie, Centocor, and Amgen. She has also received consulting fees from AbbVie, Sanofi, Novartis, Boehringer-Ingelheim, Phoenix, Amryt Pharma, and Timber Pharmaceuticals.

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When I began in private practice several eons ago, I employed only registered nurses (RNs) and licensed practical nurses (LPNs) in my office – as did, I think, most other physicians.

That is still the preferred way to go from an efficiency perspective, as well as the ability to delegate such tasks as blood collection and administering intramuscular injections. Unfortunately, the current state of medical practice – driven by payment reform, regulatory changes, technology costs, inflation, and other factors – has forced most independent practitioners to pivot from RNs and LPNs to medical assistants in a majority of situations.

Given this reality, it makes sense to understand how the use of medical assistants has changed private medical practice, and how the most effective MAs manage their roles and maximize their efficiency in the office.

A recent article by two physicians at the University of Michigan, Ann Arbor, is one of the few published papers to address this issue. It presents the results of a cross-sectional study examining the MA’s experience and key factors that enhance or reduce efficiencies.

The authors sent an email survey to 86 MAs working in six clinics within the department of family medicine at the University of Michigan Medical Center, and received responses from 75 of them, including 61 who completed the entire survey. They then singled out 18 individuals deemed “most efficient” by their peers and conducted face-to-face interviews with them.

The surveys and interviews looked at how MAs identified personal strategies for efficiency, dealt with barriers to implementing those strategies, and navigated interoffice relationships, as well as how all of this affected overall job satisfaction.

All 61 respondents who completed the full survey agreed that the MA role was “very important to keep the clinic functioning” and nearly all said that working in health care was “a calling” for them. About half agreed that their work was very stressful, and about the same percentage reported that there was inadequate MA staffing at their clinic. Others complained of limited pay and promotion opportunities.



The surveyed MAs described important work values that increased their efficiency. These included good communication, strong teamwork, and workload sharing, as well as individual strategies such as multitasking, limiting patient conversations, and completing tasks in a consistent way to improve accuracy.

Other strategies identified as contributing to an efficient operation included preclinic huddles, reviews of patient records before the patient’s arrival, and completing routine office duties before the start of office hours.

Respondents were then asked to identify barriers to clinic efficiency, and most of them involved physicians who barked orders at them, did not complete paperwork or sign orders in a timely manner, and agreed to see late-arriving patients. Some MAs suggested that physicians refrain from “talking down” to them, and teach rather than criticize. They also faulted decisions affecting patient flow made by other staffers without soliciting the MAs’ input.

Despite these barriers, the authors found that most of the surveyed MAs agreed that their work was valued by doctors. “Proper training of managers to provide ... support and ensure equitable workloads may be one strategy to ensure that staff members feel the workplace is fair and collegial,” they said.

“Many described the working relationships with physicians as critical to their satisfaction at work and indicated that strong partnerships motivated them to do their best to make the physician’s day easier,” they added.

At the same time, the authors noted that most survey subjects reported that their jobs were “stressful,” and believed that their stress went underrecognized by physicians. They argued that “it’s important for physicians to be cognizant of these patterns and clinic culture, as reducing a hierarchy-based environment will be appreciated by MAs.”

Since this study involved only MAs in a family practice setting, further studies will be needed to determine whether these results translate to specialty offices – and whether the unique issues inherent in various specialty environments elicit different efficiency contributors and barriers.

Overall, though, “staff job satisfaction is linked to improved quality of care, so treating staff well contributes to high-value care for patients,” the authors wrote. “Disseminating practices that staff members themselves have identified as effective, and being attentive to how staff members are treated, may increase individual efficiency while improving staff retention and satisfaction.”

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

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When I began in private practice several eons ago, I employed only registered nurses (RNs) and licensed practical nurses (LPNs) in my office – as did, I think, most other physicians.

That is still the preferred way to go from an efficiency perspective, as well as the ability to delegate such tasks as blood collection and administering intramuscular injections. Unfortunately, the current state of medical practice – driven by payment reform, regulatory changes, technology costs, inflation, and other factors – has forced most independent practitioners to pivot from RNs and LPNs to medical assistants in a majority of situations.

Given this reality, it makes sense to understand how the use of medical assistants has changed private medical practice, and how the most effective MAs manage their roles and maximize their efficiency in the office.

A recent article by two physicians at the University of Michigan, Ann Arbor, is one of the few published papers to address this issue. It presents the results of a cross-sectional study examining the MA’s experience and key factors that enhance or reduce efficiencies.

The authors sent an email survey to 86 MAs working in six clinics within the department of family medicine at the University of Michigan Medical Center, and received responses from 75 of them, including 61 who completed the entire survey. They then singled out 18 individuals deemed “most efficient” by their peers and conducted face-to-face interviews with them.

The surveys and interviews looked at how MAs identified personal strategies for efficiency, dealt with barriers to implementing those strategies, and navigated interoffice relationships, as well as how all of this affected overall job satisfaction.

All 61 respondents who completed the full survey agreed that the MA role was “very important to keep the clinic functioning” and nearly all said that working in health care was “a calling” for them. About half agreed that their work was very stressful, and about the same percentage reported that there was inadequate MA staffing at their clinic. Others complained of limited pay and promotion opportunities.



The surveyed MAs described important work values that increased their efficiency. These included good communication, strong teamwork, and workload sharing, as well as individual strategies such as multitasking, limiting patient conversations, and completing tasks in a consistent way to improve accuracy.

Other strategies identified as contributing to an efficient operation included preclinic huddles, reviews of patient records before the patient’s arrival, and completing routine office duties before the start of office hours.

Respondents were then asked to identify barriers to clinic efficiency, and most of them involved physicians who barked orders at them, did not complete paperwork or sign orders in a timely manner, and agreed to see late-arriving patients. Some MAs suggested that physicians refrain from “talking down” to them, and teach rather than criticize. They also faulted decisions affecting patient flow made by other staffers without soliciting the MAs’ input.

Despite these barriers, the authors found that most of the surveyed MAs agreed that their work was valued by doctors. “Proper training of managers to provide ... support and ensure equitable workloads may be one strategy to ensure that staff members feel the workplace is fair and collegial,” they said.

“Many described the working relationships with physicians as critical to their satisfaction at work and indicated that strong partnerships motivated them to do their best to make the physician’s day easier,” they added.

At the same time, the authors noted that most survey subjects reported that their jobs were “stressful,” and believed that their stress went underrecognized by physicians. They argued that “it’s important for physicians to be cognizant of these patterns and clinic culture, as reducing a hierarchy-based environment will be appreciated by MAs.”

Since this study involved only MAs in a family practice setting, further studies will be needed to determine whether these results translate to specialty offices – and whether the unique issues inherent in various specialty environments elicit different efficiency contributors and barriers.

Overall, though, “staff job satisfaction is linked to improved quality of care, so treating staff well contributes to high-value care for patients,” the authors wrote. “Disseminating practices that staff members themselves have identified as effective, and being attentive to how staff members are treated, may increase individual efficiency while improving staff retention and satisfaction.”

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

When I began in private practice several eons ago, I employed only registered nurses (RNs) and licensed practical nurses (LPNs) in my office – as did, I think, most other physicians.

That is still the preferred way to go from an efficiency perspective, as well as the ability to delegate such tasks as blood collection and administering intramuscular injections. Unfortunately, the current state of medical practice – driven by payment reform, regulatory changes, technology costs, inflation, and other factors – has forced most independent practitioners to pivot from RNs and LPNs to medical assistants in a majority of situations.

Given this reality, it makes sense to understand how the use of medical assistants has changed private medical practice, and how the most effective MAs manage their roles and maximize their efficiency in the office.

A recent article by two physicians at the University of Michigan, Ann Arbor, is one of the few published papers to address this issue. It presents the results of a cross-sectional study examining the MA’s experience and key factors that enhance or reduce efficiencies.

The authors sent an email survey to 86 MAs working in six clinics within the department of family medicine at the University of Michigan Medical Center, and received responses from 75 of them, including 61 who completed the entire survey. They then singled out 18 individuals deemed “most efficient” by their peers and conducted face-to-face interviews with them.

The surveys and interviews looked at how MAs identified personal strategies for efficiency, dealt with barriers to implementing those strategies, and navigated interoffice relationships, as well as how all of this affected overall job satisfaction.

All 61 respondents who completed the full survey agreed that the MA role was “very important to keep the clinic functioning” and nearly all said that working in health care was “a calling” for them. About half agreed that their work was very stressful, and about the same percentage reported that there was inadequate MA staffing at their clinic. Others complained of limited pay and promotion opportunities.



The surveyed MAs described important work values that increased their efficiency. These included good communication, strong teamwork, and workload sharing, as well as individual strategies such as multitasking, limiting patient conversations, and completing tasks in a consistent way to improve accuracy.

Other strategies identified as contributing to an efficient operation included preclinic huddles, reviews of patient records before the patient’s arrival, and completing routine office duties before the start of office hours.

Respondents were then asked to identify barriers to clinic efficiency, and most of them involved physicians who barked orders at them, did not complete paperwork or sign orders in a timely manner, and agreed to see late-arriving patients. Some MAs suggested that physicians refrain from “talking down” to them, and teach rather than criticize. They also faulted decisions affecting patient flow made by other staffers without soliciting the MAs’ input.

Despite these barriers, the authors found that most of the surveyed MAs agreed that their work was valued by doctors. “Proper training of managers to provide ... support and ensure equitable workloads may be one strategy to ensure that staff members feel the workplace is fair and collegial,” they said.

“Many described the working relationships with physicians as critical to their satisfaction at work and indicated that strong partnerships motivated them to do their best to make the physician’s day easier,” they added.

At the same time, the authors noted that most survey subjects reported that their jobs were “stressful,” and believed that their stress went underrecognized by physicians. They argued that “it’s important for physicians to be cognizant of these patterns and clinic culture, as reducing a hierarchy-based environment will be appreciated by MAs.”

Since this study involved only MAs in a family practice setting, further studies will be needed to determine whether these results translate to specialty offices – and whether the unique issues inherent in various specialty environments elicit different efficiency contributors and barriers.

Overall, though, “staff job satisfaction is linked to improved quality of care, so treating staff well contributes to high-value care for patients,” the authors wrote. “Disseminating practices that staff members themselves have identified as effective, and being attentive to how staff members are treated, may increase individual efficiency while improving staff retention and satisfaction.”

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

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