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Two close colleagues at New York’s Memorial Sloan Kettering Cancer Center, world leaders in hematopoietic stem cell transplantation (HSCT) who were both promoted days after COVID-19 locked down the city in 2020, were too busy battling the pandemic’s impact on patients in the summer of 2021 to notice their latest shared career milestone.

On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.

Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.

Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.

Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”

Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.

Courtesy MSKCC

Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.

“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”

When it comes to clinical science, however, English is the language of choice.
 

Global leaders in HSCT

Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.

In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).

However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.

Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).

Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.

The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.

Courtesy MSKCC

The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.

During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).

The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.

The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.

Impact of the pandemic

When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”

The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.

“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
 

Something more in common

Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.

“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.

He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.

Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”

“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”

Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”

This article was updated 1/26/22.

Two close colleagues at New York’s Memorial Sloan Kettering Cancer Center, world leaders in hematopoietic stem cell transplantation (HSCT) who were both promoted days after COVID-19 locked down the city in 2020, were too busy battling the pandemic’s impact on patients in the summer of 2021 to notice their latest shared career milestone.

On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.

Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.

Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.

Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”

Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.

Courtesy MSKCC

Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.

“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”

When it comes to clinical science, however, English is the language of choice.
 

Global leaders in HSCT

Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.

In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).

However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.

Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).

Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.

The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.

Courtesy MSKCC

The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.

During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).

The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.

The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.

Impact of the pandemic

When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”

The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.

“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
 

Something more in common

Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.

“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.

He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.

Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”

“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”

Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”

This article was updated 1/26/22.

Two close colleagues at New York’s Memorial Sloan Kettering Cancer Center, world leaders in hematopoietic stem cell transplantation (HSCT) who were both promoted days after COVID-19 locked down the city in 2020, were too busy battling the pandemic’s impact on patients in the summer of 2021 to notice their latest shared career milestone.

On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.

Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.

Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.

Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”

Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.

Courtesy MSKCC

Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.

“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”

When it comes to clinical science, however, English is the language of choice.
 

Global leaders in HSCT

Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.

In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).

However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.

Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).

Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.

The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.

Courtesy MSKCC

The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.

During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).

The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.

The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.

Impact of the pandemic

When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”

The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.

“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
 

Something more in common

Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.

“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.

He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.

Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”

“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”

Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”

This article was updated 1/26/22.

Rituximab has presented something of a conundrum for patients taking the monoclonal antibody during the COVID-19 pandemic.

Used to manage a variety of autoimmune diseases and cancers, rituximab acts against CD20 proteins expressed on the surface of B cells, causing B-cell depletion. However, it is this B-cell depletion that may put these patients at greater risk of COVID-19 development, progression to more severe disease, and in-hospital mortality. Evidence for this appears to be mixed, with studies showing both that patients using rituximab to manage various diseases are and are not at increased risk for SARS-CoV-2 infection, COVID-19 progression, and mortality.

peterschreiber_media/iStock/Getty Images

As COVID-19 vaccine rollouts take place across the world, more questions have been raised about the relationship between B-cell depletion from anti-CD20 therapies and COVID-19 vaccines. Do rituximab and other anti-CD20 therapies affect a patient’s response to COVID-19 vaccines? If this is the case, does the timing of anti-CD20 treatment matter to maximize B-cell levels and improve the vaccine’s effectiveness? And how do COVID-19 vaccine booster doses factor into the equation?

This article aims to summarize the latest research on how rituximab affects humoral and cell-mediated response following a COVID-19 vaccine primary series, and whether the addition of a COVID-19 vaccine booster dose changes patient response.
 

Humoral and cell-mediated responses following COVID-19 vaccination

First, the bad news: The vaccine is unquestionably safe to administer in patients taking rituximab, but one thing that has been well established is that antibody response to COVID-19 vaccination in these individuals does is reduced. This isn’t entirely unprecedented, as previous studies have shown a weakened immune response to pneumococcal polysaccharide and keyhole limpet hemocyanin vaccines among patients taking rituximab.

“Compromised immunogenicity to the SARS-CoV-2 vaccines has been demonstrated in rituximab-treated patients, which is of particular concern given the observation that B-cell–depleting therapies may be associated with worse COVID outcomes,” Robert F. Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York, said in an interview.

For example, in a recent study from the Medical University of Vienna, 29 (39%) of 74 patients receiving rituximab (43% as monotherapy, 57% with conventional-synthetic disease-modifying antirheumatic drugs) who were vaccinated with either the Comirnaty (Pfizer-BioNTech) or Spikevax (Moderna) COVID-19 vaccine achieved seroconversion, compared with 100% of patients in a healthy control group, and all but 1 patient without detectable CD19+ peripheral B cells did not develop anti–SARS-CoV-2 receptor-binding domain antibodies.

“There is an increasing number of studies in this field, and they confirm that patients treated with rituximab and other anti-CD20 agents have severely reduced serological responses to COVID-19 vaccines,” Ingrid Jyssum, MD, of the division of rheumatology and research at Diakonhjemmet Hospital in Oslo, said in an interview.

One silver lining is that patients treated with anti-CD20 therapies appear to have a cell-mediated response following vaccination even if they don’t develop SARS-CoV-2 antibodies. “Studies that also investigate T-cell responses are starting to emerge, and so far, they show that, even if the patients do not have antibodies, they may have T-cell responses,” Dr. Jyssum said.

One study of 24 patients with autoimmune diseases taking rituximab that evaluated humoral and T-cell responses following vaccination with the Comirnaty vaccine found that none had a humoral response to the vaccine, but the T-cell response from that group did not significantly differ from 35 patients receiving other immunosuppressants and 26 patients in a healthy control group. In another study of rituximab- or ocrelizumab-treated patients who received mRNA-based COVID-19 vaccines, 69.4% developed SARS-CoV-2–specific antibodies, compared with a control group, but 96.2% of patients taking ocrelizumab and 81.8% of patients taking rituximab mounted a spike-specific CD8+ T-cell response, compared with 66.7% in the control group, and there were comparable rates (85%-90%) of spike-specific CD4+ T cells in all groups. In the study from the Medical University of Vienna, T-cell response was detected in rituximab-treated patients who both did and did not mount an antibody response.

The clinical relevance of how a blunted humoral immune response but a respectable T-cell response to COVID-19 vaccines affects patients treated with anti-CD20 therapies isn’t currently known, Dr. Jyssum said.

While these data are reassuring, they’re also incomplete, Dr. Spiera noted. “The ultimate outcome of relevance to assess vaccine efficacy is protection from COVID and from severe outcomes of COVID infection (i.e., hospitalization, mechanical ventilation, death). That data will require assessment of very large numbers of rituximab-treated vaccinated patients to be compared with rituximab-treated unvaccinated patients, and is unlikely to be forthcoming in the very near future.

“In the meantime, however, achieving serologic positivity, meaning having evidence of serologic as well as cellular immunity following vaccination, is a desired outcome, and likely implies more robust immunity.”
 

Does treatment timing impact COVID-19 vaccine response?

Given enough time, B-cell reconstitution will occur in patients taking rituximab. With that in mind, is it beneficial to wait a certain amount of time after a patient has stopped rituximab therapy or time since their last dose before giving them a COVID-19 vaccine? In their guidance on COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases, the American College of Rheumatology said there is moderate evidence to consider “optimal timing of dosing and vaccination with the rheumatology provider before proceeding.”

“Guidelines and preliminary studies of serologic response to COVID vaccine in rituximab-treated patients have suggested that longer time from last rituximab exposure is associated with a greater likelihood of a serologic response,” Dr. Spiera said.

In a brief report published in Arthritis & Rheumatology, Dr. Spiera and colleagues performed a retrospective chart review of 56 patients with varying levels of last exposure to rituximab who received a COVID-19 vaccine. Their results showed that, when patients were vaccinated 6-12 months after the last rituximab dose, 55% were seronegative, and when this was more than 12 months, only 13% were seronegative, compared with seronegativity in 86% who were vaccinated less than 6 months after their last rituximab dose.

The RituxiVac trial, conducted by researchers in Switzerland, also examined vaccine responses of 96 rituximab-treated patients who received Comirnaty or Spikevax; results recently published in The Lancet Rheumatology showed findings similar to other studies, with reduced humoral and cell-mediated responses. In the RituxiVac trial, the median time to last anti-CD20 treatment was 1.07 years.

“The typical interval between rituximab doses [for treatment of rheumatoid arthritis, as well as for remission maintenance in antineutrophil cytoplasmic antibody–associated vasculitis] is typically 6 months, and this has become widely used as the interval from last rituximab to time of COVID vaccination, with a recommendation to wait 4 weeks (if possible) from time of vaccination until the next rituximab administration,” Dr. Spiera explained. However, this window seems to vary depending on the study.

Recent research published in Arthritis & Rheumatology indicates B-cell levels could be a relevant indicator for humoral and cell-mediated response in patients with rheumatic diseases treated with rituximab, with a level of 10 B cells/mcL (0.4% of lymphocytes) identified as one potential marker for likely seroconversion following COVID-19 vaccination.

“In some smaller case series, it has been further recognized that rituximab-treated patients who were beginning to reconstitute peripheral B cells were most likely to respond serologically. Our present study confirmed those findings, demonstrating that the presence of detectable B cells was strongly associated with vaccine responsiveness, and affords complementary information to time from last [rituximab dose] in informing the likelihood of a vaccine response,” Dr. Spiera said.

However, the literature is limited in this area, and an exact cutoff for B-cell counts in these patients isn’t currently known, Dr. Jyssum said. A better metric is time away from anti-CD20 therapies, with CD19 cell count being highly correlated with last infusion.

Dr. Spiera agreed that there is no consistent B-cell percentage that works as a cutoff. “In our study, we looked at it as a binary variable, although we did find that a higher percentage of B cells in the peripheral lymphocyte population was associated with a higher likelihood of seroconversion. We did not, however, identify a ‘threshold’ for vaccine serologic responsiveness.”

Should clinicians measure antibodies?

The Food and Drug Administration and the Centers for Disease Control and Prevention have recommended that health care providers and the public not use COVID-19 antibody tests as a way to gauge immunity after exposure to SARS-CoV-2 and after receiving a COVID-19 vaccination. The ACR’s guidance on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases strongly recommends against ordering antibody tests for patients with autoimmune inflammatory rheumatic diseases as a way to measure immunity.

“Generally, such measurements are not recommended as the clinical correlate of various antibody levels are not known,” Dr. Jyssum said. “With regular infusions of rituximab or other anti-CD20 agents, one cannot expect that these patients will develop significant levels of antibodies.”

However, she said there might be situations where it’s useful to know whether a patient has developed antibodies at all. “Assessing the significance of specific antibody levels is difficult, and the subject of scientific studies. Patients lacking a humoral vaccine response are left to rely on their T-cell responses and on infectious control measures to prevent disease.”

Dr. Spiera said he disagreed with guidelines recommending against checking antibody levels after vaccination, “particularly in patients treated with immunosuppressive medications that might be expected to blunt their serologic response to the vaccines.

“Although we cannot be sure what level of measurable antibodies offer what level of protection, most clinicians would agree that patients who demonstrate no detectable antibodies (which is a common finding in rituximab-treated patients) should be considered at higher risk,” he said. “Indeed, recommendations regarding booster vaccine administration in general was initially based on the observation of declining antibody levels with longer time from vaccination.”

Do COVID-19 vaccine boosters help patients on anti-CD20 therapy?

As of January 2022, the FDA and CDC have recommended a third primary series shot of COVID-19 vaccines for some moderately to severely immunocompromised patients as young as 5 years old (for Comirnaty vaccine) or a booster shot of either Comirnaty or Spikevax for everyone aged 12 years and older, including immunocompromised people, while the ACR goes into more detail and recommends clinicians time a patient’s booster shot with temporary treatment interruption.

In The Lancet Rheumatology, Dr. Jyssum and colleagues recently published results from the prospective Nor-vaC study examining the humoral and cell-mediated immune responses of 87 patients with RA being treated with rituximab who received the Comirnaty, Spikevax, or Vaxzevria (AstraZeneca) COVID-19 vaccines; of these, 49 patients received a booster dose at a median of 70 days after completing their primary series. The results showed 19 patients (28.1%) had a serologic response after their primary series, while 8 of 49 patients (16.3%) who received their booster dose had a serologic response.

All patients who received a third dose in the study had a T-cell response, Dr. Jyssum said. “This is reassuring for patients and clinicians. T cells have been found to be important in countering COVID-19 disease, but whether we can rely on the T-cell response alone in the absence of antibodies to protect patients from infection or from serious COVID disease is still not determined,” she said.

When asked if she would recommend COVID-19 vaccine booster doses for patients on rituximab, Dr. Jyssum replied: “Absolutely.”

Another study, recently published in Annals of the Rheumatic Diseases, examined heterologous and homologous booster doses for 60 patients receiving rituximab without seroconversion after their COVID-19 vaccine primary series. The results showed no significant difference in new seroconversion at 4 weeks based on whether the patient received a vector or mRNA vaccine (22% vs. 32%), but all patients who received a booster dose with a vector vaccine had specific T-cell responses, compared with 81% of patients who received an mRNA vaccine booster. There was a new humoral and/or cellular response in 9 of 11 patients (82%), and most patients with peripheral B cells (12 of 18 patients; 67%) achieved seroconversion.

“Our data show that a cellular and/or humoral immune response can be achieved on a third COVID-19 vaccination in most of the patients who initially developed neither a humoral nor a cellular immune response,” the researchers concluded. “The efficacy data together with the safety data seen in our trial provide a favorable risk/benefit ratio and support the implementation of a third vaccination for nonseroconverted high-risk autoimmune disease patients treated with B-cell–depleting agents.”

Dr. Spiera said booster doses are an important part of the equation, and “it is important to consider factors that would be associated with a greater likelihood of achieving a serologic response, particularly in those patients who did not demonstrate a serologic response to the initial vaccines series.

“Preliminary data shows that the beginnings of B-cell reconstitution is also associated with a positive serologic response following a booster of the COVID-19 vaccine,” he said.

The authors of the cited studies reported numerous relevant financial disclosures. Dr. Spiera and Dr. Jyssum reported no relevant financial disclosures.

Rituximab has presented something of a conundrum for patients taking the monoclonal antibody during the COVID-19 pandemic.

Used to manage a variety of autoimmune diseases and cancers, rituximab acts against CD20 proteins expressed on the surface of B cells, causing B-cell depletion. However, it is this B-cell depletion that may put these patients at greater risk of COVID-19 development, progression to more severe disease, and in-hospital mortality. Evidence for this appears to be mixed, with studies showing both that patients using rituximab to manage various diseases are and are not at increased risk for SARS-CoV-2 infection, COVID-19 progression, and mortality.

peterschreiber_media/iStock/Getty Images

As COVID-19 vaccine rollouts take place across the world, more questions have been raised about the relationship between B-cell depletion from anti-CD20 therapies and COVID-19 vaccines. Do rituximab and other anti-CD20 therapies affect a patient’s response to COVID-19 vaccines? If this is the case, does the timing of anti-CD20 treatment matter to maximize B-cell levels and improve the vaccine’s effectiveness? And how do COVID-19 vaccine booster doses factor into the equation?

This article aims to summarize the latest research on how rituximab affects humoral and cell-mediated response following a COVID-19 vaccine primary series, and whether the addition of a COVID-19 vaccine booster dose changes patient response.
 

Humoral and cell-mediated responses following COVID-19 vaccination

First, the bad news: The vaccine is unquestionably safe to administer in patients taking rituximab, but one thing that has been well established is that antibody response to COVID-19 vaccination in these individuals does is reduced. This isn’t entirely unprecedented, as previous studies have shown a weakened immune response to pneumococcal polysaccharide and keyhole limpet hemocyanin vaccines among patients taking rituximab.

“Compromised immunogenicity to the SARS-CoV-2 vaccines has been demonstrated in rituximab-treated patients, which is of particular concern given the observation that B-cell–depleting therapies may be associated with worse COVID outcomes,” Robert F. Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York, said in an interview.

For example, in a recent study from the Medical University of Vienna, 29 (39%) of 74 patients receiving rituximab (43% as monotherapy, 57% with conventional-synthetic disease-modifying antirheumatic drugs) who were vaccinated with either the Comirnaty (Pfizer-BioNTech) or Spikevax (Moderna) COVID-19 vaccine achieved seroconversion, compared with 100% of patients in a healthy control group, and all but 1 patient without detectable CD19+ peripheral B cells did not develop anti–SARS-CoV-2 receptor-binding domain antibodies.

“There is an increasing number of studies in this field, and they confirm that patients treated with rituximab and other anti-CD20 agents have severely reduced serological responses to COVID-19 vaccines,” Ingrid Jyssum, MD, of the division of rheumatology and research at Diakonhjemmet Hospital in Oslo, said in an interview.

One silver lining is that patients treated with anti-CD20 therapies appear to have a cell-mediated response following vaccination even if they don’t develop SARS-CoV-2 antibodies. “Studies that also investigate T-cell responses are starting to emerge, and so far, they show that, even if the patients do not have antibodies, they may have T-cell responses,” Dr. Jyssum said.

One study of 24 patients with autoimmune diseases taking rituximab that evaluated humoral and T-cell responses following vaccination with the Comirnaty vaccine found that none had a humoral response to the vaccine, but the T-cell response from that group did not significantly differ from 35 patients receiving other immunosuppressants and 26 patients in a healthy control group. In another study of rituximab- or ocrelizumab-treated patients who received mRNA-based COVID-19 vaccines, 69.4% developed SARS-CoV-2–specific antibodies, compared with a control group, but 96.2% of patients taking ocrelizumab and 81.8% of patients taking rituximab mounted a spike-specific CD8+ T-cell response, compared with 66.7% in the control group, and there were comparable rates (85%-90%) of spike-specific CD4+ T cells in all groups. In the study from the Medical University of Vienna, T-cell response was detected in rituximab-treated patients who both did and did not mount an antibody response.

The clinical relevance of how a blunted humoral immune response but a respectable T-cell response to COVID-19 vaccines affects patients treated with anti-CD20 therapies isn’t currently known, Dr. Jyssum said.

While these data are reassuring, they’re also incomplete, Dr. Spiera noted. “The ultimate outcome of relevance to assess vaccine efficacy is protection from COVID and from severe outcomes of COVID infection (i.e., hospitalization, mechanical ventilation, death). That data will require assessment of very large numbers of rituximab-treated vaccinated patients to be compared with rituximab-treated unvaccinated patients, and is unlikely to be forthcoming in the very near future.

“In the meantime, however, achieving serologic positivity, meaning having evidence of serologic as well as cellular immunity following vaccination, is a desired outcome, and likely implies more robust immunity.”
 

Does treatment timing impact COVID-19 vaccine response?

Given enough time, B-cell reconstitution will occur in patients taking rituximab. With that in mind, is it beneficial to wait a certain amount of time after a patient has stopped rituximab therapy or time since their last dose before giving them a COVID-19 vaccine? In their guidance on COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases, the American College of Rheumatology said there is moderate evidence to consider “optimal timing of dosing and vaccination with the rheumatology provider before proceeding.”

“Guidelines and preliminary studies of serologic response to COVID vaccine in rituximab-treated patients have suggested that longer time from last rituximab exposure is associated with a greater likelihood of a serologic response,” Dr. Spiera said.

In a brief report published in Arthritis & Rheumatology, Dr. Spiera and colleagues performed a retrospective chart review of 56 patients with varying levels of last exposure to rituximab who received a COVID-19 vaccine. Their results showed that, when patients were vaccinated 6-12 months after the last rituximab dose, 55% were seronegative, and when this was more than 12 months, only 13% were seronegative, compared with seronegativity in 86% who were vaccinated less than 6 months after their last rituximab dose.

The RituxiVac trial, conducted by researchers in Switzerland, also examined vaccine responses of 96 rituximab-treated patients who received Comirnaty or Spikevax; results recently published in The Lancet Rheumatology showed findings similar to other studies, with reduced humoral and cell-mediated responses. In the RituxiVac trial, the median time to last anti-CD20 treatment was 1.07 years.

“The typical interval between rituximab doses [for treatment of rheumatoid arthritis, as well as for remission maintenance in antineutrophil cytoplasmic antibody–associated vasculitis] is typically 6 months, and this has become widely used as the interval from last rituximab to time of COVID vaccination, with a recommendation to wait 4 weeks (if possible) from time of vaccination until the next rituximab administration,” Dr. Spiera explained. However, this window seems to vary depending on the study.

Recent research published in Arthritis & Rheumatology indicates B-cell levels could be a relevant indicator for humoral and cell-mediated response in patients with rheumatic diseases treated with rituximab, with a level of 10 B cells/mcL (0.4% of lymphocytes) identified as one potential marker for likely seroconversion following COVID-19 vaccination.

“In some smaller case series, it has been further recognized that rituximab-treated patients who were beginning to reconstitute peripheral B cells were most likely to respond serologically. Our present study confirmed those findings, demonstrating that the presence of detectable B cells was strongly associated with vaccine responsiveness, and affords complementary information to time from last [rituximab dose] in informing the likelihood of a vaccine response,” Dr. Spiera said.

However, the literature is limited in this area, and an exact cutoff for B-cell counts in these patients isn’t currently known, Dr. Jyssum said. A better metric is time away from anti-CD20 therapies, with CD19 cell count being highly correlated with last infusion.

Dr. Spiera agreed that there is no consistent B-cell percentage that works as a cutoff. “In our study, we looked at it as a binary variable, although we did find that a higher percentage of B cells in the peripheral lymphocyte population was associated with a higher likelihood of seroconversion. We did not, however, identify a ‘threshold’ for vaccine serologic responsiveness.”

Should clinicians measure antibodies?

The Food and Drug Administration and the Centers for Disease Control and Prevention have recommended that health care providers and the public not use COVID-19 antibody tests as a way to gauge immunity after exposure to SARS-CoV-2 and after receiving a COVID-19 vaccination. The ACR’s guidance on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases strongly recommends against ordering antibody tests for patients with autoimmune inflammatory rheumatic diseases as a way to measure immunity.

“Generally, such measurements are not recommended as the clinical correlate of various antibody levels are not known,” Dr. Jyssum said. “With regular infusions of rituximab or other anti-CD20 agents, one cannot expect that these patients will develop significant levels of antibodies.”

However, she said there might be situations where it’s useful to know whether a patient has developed antibodies at all. “Assessing the significance of specific antibody levels is difficult, and the subject of scientific studies. Patients lacking a humoral vaccine response are left to rely on their T-cell responses and on infectious control measures to prevent disease.”

Dr. Spiera said he disagreed with guidelines recommending against checking antibody levels after vaccination, “particularly in patients treated with immunosuppressive medications that might be expected to blunt their serologic response to the vaccines.

“Although we cannot be sure what level of measurable antibodies offer what level of protection, most clinicians would agree that patients who demonstrate no detectable antibodies (which is a common finding in rituximab-treated patients) should be considered at higher risk,” he said. “Indeed, recommendations regarding booster vaccine administration in general was initially based on the observation of declining antibody levels with longer time from vaccination.”

Do COVID-19 vaccine boosters help patients on anti-CD20 therapy?

As of January 2022, the FDA and CDC have recommended a third primary series shot of COVID-19 vaccines for some moderately to severely immunocompromised patients as young as 5 years old (for Comirnaty vaccine) or a booster shot of either Comirnaty or Spikevax for everyone aged 12 years and older, including immunocompromised people, while the ACR goes into more detail and recommends clinicians time a patient’s booster shot with temporary treatment interruption.

In The Lancet Rheumatology, Dr. Jyssum and colleagues recently published results from the prospective Nor-vaC study examining the humoral and cell-mediated immune responses of 87 patients with RA being treated with rituximab who received the Comirnaty, Spikevax, or Vaxzevria (AstraZeneca) COVID-19 vaccines; of these, 49 patients received a booster dose at a median of 70 days after completing their primary series. The results showed 19 patients (28.1%) had a serologic response after their primary series, while 8 of 49 patients (16.3%) who received their booster dose had a serologic response.

All patients who received a third dose in the study had a T-cell response, Dr. Jyssum said. “This is reassuring for patients and clinicians. T cells have been found to be important in countering COVID-19 disease, but whether we can rely on the T-cell response alone in the absence of antibodies to protect patients from infection or from serious COVID disease is still not determined,” she said.

When asked if she would recommend COVID-19 vaccine booster doses for patients on rituximab, Dr. Jyssum replied: “Absolutely.”

Another study, recently published in Annals of the Rheumatic Diseases, examined heterologous and homologous booster doses for 60 patients receiving rituximab without seroconversion after their COVID-19 vaccine primary series. The results showed no significant difference in new seroconversion at 4 weeks based on whether the patient received a vector or mRNA vaccine (22% vs. 32%), but all patients who received a booster dose with a vector vaccine had specific T-cell responses, compared with 81% of patients who received an mRNA vaccine booster. There was a new humoral and/or cellular response in 9 of 11 patients (82%), and most patients with peripheral B cells (12 of 18 patients; 67%) achieved seroconversion.

“Our data show that a cellular and/or humoral immune response can be achieved on a third COVID-19 vaccination in most of the patients who initially developed neither a humoral nor a cellular immune response,” the researchers concluded. “The efficacy data together with the safety data seen in our trial provide a favorable risk/benefit ratio and support the implementation of a third vaccination for nonseroconverted high-risk autoimmune disease patients treated with B-cell–depleting agents.”

Dr. Spiera said booster doses are an important part of the equation, and “it is important to consider factors that would be associated with a greater likelihood of achieving a serologic response, particularly in those patients who did not demonstrate a serologic response to the initial vaccines series.

“Preliminary data shows that the beginnings of B-cell reconstitution is also associated with a positive serologic response following a booster of the COVID-19 vaccine,” he said.

The authors of the cited studies reported numerous relevant financial disclosures. Dr. Spiera and Dr. Jyssum reported no relevant financial disclosures.

Rituximab has presented something of a conundrum for patients taking the monoclonal antibody during the COVID-19 pandemic.

Used to manage a variety of autoimmune diseases and cancers, rituximab acts against CD20 proteins expressed on the surface of B cells, causing B-cell depletion. However, it is this B-cell depletion that may put these patients at greater risk of COVID-19 development, progression to more severe disease, and in-hospital mortality. Evidence for this appears to be mixed, with studies showing both that patients using rituximab to manage various diseases are and are not at increased risk for SARS-CoV-2 infection, COVID-19 progression, and mortality.

peterschreiber_media/iStock/Getty Images

As COVID-19 vaccine rollouts take place across the world, more questions have been raised about the relationship between B-cell depletion from anti-CD20 therapies and COVID-19 vaccines. Do rituximab and other anti-CD20 therapies affect a patient’s response to COVID-19 vaccines? If this is the case, does the timing of anti-CD20 treatment matter to maximize B-cell levels and improve the vaccine’s effectiveness? And how do COVID-19 vaccine booster doses factor into the equation?

This article aims to summarize the latest research on how rituximab affects humoral and cell-mediated response following a COVID-19 vaccine primary series, and whether the addition of a COVID-19 vaccine booster dose changes patient response.
 

Humoral and cell-mediated responses following COVID-19 vaccination

First, the bad news: The vaccine is unquestionably safe to administer in patients taking rituximab, but one thing that has been well established is that antibody response to COVID-19 vaccination in these individuals does is reduced. This isn’t entirely unprecedented, as previous studies have shown a weakened immune response to pneumococcal polysaccharide and keyhole limpet hemocyanin vaccines among patients taking rituximab.

“Compromised immunogenicity to the SARS-CoV-2 vaccines has been demonstrated in rituximab-treated patients, which is of particular concern given the observation that B-cell–depleting therapies may be associated with worse COVID outcomes,” Robert F. Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York, said in an interview.

For example, in a recent study from the Medical University of Vienna, 29 (39%) of 74 patients receiving rituximab (43% as monotherapy, 57% with conventional-synthetic disease-modifying antirheumatic drugs) who were vaccinated with either the Comirnaty (Pfizer-BioNTech) or Spikevax (Moderna) COVID-19 vaccine achieved seroconversion, compared with 100% of patients in a healthy control group, and all but 1 patient without detectable CD19+ peripheral B cells did not develop anti–SARS-CoV-2 receptor-binding domain antibodies.

“There is an increasing number of studies in this field, and they confirm that patients treated with rituximab and other anti-CD20 agents have severely reduced serological responses to COVID-19 vaccines,” Ingrid Jyssum, MD, of the division of rheumatology and research at Diakonhjemmet Hospital in Oslo, said in an interview.

One silver lining is that patients treated with anti-CD20 therapies appear to have a cell-mediated response following vaccination even if they don’t develop SARS-CoV-2 antibodies. “Studies that also investigate T-cell responses are starting to emerge, and so far, they show that, even if the patients do not have antibodies, they may have T-cell responses,” Dr. Jyssum said.

One study of 24 patients with autoimmune diseases taking rituximab that evaluated humoral and T-cell responses following vaccination with the Comirnaty vaccine found that none had a humoral response to the vaccine, but the T-cell response from that group did not significantly differ from 35 patients receiving other immunosuppressants and 26 patients in a healthy control group. In another study of rituximab- or ocrelizumab-treated patients who received mRNA-based COVID-19 vaccines, 69.4% developed SARS-CoV-2–specific antibodies, compared with a control group, but 96.2% of patients taking ocrelizumab and 81.8% of patients taking rituximab mounted a spike-specific CD8+ T-cell response, compared with 66.7% in the control group, and there were comparable rates (85%-90%) of spike-specific CD4+ T cells in all groups. In the study from the Medical University of Vienna, T-cell response was detected in rituximab-treated patients who both did and did not mount an antibody response.

The clinical relevance of how a blunted humoral immune response but a respectable T-cell response to COVID-19 vaccines affects patients treated with anti-CD20 therapies isn’t currently known, Dr. Jyssum said.

While these data are reassuring, they’re also incomplete, Dr. Spiera noted. “The ultimate outcome of relevance to assess vaccine efficacy is protection from COVID and from severe outcomes of COVID infection (i.e., hospitalization, mechanical ventilation, death). That data will require assessment of very large numbers of rituximab-treated vaccinated patients to be compared with rituximab-treated unvaccinated patients, and is unlikely to be forthcoming in the very near future.

“In the meantime, however, achieving serologic positivity, meaning having evidence of serologic as well as cellular immunity following vaccination, is a desired outcome, and likely implies more robust immunity.”
 

Does treatment timing impact COVID-19 vaccine response?

Given enough time, B-cell reconstitution will occur in patients taking rituximab. With that in mind, is it beneficial to wait a certain amount of time after a patient has stopped rituximab therapy or time since their last dose before giving them a COVID-19 vaccine? In their guidance on COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases, the American College of Rheumatology said there is moderate evidence to consider “optimal timing of dosing and vaccination with the rheumatology provider before proceeding.”

“Guidelines and preliminary studies of serologic response to COVID vaccine in rituximab-treated patients have suggested that longer time from last rituximab exposure is associated with a greater likelihood of a serologic response,” Dr. Spiera said.

In a brief report published in Arthritis & Rheumatology, Dr. Spiera and colleagues performed a retrospective chart review of 56 patients with varying levels of last exposure to rituximab who received a COVID-19 vaccine. Their results showed that, when patients were vaccinated 6-12 months after the last rituximab dose, 55% were seronegative, and when this was more than 12 months, only 13% were seronegative, compared with seronegativity in 86% who were vaccinated less than 6 months after their last rituximab dose.

The RituxiVac trial, conducted by researchers in Switzerland, also examined vaccine responses of 96 rituximab-treated patients who received Comirnaty or Spikevax; results recently published in The Lancet Rheumatology showed findings similar to other studies, with reduced humoral and cell-mediated responses. In the RituxiVac trial, the median time to last anti-CD20 treatment was 1.07 years.

“The typical interval between rituximab doses [for treatment of rheumatoid arthritis, as well as for remission maintenance in antineutrophil cytoplasmic antibody–associated vasculitis] is typically 6 months, and this has become widely used as the interval from last rituximab to time of COVID vaccination, with a recommendation to wait 4 weeks (if possible) from time of vaccination until the next rituximab administration,” Dr. Spiera explained. However, this window seems to vary depending on the study.

Recent research published in Arthritis & Rheumatology indicates B-cell levels could be a relevant indicator for humoral and cell-mediated response in patients with rheumatic diseases treated with rituximab, with a level of 10 B cells/mcL (0.4% of lymphocytes) identified as one potential marker for likely seroconversion following COVID-19 vaccination.

“In some smaller case series, it has been further recognized that rituximab-treated patients who were beginning to reconstitute peripheral B cells were most likely to respond serologically. Our present study confirmed those findings, demonstrating that the presence of detectable B cells was strongly associated with vaccine responsiveness, and affords complementary information to time from last [rituximab dose] in informing the likelihood of a vaccine response,” Dr. Spiera said.

However, the literature is limited in this area, and an exact cutoff for B-cell counts in these patients isn’t currently known, Dr. Jyssum said. A better metric is time away from anti-CD20 therapies, with CD19 cell count being highly correlated with last infusion.

Dr. Spiera agreed that there is no consistent B-cell percentage that works as a cutoff. “In our study, we looked at it as a binary variable, although we did find that a higher percentage of B cells in the peripheral lymphocyte population was associated with a higher likelihood of seroconversion. We did not, however, identify a ‘threshold’ for vaccine serologic responsiveness.”

Should clinicians measure antibodies?

The Food and Drug Administration and the Centers for Disease Control and Prevention have recommended that health care providers and the public not use COVID-19 antibody tests as a way to gauge immunity after exposure to SARS-CoV-2 and after receiving a COVID-19 vaccination. The ACR’s guidance on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases strongly recommends against ordering antibody tests for patients with autoimmune inflammatory rheumatic diseases as a way to measure immunity.

“Generally, such measurements are not recommended as the clinical correlate of various antibody levels are not known,” Dr. Jyssum said. “With regular infusions of rituximab or other anti-CD20 agents, one cannot expect that these patients will develop significant levels of antibodies.”

However, she said there might be situations where it’s useful to know whether a patient has developed antibodies at all. “Assessing the significance of specific antibody levels is difficult, and the subject of scientific studies. Patients lacking a humoral vaccine response are left to rely on their T-cell responses and on infectious control measures to prevent disease.”

Dr. Spiera said he disagreed with guidelines recommending against checking antibody levels after vaccination, “particularly in patients treated with immunosuppressive medications that might be expected to blunt their serologic response to the vaccines.

“Although we cannot be sure what level of measurable antibodies offer what level of protection, most clinicians would agree that patients who demonstrate no detectable antibodies (which is a common finding in rituximab-treated patients) should be considered at higher risk,” he said. “Indeed, recommendations regarding booster vaccine administration in general was initially based on the observation of declining antibody levels with longer time from vaccination.”

Do COVID-19 vaccine boosters help patients on anti-CD20 therapy?

As of January 2022, the FDA and CDC have recommended a third primary series shot of COVID-19 vaccines for some moderately to severely immunocompromised patients as young as 5 years old (for Comirnaty vaccine) or a booster shot of either Comirnaty or Spikevax for everyone aged 12 years and older, including immunocompromised people, while the ACR goes into more detail and recommends clinicians time a patient’s booster shot with temporary treatment interruption.

In The Lancet Rheumatology, Dr. Jyssum and colleagues recently published results from the prospective Nor-vaC study examining the humoral and cell-mediated immune responses of 87 patients with RA being treated with rituximab who received the Comirnaty, Spikevax, or Vaxzevria (AstraZeneca) COVID-19 vaccines; of these, 49 patients received a booster dose at a median of 70 days after completing their primary series. The results showed 19 patients (28.1%) had a serologic response after their primary series, while 8 of 49 patients (16.3%) who received their booster dose had a serologic response.

All patients who received a third dose in the study had a T-cell response, Dr. Jyssum said. “This is reassuring for patients and clinicians. T cells have been found to be important in countering COVID-19 disease, but whether we can rely on the T-cell response alone in the absence of antibodies to protect patients from infection or from serious COVID disease is still not determined,” she said.

When asked if she would recommend COVID-19 vaccine booster doses for patients on rituximab, Dr. Jyssum replied: “Absolutely.”

Another study, recently published in Annals of the Rheumatic Diseases, examined heterologous and homologous booster doses for 60 patients receiving rituximab without seroconversion after their COVID-19 vaccine primary series. The results showed no significant difference in new seroconversion at 4 weeks based on whether the patient received a vector or mRNA vaccine (22% vs. 32%), but all patients who received a booster dose with a vector vaccine had specific T-cell responses, compared with 81% of patients who received an mRNA vaccine booster. There was a new humoral and/or cellular response in 9 of 11 patients (82%), and most patients with peripheral B cells (12 of 18 patients; 67%) achieved seroconversion.

“Our data show that a cellular and/or humoral immune response can be achieved on a third COVID-19 vaccination in most of the patients who initially developed neither a humoral nor a cellular immune response,” the researchers concluded. “The efficacy data together with the safety data seen in our trial provide a favorable risk/benefit ratio and support the implementation of a third vaccination for nonseroconverted high-risk autoimmune disease patients treated with B-cell–depleting agents.”

Dr. Spiera said booster doses are an important part of the equation, and “it is important to consider factors that would be associated with a greater likelihood of achieving a serologic response, particularly in those patients who did not demonstrate a serologic response to the initial vaccines series.

“Preliminary data shows that the beginnings of B-cell reconstitution is also associated with a positive serologic response following a booster of the COVID-19 vaccine,” he said.

The authors of the cited studies reported numerous relevant financial disclosures. Dr. Spiera and Dr. Jyssum reported no relevant financial disclosures.

BUENOS AIRES – The Latin American Association of Cardiac and Endovascular Surgery (LACES) has demanded “urgent reconsideration” of the decision to downgrade the strength of the recommendation for revascularization or coronary artery bypass graft (CABG) surgery for multivessel disease in the new guideline on coronary artery revascularization, putting it in the same class as the recommendation for percutaneous coronary intervention, which has no apparent advantage over optimal medical therapy.

With the prevalence of stable ischemic heart disease in patients with multivessel disease, the contradiction between the evidence and the new recommendation “may affect the lives and survival of millions of patients worldwide and have a major socio-economic impact,” the association warned in a public letter.

In the 2011 guideline, CABG for patients with multivessel coronary artery disease was given a class I recommendation, which means that it is considered useful and effective and should be performed in the majority of patients in most circumstances. But the new, much weaker class IIb recommendation suggests that the benefit only marginally exceeds the risk and that it should be used selectively and only after careful consideration.

“It is an incomprehensible rollercoaster drop in the recommendation level. We totally disagree. In the absence of evidence, a IIb level provides equal freedom to send a patient to surgery or not. And in patients who are not being sent to surgery, it could take years of survival before we can be sure that we are doing the right thing,” said LACES president Víctor Dayan, MD, PhD, from the cardiovascular center at the Hospital de Clínicas “Dr. Manuel Quintela”, which is part of the School of Medicine at the University of the Republic, Montevideo, Uruguay.

The change in the recommendation for this indication “reflects new evidence showing no advantage of coronary artery bypass grafting over medical therapy alone to improve survival in patients with three-vessel coronary disease with preserved left ventricular function and no left main disease,” according to the authors of the guideline, issued jointly by the American College of Cardiology (ACC), the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI). In particular, they cite the 2019 ISCHEMIA clinical study that failed to show that an early invasive strategy reduces major adverse cardiovascular events, compared with optimal medical therapy and a handful of meta-analyses.

However, ISCHEMIA did not discriminate between the two types of invasive strategy – CABG and percutaneous coronary intervention (PCI) – so cannot be considered as a basis to downgrade the CABG recommendation, Dr. Dayan explained.

“Furthermore, the authors neglected previous RCTs that have shown the survival benefit of CABG in these patients and decided to put PCI in the same [class of recommendation], although no RCT has been able to show any survival advantage of PCI compared to optimal medical treatment,” the LACES letter states.

Basis should be evidence, ‘not inferences’

Three large randomized clinical trials and a 1994 meta-analysis with individual patient data from seven studies firmly established that survival is better with CABG than with medical treatment, the letter continues. However, the guideline authors did not provide any additional randomized clinical trials that refute this evidence.

“Furthermore, the committee disregarded data from the Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) randomized control[led] trial, which showed a lower incidence of cardiac mortality (as part of its secondary outcomes) following CABG compared to optimal medical therapy and PCI,” the letter explains.

The guideline authors might have judged current optimal medical therapy to be better than what existed 10, 15, or 30 years ago, diluting the relative benefits of surgery, but the “recommendation in a guideline must act on evidence, not inferences. And there is no evidence to support this drop in recommendation class,” Dr. Dayan said.

Other experts have drawn attention to the fact that two surgical societies – the American Association for Thoracic Surgery (AAST) and the Society of Thoracic Surgeons (STS) – did not endorse the final document, despite having participated in its review, reported this news organization.

“This is a very disappointing update that will negatively affect the lives of many people,” tweeted Marc Pelletier, MD, head of cardiac surgery at University Hospitals, Case Western Reserve University, Cleveland.

Contradictions in the text that examines the evidence and the final recommendations, are “unclear” and “open to various interpretations, when they should be a pillar for decisionmaking,” said Javier Ferrari Ayarragaray, MD, president of the Argentine College of Cardiovascular Surgeons (CACCV) and vice president of LACES.

The new guidelines “show no additional randomized controlled trial to support this downgrade in the level of evidence,” according to a recent CACCV statement. “The inclusion, approval and endorsement of this type of [recommendation,] including [other] international surgical scientific societies, such as STS, AATS, EACTS, LACES[,] is necessary to obtain a better understanding and agreement on the current evidence.”

In a Dec. 17, 2021 response to LACES, Patrick O’Gara, MD, who was chair of the ACC/AHA Joint Committee on Clinical Practice Guidelines at the time, and his successor, Joshua Beckman, MD, explained that both organizations approved the guideline for publication and support its authors “in their interpretation of the published evidence and findings.”

The pair pointed out that the drafting committee members, who have extensive clinical judgment and experience, deliberated extensively on the issue and that the change from a class I to a class IIb recommendation was “carefully considered after a review of the entire available and relevant evidence.”

“When we bring together multiple organizations to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of published and peer-reviewed literature and create clinical practice recommendations,” said Thomas Getchius, director of guideline strategy and operations at the AHA.

“The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed upon by the ACC, AHA, SCAI, and the full drafting committee,” Mr. Getchius said.

Dr. Dayan and Dr. Ferrari Ayarragaray have disclosed no relevant financial relationships. Mr. Getchius is an employee of the American Heart Association.

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

BUENOS AIRES – The Latin American Association of Cardiac and Endovascular Surgery (LACES) has demanded “urgent reconsideration” of the decision to downgrade the strength of the recommendation for revascularization or coronary artery bypass graft (CABG) surgery for multivessel disease in the new guideline on coronary artery revascularization, putting it in the same class as the recommendation for percutaneous coronary intervention, which has no apparent advantage over optimal medical therapy.

With the prevalence of stable ischemic heart disease in patients with multivessel disease, the contradiction between the evidence and the new recommendation “may affect the lives and survival of millions of patients worldwide and have a major socio-economic impact,” the association warned in a public letter.

In the 2011 guideline, CABG for patients with multivessel coronary artery disease was given a class I recommendation, which means that it is considered useful and effective and should be performed in the majority of patients in most circumstances. But the new, much weaker class IIb recommendation suggests that the benefit only marginally exceeds the risk and that it should be used selectively and only after careful consideration.

“It is an incomprehensible rollercoaster drop in the recommendation level. We totally disagree. In the absence of evidence, a IIb level provides equal freedom to send a patient to surgery or not. And in patients who are not being sent to surgery, it could take years of survival before we can be sure that we are doing the right thing,” said LACES president Víctor Dayan, MD, PhD, from the cardiovascular center at the Hospital de Clínicas “Dr. Manuel Quintela”, which is part of the School of Medicine at the University of the Republic, Montevideo, Uruguay.

The change in the recommendation for this indication “reflects new evidence showing no advantage of coronary artery bypass grafting over medical therapy alone to improve survival in patients with three-vessel coronary disease with preserved left ventricular function and no left main disease,” according to the authors of the guideline, issued jointly by the American College of Cardiology (ACC), the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI). In particular, they cite the 2019 ISCHEMIA clinical study that failed to show that an early invasive strategy reduces major adverse cardiovascular events, compared with optimal medical therapy and a handful of meta-analyses.

However, ISCHEMIA did not discriminate between the two types of invasive strategy – CABG and percutaneous coronary intervention (PCI) – so cannot be considered as a basis to downgrade the CABG recommendation, Dr. Dayan explained.

“Furthermore, the authors neglected previous RCTs that have shown the survival benefit of CABG in these patients and decided to put PCI in the same [class of recommendation], although no RCT has been able to show any survival advantage of PCI compared to optimal medical treatment,” the LACES letter states.

Basis should be evidence, ‘not inferences’

Three large randomized clinical trials and a 1994 meta-analysis with individual patient data from seven studies firmly established that survival is better with CABG than with medical treatment, the letter continues. However, the guideline authors did not provide any additional randomized clinical trials that refute this evidence.

“Furthermore, the committee disregarded data from the Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) randomized control[led] trial, which showed a lower incidence of cardiac mortality (as part of its secondary outcomes) following CABG compared to optimal medical therapy and PCI,” the letter explains.

The guideline authors might have judged current optimal medical therapy to be better than what existed 10, 15, or 30 years ago, diluting the relative benefits of surgery, but the “recommendation in a guideline must act on evidence, not inferences. And there is no evidence to support this drop in recommendation class,” Dr. Dayan said.

Other experts have drawn attention to the fact that two surgical societies – the American Association for Thoracic Surgery (AAST) and the Society of Thoracic Surgeons (STS) – did not endorse the final document, despite having participated in its review, reported this news organization.

“This is a very disappointing update that will negatively affect the lives of many people,” tweeted Marc Pelletier, MD, head of cardiac surgery at University Hospitals, Case Western Reserve University, Cleveland.

Contradictions in the text that examines the evidence and the final recommendations, are “unclear” and “open to various interpretations, when they should be a pillar for decisionmaking,” said Javier Ferrari Ayarragaray, MD, president of the Argentine College of Cardiovascular Surgeons (CACCV) and vice president of LACES.

The new guidelines “show no additional randomized controlled trial to support this downgrade in the level of evidence,” according to a recent CACCV statement. “The inclusion, approval and endorsement of this type of [recommendation,] including [other] international surgical scientific societies, such as STS, AATS, EACTS, LACES[,] is necessary to obtain a better understanding and agreement on the current evidence.”

In a Dec. 17, 2021 response to LACES, Patrick O’Gara, MD, who was chair of the ACC/AHA Joint Committee on Clinical Practice Guidelines at the time, and his successor, Joshua Beckman, MD, explained that both organizations approved the guideline for publication and support its authors “in their interpretation of the published evidence and findings.”

The pair pointed out that the drafting committee members, who have extensive clinical judgment and experience, deliberated extensively on the issue and that the change from a class I to a class IIb recommendation was “carefully considered after a review of the entire available and relevant evidence.”

“When we bring together multiple organizations to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of published and peer-reviewed literature and create clinical practice recommendations,” said Thomas Getchius, director of guideline strategy and operations at the AHA.

“The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed upon by the ACC, AHA, SCAI, and the full drafting committee,” Mr. Getchius said.

Dr. Dayan and Dr. Ferrari Ayarragaray have disclosed no relevant financial relationships. Mr. Getchius is an employee of the American Heart Association.

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

BUENOS AIRES – The Latin American Association of Cardiac and Endovascular Surgery (LACES) has demanded “urgent reconsideration” of the decision to downgrade the strength of the recommendation for revascularization or coronary artery bypass graft (CABG) surgery for multivessel disease in the new guideline on coronary artery revascularization, putting it in the same class as the recommendation for percutaneous coronary intervention, which has no apparent advantage over optimal medical therapy.

With the prevalence of stable ischemic heart disease in patients with multivessel disease, the contradiction between the evidence and the new recommendation “may affect the lives and survival of millions of patients worldwide and have a major socio-economic impact,” the association warned in a public letter.

In the 2011 guideline, CABG for patients with multivessel coronary artery disease was given a class I recommendation, which means that it is considered useful and effective and should be performed in the majority of patients in most circumstances. But the new, much weaker class IIb recommendation suggests that the benefit only marginally exceeds the risk and that it should be used selectively and only after careful consideration.

“It is an incomprehensible rollercoaster drop in the recommendation level. We totally disagree. In the absence of evidence, a IIb level provides equal freedom to send a patient to surgery or not. And in patients who are not being sent to surgery, it could take years of survival before we can be sure that we are doing the right thing,” said LACES president Víctor Dayan, MD, PhD, from the cardiovascular center at the Hospital de Clínicas “Dr. Manuel Quintela”, which is part of the School of Medicine at the University of the Republic, Montevideo, Uruguay.

The change in the recommendation for this indication “reflects new evidence showing no advantage of coronary artery bypass grafting over medical therapy alone to improve survival in patients with three-vessel coronary disease with preserved left ventricular function and no left main disease,” according to the authors of the guideline, issued jointly by the American College of Cardiology (ACC), the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI). In particular, they cite the 2019 ISCHEMIA clinical study that failed to show that an early invasive strategy reduces major adverse cardiovascular events, compared with optimal medical therapy and a handful of meta-analyses.

However, ISCHEMIA did not discriminate between the two types of invasive strategy – CABG and percutaneous coronary intervention (PCI) – so cannot be considered as a basis to downgrade the CABG recommendation, Dr. Dayan explained.

“Furthermore, the authors neglected previous RCTs that have shown the survival benefit of CABG in these patients and decided to put PCI in the same [class of recommendation], although no RCT has been able to show any survival advantage of PCI compared to optimal medical treatment,” the LACES letter states.

Basis should be evidence, ‘not inferences’

Three large randomized clinical trials and a 1994 meta-analysis with individual patient data from seven studies firmly established that survival is better with CABG than with medical treatment, the letter continues. However, the guideline authors did not provide any additional randomized clinical trials that refute this evidence.

“Furthermore, the committee disregarded data from the Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) randomized control[led] trial, which showed a lower incidence of cardiac mortality (as part of its secondary outcomes) following CABG compared to optimal medical therapy and PCI,” the letter explains.

The guideline authors might have judged current optimal medical therapy to be better than what existed 10, 15, or 30 years ago, diluting the relative benefits of surgery, but the “recommendation in a guideline must act on evidence, not inferences. And there is no evidence to support this drop in recommendation class,” Dr. Dayan said.

Other experts have drawn attention to the fact that two surgical societies – the American Association for Thoracic Surgery (AAST) and the Society of Thoracic Surgeons (STS) – did not endorse the final document, despite having participated in its review, reported this news organization.

“This is a very disappointing update that will negatively affect the lives of many people,” tweeted Marc Pelletier, MD, head of cardiac surgery at University Hospitals, Case Western Reserve University, Cleveland.

Contradictions in the text that examines the evidence and the final recommendations, are “unclear” and “open to various interpretations, when they should be a pillar for decisionmaking,” said Javier Ferrari Ayarragaray, MD, president of the Argentine College of Cardiovascular Surgeons (CACCV) and vice president of LACES.

The new guidelines “show no additional randomized controlled trial to support this downgrade in the level of evidence,” according to a recent CACCV statement. “The inclusion, approval and endorsement of this type of [recommendation,] including [other] international surgical scientific societies, such as STS, AATS, EACTS, LACES[,] is necessary to obtain a better understanding and agreement on the current evidence.”

In a Dec. 17, 2021 response to LACES, Patrick O’Gara, MD, who was chair of the ACC/AHA Joint Committee on Clinical Practice Guidelines at the time, and his successor, Joshua Beckman, MD, explained that both organizations approved the guideline for publication and support its authors “in their interpretation of the published evidence and findings.”

The pair pointed out that the drafting committee members, who have extensive clinical judgment and experience, deliberated extensively on the issue and that the change from a class I to a class IIb recommendation was “carefully considered after a review of the entire available and relevant evidence.”

“When we bring together multiple organizations to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of published and peer-reviewed literature and create clinical practice recommendations,” said Thomas Getchius, director of guideline strategy and operations at the AHA.

“The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed upon by the ACC, AHA, SCAI, and the full drafting committee,” Mr. Getchius said.

Dr. Dayan and Dr. Ferrari Ayarragaray have disclosed no relevant financial relationships. Mr. Getchius is an employee of the American Heart Association.

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

When Mechtild Harf was diagnosed with acute leukemia in 1990, physicians told her and her husband Peter that a bone marrow transplant was her best hope for survival. Back then, her native Germany had only 3,000 registered donors, and none was a match.

“My dad just went crazy, you know, to save his wife,” recalled Katharina Harf, who was a young teen at the time of her mother’s diagnosis.

Courtesy DKMS.org

In the course of 1 year, the Harfs recruited more than 68,000 potential bone marrow donors, but their heroic efforts couldn’t save Mechtild.

“She unfortunately didn’t make it. She died because of leukemia,” Katharina said.

Although Mechtild Harf did not survive, her legacy lives on in the bone marrow and stem cell donor recruitment organization DKMS (Deutsche Knochenmarkspenderdatei, or German Bone Marrow Donor Center).

In May of 1991, Peter Harf and Gerhard Ehninger, MD, the hematologist who treated Mechtild, founded DKMS with the mission, as its website states, “to provide as many blood cancer patients as possible with a second chance at life.”

From its German roots, the nonprofit organization has extended its mission to the United States (where it was initially known as Delete Blood Cancer DKMS), Poland, the United Kingdom, Chile, and in 2021, to South Africa.

Three decades after her mother’s death, Katharina Harf serves as Executive Chairwoman of DKMS U.S., based in New York.
 

World’s largest registry

“DKMS has the largest number of unrelated donors of any organization in the world,” noted Richard E. Champlin, MD, chair of the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.

“In a large fraction of our donor searches, we find matches that are in the DKMS registry,” he said in an interview,

In 2022, DKMS is the largest global bone marrow donor recruitment organization, with more than 10.6 million potential donors registered. Worldwide, more than 91,000 patients have received bone marrow or stem cell grafts donated by registered volunteers.

Alexander Schmidt, MD, PhD, global chief medical officer for DKMS, said that approximately 25% of all registered donors worldwide were recruited by his organization, and 39% of all unrelated donor transplants are made with peripheral blood stem cell or bone marrow products, donated by volunteers who are recruited by DKMS.

Since its founding, DKMS has registered 7.1 million potential donors in Germany, who made a total of 80,000 stem cell donations. DKMS U.S., which began operations in 2004, has registered 1.1 million donors and enabled 4,700 donations.
 

Global partners

DKMS partners with donor centers and recruitment organizations in each country where it operates. In the United States, DKMS works with the National Marrow Donor Program (NMDP) and its “Be The Match” donor registry.

“DKMS donors, both those from DKMS in Germany and those from DKMS in the United States are also listed in the NMDP registry, to make it easier for US search coordinators to accept these donors,” Dr. Schmidt explained in an interview.

The international cooperation and coordination makes it possible for a donor in the UK, for example, to save a life of a patient in Germany, the U.S., Chile, India, or many other parts of the world – anywhere that can be reached in time for a patient in need to receive a stem cell donation.
 

Pandemic affects donations

But, as with just about every aspect of life, the COVID-19 pandemic has created enormous challenges for recruiters, donor centers, and stem cell transplant centers.

Dr. Schmidt said that decline in donations during the pandemic was less severe than initially feared, with a decrease of just 3.5% in 2020, compared with the prepandemic year of 2019. In contrast, though, the average annual growth rate for donations prior to the pandemic was about 4%.

“Nevertheless, at the beginning of the pandemic in March 2020, for a few days things looked quite terrible, because all the borders were closed and flights were canceled, and about 50% of all stem cell products go abroad, and between 20% and 25% go intercontinental,” Dr. Schmidt said.

However, close cooperation and coordination between donor centers and national health authorities soon resolved the problem and helped insure that the flow of life-saving donations could continue with minimal disruption, he noted.

“I don’t think we had any product that could not be delivered at the end of the day, due to the pandemic,” he told this news organization.
 

Workforce and clinical problems

Although the flow of donations within and between nations has continued, the COVID-19 pandemic has had profound negative effects on transplant centers, particularly during the wave of infections caused by the Omicron variant, according to a transplant expert.

“With this most recent strain and how transmissible it is, what we’re dealing with is mass workforce shortages,” said Yi-Bin Chen, MD, director of the bone marrow transplant program at Massachusetts General Hospital in Boston.

“On top of a short-staffed hospital, you then take a very transmissible variant and deplete it even more due to the need to quarantine,” he said in an interview.

Both Dr. Champlin and Dr. Chen said that on-again, off-again pandemic travel bans and donor illnesses have necessitated first obtaining products and cryopreserving them before starting the recipient on a conditioning regimen for the transplant.

“The problem is that, while you can preserve peripheral blood stem cells pretty reliably, cryopreserving bone marrow is a bit more difficult,” Dr. Chen said.

In addition, evidence from recent studies comparing stem cell sources suggest that outcomes are less good with cryopreserved products than with fresh products, and with peripheral blood stem cells compared with bone marrow.

“But you’ve got to make do. A transplant with a cryopreserved product is better than no transplant,” Dr. Chen said.

To make things even more frustrating, as the pandemic waxed and waned throughout 2020 and 2021, the recommendations from donor centers seesawed between using fresh or cryopreserved product, making it difficult to plan a transplant for an individual patient.

The Omicron wave has also resulted in a much higher rate of donor dropout than anticipated, making it that much harder to schedule a transplant, Dr. Chen noted.
 

‘Every patient saved’

The pandemic will eventually subside, however, while the need for stem cell transplantation to treat hematologic malignancies will continue.

DKMS recently launched special aid programs to improve access to stem cell transplants in developing nations by offering financial support, free HLA typing, and other services.

In addition to its core mission of recruiting donors, DKMS is dedicated to improving the quality and efficiency of stem cell transplants. For example, in 2017 scientists in DKMS’ Life Science Lab created an antibody test for donor cytomegalovirus (CMV) infection, using a simple buccal swab rather than a more invasive blood sample. CMV infections can compromise the integrity of stem cell grafts and could be fatal to immunocompromised transplant recipients.

The last word goes to Mechtild Harf’s daughter Katharina.

“My big dream is that every patient will be saved from blood cancer,” she said in a video posted on the DKMS website. “When they get sick, we have a solution for them, whether it’s because they need a donor, with research, building hospitals, providing them with the best medical care we can. I will just keep fighting and keep spreading the word, recruiting donors, raising money – all the things that it takes for us to delete blood cancer.”

“I have to believe that this dream will come true because otherwise, why dream, right?” she said.

Dr. Champlin was the recipient of a Mechtild Harf Science Award and is a member of the board of DKMS U.S. Dr. Schmidt is employed by DKMS. Dr. Chen reported having no relevant disclosures.

When Mechtild Harf was diagnosed with acute leukemia in 1990, physicians told her and her husband Peter that a bone marrow transplant was her best hope for survival. Back then, her native Germany had only 3,000 registered donors, and none was a match.

“My dad just went crazy, you know, to save his wife,” recalled Katharina Harf, who was a young teen at the time of her mother’s diagnosis.

Courtesy DKMS.org

In the course of 1 year, the Harfs recruited more than 68,000 potential bone marrow donors, but their heroic efforts couldn’t save Mechtild.

“She unfortunately didn’t make it. She died because of leukemia,” Katharina said.

Although Mechtild Harf did not survive, her legacy lives on in the bone marrow and stem cell donor recruitment organization DKMS (Deutsche Knochenmarkspenderdatei, or German Bone Marrow Donor Center).

In May of 1991, Peter Harf and Gerhard Ehninger, MD, the hematologist who treated Mechtild, founded DKMS with the mission, as its website states, “to provide as many blood cancer patients as possible with a second chance at life.”

From its German roots, the nonprofit organization has extended its mission to the United States (where it was initially known as Delete Blood Cancer DKMS), Poland, the United Kingdom, Chile, and in 2021, to South Africa.

Three decades after her mother’s death, Katharina Harf serves as Executive Chairwoman of DKMS U.S., based in New York.
 

World’s largest registry

“DKMS has the largest number of unrelated donors of any organization in the world,” noted Richard E. Champlin, MD, chair of the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.

“In a large fraction of our donor searches, we find matches that are in the DKMS registry,” he said in an interview,

In 2022, DKMS is the largest global bone marrow donor recruitment organization, with more than 10.6 million potential donors registered. Worldwide, more than 91,000 patients have received bone marrow or stem cell grafts donated by registered volunteers.

Alexander Schmidt, MD, PhD, global chief medical officer for DKMS, said that approximately 25% of all registered donors worldwide were recruited by his organization, and 39% of all unrelated donor transplants are made with peripheral blood stem cell or bone marrow products, donated by volunteers who are recruited by DKMS.

Since its founding, DKMS has registered 7.1 million potential donors in Germany, who made a total of 80,000 stem cell donations. DKMS U.S., which began operations in 2004, has registered 1.1 million donors and enabled 4,700 donations.
 

Global partners

DKMS partners with donor centers and recruitment organizations in each country where it operates. In the United States, DKMS works with the National Marrow Donor Program (NMDP) and its “Be The Match” donor registry.

“DKMS donors, both those from DKMS in Germany and those from DKMS in the United States are also listed in the NMDP registry, to make it easier for US search coordinators to accept these donors,” Dr. Schmidt explained in an interview.

The international cooperation and coordination makes it possible for a donor in the UK, for example, to save a life of a patient in Germany, the U.S., Chile, India, or many other parts of the world – anywhere that can be reached in time for a patient in need to receive a stem cell donation.
 

Pandemic affects donations

But, as with just about every aspect of life, the COVID-19 pandemic has created enormous challenges for recruiters, donor centers, and stem cell transplant centers.

Dr. Schmidt said that decline in donations during the pandemic was less severe than initially feared, with a decrease of just 3.5% in 2020, compared with the prepandemic year of 2019. In contrast, though, the average annual growth rate for donations prior to the pandemic was about 4%.

“Nevertheless, at the beginning of the pandemic in March 2020, for a few days things looked quite terrible, because all the borders were closed and flights were canceled, and about 50% of all stem cell products go abroad, and between 20% and 25% go intercontinental,” Dr. Schmidt said.

However, close cooperation and coordination between donor centers and national health authorities soon resolved the problem and helped insure that the flow of life-saving donations could continue with minimal disruption, he noted.

“I don’t think we had any product that could not be delivered at the end of the day, due to the pandemic,” he told this news organization.
 

Workforce and clinical problems

Although the flow of donations within and between nations has continued, the COVID-19 pandemic has had profound negative effects on transplant centers, particularly during the wave of infections caused by the Omicron variant, according to a transplant expert.

“With this most recent strain and how transmissible it is, what we’re dealing with is mass workforce shortages,” said Yi-Bin Chen, MD, director of the bone marrow transplant program at Massachusetts General Hospital in Boston.

“On top of a short-staffed hospital, you then take a very transmissible variant and deplete it even more due to the need to quarantine,” he said in an interview.

Both Dr. Champlin and Dr. Chen said that on-again, off-again pandemic travel bans and donor illnesses have necessitated first obtaining products and cryopreserving them before starting the recipient on a conditioning regimen for the transplant.

“The problem is that, while you can preserve peripheral blood stem cells pretty reliably, cryopreserving bone marrow is a bit more difficult,” Dr. Chen said.

In addition, evidence from recent studies comparing stem cell sources suggest that outcomes are less good with cryopreserved products than with fresh products, and with peripheral blood stem cells compared with bone marrow.

“But you’ve got to make do. A transplant with a cryopreserved product is better than no transplant,” Dr. Chen said.

To make things even more frustrating, as the pandemic waxed and waned throughout 2020 and 2021, the recommendations from donor centers seesawed between using fresh or cryopreserved product, making it difficult to plan a transplant for an individual patient.

The Omicron wave has also resulted in a much higher rate of donor dropout than anticipated, making it that much harder to schedule a transplant, Dr. Chen noted.
 

‘Every patient saved’

The pandemic will eventually subside, however, while the need for stem cell transplantation to treat hematologic malignancies will continue.

DKMS recently launched special aid programs to improve access to stem cell transplants in developing nations by offering financial support, free HLA typing, and other services.

In addition to its core mission of recruiting donors, DKMS is dedicated to improving the quality and efficiency of stem cell transplants. For example, in 2017 scientists in DKMS’ Life Science Lab created an antibody test for donor cytomegalovirus (CMV) infection, using a simple buccal swab rather than a more invasive blood sample. CMV infections can compromise the integrity of stem cell grafts and could be fatal to immunocompromised transplant recipients.

The last word goes to Mechtild Harf’s daughter Katharina.

“My big dream is that every patient will be saved from blood cancer,” she said in a video posted on the DKMS website. “When they get sick, we have a solution for them, whether it’s because they need a donor, with research, building hospitals, providing them with the best medical care we can. I will just keep fighting and keep spreading the word, recruiting donors, raising money – all the things that it takes for us to delete blood cancer.”

“I have to believe that this dream will come true because otherwise, why dream, right?” she said.

Dr. Champlin was the recipient of a Mechtild Harf Science Award and is a member of the board of DKMS U.S. Dr. Schmidt is employed by DKMS. Dr. Chen reported having no relevant disclosures.

When Mechtild Harf was diagnosed with acute leukemia in 1990, physicians told her and her husband Peter that a bone marrow transplant was her best hope for survival. Back then, her native Germany had only 3,000 registered donors, and none was a match.

“My dad just went crazy, you know, to save his wife,” recalled Katharina Harf, who was a young teen at the time of her mother’s diagnosis.

Courtesy DKMS.org

In the course of 1 year, the Harfs recruited more than 68,000 potential bone marrow donors, but their heroic efforts couldn’t save Mechtild.

“She unfortunately didn’t make it. She died because of leukemia,” Katharina said.

Although Mechtild Harf did not survive, her legacy lives on in the bone marrow and stem cell donor recruitment organization DKMS (Deutsche Knochenmarkspenderdatei, or German Bone Marrow Donor Center).

In May of 1991, Peter Harf and Gerhard Ehninger, MD, the hematologist who treated Mechtild, founded DKMS with the mission, as its website states, “to provide as many blood cancer patients as possible with a second chance at life.”

From its German roots, the nonprofit organization has extended its mission to the United States (where it was initially known as Delete Blood Cancer DKMS), Poland, the United Kingdom, Chile, and in 2021, to South Africa.

Three decades after her mother’s death, Katharina Harf serves as Executive Chairwoman of DKMS U.S., based in New York.
 

World’s largest registry

“DKMS has the largest number of unrelated donors of any organization in the world,” noted Richard E. Champlin, MD, chair of the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.

“In a large fraction of our donor searches, we find matches that are in the DKMS registry,” he said in an interview,

In 2022, DKMS is the largest global bone marrow donor recruitment organization, with more than 10.6 million potential donors registered. Worldwide, more than 91,000 patients have received bone marrow or stem cell grafts donated by registered volunteers.

Alexander Schmidt, MD, PhD, global chief medical officer for DKMS, said that approximately 25% of all registered donors worldwide were recruited by his organization, and 39% of all unrelated donor transplants are made with peripheral blood stem cell or bone marrow products, donated by volunteers who are recruited by DKMS.

Since its founding, DKMS has registered 7.1 million potential donors in Germany, who made a total of 80,000 stem cell donations. DKMS U.S., which began operations in 2004, has registered 1.1 million donors and enabled 4,700 donations.
 

Global partners

DKMS partners with donor centers and recruitment organizations in each country where it operates. In the United States, DKMS works with the National Marrow Donor Program (NMDP) and its “Be The Match” donor registry.

“DKMS donors, both those from DKMS in Germany and those from DKMS in the United States are also listed in the NMDP registry, to make it easier for US search coordinators to accept these donors,” Dr. Schmidt explained in an interview.

The international cooperation and coordination makes it possible for a donor in the UK, for example, to save a life of a patient in Germany, the U.S., Chile, India, or many other parts of the world – anywhere that can be reached in time for a patient in need to receive a stem cell donation.
 

Pandemic affects donations

But, as with just about every aspect of life, the COVID-19 pandemic has created enormous challenges for recruiters, donor centers, and stem cell transplant centers.

Dr. Schmidt said that decline in donations during the pandemic was less severe than initially feared, with a decrease of just 3.5% in 2020, compared with the prepandemic year of 2019. In contrast, though, the average annual growth rate for donations prior to the pandemic was about 4%.

“Nevertheless, at the beginning of the pandemic in March 2020, for a few days things looked quite terrible, because all the borders were closed and flights were canceled, and about 50% of all stem cell products go abroad, and between 20% and 25% go intercontinental,” Dr. Schmidt said.

However, close cooperation and coordination between donor centers and national health authorities soon resolved the problem and helped insure that the flow of life-saving donations could continue with minimal disruption, he noted.

“I don’t think we had any product that could not be delivered at the end of the day, due to the pandemic,” he told this news organization.
 

Workforce and clinical problems

Although the flow of donations within and between nations has continued, the COVID-19 pandemic has had profound negative effects on transplant centers, particularly during the wave of infections caused by the Omicron variant, according to a transplant expert.

“With this most recent strain and how transmissible it is, what we’re dealing with is mass workforce shortages,” said Yi-Bin Chen, MD, director of the bone marrow transplant program at Massachusetts General Hospital in Boston.

“On top of a short-staffed hospital, you then take a very transmissible variant and deplete it even more due to the need to quarantine,” he said in an interview.

Both Dr. Champlin and Dr. Chen said that on-again, off-again pandemic travel bans and donor illnesses have necessitated first obtaining products and cryopreserving them before starting the recipient on a conditioning regimen for the transplant.

“The problem is that, while you can preserve peripheral blood stem cells pretty reliably, cryopreserving bone marrow is a bit more difficult,” Dr. Chen said.

In addition, evidence from recent studies comparing stem cell sources suggest that outcomes are less good with cryopreserved products than with fresh products, and with peripheral blood stem cells compared with bone marrow.

“But you’ve got to make do. A transplant with a cryopreserved product is better than no transplant,” Dr. Chen said.

To make things even more frustrating, as the pandemic waxed and waned throughout 2020 and 2021, the recommendations from donor centers seesawed between using fresh or cryopreserved product, making it difficult to plan a transplant for an individual patient.

The Omicron wave has also resulted in a much higher rate of donor dropout than anticipated, making it that much harder to schedule a transplant, Dr. Chen noted.
 

‘Every patient saved’

The pandemic will eventually subside, however, while the need for stem cell transplantation to treat hematologic malignancies will continue.

DKMS recently launched special aid programs to improve access to stem cell transplants in developing nations by offering financial support, free HLA typing, and other services.

In addition to its core mission of recruiting donors, DKMS is dedicated to improving the quality and efficiency of stem cell transplants. For example, in 2017 scientists in DKMS’ Life Science Lab created an antibody test for donor cytomegalovirus (CMV) infection, using a simple buccal swab rather than a more invasive blood sample. CMV infections can compromise the integrity of stem cell grafts and could be fatal to immunocompromised transplant recipients.

The last word goes to Mechtild Harf’s daughter Katharina.

“My big dream is that every patient will be saved from blood cancer,” she said in a video posted on the DKMS website. “When they get sick, we have a solution for them, whether it’s because they need a donor, with research, building hospitals, providing them with the best medical care we can. I will just keep fighting and keep spreading the word, recruiting donors, raising money – all the things that it takes for us to delete blood cancer.”

“I have to believe that this dream will come true because otherwise, why dream, right?” she said.

Dr. Champlin was the recipient of a Mechtild Harf Science Award and is a member of the board of DKMS U.S. Dr. Schmidt is employed by DKMS. Dr. Chen reported having no relevant disclosures.

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Almost 4 years had passed since Pearl Harbor forced the United States into the Second World War when three military and government services members went to the American Psychiatric Association with a plea: They needed soldiers who could pass the military’s mental and emotional health screening.

The military had rejected or discharged more than 2.5 million servicemen and volunteers on mental health grounds, and frustrated psychiatrists in the service didn’t know where else to turn but to their century-old professional psychiatric organization.

But the APA had grown so large and unwieldy by then that its size, bureaucracy, and singular focus on research left few resources for helping solve an urgent national mental health problem, no matter how worthy it was.

“At the time, the APA was kind of the face of organized psychiatry, but it was organized in a way that did not lend itself to addressing the needs of the military,” said Jack W. Bonner III, MD, professor emeritus of psychiatry at the University of South Carolina, Greenville. “It was considered sort of a stodgy organization that really wasn’t nimble enough to reorganize to look at those needs at that point in time.”

And that, the military psychiatrists decided, would not do. Desperate to solve the problem, they took matters into their own hands.

Nearly 2 years later, 15 psychiatrists, mostly military or ex-military, gathered in the hotel room of the U.S. Army Medical Corps chief of neuropsychiatry the night before the annual APA conference. It was 1946, and America had won the war – but with a huge toll on mental health, both in and out of the military. Aside from veterans’ “shell shock” and the specter of inadequate troops for potential future conflicts, huge social shifts had occurred during the war, and public mental health hospitals and community resources had deteriorated just as demand for psychiatrists and mental health personnel well outstripped supply.

If the APA wasn’t going to tackle these problems head on, the 15 psychiatrists decided, they would force it to, and they enshrined that goal in the name they gave themselves: the Group for the Advancement of Psychiatry. Two days later, three of them challenged incumbent APA officers in elections and won. The infiltration of these “Young Turks,” as they thought of themselves, had begun. From that point forward, GAP members have frequently held APA leadership positions, and APA leaders have often gone on to join GAP. Gradually, the smaller upstart organization nudged the behemoth toward more involvement with social issues, but GAP remains more nimble given its size.

“The APA is a pretty leviathan organization and can’t deal with issues in the same way a smaller organization can, and GAP can fulfill that role of being much more responsive to contemporary issues,” said Dr. Bonner, who is a member of GAP’s planning, marketing, and communications committee.
 

The think tank of psychiatry

If it seems strange today that such progressivism arose from military medical officers, equally striking is how that nascent group has improbably grown from its modest, pragmatic beginnings into a psychiatry “think tank” today. Now in its 75th year, GAP can boast of its influence at the locus of nearly every intersection of society and psychiatry, from mental health care in prisons to use of controversial treatments such as shock therapy, from racial tensions to gender inequality, from medical school curricula to mental institution standards, from LBGTQ rights to climate change.

“We’re not here to do the latest double-blind, placebo-controlled research on things,” said Lawrence S. Gross, MD, president of GAP, professor of clinical psychiatry and the behavioral sciences at the University of Southern California, Los Angeles, and a member of the committee on psychopharmacology. “It’s more for leaders to think about issues in different areas that affect the field of psychiatry and how they interface with society.”

Or, more simply, “GAP is a group that predominantly exists for one major purpose, and that is to add to the body of knowledge in the field,” said Sy Saeed, MD, MS, chair of the department of psychiatry at East Carolina University, Greenville, N.C., and chair of the group’s administration and leadership committee.

And the organization doesn’t shy from controversial topics, either, such as examining direct-to-consumer marketing and when patients should stop antidepressant therapy.

“We’re very good at getting marketed to on when to start medications, but how good are we at actually timing when to cut back on them? How long is long enough to treat?” Dr. Gross asked. The organization continues to have “an undercurrent of recognizing and fostering change and making people aware of things that may be controversial at times but also further the field by looking at these different areas of psychiatry.”

Despite the group’s relatively small size of about 200 members, its impact touches nearly everyone in the profession, whether they realize it or not. And though the group certainly has its weaknesses – such as steep membership fees that may deter some from joining and its need to improve membership diversity – GAP actively seeks ways to address these internal challenges just as it does external ones.

“It’s probably one of the best-kept secrets in psychiatry,” Dr. Gross said. But it’s a secret the members want out. That’s one reason members consider the organization’s crown jewel to be its fellowship program. In fact, Steven S. Sharfstein, MD, MPA, a former GAP president, clinical professor of psychiatry at the University of Maryland, Baltimore, and chair of the planning, marketing, and communications committee, did not formally join GAP until the 1980s. But he first became involved with the group as a resident in the fellowship program in 1969.

In its current incarnation, 12 fellows spend 2 years as working members of GAP, assigned to one of its committees to put in work just like every other member is expected to do, but they reap the wisdom and mentorship of its members at the same time.

One thing that makes GAP so special to its members is the ability “to mentor young psychiatrists, going from generation to generation trying to identify leaders and facilitate their growth,” Dr. Gross said. And that process, through not only the fellowship program but also through the members’ diversity of ages and career stages, sustains the organization’s vigor.

“Its strength is that you create this continuum where senior people get to mentor people who are early in their career, and this way, the knowledge continues,” Dr. Saaed said.
 

Creation, not death, by committee

In the early years, GAP’s longevity was in question. Once it had successfully steered the APA toward taking more action to address social problems, did it still have a role to play? A majority of members decided that it did. “New problems arose as old ones were solved,” wrote the late Albert Deutsch in an early history of GAP, and “some steps which were confidently expected to repair an ill or defect did not turn out to be completely effective.” In its first decade, GAP members led the APA to establish new medical director and director of information positions, to improve professional standards and facilitate improvement of mental health facilities, and to expand training.

But where GAP really excelled was in developing projects, something the APA wasn’t well-suited to do, explained Carol C. Nadelson, MD, professor of psychiatry at Harvard Medical School, Boston, a member of the gender and mental health committee, and a past president of GAP. And the breadth of those projects has “expanded as the field has changed and evolved,” said Dr. Nadelson, the first woman president of the APA.

Those projects, the beating heart of GAP’s work, come from its specialized working committees, groups of 6-12 members who spend a couple years focused on a single question or problem in psychiatry that the committee has decided needs attention. The number of committees has grown from 9 at its founding to 32 today, shrinking and expanding as society’s needs demand. Each committee looks for an area it thinks is important and needs attention or updating and then decides how to proceed in addressing it. This structure as a confederation of committees differs greatly from other medical organizations.

“Committees really function in an autonomous, almost independent manner,” Dr. Bonner said. “They control their work, what they do, and how they do it, and the executive structure of the organization has very little impact on those individual committees.”

It’s only when a committee produces whatever project it’s working on that it’s disseminated to the rest of the organization for review.

“The fact that it’s such a federated organization is both a strength and a weakness,” said Roberto Lewis-Fernández, MD, professor of clinical psychiatry at Columbia University, New York, and chair of the cultural psychiatry committee. The tension between becoming too siloed within a committee and needing some sense of greater unity and the cross-pollination that provides is always present, but it’s perhaps also part of the organization’s vibrancy as it constantly seeks the right balance.

It also sometimes allows for fruitful collaborations, such as a recent publication produced by both the religion committee and the LGBTQ+ committee on helping LGBTQ+ teenagers and communities of faith, pointed out Jack Drescher, MD, a GAP past president who serves as clinical professor of psychiatry at Columbia University, and a member of the LGBTQ and media committees.

GAP is also unique in expecting every member to actively put in work toward its mission.

“If you join the APA, you can do absolutely nothing, or you can go to a conference once a year and learn from other people, but you don’t have to be active,” said Gail Robinson, MD, professor of psychiatry and ob.gyn. at the University of Toronto and chair of GAP’s gender and mental health committee. But if you’re a GAP member who isn’t contributing, expect to hear from someone asking how they can help you figure out how you can contribute.

Expecting that much work from members means meeting more often than most medical societies. Except during the pandemic, GAP members have always met twice a year for a long weekend in White Plains, N.Y., to focus almost exclusively on the committees’ current projects. Each meeting allows members “to immerse themselves in thinking about topics that the various committees find of interest and think might be of interest to the rest of the world,” said David Adler, MD, a professor of psychiatry and medicine at Tufts Medical Center in Boston, and chair of the GAP publication board. Whereas APA meetings are massive, frenetic events focused primarily on new research and continuing education for tens of thousands of attendees, GAP meetings are more intimidate and meditative, “a time in which the leaders can exchange ideas in a more private setting,” Dr. Adler said.

What makes GAP’s meetings so special is that they provide a temporary refuge with the explicit goal of encouraging unhurried discussion and deliberation about big ideas that matter, Dr. Robinson said.

“One of the enjoyable parts of GAP is that you have time to think,” Dr. Robinson said. “In your regular life, you’re seeing patients, you’re doing research or organizing things, but in GAP, you can sit with a group of like-minded, interested people and toss some ideas around about what’s important right now. What should we be looking at? What is the field not paying enough attention to? And then the ideas bubble up. In a lot of other organizations, you’re doing specific work, some of it political, some in terms of the organization, but to just sort of sit and think about what’s important in your field and what people should know more about is a different kind of feeling.”
 

A force for change

The work GAP produces has had a substantial impact on the field of psychiatry and society in general over the past 7 and a half decades. Consider this list of just a handful of GAP contributions in its first decade.

• Guidance regarding electroconvulsive therapy in 1947, followed by an update, in response to reaction to the first document, in 1950.
• A guide to school integration after Brown v. Board of Education that considered the psychiatric challenges of integration.
• A report for employers on workers with epilepsy for occupational health and safety.
• Publications that raised mental hospital standards in the 1950s.
• A range of action documents used by medical schools, psychology and social work departments and agencies, governmental bodies, courts, industry, public schools, and community health and welfare agencies.

Over the years, GAP’s influence has sometimes been overt – such as publishing the only diagnostic and statistical manual for child psychiatry for years before that material was incorporated into the official DSM. Sometimes it’s just ahead of the curve, such as the women’s mental health committee publishing a paper that reviewed the evidence on “abortion trauma syndrome” and concluding that it doesn’t exist shortly before the American Psychological Association and the U.K.’s Royal College of Psychiatrists published reviews with similar conclusions. In a few instances, GAP has caused shifts in how the APA operates, such as encouraging the larger organization to publish books on mental health, said Dr. Sharfstein, a past president of the APA.

Much of the organization’s impact occurs through its effects on education, which affects clinical psychiatry at large.“Some reports are very much designed to have an impact on psychiatry education, residency training and curriculum development, which would have a big impact on practice,” Dr. Sharfstein said. An example is the committee on disasters, which examines the best ways for mental health professionals to respond to and mitigate the mental health fallout from the consequences of natural and manmade disasters.

Most often, though, GAP’s influence is akin to strategically planting very carefully cultivated seeds throughout the academic and clinical media ecosystems and letting them bloom how they will. For example, Dr. Lewis-Fernández described a project the cultural committee published in 2013: a checklist for how a psychiatry research article should address topics related to race, ethnicity, and culture. After reviewing articles in the field and their methodologies, the group developed a checklist of best practices and tested them with articles in the field to see how the checklist held up before publishing it.

“Initially, some people read it, some people didn’t, but over time, it’s gotten picked up, and it’s now about to be used in a journal on psychiatric services as a guide to authors and reviews on the appropriate use of these concepts,” Dr. Lewis-Fernández said.

GAP’s influence also blooms through the cross-pollination that occurs at meetings, where leaders in psychiatry from all across the country come together, discuss ideas, and then take new ideas back to their universities, where they teach them to their residents. Perhaps the best example of this influence in recent years has been a increasing shift in teaching about LGBTQ+ issues.

“There’s an underrepresentation of teaching about LGBTQ+ issues in many psychiatric training programs in many medical schools,” Dr. Drescher said. The organization has worked to raise awareness about these gaps in the education of medical students and mental health professionals and then address it, such as designing an online module curriculum in the early 2000s for how to teach residents about LGBTQ+ mental health issues and then updating it as needed.

Perhaps GAP’s greatest lifetime achievement is forcing the field of psychiatry to confront the fact that it – and its patients – do not stand apart from the society in which they exist.

“People aren’t just psychiatric disorders. They live in society, and society has an impact on them, and that affects how people cope,” Dr. Robinson said. That was once a radical concept, but now “psychiatry as a whole has moved to be more broadly expansive” just as GAP itself has broadened its scope, as evidenced by the wide range of committees, more than triple what the organization had at its founding. “GAP was really at the vanguard of that expansion into the recognizing the need to consider the interaction between the individual and the environment they live in socially.”

That’s never been more true than during the COVID-19 pandemic, contributing to perhaps the greatest mental health crisis in the nation’s history since World War II. But the pandemic hasn’t slowed down GAP’s work. In fact, in some ways, the pandemic has facilitated the group’s ability to meet more often virtually and focus on acute issues the pandemic itself has caused. The psychopathology committee published one paper on the impact of telehealth on treating the chronic mentally ill during COVID, and another delved into rethinking where things stand with institutional racism within psychiatry. The women’s mental health committee published articles on the impact of COVID on pregnant and postpartum women, and the impact of COVID on minority women.
 

Confronting challenges within, too

For all its positive influence, GAP has its weaknesses as well. Two of the biggest barriers to membership, for example, are the steep dues and travel to the twice annual meetings, Dr. Lewis-Fernández said.

The membership dues are not needlessly high: The organization relies on philanthropy and dues for all of its activities, most recently, secured endowments from institutional and individual donors to fund all of the GAP fellows, Dr. Gross said.

“With a low number of members, the cost is larger per member,” Dr. Bonner explained. In fact, GAP has only recently overcome a period of financial uncertainty, now finally on solid ground in terms of fundings.

While the dues can be onerous, Dr. Lewis-Fernández said the organization has been actively thinking about ways to reduce it, particularly for those who may need help if traveling from farther away or younger-career individuals, such as those without tenure or with young families.

It can also be difficult for the organization to attract diverse members from different racial and ethnic groups when leaders in psychiatry from those backgrounds are courted by many other groups, or just to attract younger members in general, but GAP continues to seek ways to overcome those challenges.

“The majority of people in GAP have some kind of academic interest, and the nature of being an early career psychiatrist in academia is that you have to publish to get promoted,” Dr. Bonner said. GAP’s historical practice of producing publications by committee without individual attribution was a disincentive to those early-career folks. “More recently, we’ve changed that so that now individuals can put their names on their product, which has eliminated that particular barriers for young people.”

As the organization continues to seek ways to address those issues, it also faces the same challenges as every other scientific group: Staying relevant in the new, and constantly changing, media landscape.

“It’s an interesting evolution because it started off with books and monographs for many, many years,” Dr. Robinson said, “and then it kind of moved away from that to more articles.” More recently, some committees have returned to writing books while others explore other forms of media to keep up with the times. Long gone are the days when a committee might spend 2-10 years producing one monograph.

“In today’s world, you can’t be relevant operating that way,” said Dr. Bonner, noting that some committees have produced videos or podcasts.

But the sheer amount of information out there is intimidating as well. “Nowadays, a lot of people get their information off the Internet, and how do you actually sift through that?” Dr. Saeed said. “How you find signal in this noise is a whole different thing now, so how GAP produces its information is at that trajectory right now. Should we be producing more electronic books? What should be our peer-review process? How do we make sure the information is current? If we are about sharing information and generating new knowledge, what’s the best way of disseminating that?”

A testament to the organization’s willingness to confront that challenge, however, is its exploration of every possible platform – even those well outside the traditional ones. The climate committee, for example, recently set about addressing climate anxiety in children, but they didn’t produce a report or develop a teaching module or even develop a series of podcasts. Instead, the committee collaborated with Jeremy D. Wortzel, MPhil, an MD and MPH candidate at the University of Pennsylvania, Philadelphia, and Lena K. Champlin, a doctoral candidate in environmental science at Drexel University, Philadelpha, to write a children’s book. “Coco’s Fire: Changing Climate Anxiety into Climate Action” was published in October 2021.
 

GAP continues to leave its mark

For all the work that members put into the organization, members say they reap substantial benefits as well. Dr. Saaed recalls feeling flattered when invited to join the organization because of how influential it is and the opportunity to work with so many leaders in psychiatry. “When you come to GAP committee meetings, you would run into people whose book or research you might have read and who are very prominent in the field,” he said.

Dr. Drescher credited GAP with helping him develop his voice and polish his editing skills, which later aided him when he became editor of the Journal of Gay and Lesbian Mental Health. When the LGBTQ+ committee shifted from reports to writing op-eds, members learned how to write opinion pieces and then teach members of other committees those skills, resulting in GAP-produced op-eds in consumer and trade publications. And then there are the intangible rewards that leave a profound impact on members.

Some members see GAP as central to their professional lives and perhaps legacies.

“Outside of the medical center, this has probably been the most important professional organization of my career, and I think there are a lot of people who feel that way,” Dr. Adler said. “It’s a very unique experience, and the goal is to examine today’s critical issues and say something about them in a way in which maybe the world will take notice.”

Almost 4 years had passed since Pearl Harbor forced the United States into the Second World War when three military and government services members went to the American Psychiatric Association with a plea: They needed soldiers who could pass the military’s mental and emotional health screening.

The military had rejected or discharged more than 2.5 million servicemen and volunteers on mental health grounds, and frustrated psychiatrists in the service didn’t know where else to turn but to their century-old professional psychiatric organization.

But the APA had grown so large and unwieldy by then that its size, bureaucracy, and singular focus on research left few resources for helping solve an urgent national mental health problem, no matter how worthy it was.

“At the time, the APA was kind of the face of organized psychiatry, but it was organized in a way that did not lend itself to addressing the needs of the military,” said Jack W. Bonner III, MD, professor emeritus of psychiatry at the University of South Carolina, Greenville. “It was considered sort of a stodgy organization that really wasn’t nimble enough to reorganize to look at those needs at that point in time.”

And that, the military psychiatrists decided, would not do. Desperate to solve the problem, they took matters into their own hands.

Nearly 2 years later, 15 psychiatrists, mostly military or ex-military, gathered in the hotel room of the U.S. Army Medical Corps chief of neuropsychiatry the night before the annual APA conference. It was 1946, and America had won the war – but with a huge toll on mental health, both in and out of the military. Aside from veterans’ “shell shock” and the specter of inadequate troops for potential future conflicts, huge social shifts had occurred during the war, and public mental health hospitals and community resources had deteriorated just as demand for psychiatrists and mental health personnel well outstripped supply.

If the APA wasn’t going to tackle these problems head on, the 15 psychiatrists decided, they would force it to, and they enshrined that goal in the name they gave themselves: the Group for the Advancement of Psychiatry. Two days later, three of them challenged incumbent APA officers in elections and won. The infiltration of these “Young Turks,” as they thought of themselves, had begun. From that point forward, GAP members have frequently held APA leadership positions, and APA leaders have often gone on to join GAP. Gradually, the smaller upstart organization nudged the behemoth toward more involvement with social issues, but GAP remains more nimble given its size.

“The APA is a pretty leviathan organization and can’t deal with issues in the same way a smaller organization can, and GAP can fulfill that role of being much more responsive to contemporary issues,” said Dr. Bonner, who is a member of GAP’s planning, marketing, and communications committee.
 

The think tank of psychiatry

If it seems strange today that such progressivism arose from military medical officers, equally striking is how that nascent group has improbably grown from its modest, pragmatic beginnings into a psychiatry “think tank” today. Now in its 75th year, GAP can boast of its influence at the locus of nearly every intersection of society and psychiatry, from mental health care in prisons to use of controversial treatments such as shock therapy, from racial tensions to gender inequality, from medical school curricula to mental institution standards, from LBGTQ rights to climate change.

“We’re not here to do the latest double-blind, placebo-controlled research on things,” said Lawrence S. Gross, MD, president of GAP, professor of clinical psychiatry and the behavioral sciences at the University of Southern California, Los Angeles, and a member of the committee on psychopharmacology. “It’s more for leaders to think about issues in different areas that affect the field of psychiatry and how they interface with society.”

Or, more simply, “GAP is a group that predominantly exists for one major purpose, and that is to add to the body of knowledge in the field,” said Sy Saeed, MD, MS, chair of the department of psychiatry at East Carolina University, Greenville, N.C., and chair of the group’s administration and leadership committee.

And the organization doesn’t shy from controversial topics, either, such as examining direct-to-consumer marketing and when patients should stop antidepressant therapy.

“We’re very good at getting marketed to on when to start medications, but how good are we at actually timing when to cut back on them? How long is long enough to treat?” Dr. Gross asked. The organization continues to have “an undercurrent of recognizing and fostering change and making people aware of things that may be controversial at times but also further the field by looking at these different areas of psychiatry.”

Despite the group’s relatively small size of about 200 members, its impact touches nearly everyone in the profession, whether they realize it or not. And though the group certainly has its weaknesses – such as steep membership fees that may deter some from joining and its need to improve membership diversity – GAP actively seeks ways to address these internal challenges just as it does external ones.

“It’s probably one of the best-kept secrets in psychiatry,” Dr. Gross said. But it’s a secret the members want out. That’s one reason members consider the organization’s crown jewel to be its fellowship program. In fact, Steven S. Sharfstein, MD, MPA, a former GAP president, clinical professor of psychiatry at the University of Maryland, Baltimore, and chair of the planning, marketing, and communications committee, did not formally join GAP until the 1980s. But he first became involved with the group as a resident in the fellowship program in 1969.

In its current incarnation, 12 fellows spend 2 years as working members of GAP, assigned to one of its committees to put in work just like every other member is expected to do, but they reap the wisdom and mentorship of its members at the same time.

One thing that makes GAP so special to its members is the ability “to mentor young psychiatrists, going from generation to generation trying to identify leaders and facilitate their growth,” Dr. Gross said. And that process, through not only the fellowship program but also through the members’ diversity of ages and career stages, sustains the organization’s vigor.

“Its strength is that you create this continuum where senior people get to mentor people who are early in their career, and this way, the knowledge continues,” Dr. Saaed said.
 

Creation, not death, by committee

In the early years, GAP’s longevity was in question. Once it had successfully steered the APA toward taking more action to address social problems, did it still have a role to play? A majority of members decided that it did. “New problems arose as old ones were solved,” wrote the late Albert Deutsch in an early history of GAP, and “some steps which were confidently expected to repair an ill or defect did not turn out to be completely effective.” In its first decade, GAP members led the APA to establish new medical director and director of information positions, to improve professional standards and facilitate improvement of mental health facilities, and to expand training.

But where GAP really excelled was in developing projects, something the APA wasn’t well-suited to do, explained Carol C. Nadelson, MD, professor of psychiatry at Harvard Medical School, Boston, a member of the gender and mental health committee, and a past president of GAP. And the breadth of those projects has “expanded as the field has changed and evolved,” said Dr. Nadelson, the first woman president of the APA.

Those projects, the beating heart of GAP’s work, come from its specialized working committees, groups of 6-12 members who spend a couple years focused on a single question or problem in psychiatry that the committee has decided needs attention. The number of committees has grown from 9 at its founding to 32 today, shrinking and expanding as society’s needs demand. Each committee looks for an area it thinks is important and needs attention or updating and then decides how to proceed in addressing it. This structure as a confederation of committees differs greatly from other medical organizations.

“Committees really function in an autonomous, almost independent manner,” Dr. Bonner said. “They control their work, what they do, and how they do it, and the executive structure of the organization has very little impact on those individual committees.”

It’s only when a committee produces whatever project it’s working on that it’s disseminated to the rest of the organization for review.

“The fact that it’s such a federated organization is both a strength and a weakness,” said Roberto Lewis-Fernández, MD, professor of clinical psychiatry at Columbia University, New York, and chair of the cultural psychiatry committee. The tension between becoming too siloed within a committee and needing some sense of greater unity and the cross-pollination that provides is always present, but it’s perhaps also part of the organization’s vibrancy as it constantly seeks the right balance.

It also sometimes allows for fruitful collaborations, such as a recent publication produced by both the religion committee and the LGBTQ+ committee on helping LGBTQ+ teenagers and communities of faith, pointed out Jack Drescher, MD, a GAP past president who serves as clinical professor of psychiatry at Columbia University, and a member of the LGBTQ and media committees.

GAP is also unique in expecting every member to actively put in work toward its mission.

“If you join the APA, you can do absolutely nothing, or you can go to a conference once a year and learn from other people, but you don’t have to be active,” said Gail Robinson, MD, professor of psychiatry and ob.gyn. at the University of Toronto and chair of GAP’s gender and mental health committee. But if you’re a GAP member who isn’t contributing, expect to hear from someone asking how they can help you figure out how you can contribute.

Expecting that much work from members means meeting more often than most medical societies. Except during the pandemic, GAP members have always met twice a year for a long weekend in White Plains, N.Y., to focus almost exclusively on the committees’ current projects. Each meeting allows members “to immerse themselves in thinking about topics that the various committees find of interest and think might be of interest to the rest of the world,” said David Adler, MD, a professor of psychiatry and medicine at Tufts Medical Center in Boston, and chair of the GAP publication board. Whereas APA meetings are massive, frenetic events focused primarily on new research and continuing education for tens of thousands of attendees, GAP meetings are more intimidate and meditative, “a time in which the leaders can exchange ideas in a more private setting,” Dr. Adler said.

What makes GAP’s meetings so special is that they provide a temporary refuge with the explicit goal of encouraging unhurried discussion and deliberation about big ideas that matter, Dr. Robinson said.

“One of the enjoyable parts of GAP is that you have time to think,” Dr. Robinson said. “In your regular life, you’re seeing patients, you’re doing research or organizing things, but in GAP, you can sit with a group of like-minded, interested people and toss some ideas around about what’s important right now. What should we be looking at? What is the field not paying enough attention to? And then the ideas bubble up. In a lot of other organizations, you’re doing specific work, some of it political, some in terms of the organization, but to just sort of sit and think about what’s important in your field and what people should know more about is a different kind of feeling.”
 

A force for change

The work GAP produces has had a substantial impact on the field of psychiatry and society in general over the past 7 and a half decades. Consider this list of just a handful of GAP contributions in its first decade.

• Guidance regarding electroconvulsive therapy in 1947, followed by an update, in response to reaction to the first document, in 1950.
• A guide to school integration after Brown v. Board of Education that considered the psychiatric challenges of integration.
• A report for employers on workers with epilepsy for occupational health and safety.
• Publications that raised mental hospital standards in the 1950s.
• A range of action documents used by medical schools, psychology and social work departments and agencies, governmental bodies, courts, industry, public schools, and community health and welfare agencies.

Over the years, GAP’s influence has sometimes been overt – such as publishing the only diagnostic and statistical manual for child psychiatry for years before that material was incorporated into the official DSM. Sometimes it’s just ahead of the curve, such as the women’s mental health committee publishing a paper that reviewed the evidence on “abortion trauma syndrome” and concluding that it doesn’t exist shortly before the American Psychological Association and the U.K.’s Royal College of Psychiatrists published reviews with similar conclusions. In a few instances, GAP has caused shifts in how the APA operates, such as encouraging the larger organization to publish books on mental health, said Dr. Sharfstein, a past president of the APA.

Much of the organization’s impact occurs through its effects on education, which affects clinical psychiatry at large.“Some reports are very much designed to have an impact on psychiatry education, residency training and curriculum development, which would have a big impact on practice,” Dr. Sharfstein said. An example is the committee on disasters, which examines the best ways for mental health professionals to respond to and mitigate the mental health fallout from the consequences of natural and manmade disasters.

Most often, though, GAP’s influence is akin to strategically planting very carefully cultivated seeds throughout the academic and clinical media ecosystems and letting them bloom how they will. For example, Dr. Lewis-Fernández described a project the cultural committee published in 2013: a checklist for how a psychiatry research article should address topics related to race, ethnicity, and culture. After reviewing articles in the field and their methodologies, the group developed a checklist of best practices and tested them with articles in the field to see how the checklist held up before publishing it.

“Initially, some people read it, some people didn’t, but over time, it’s gotten picked up, and it’s now about to be used in a journal on psychiatric services as a guide to authors and reviews on the appropriate use of these concepts,” Dr. Lewis-Fernández said.

GAP’s influence also blooms through the cross-pollination that occurs at meetings, where leaders in psychiatry from all across the country come together, discuss ideas, and then take new ideas back to their universities, where they teach them to their residents. Perhaps the best example of this influence in recent years has been a increasing shift in teaching about LGBTQ+ issues.

“There’s an underrepresentation of teaching about LGBTQ+ issues in many psychiatric training programs in many medical schools,” Dr. Drescher said. The organization has worked to raise awareness about these gaps in the education of medical students and mental health professionals and then address it, such as designing an online module curriculum in the early 2000s for how to teach residents about LGBTQ+ mental health issues and then updating it as needed.

Perhaps GAP’s greatest lifetime achievement is forcing the field of psychiatry to confront the fact that it – and its patients – do not stand apart from the society in which they exist.

“People aren’t just psychiatric disorders. They live in society, and society has an impact on them, and that affects how people cope,” Dr. Robinson said. That was once a radical concept, but now “psychiatry as a whole has moved to be more broadly expansive” just as GAP itself has broadened its scope, as evidenced by the wide range of committees, more than triple what the organization had at its founding. “GAP was really at the vanguard of that expansion into the recognizing the need to consider the interaction between the individual and the environment they live in socially.”

That’s never been more true than during the COVID-19 pandemic, contributing to perhaps the greatest mental health crisis in the nation’s history since World War II. But the pandemic hasn’t slowed down GAP’s work. In fact, in some ways, the pandemic has facilitated the group’s ability to meet more often virtually and focus on acute issues the pandemic itself has caused. The psychopathology committee published one paper on the impact of telehealth on treating the chronic mentally ill during COVID, and another delved into rethinking where things stand with institutional racism within psychiatry. The women’s mental health committee published articles on the impact of COVID on pregnant and postpartum women, and the impact of COVID on minority women.
 

Confronting challenges within, too

For all its positive influence, GAP has its weaknesses as well. Two of the biggest barriers to membership, for example, are the steep dues and travel to the twice annual meetings, Dr. Lewis-Fernández said.

The membership dues are not needlessly high: The organization relies on philanthropy and dues for all of its activities, most recently, secured endowments from institutional and individual donors to fund all of the GAP fellows, Dr. Gross said.

“With a low number of members, the cost is larger per member,” Dr. Bonner explained. In fact, GAP has only recently overcome a period of financial uncertainty, now finally on solid ground in terms of fundings.

While the dues can be onerous, Dr. Lewis-Fernández said the organization has been actively thinking about ways to reduce it, particularly for those who may need help if traveling from farther away or younger-career individuals, such as those without tenure or with young families.

It can also be difficult for the organization to attract diverse members from different racial and ethnic groups when leaders in psychiatry from those backgrounds are courted by many other groups, or just to attract younger members in general, but GAP continues to seek ways to overcome those challenges.

“The majority of people in GAP have some kind of academic interest, and the nature of being an early career psychiatrist in academia is that you have to publish to get promoted,” Dr. Bonner said. GAP’s historical practice of producing publications by committee without individual attribution was a disincentive to those early-career folks. “More recently, we’ve changed that so that now individuals can put their names on their product, which has eliminated that particular barriers for young people.”

As the organization continues to seek ways to address those issues, it also faces the same challenges as every other scientific group: Staying relevant in the new, and constantly changing, media landscape.

“It’s an interesting evolution because it started off with books and monographs for many, many years,” Dr. Robinson said, “and then it kind of moved away from that to more articles.” More recently, some committees have returned to writing books while others explore other forms of media to keep up with the times. Long gone are the days when a committee might spend 2-10 years producing one monograph.

“In today’s world, you can’t be relevant operating that way,” said Dr. Bonner, noting that some committees have produced videos or podcasts.

But the sheer amount of information out there is intimidating as well. “Nowadays, a lot of people get their information off the Internet, and how do you actually sift through that?” Dr. Saeed said. “How you find signal in this noise is a whole different thing now, so how GAP produces its information is at that trajectory right now. Should we be producing more electronic books? What should be our peer-review process? How do we make sure the information is current? If we are about sharing information and generating new knowledge, what’s the best way of disseminating that?”

A testament to the organization’s willingness to confront that challenge, however, is its exploration of every possible platform – even those well outside the traditional ones. The climate committee, for example, recently set about addressing climate anxiety in children, but they didn’t produce a report or develop a teaching module or even develop a series of podcasts. Instead, the committee collaborated with Jeremy D. Wortzel, MPhil, an MD and MPH candidate at the University of Pennsylvania, Philadelphia, and Lena K. Champlin, a doctoral candidate in environmental science at Drexel University, Philadelpha, to write a children’s book. “Coco’s Fire: Changing Climate Anxiety into Climate Action” was published in October 2021.
 

GAP continues to leave its mark

For all the work that members put into the organization, members say they reap substantial benefits as well. Dr. Saaed recalls feeling flattered when invited to join the organization because of how influential it is and the opportunity to work with so many leaders in psychiatry. “When you come to GAP committee meetings, you would run into people whose book or research you might have read and who are very prominent in the field,” he said.

Dr. Drescher credited GAP with helping him develop his voice and polish his editing skills, which later aided him when he became editor of the Journal of Gay and Lesbian Mental Health. When the LGBTQ+ committee shifted from reports to writing op-eds, members learned how to write opinion pieces and then teach members of other committees those skills, resulting in GAP-produced op-eds in consumer and trade publications. And then there are the intangible rewards that leave a profound impact on members.

Some members see GAP as central to their professional lives and perhaps legacies.

“Outside of the medical center, this has probably been the most important professional organization of my career, and I think there are a lot of people who feel that way,” Dr. Adler said. “It’s a very unique experience, and the goal is to examine today’s critical issues and say something about them in a way in which maybe the world will take notice.”

Almost 4 years had passed since Pearl Harbor forced the United States into the Second World War when three military and government services members went to the American Psychiatric Association with a plea: They needed soldiers who could pass the military’s mental and emotional health screening.

The military had rejected or discharged more than 2.5 million servicemen and volunteers on mental health grounds, and frustrated psychiatrists in the service didn’t know where else to turn but to their century-old professional psychiatric organization.

But the APA had grown so large and unwieldy by then that its size, bureaucracy, and singular focus on research left few resources for helping solve an urgent national mental health problem, no matter how worthy it was.

“At the time, the APA was kind of the face of organized psychiatry, but it was organized in a way that did not lend itself to addressing the needs of the military,” said Jack W. Bonner III, MD, professor emeritus of psychiatry at the University of South Carolina, Greenville. “It was considered sort of a stodgy organization that really wasn’t nimble enough to reorganize to look at those needs at that point in time.”

And that, the military psychiatrists decided, would not do. Desperate to solve the problem, they took matters into their own hands.

Nearly 2 years later, 15 psychiatrists, mostly military or ex-military, gathered in the hotel room of the U.S. Army Medical Corps chief of neuropsychiatry the night before the annual APA conference. It was 1946, and America had won the war – but with a huge toll on mental health, both in and out of the military. Aside from veterans’ “shell shock” and the specter of inadequate troops for potential future conflicts, huge social shifts had occurred during the war, and public mental health hospitals and community resources had deteriorated just as demand for psychiatrists and mental health personnel well outstripped supply.

If the APA wasn’t going to tackle these problems head on, the 15 psychiatrists decided, they would force it to, and they enshrined that goal in the name they gave themselves: the Group for the Advancement of Psychiatry. Two days later, three of them challenged incumbent APA officers in elections and won. The infiltration of these “Young Turks,” as they thought of themselves, had begun. From that point forward, GAP members have frequently held APA leadership positions, and APA leaders have often gone on to join GAP. Gradually, the smaller upstart organization nudged the behemoth toward more involvement with social issues, but GAP remains more nimble given its size.

“The APA is a pretty leviathan organization and can’t deal with issues in the same way a smaller organization can, and GAP can fulfill that role of being much more responsive to contemporary issues,” said Dr. Bonner, who is a member of GAP’s planning, marketing, and communications committee.
 

The think tank of psychiatry

If it seems strange today that such progressivism arose from military medical officers, equally striking is how that nascent group has improbably grown from its modest, pragmatic beginnings into a psychiatry “think tank” today. Now in its 75th year, GAP can boast of its influence at the locus of nearly every intersection of society and psychiatry, from mental health care in prisons to use of controversial treatments such as shock therapy, from racial tensions to gender inequality, from medical school curricula to mental institution standards, from LBGTQ rights to climate change.

“We’re not here to do the latest double-blind, placebo-controlled research on things,” said Lawrence S. Gross, MD, president of GAP, professor of clinical psychiatry and the behavioral sciences at the University of Southern California, Los Angeles, and a member of the committee on psychopharmacology. “It’s more for leaders to think about issues in different areas that affect the field of psychiatry and how they interface with society.”

Or, more simply, “GAP is a group that predominantly exists for one major purpose, and that is to add to the body of knowledge in the field,” said Sy Saeed, MD, MS, chair of the department of psychiatry at East Carolina University, Greenville, N.C., and chair of the group’s administration and leadership committee.

And the organization doesn’t shy from controversial topics, either, such as examining direct-to-consumer marketing and when patients should stop antidepressant therapy.

“We’re very good at getting marketed to on when to start medications, but how good are we at actually timing when to cut back on them? How long is long enough to treat?” Dr. Gross asked. The organization continues to have “an undercurrent of recognizing and fostering change and making people aware of things that may be controversial at times but also further the field by looking at these different areas of psychiatry.”

Despite the group’s relatively small size of about 200 members, its impact touches nearly everyone in the profession, whether they realize it or not. And though the group certainly has its weaknesses – such as steep membership fees that may deter some from joining and its need to improve membership diversity – GAP actively seeks ways to address these internal challenges just as it does external ones.

“It’s probably one of the best-kept secrets in psychiatry,” Dr. Gross said. But it’s a secret the members want out. That’s one reason members consider the organization’s crown jewel to be its fellowship program. In fact, Steven S. Sharfstein, MD, MPA, a former GAP president, clinical professor of psychiatry at the University of Maryland, Baltimore, and chair of the planning, marketing, and communications committee, did not formally join GAP until the 1980s. But he first became involved with the group as a resident in the fellowship program in 1969.

In its current incarnation, 12 fellows spend 2 years as working members of GAP, assigned to one of its committees to put in work just like every other member is expected to do, but they reap the wisdom and mentorship of its members at the same time.

One thing that makes GAP so special to its members is the ability “to mentor young psychiatrists, going from generation to generation trying to identify leaders and facilitate their growth,” Dr. Gross said. And that process, through not only the fellowship program but also through the members’ diversity of ages and career stages, sustains the organization’s vigor.

“Its strength is that you create this continuum where senior people get to mentor people who are early in their career, and this way, the knowledge continues,” Dr. Saaed said.
 

Creation, not death, by committee

In the early years, GAP’s longevity was in question. Once it had successfully steered the APA toward taking more action to address social problems, did it still have a role to play? A majority of members decided that it did. “New problems arose as old ones were solved,” wrote the late Albert Deutsch in an early history of GAP, and “some steps which were confidently expected to repair an ill or defect did not turn out to be completely effective.” In its first decade, GAP members led the APA to establish new medical director and director of information positions, to improve professional standards and facilitate improvement of mental health facilities, and to expand training.

But where GAP really excelled was in developing projects, something the APA wasn’t well-suited to do, explained Carol C. Nadelson, MD, professor of psychiatry at Harvard Medical School, Boston, a member of the gender and mental health committee, and a past president of GAP. And the breadth of those projects has “expanded as the field has changed and evolved,” said Dr. Nadelson, the first woman president of the APA.

Those projects, the beating heart of GAP’s work, come from its specialized working committees, groups of 6-12 members who spend a couple years focused on a single question or problem in psychiatry that the committee has decided needs attention. The number of committees has grown from 9 at its founding to 32 today, shrinking and expanding as society’s needs demand. Each committee looks for an area it thinks is important and needs attention or updating and then decides how to proceed in addressing it. This structure as a confederation of committees differs greatly from other medical organizations.

“Committees really function in an autonomous, almost independent manner,” Dr. Bonner said. “They control their work, what they do, and how they do it, and the executive structure of the organization has very little impact on those individual committees.”

It’s only when a committee produces whatever project it’s working on that it’s disseminated to the rest of the organization for review.

“The fact that it’s such a federated organization is both a strength and a weakness,” said Roberto Lewis-Fernández, MD, professor of clinical psychiatry at Columbia University, New York, and chair of the cultural psychiatry committee. The tension between becoming too siloed within a committee and needing some sense of greater unity and the cross-pollination that provides is always present, but it’s perhaps also part of the organization’s vibrancy as it constantly seeks the right balance.

It also sometimes allows for fruitful collaborations, such as a recent publication produced by both the religion committee and the LGBTQ+ committee on helping LGBTQ+ teenagers and communities of faith, pointed out Jack Drescher, MD, a GAP past president who serves as clinical professor of psychiatry at Columbia University, and a member of the LGBTQ and media committees.

GAP is also unique in expecting every member to actively put in work toward its mission.

“If you join the APA, you can do absolutely nothing, or you can go to a conference once a year and learn from other people, but you don’t have to be active,” said Gail Robinson, MD, professor of psychiatry and ob.gyn. at the University of Toronto and chair of GAP’s gender and mental health committee. But if you’re a GAP member who isn’t contributing, expect to hear from someone asking how they can help you figure out how you can contribute.

Expecting that much work from members means meeting more often than most medical societies. Except during the pandemic, GAP members have always met twice a year for a long weekend in White Plains, N.Y., to focus almost exclusively on the committees’ current projects. Each meeting allows members “to immerse themselves in thinking about topics that the various committees find of interest and think might be of interest to the rest of the world,” said David Adler, MD, a professor of psychiatry and medicine at Tufts Medical Center in Boston, and chair of the GAP publication board. Whereas APA meetings are massive, frenetic events focused primarily on new research and continuing education for tens of thousands of attendees, GAP meetings are more intimidate and meditative, “a time in which the leaders can exchange ideas in a more private setting,” Dr. Adler said.

What makes GAP’s meetings so special is that they provide a temporary refuge with the explicit goal of encouraging unhurried discussion and deliberation about big ideas that matter, Dr. Robinson said.

“One of the enjoyable parts of GAP is that you have time to think,” Dr. Robinson said. “In your regular life, you’re seeing patients, you’re doing research or organizing things, but in GAP, you can sit with a group of like-minded, interested people and toss some ideas around about what’s important right now. What should we be looking at? What is the field not paying enough attention to? And then the ideas bubble up. In a lot of other organizations, you’re doing specific work, some of it political, some in terms of the organization, but to just sort of sit and think about what’s important in your field and what people should know more about is a different kind of feeling.”
 

A force for change

The work GAP produces has had a substantial impact on the field of psychiatry and society in general over the past 7 and a half decades. Consider this list of just a handful of GAP contributions in its first decade.

• Guidance regarding electroconvulsive therapy in 1947, followed by an update, in response to reaction to the first document, in 1950.
• A guide to school integration after Brown v. Board of Education that considered the psychiatric challenges of integration.
• A report for employers on workers with epilepsy for occupational health and safety.
• Publications that raised mental hospital standards in the 1950s.
• A range of action documents used by medical schools, psychology and social work departments and agencies, governmental bodies, courts, industry, public schools, and community health and welfare agencies.

Over the years, GAP’s influence has sometimes been overt – such as publishing the only diagnostic and statistical manual for child psychiatry for years before that material was incorporated into the official DSM. Sometimes it’s just ahead of the curve, such as the women’s mental health committee publishing a paper that reviewed the evidence on “abortion trauma syndrome” and concluding that it doesn’t exist shortly before the American Psychological Association and the U.K.’s Royal College of Psychiatrists published reviews with similar conclusions. In a few instances, GAP has caused shifts in how the APA operates, such as encouraging the larger organization to publish books on mental health, said Dr. Sharfstein, a past president of the APA.

Much of the organization’s impact occurs through its effects on education, which affects clinical psychiatry at large.“Some reports are very much designed to have an impact on psychiatry education, residency training and curriculum development, which would have a big impact on practice,” Dr. Sharfstein said. An example is the committee on disasters, which examines the best ways for mental health professionals to respond to and mitigate the mental health fallout from the consequences of natural and manmade disasters.

Most often, though, GAP’s influence is akin to strategically planting very carefully cultivated seeds throughout the academic and clinical media ecosystems and letting them bloom how they will. For example, Dr. Lewis-Fernández described a project the cultural committee published in 2013: a checklist for how a psychiatry research article should address topics related to race, ethnicity, and culture. After reviewing articles in the field and their methodologies, the group developed a checklist of best practices and tested them with articles in the field to see how the checklist held up before publishing it.

“Initially, some people read it, some people didn’t, but over time, it’s gotten picked up, and it’s now about to be used in a journal on psychiatric services as a guide to authors and reviews on the appropriate use of these concepts,” Dr. Lewis-Fernández said.

GAP’s influence also blooms through the cross-pollination that occurs at meetings, where leaders in psychiatry from all across the country come together, discuss ideas, and then take new ideas back to their universities, where they teach them to their residents. Perhaps the best example of this influence in recent years has been a increasing shift in teaching about LGBTQ+ issues.

“There’s an underrepresentation of teaching about LGBTQ+ issues in many psychiatric training programs in many medical schools,” Dr. Drescher said. The organization has worked to raise awareness about these gaps in the education of medical students and mental health professionals and then address it, such as designing an online module curriculum in the early 2000s for how to teach residents about LGBTQ+ mental health issues and then updating it as needed.

Perhaps GAP’s greatest lifetime achievement is forcing the field of psychiatry to confront the fact that it – and its patients – do not stand apart from the society in which they exist.

“People aren’t just psychiatric disorders. They live in society, and society has an impact on them, and that affects how people cope,” Dr. Robinson said. That was once a radical concept, but now “psychiatry as a whole has moved to be more broadly expansive” just as GAP itself has broadened its scope, as evidenced by the wide range of committees, more than triple what the organization had at its founding. “GAP was really at the vanguard of that expansion into the recognizing the need to consider the interaction between the individual and the environment they live in socially.”

That’s never been more true than during the COVID-19 pandemic, contributing to perhaps the greatest mental health crisis in the nation’s history since World War II. But the pandemic hasn’t slowed down GAP’s work. In fact, in some ways, the pandemic has facilitated the group’s ability to meet more often virtually and focus on acute issues the pandemic itself has caused. The psychopathology committee published one paper on the impact of telehealth on treating the chronic mentally ill during COVID, and another delved into rethinking where things stand with institutional racism within psychiatry. The women’s mental health committee published articles on the impact of COVID on pregnant and postpartum women, and the impact of COVID on minority women.
 

Confronting challenges within, too

For all its positive influence, GAP has its weaknesses as well. Two of the biggest barriers to membership, for example, are the steep dues and travel to the twice annual meetings, Dr. Lewis-Fernández said.

The membership dues are not needlessly high: The organization relies on philanthropy and dues for all of its activities, most recently, secured endowments from institutional and individual donors to fund all of the GAP fellows, Dr. Gross said.

“With a low number of members, the cost is larger per member,” Dr. Bonner explained. In fact, GAP has only recently overcome a period of financial uncertainty, now finally on solid ground in terms of fundings.

While the dues can be onerous, Dr. Lewis-Fernández said the organization has been actively thinking about ways to reduce it, particularly for those who may need help if traveling from farther away or younger-career individuals, such as those without tenure or with young families.

It can also be difficult for the organization to attract diverse members from different racial and ethnic groups when leaders in psychiatry from those backgrounds are courted by many other groups, or just to attract younger members in general, but GAP continues to seek ways to overcome those challenges.

“The majority of people in GAP have some kind of academic interest, and the nature of being an early career psychiatrist in academia is that you have to publish to get promoted,” Dr. Bonner said. GAP’s historical practice of producing publications by committee without individual attribution was a disincentive to those early-career folks. “More recently, we’ve changed that so that now individuals can put their names on their product, which has eliminated that particular barriers for young people.”

As the organization continues to seek ways to address those issues, it also faces the same challenges as every other scientific group: Staying relevant in the new, and constantly changing, media landscape.

“It’s an interesting evolution because it started off with books and monographs for many, many years,” Dr. Robinson said, “and then it kind of moved away from that to more articles.” More recently, some committees have returned to writing books while others explore other forms of media to keep up with the times. Long gone are the days when a committee might spend 2-10 years producing one monograph.

“In today’s world, you can’t be relevant operating that way,” said Dr. Bonner, noting that some committees have produced videos or podcasts.

But the sheer amount of information out there is intimidating as well. “Nowadays, a lot of people get their information off the Internet, and how do you actually sift through that?” Dr. Saeed said. “How you find signal in this noise is a whole different thing now, so how GAP produces its information is at that trajectory right now. Should we be producing more electronic books? What should be our peer-review process? How do we make sure the information is current? If we are about sharing information and generating new knowledge, what’s the best way of disseminating that?”

A testament to the organization’s willingness to confront that challenge, however, is its exploration of every possible platform – even those well outside the traditional ones. The climate committee, for example, recently set about addressing climate anxiety in children, but they didn’t produce a report or develop a teaching module or even develop a series of podcasts. Instead, the committee collaborated with Jeremy D. Wortzel, MPhil, an MD and MPH candidate at the University of Pennsylvania, Philadelphia, and Lena K. Champlin, a doctoral candidate in environmental science at Drexel University, Philadelpha, to write a children’s book. “Coco’s Fire: Changing Climate Anxiety into Climate Action” was published in October 2021.
 

GAP continues to leave its mark

For all the work that members put into the organization, members say they reap substantial benefits as well. Dr. Saaed recalls feeling flattered when invited to join the organization because of how influential it is and the opportunity to work with so many leaders in psychiatry. “When you come to GAP committee meetings, you would run into people whose book or research you might have read and who are very prominent in the field,” he said.

Dr. Drescher credited GAP with helping him develop his voice and polish his editing skills, which later aided him when he became editor of the Journal of Gay and Lesbian Mental Health. When the LGBTQ+ committee shifted from reports to writing op-eds, members learned how to write opinion pieces and then teach members of other committees those skills, resulting in GAP-produced op-eds in consumer and trade publications. And then there are the intangible rewards that leave a profound impact on members.

Some members see GAP as central to their professional lives and perhaps legacies.

“Outside of the medical center, this has probably been the most important professional organization of my career, and I think there are a lot of people who feel that way,” Dr. Adler said. “It’s a very unique experience, and the goal is to examine today’s critical issues and say something about them in a way in which maybe the world will take notice.”

In space, no one can hear your red blood cells scream

There are many reasons why space is the final frontier, not least of which are the major health issues space travel places on the human body. So until a shady billionaire finds an alien protomolecule on a Saturnian moon and starts splicing it with human DNA so we can hang out in space all day without a spacesuit, we’re stuck with things like space anemia, a condition many astronauts develop after extended time in space.

Space anemia has been known for many years, but it was assumed that it developed as a reaction to microgravity and was a short-term phenomenon only – a temporary compensation as fluids and blood volume adjusted themselves. But as new research shows, that assumption seems to be wrong.

Courtesy NASA

For the study, published in Nature Medicine, 13 astronauts who were in space for at least 120 days – long enough for all their red blood cells to have been produced in space – had their blood tested consistently. Before their flights, the astronauts created and destroyed 2 million red blood cells per second, but while they were in space, they destroyed 3 million cells per second. Notably, this process continued for the entire duration of the space flight. So, not a temporary reaction.

Consequently, 5 of the 13 astronauts developed anemia when they returned to Earth. (Interesting space fact: Having fewer blood cells isn’t a problem while you’re in space; the effects of anemia only manifest when the body returns to full gravity.) The anemia disappeared after a few months, but the astronauts were still destroying 30% more red blood cells a year after their spaceflight than they were before leaving Earth.

You may be thinking: Well, if they were destroying 50% more red blood cells while in space, how come they didn’t all develop severe anemia? The researchers theorized that production was boosted as well, which sounds like a good thing. The body is compensating, as it should. Unfortunately, that increased production stresses bone marrow function and the demand for energy spikes. That’s not such a good thing. And of course, many of the astronauts got anemia anyway.

To tackle the issue, the researchers emphasized the importance of feeding astronauts a proper diet, plus potential supplements before spaceflight. So don’t worry, Captain Kirk will be able to arm wrestle Klingons and romance suspiciously human-looking aliens without fear of keeling over from anemia-induced fatigue. Earth will stay safe.
 

Tell me with your eyes

Communication can be hard, even under the best of circumstances, but for many nonverbal patients in the intensive care unit who can’t move, getting a point across to the health care team can be a huge struggle in itself.

Health care professionals have been making do with eye-blinking or head-nodding, but what if that’s just not enough? New research shows that it’s not, and there’s a more effective way for patients to say what they mean just by looking.

BG Universitätsklinikum Bergmannsheil

In a study published in the Journal of Trauma and Acute Care Surgery, researchers looked into using eye-tracking systems for nonverbal ICU patients to communicate. Eye-tracking isn’t anything new, but using it as a form of communication among nonverbal patients with critical illness hasn’t been looked at before.

How does it work? The eye-tracking system is set up in the patient’s line of sight and its various algorithms and software collect data to calculate where exactly the patient is looking. Established scores and scales assess the patient’s mood, quality of life, pain, and self-esteem.

The researchers found that participating patients were actually experiencing more negative moods, pain, and feelings of frustration than was once believed. Making this tool even more valuable for treatment adjustment and meeting patients’ needs.

In this case, it means that health care providers are getting an eyeful … of communication.
 

Make America grave again

Here we go again. Somebody just found something else that the United States is not the best at. To go along with math and science education, infrastructure investment, quality of life …

That’s going to go on for a while, so let’s get to the new stuff. An international group of researchers surveyed end-of-life care in 81 countries and ranked them based on the assessment of 181 experts in those countries. They looked at 13 different factors, including proper management of pain and comfort, having a clean and safe space, being treated kindly, lack of cost barriers to appropriate care, and treatments that address quality of life and don’t just extend life.

… press freedom, industrial production, racial equality, Internet connectivity …

truthseeker08/Pixabay

Their report card, published in the Journal of Pain and Symptom Management, gave six countries an A, with Great Britain at the top. The other five were Ireland, Taiwan, Australia, South Korea, and Costa Rica. The lowest grade went to Paraguay in 81st place, with Lebanon, Brazil, Senegal, and Haiti just ahead.

… environmental stewardship, body-mass index, social mobility, COVID safeness …

The United States, getting a firm grasp on mediocrity, ranked 43rd. Here are some countries that did better: North Macedonia (7th), Sri Lanka (16th), Uganda (31st), and Uruguay 33rd). In the United States, “we spend so much money trying to get people to live longer, but we don’t spend enough money in helping people die better,” lead author Eric A. Finkelstein, PhD, said in a written statement.

… economic stability, and soccer; we’re also not the best at dying. Wait, did we already say that?
 

The face mask that launched a thousand ships

Face masks, clearly, have been a source of social strife during the pandemic. People may not agree on mandates, but a mask can be a pretty-low-maintenance face shield if you don’t feel like putting on make-up or want to cover up some blemishes.

Before the pandemic, people thought that those wearing face masks were less attractive because the masks represented illness or disease, according to Dr. Michael Lewis of Cardiff (Wales) University. Back then, no one really wore masks besides doctors and nurses, so if you saw someone wearing one on the street, you probably wondered what they were trying to hide.

Bicanski/Pixnio

Now, though, the subject of face mask attractiveness has been revisited by Dr. Lewis and his associate, Oliver Hies, who found that face masks now make people more attractive.

“Our study suggests faces are considered most attractive when covered by medical face masks. … At a time when we feel vulnerable, we may find the wearing of medical masks reassuring and so feel more positive towards the wearer,” Dr. Lewis told the Guardian.

He suggested that we’re no longer looking at people wearing a mask as disease riddled, but rather doing their part to protect society. Or maybe we focus more on someone’s eyes when that’s all there is to look at. Or, maybe we wind up making up what the rest of someone’s face looks like to meet our attractiveness criteria.

However you feel about masks, they’re cheaper than plastic surgery. And you can go out wearing a new face every day.
 

In space, no one can hear your red blood cells scream

There are many reasons why space is the final frontier, not least of which are the major health issues space travel places on the human body. So until a shady billionaire finds an alien protomolecule on a Saturnian moon and starts splicing it with human DNA so we can hang out in space all day without a spacesuit, we’re stuck with things like space anemia, a condition many astronauts develop after extended time in space.

Space anemia has been known for many years, but it was assumed that it developed as a reaction to microgravity and was a short-term phenomenon only – a temporary compensation as fluids and blood volume adjusted themselves. But as new research shows, that assumption seems to be wrong.

Courtesy NASA

For the study, published in Nature Medicine, 13 astronauts who were in space for at least 120 days – long enough for all their red blood cells to have been produced in space – had their blood tested consistently. Before their flights, the astronauts created and destroyed 2 million red blood cells per second, but while they were in space, they destroyed 3 million cells per second. Notably, this process continued for the entire duration of the space flight. So, not a temporary reaction.

Consequently, 5 of the 13 astronauts developed anemia when they returned to Earth. (Interesting space fact: Having fewer blood cells isn’t a problem while you’re in space; the effects of anemia only manifest when the body returns to full gravity.) The anemia disappeared after a few months, but the astronauts were still destroying 30% more red blood cells a year after their spaceflight than they were before leaving Earth.

You may be thinking: Well, if they were destroying 50% more red blood cells while in space, how come they didn’t all develop severe anemia? The researchers theorized that production was boosted as well, which sounds like a good thing. The body is compensating, as it should. Unfortunately, that increased production stresses bone marrow function and the demand for energy spikes. That’s not such a good thing. And of course, many of the astronauts got anemia anyway.

To tackle the issue, the researchers emphasized the importance of feeding astronauts a proper diet, plus potential supplements before spaceflight. So don’t worry, Captain Kirk will be able to arm wrestle Klingons and romance suspiciously human-looking aliens without fear of keeling over from anemia-induced fatigue. Earth will stay safe.
 

Tell me with your eyes

Communication can be hard, even under the best of circumstances, but for many nonverbal patients in the intensive care unit who can’t move, getting a point across to the health care team can be a huge struggle in itself.

Health care professionals have been making do with eye-blinking or head-nodding, but what if that’s just not enough? New research shows that it’s not, and there’s a more effective way for patients to say what they mean just by looking.

BG Universitätsklinikum Bergmannsheil

In a study published in the Journal of Trauma and Acute Care Surgery, researchers looked into using eye-tracking systems for nonverbal ICU patients to communicate. Eye-tracking isn’t anything new, but using it as a form of communication among nonverbal patients with critical illness hasn’t been looked at before.

How does it work? The eye-tracking system is set up in the patient’s line of sight and its various algorithms and software collect data to calculate where exactly the patient is looking. Established scores and scales assess the patient’s mood, quality of life, pain, and self-esteem.

The researchers found that participating patients were actually experiencing more negative moods, pain, and feelings of frustration than was once believed. Making this tool even more valuable for treatment adjustment and meeting patients’ needs.

In this case, it means that health care providers are getting an eyeful … of communication.
 

Make America grave again

Here we go again. Somebody just found something else that the United States is not the best at. To go along with math and science education, infrastructure investment, quality of life …

That’s going to go on for a while, so let’s get to the new stuff. An international group of researchers surveyed end-of-life care in 81 countries and ranked them based on the assessment of 181 experts in those countries. They looked at 13 different factors, including proper management of pain and comfort, having a clean and safe space, being treated kindly, lack of cost barriers to appropriate care, and treatments that address quality of life and don’t just extend life.

… press freedom, industrial production, racial equality, Internet connectivity …

truthseeker08/Pixabay

Their report card, published in the Journal of Pain and Symptom Management, gave six countries an A, with Great Britain at the top. The other five were Ireland, Taiwan, Australia, South Korea, and Costa Rica. The lowest grade went to Paraguay in 81st place, with Lebanon, Brazil, Senegal, and Haiti just ahead.

… environmental stewardship, body-mass index, social mobility, COVID safeness …

The United States, getting a firm grasp on mediocrity, ranked 43rd. Here are some countries that did better: North Macedonia (7th), Sri Lanka (16th), Uganda (31st), and Uruguay 33rd). In the United States, “we spend so much money trying to get people to live longer, but we don’t spend enough money in helping people die better,” lead author Eric A. Finkelstein, PhD, said in a written statement.

… economic stability, and soccer; we’re also not the best at dying. Wait, did we already say that?
 

The face mask that launched a thousand ships

Face masks, clearly, have been a source of social strife during the pandemic. People may not agree on mandates, but a mask can be a pretty-low-maintenance face shield if you don’t feel like putting on make-up or want to cover up some blemishes.

Before the pandemic, people thought that those wearing face masks were less attractive because the masks represented illness or disease, according to Dr. Michael Lewis of Cardiff (Wales) University. Back then, no one really wore masks besides doctors and nurses, so if you saw someone wearing one on the street, you probably wondered what they were trying to hide.

Bicanski/Pixnio

Now, though, the subject of face mask attractiveness has been revisited by Dr. Lewis and his associate, Oliver Hies, who found that face masks now make people more attractive.

“Our study suggests faces are considered most attractive when covered by medical face masks. … At a time when we feel vulnerable, we may find the wearing of medical masks reassuring and so feel more positive towards the wearer,” Dr. Lewis told the Guardian.

He suggested that we’re no longer looking at people wearing a mask as disease riddled, but rather doing their part to protect society. Or maybe we focus more on someone’s eyes when that’s all there is to look at. Or, maybe we wind up making up what the rest of someone’s face looks like to meet our attractiveness criteria.

However you feel about masks, they’re cheaper than plastic surgery. And you can go out wearing a new face every day.
 

In space, no one can hear your red blood cells scream

There are many reasons why space is the final frontier, not least of which are the major health issues space travel places on the human body. So until a shady billionaire finds an alien protomolecule on a Saturnian moon and starts splicing it with human DNA so we can hang out in space all day without a spacesuit, we’re stuck with things like space anemia, a condition many astronauts develop after extended time in space.

Space anemia has been known for many years, but it was assumed that it developed as a reaction to microgravity and was a short-term phenomenon only – a temporary compensation as fluids and blood volume adjusted themselves. But as new research shows, that assumption seems to be wrong.

Courtesy NASA

For the study, published in Nature Medicine, 13 astronauts who were in space for at least 120 days – long enough for all their red blood cells to have been produced in space – had their blood tested consistently. Before their flights, the astronauts created and destroyed 2 million red blood cells per second, but while they were in space, they destroyed 3 million cells per second. Notably, this process continued for the entire duration of the space flight. So, not a temporary reaction.

Consequently, 5 of the 13 astronauts developed anemia when they returned to Earth. (Interesting space fact: Having fewer blood cells isn’t a problem while you’re in space; the effects of anemia only manifest when the body returns to full gravity.) The anemia disappeared after a few months, but the astronauts were still destroying 30% more red blood cells a year after their spaceflight than they were before leaving Earth.

You may be thinking: Well, if they were destroying 50% more red blood cells while in space, how come they didn’t all develop severe anemia? The researchers theorized that production was boosted as well, which sounds like a good thing. The body is compensating, as it should. Unfortunately, that increased production stresses bone marrow function and the demand for energy spikes. That’s not such a good thing. And of course, many of the astronauts got anemia anyway.

To tackle the issue, the researchers emphasized the importance of feeding astronauts a proper diet, plus potential supplements before spaceflight. So don’t worry, Captain Kirk will be able to arm wrestle Klingons and romance suspiciously human-looking aliens without fear of keeling over from anemia-induced fatigue. Earth will stay safe.
 

Tell me with your eyes

Communication can be hard, even under the best of circumstances, but for many nonverbal patients in the intensive care unit who can’t move, getting a point across to the health care team can be a huge struggle in itself.

Health care professionals have been making do with eye-blinking or head-nodding, but what if that’s just not enough? New research shows that it’s not, and there’s a more effective way for patients to say what they mean just by looking.

BG Universitätsklinikum Bergmannsheil

In a study published in the Journal of Trauma and Acute Care Surgery, researchers looked into using eye-tracking systems for nonverbal ICU patients to communicate. Eye-tracking isn’t anything new, but using it as a form of communication among nonverbal patients with critical illness hasn’t been looked at before.

How does it work? The eye-tracking system is set up in the patient’s line of sight and its various algorithms and software collect data to calculate where exactly the patient is looking. Established scores and scales assess the patient’s mood, quality of life, pain, and self-esteem.

The researchers found that participating patients were actually experiencing more negative moods, pain, and feelings of frustration than was once believed. Making this tool even more valuable for treatment adjustment and meeting patients’ needs.

In this case, it means that health care providers are getting an eyeful … of communication.
 

Make America grave again

Here we go again. Somebody just found something else that the United States is not the best at. To go along with math and science education, infrastructure investment, quality of life …

That’s going to go on for a while, so let’s get to the new stuff. An international group of researchers surveyed end-of-life care in 81 countries and ranked them based on the assessment of 181 experts in those countries. They looked at 13 different factors, including proper management of pain and comfort, having a clean and safe space, being treated kindly, lack of cost barriers to appropriate care, and treatments that address quality of life and don’t just extend life.

… press freedom, industrial production, racial equality, Internet connectivity …

truthseeker08/Pixabay

Their report card, published in the Journal of Pain and Symptom Management, gave six countries an A, with Great Britain at the top. The other five were Ireland, Taiwan, Australia, South Korea, and Costa Rica. The lowest grade went to Paraguay in 81st place, with Lebanon, Brazil, Senegal, and Haiti just ahead.

… environmental stewardship, body-mass index, social mobility, COVID safeness …

The United States, getting a firm grasp on mediocrity, ranked 43rd. Here are some countries that did better: North Macedonia (7th), Sri Lanka (16th), Uganda (31st), and Uruguay 33rd). In the United States, “we spend so much money trying to get people to live longer, but we don’t spend enough money in helping people die better,” lead author Eric A. Finkelstein, PhD, said in a written statement.

… economic stability, and soccer; we’re also not the best at dying. Wait, did we already say that?
 

The face mask that launched a thousand ships

Face masks, clearly, have been a source of social strife during the pandemic. People may not agree on mandates, but a mask can be a pretty-low-maintenance face shield if you don’t feel like putting on make-up or want to cover up some blemishes.

Before the pandemic, people thought that those wearing face masks were less attractive because the masks represented illness or disease, according to Dr. Michael Lewis of Cardiff (Wales) University. Back then, no one really wore masks besides doctors and nurses, so if you saw someone wearing one on the street, you probably wondered what they were trying to hide.

Bicanski/Pixnio

Now, though, the subject of face mask attractiveness has been revisited by Dr. Lewis and his associate, Oliver Hies, who found that face masks now make people more attractive.

“Our study suggests faces are considered most attractive when covered by medical face masks. … At a time when we feel vulnerable, we may find the wearing of medical masks reassuring and so feel more positive towards the wearer,” Dr. Lewis told the Guardian.

He suggested that we’re no longer looking at people wearing a mask as disease riddled, but rather doing their part to protect society. Or maybe we focus more on someone’s eyes when that’s all there is to look at. Or, maybe we wind up making up what the rest of someone’s face looks like to meet our attractiveness criteria.

However you feel about masks, they’re cheaper than plastic surgery. And you can go out wearing a new face every day.
 

Patients looking to refill a prescription for apixaban (Eliquis) through CVS Caremark may be in for a surprise following its decision to exclude the direct oral anticoagulant (DOAC) from its formulary starting Jan. 1.

The move leaves just one DOAC, rivaroxaban (Xarelto), on CVS’ commercial formulary and is being assailed as the latest example of “nonmedical switching” used by health insurers to control costs.

In a letter to CVS Caremark backed by 14 provider and patient organizations, the nonprofit Partnership to Advance Cardiovascular Health (PACH) calls on the pharmacy chain to reverse its “dangerously disruptive” decision to force stable patients at high risk of cardiovascular events to switch anticoagulation, without an apparent option to be grandfathered into the new plan.

PACH president Dharmesh Patel, MD, Stern Cardiovascular Center, Memphis, called the formulary change “reckless and irresponsible, especially because the decision is not based in science and evidence, but on budgets. Patients and their health care providers, not insurance companies, need to be trusted to determine what medication is best,” he said in a statement.

Craig Beavers, PharmD, vice president of Baptist Health Paducah, Kentucky, said that, as chair of the American College of Cardiology’s Cardiovascular Team Section, he and other organizations have met with CVS Caremark medical leadership to advocate for patients and to understand the company’s perspective.

“The underlying driver is cost,” he told this news organization.

Current guidelines recommend DOACs in general for a variety of indications, including to reduce the risk of stroke and embolism in nonvalvular atrial fibrillation and to prevent deep vein thrombosis, but there are select instances where a particular DOAC might be more appropriate, he observed.

“Apixaban may be better for a patient with a history of GI bleeding because there’s less GI bleeding, but the guidelines don’t necessarily spell those things out,” Dr. Beavers said. “That’s where the clinician should advocate for their patient and, unfortunately, they are making their decision strictly based off the guidelines.”

Requests to speak with medical officers at CVS Caremark went unanswered, but its executive director of communications, Christina Peaslee, told this news organization that the formulary decision “maintains clinically appropriate, cost-effective prescription coverage” for its clients and members.

“Both the American Heart Association/American College of Cardiology/Heart Rhythm Society and 2021 CHEST guidelines recommend DOACs over warfarin for treatment of various cardiology conditions such as atrial fibrillation, but neither list a specific agent as preferred – showing that consensus clinical guidelines do not favor one over the other,” she said in an email. “Further, Xarelto has more FDA-approved indications than Eliquis (e.g., Xarelto is approved for a reduction in risk of major CV events in patients with CAD or PAD) in addition to all the same FDA indications as Eliquis.”

Ms. Peaslee pointed out that all formulary changes are evaluated by an external medical expert specializing in the disease state, followed by review and approval by an independent national Pharmacy & Therapeutics Committee.

The decision to exclude apixaban is also limited to a “subset of commercial drug lists,” she said, although specifics on which plans and the number of affected patients were not forthcoming.

The choice of DOAC is a timely question in cardiology, with recent studies suggesting an advantage for apixaban over rivaroxaban in reducing the risk of recurrent venous thromboembolism, as well as reducing the risk of major ischemic or hemorrhagic events in atrial fibrillation.

Ms. Peaslee said CVS Caremark closely monitors medical literature for relevant clinical trial data and that most clients allow reasonable formulary exceptions when justified. “This formulary exceptions process has been successfully used for changes of this type and allows patients to get a medication that is safe and effective, as determined by their prescriber.”

The company will also continue to provide “robust, personalized outreach to the small number of members who will need to switch to an alternative medication,” she added.

Dr. Beavers said negotiations with CVS are still in the early stages, but, in the meantime, the ACC is providing health care providers with tools, such as drug copay cards and electronic prior authorizations, to help ensure patients don’t have gaps in coverage.

In a Jan. 14 news release addressing the formulary change, ACC notes that a patient’s pharmacy can also request a one-time override when trying to fill a nonpreferred DOAC in January to buy time if switching medications with their clinician or requesting a formulary exception.

During discussions with CVS Caremark, it says the ACC and the American Society of Hematology “underscored the negative impacts of this decision on patients currently taking one of the nonpreferred DOACs and on those who have previously tried rivaroxaban and changed medications.”

The groups also highlighted difficulties with other prior authorization programs in terms of the need for dedicated staff and time away from direct patient care.

“The ACC and ASH will continue discussions with CVS Caremark regarding the burden on clinicians and the effect of the formulary decision on patient access,” the release says.

In its letter to CVS, PACH argues that the apixaban exclusion will disproportionately affect historically disadvantaged patients, leaving those who can least afford the change with limited options. Notably, no generic is available for either apixaban or rivaroxaban.

The group also highlights a 2019 national poll, in which nearly 40% of patients who had their medication switched were so frustrated that they stopped their medication altogether.

PACH has an online petition against nonmedical switching, which at press time had garnered 2,126 signatures.

One signee, Jan Griffin, who survived bilateral pulmonary embolisms, writes that she has been on Eliquis [apixaban] successfully since her hospital discharge. “Now, as of midnight, Caremark apparently knows better than my hematologist as to what blood thinner is better for me and will no longer cover my Eliquis prescription. This is criminal, immoral, and unethical. #StopTheSwitch.”

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

Patients looking to refill a prescription for apixaban (Eliquis) through CVS Caremark may be in for a surprise following its decision to exclude the direct oral anticoagulant (DOAC) from its formulary starting Jan. 1.

The move leaves just one DOAC, rivaroxaban (Xarelto), on CVS’ commercial formulary and is being assailed as the latest example of “nonmedical switching” used by health insurers to control costs.

In a letter to CVS Caremark backed by 14 provider and patient organizations, the nonprofit Partnership to Advance Cardiovascular Health (PACH) calls on the pharmacy chain to reverse its “dangerously disruptive” decision to force stable patients at high risk of cardiovascular events to switch anticoagulation, without an apparent option to be grandfathered into the new plan.

PACH president Dharmesh Patel, MD, Stern Cardiovascular Center, Memphis, called the formulary change “reckless and irresponsible, especially because the decision is not based in science and evidence, but on budgets. Patients and their health care providers, not insurance companies, need to be trusted to determine what medication is best,” he said in a statement.

Craig Beavers, PharmD, vice president of Baptist Health Paducah, Kentucky, said that, as chair of the American College of Cardiology’s Cardiovascular Team Section, he and other organizations have met with CVS Caremark medical leadership to advocate for patients and to understand the company’s perspective.

“The underlying driver is cost,” he told this news organization.

Current guidelines recommend DOACs in general for a variety of indications, including to reduce the risk of stroke and embolism in nonvalvular atrial fibrillation and to prevent deep vein thrombosis, but there are select instances where a particular DOAC might be more appropriate, he observed.

“Apixaban may be better for a patient with a history of GI bleeding because there’s less GI bleeding, but the guidelines don’t necessarily spell those things out,” Dr. Beavers said. “That’s where the clinician should advocate for their patient and, unfortunately, they are making their decision strictly based off the guidelines.”

Requests to speak with medical officers at CVS Caremark went unanswered, but its executive director of communications, Christina Peaslee, told this news organization that the formulary decision “maintains clinically appropriate, cost-effective prescription coverage” for its clients and members.

“Both the American Heart Association/American College of Cardiology/Heart Rhythm Society and 2021 CHEST guidelines recommend DOACs over warfarin for treatment of various cardiology conditions such as atrial fibrillation, but neither list a specific agent as preferred – showing that consensus clinical guidelines do not favor one over the other,” she said in an email. “Further, Xarelto has more FDA-approved indications than Eliquis (e.g., Xarelto is approved for a reduction in risk of major CV events in patients with CAD or PAD) in addition to all the same FDA indications as Eliquis.”

Ms. Peaslee pointed out that all formulary changes are evaluated by an external medical expert specializing in the disease state, followed by review and approval by an independent national Pharmacy & Therapeutics Committee.

The decision to exclude apixaban is also limited to a “subset of commercial drug lists,” she said, although specifics on which plans and the number of affected patients were not forthcoming.

The choice of DOAC is a timely question in cardiology, with recent studies suggesting an advantage for apixaban over rivaroxaban in reducing the risk of recurrent venous thromboembolism, as well as reducing the risk of major ischemic or hemorrhagic events in atrial fibrillation.

Ms. Peaslee said CVS Caremark closely monitors medical literature for relevant clinical trial data and that most clients allow reasonable formulary exceptions when justified. “This formulary exceptions process has been successfully used for changes of this type and allows patients to get a medication that is safe and effective, as determined by their prescriber.”

The company will also continue to provide “robust, personalized outreach to the small number of members who will need to switch to an alternative medication,” she added.

Dr. Beavers said negotiations with CVS are still in the early stages, but, in the meantime, the ACC is providing health care providers with tools, such as drug copay cards and electronic prior authorizations, to help ensure patients don’t have gaps in coverage.

In a Jan. 14 news release addressing the formulary change, ACC notes that a patient’s pharmacy can also request a one-time override when trying to fill a nonpreferred DOAC in January to buy time if switching medications with their clinician or requesting a formulary exception.

During discussions with CVS Caremark, it says the ACC and the American Society of Hematology “underscored the negative impacts of this decision on patients currently taking one of the nonpreferred DOACs and on those who have previously tried rivaroxaban and changed medications.”

The groups also highlighted difficulties with other prior authorization programs in terms of the need for dedicated staff and time away from direct patient care.

“The ACC and ASH will continue discussions with CVS Caremark regarding the burden on clinicians and the effect of the formulary decision on patient access,” the release says.

In its letter to CVS, PACH argues that the apixaban exclusion will disproportionately affect historically disadvantaged patients, leaving those who can least afford the change with limited options. Notably, no generic is available for either apixaban or rivaroxaban.

The group also highlights a 2019 national poll, in which nearly 40% of patients who had their medication switched were so frustrated that they stopped their medication altogether.

PACH has an online petition against nonmedical switching, which at press time had garnered 2,126 signatures.

One signee, Jan Griffin, who survived bilateral pulmonary embolisms, writes that she has been on Eliquis [apixaban] successfully since her hospital discharge. “Now, as of midnight, Caremark apparently knows better than my hematologist as to what blood thinner is better for me and will no longer cover my Eliquis prescription. This is criminal, immoral, and unethical. #StopTheSwitch.”

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

Patients looking to refill a prescription for apixaban (Eliquis) through CVS Caremark may be in for a surprise following its decision to exclude the direct oral anticoagulant (DOAC) from its formulary starting Jan. 1.

The move leaves just one DOAC, rivaroxaban (Xarelto), on CVS’ commercial formulary and is being assailed as the latest example of “nonmedical switching” used by health insurers to control costs.

In a letter to CVS Caremark backed by 14 provider and patient organizations, the nonprofit Partnership to Advance Cardiovascular Health (PACH) calls on the pharmacy chain to reverse its “dangerously disruptive” decision to force stable patients at high risk of cardiovascular events to switch anticoagulation, without an apparent option to be grandfathered into the new plan.

PACH president Dharmesh Patel, MD, Stern Cardiovascular Center, Memphis, called the formulary change “reckless and irresponsible, especially because the decision is not based in science and evidence, but on budgets. Patients and their health care providers, not insurance companies, need to be trusted to determine what medication is best,” he said in a statement.

Craig Beavers, PharmD, vice president of Baptist Health Paducah, Kentucky, said that, as chair of the American College of Cardiology’s Cardiovascular Team Section, he and other organizations have met with CVS Caremark medical leadership to advocate for patients and to understand the company’s perspective.

“The underlying driver is cost,” he told this news organization.

Current guidelines recommend DOACs in general for a variety of indications, including to reduce the risk of stroke and embolism in nonvalvular atrial fibrillation and to prevent deep vein thrombosis, but there are select instances where a particular DOAC might be more appropriate, he observed.

“Apixaban may be better for a patient with a history of GI bleeding because there’s less GI bleeding, but the guidelines don’t necessarily spell those things out,” Dr. Beavers said. “That’s where the clinician should advocate for their patient and, unfortunately, they are making their decision strictly based off the guidelines.”

Requests to speak with medical officers at CVS Caremark went unanswered, but its executive director of communications, Christina Peaslee, told this news organization that the formulary decision “maintains clinically appropriate, cost-effective prescription coverage” for its clients and members.

“Both the American Heart Association/American College of Cardiology/Heart Rhythm Society and 2021 CHEST guidelines recommend DOACs over warfarin for treatment of various cardiology conditions such as atrial fibrillation, but neither list a specific agent as preferred – showing that consensus clinical guidelines do not favor one over the other,” she said in an email. “Further, Xarelto has more FDA-approved indications than Eliquis (e.g., Xarelto is approved for a reduction in risk of major CV events in patients with CAD or PAD) in addition to all the same FDA indications as Eliquis.”

Ms. Peaslee pointed out that all formulary changes are evaluated by an external medical expert specializing in the disease state, followed by review and approval by an independent national Pharmacy & Therapeutics Committee.

The decision to exclude apixaban is also limited to a “subset of commercial drug lists,” she said, although specifics on which plans and the number of affected patients were not forthcoming.

The choice of DOAC is a timely question in cardiology, with recent studies suggesting an advantage for apixaban over rivaroxaban in reducing the risk of recurrent venous thromboembolism, as well as reducing the risk of major ischemic or hemorrhagic events in atrial fibrillation.

Ms. Peaslee said CVS Caremark closely monitors medical literature for relevant clinical trial data and that most clients allow reasonable formulary exceptions when justified. “This formulary exceptions process has been successfully used for changes of this type and allows patients to get a medication that is safe and effective, as determined by their prescriber.”

The company will also continue to provide “robust, personalized outreach to the small number of members who will need to switch to an alternative medication,” she added.

Dr. Beavers said negotiations with CVS are still in the early stages, but, in the meantime, the ACC is providing health care providers with tools, such as drug copay cards and electronic prior authorizations, to help ensure patients don’t have gaps in coverage.

In a Jan. 14 news release addressing the formulary change, ACC notes that a patient’s pharmacy can also request a one-time override when trying to fill a nonpreferred DOAC in January to buy time if switching medications with their clinician or requesting a formulary exception.

During discussions with CVS Caremark, it says the ACC and the American Society of Hematology “underscored the negative impacts of this decision on patients currently taking one of the nonpreferred DOACs and on those who have previously tried rivaroxaban and changed medications.”

The groups also highlighted difficulties with other prior authorization programs in terms of the need for dedicated staff and time away from direct patient care.

“The ACC and ASH will continue discussions with CVS Caremark regarding the burden on clinicians and the effect of the formulary decision on patient access,” the release says.

In its letter to CVS, PACH argues that the apixaban exclusion will disproportionately affect historically disadvantaged patients, leaving those who can least afford the change with limited options. Notably, no generic is available for either apixaban or rivaroxaban.

The group also highlights a 2019 national poll, in which nearly 40% of patients who had their medication switched were so frustrated that they stopped their medication altogether.

PACH has an online petition against nonmedical switching, which at press time had garnered 2,126 signatures.

One signee, Jan Griffin, who survived bilateral pulmonary embolisms, writes that she has been on Eliquis [apixaban] successfully since her hospital discharge. “Now, as of midnight, Caremark apparently knows better than my hematologist as to what blood thinner is better for me and will no longer cover my Eliquis prescription. This is criminal, immoral, and unethical. #StopTheSwitch.”

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

First-year psychiatry resident Jake Goodman, MD, knew he was taking a chance when he opened up on his popular social media platforms about his personal mental health battle. He mulled over the decision for several weeks before deciding to take the plunge.

As he voiced recently on his TikTok page, his biggest social media fanbase, with 1.3 million followers, it felt freeing to get his personal struggle off his chest.

“I’m a doctor in training, and most doctors would advise me not to post this,” the 29-year-old from Miami said in the video last month, which garnered 1.2 million views on TikTok alone. “They would say it’s risky for my career. But I didn’t join the medical field to continue the toxic status quo. I’m part of a new generation of health care professionals that are not afraid to be vulnerable and talk about mental health.”

“Dr. Jake,” as he calls himself on social media, admitted he was a physician who treats mental illness and also takes medication for it. “It felt good to say that. And by the way, I’m proud of it,” he said in the TikTok post.

A champion of mental health throughout the pandemic, Dr. Goodman called attention to the illness in the medical field. In a message on Instagram, he stated, “Opening up about your mental health as a medical professional, especially as a doctor who treats mental illness, can be taboo ... So here’s me leading by example.”

He also cited statistics on the challenge: “1 in 2 people will be diagnosed with a mental health illness at some point in their life. Yet many of us will never take medication that can help correct the chemical imbalance in our brains due to medication stigma: the fear that taking medications for our mental health somehow makes us weak.”

Mental health remains an issue among residents. Nearly 70% of residents polled by Medscape in its 2021 Residents Lifestyle & Happiness Report said they strongly or somewhat agree there’s a stigma against seeking mental health help. And nearly half, or 47% of those polled, said they sometimes (36%) or always/most of the time (11%) were depressed. The latter category rose in the past year.

Dr. Goodman told this news organization that he became passionate about mental health when he lost a college friend to suicide. “It really exposed the stigma” of mental health, he said. “I always knew it was there, but it took me seeing someone lose his life and [asking] why didn’t he feel comfortable talking to us, and why didn’t I feel comfortable talking to him?”
 

Stress of medical training

The decision to pursue psychiatry as his specialty came after a rotation in a clinic for people struggling with substance use disorders. “I was enthralled to see people change their life ... just by mental health care.” It’s why he went into medicine, he tells this news organization. “I always wanted to be in a field to help people [before they hit] rock bottom, when no one else could be there for them.”

Dr. Goodman’s personal battle with mental health didn’t arise until he started residency. “I was not really myself.” He said he felt numb and burned out. “I was not getting as much enjoyment out of things.” A friend pointed out that he might be depressed, so he went to see a therapist and then a psychiatrist and started on medication. “It had a profound impact on how I felt.”

Still, it took a while before Dr. Goodman was comfortable sharing his story with the 1.6 million followers he had already built across his social media platforms.

“I started on social media in 2020 with the goal of advocating for mental health and inspiring future doctors.” He said the message seemed to resonate with people struggling during the early part of the pandemic. On his social media accounts, he also talks about medical school, residency, and being a health care provider. His fiancé is also a resident doctor, in internal medicine.

Dr. Goodman is also trying to create a more realistic image of doctors than the superheroes he believed they were growing up. He wants those who grow up wanting to be doctors and who look up to him to see him as a human being with vulnerabilities, such as mental health.

“You can be a doctor and have mental health issues. Seeking treatment for mental health makes you a better doctor, and for other health care workers suffering in the midst of the pandemic, I want to let them know they are not alone.”

He pointed to the statistic that doctors have one of the highest suicide rates of any professions. “It’s better to talk about that in the early stages of training.”

Students, residents, or attending physicians who have mental health challenges shouldn’t allow their symptoms to go untreated, Dr. Goodman added. “Holding in all the stress and anxiety and feelings in a very traumatic field may be dangerous. Opening up and seeking treatment, that’s the brave thing to do.”

One of his goals is to campaign for the removal of a question on state medical licensing forms requiring doctors to report any mental health diagnosis. It’s why doctors may be afraid to admit that they are struggling. “I’m still here. It didn’t ruin my career.”

Doctors who seek treatment for mental health are theoretically protected under the Americans With Disabilities Act from being refused a license on the basis of that diagnosis. Dr. Goodman hopes to advocate at the state level to reduce discrimination and increase accessibility for doctors to seek mental health care.

Still, Dr. Goodman concedes he was initially fearful of the repercussions. “I opened up about it because this post could save lives. I was doing what I believed in.”

So if he runs into barriers to receive his medical license because of his admission, “that’s a serious problem,” he said. “There is already a shortage of doctors. We’ll see what happens in a few years. I am not the only one who will answer ‘yes’ to having sought treatment for a mental illness. The questions do not really need to be there.”

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

First-year psychiatry resident Jake Goodman, MD, knew he was taking a chance when he opened up on his popular social media platforms about his personal mental health battle. He mulled over the decision for several weeks before deciding to take the plunge.

As he voiced recently on his TikTok page, his biggest social media fanbase, with 1.3 million followers, it felt freeing to get his personal struggle off his chest.

“I’m a doctor in training, and most doctors would advise me not to post this,” the 29-year-old from Miami said in the video last month, which garnered 1.2 million views on TikTok alone. “They would say it’s risky for my career. But I didn’t join the medical field to continue the toxic status quo. I’m part of a new generation of health care professionals that are not afraid to be vulnerable and talk about mental health.”

“Dr. Jake,” as he calls himself on social media, admitted he was a physician who treats mental illness and also takes medication for it. “It felt good to say that. And by the way, I’m proud of it,” he said in the TikTok post.

A champion of mental health throughout the pandemic, Dr. Goodman called attention to the illness in the medical field. In a message on Instagram, he stated, “Opening up about your mental health as a medical professional, especially as a doctor who treats mental illness, can be taboo ... So here’s me leading by example.”

He also cited statistics on the challenge: “1 in 2 people will be diagnosed with a mental health illness at some point in their life. Yet many of us will never take medication that can help correct the chemical imbalance in our brains due to medication stigma: the fear that taking medications for our mental health somehow makes us weak.”

Mental health remains an issue among residents. Nearly 70% of residents polled by Medscape in its 2021 Residents Lifestyle & Happiness Report said they strongly or somewhat agree there’s a stigma against seeking mental health help. And nearly half, or 47% of those polled, said they sometimes (36%) or always/most of the time (11%) were depressed. The latter category rose in the past year.

Dr. Goodman told this news organization that he became passionate about mental health when he lost a college friend to suicide. “It really exposed the stigma” of mental health, he said. “I always knew it was there, but it took me seeing someone lose his life and [asking] why didn’t he feel comfortable talking to us, and why didn’t I feel comfortable talking to him?”
 

Stress of medical training

The decision to pursue psychiatry as his specialty came after a rotation in a clinic for people struggling with substance use disorders. “I was enthralled to see people change their life ... just by mental health care.” It’s why he went into medicine, he tells this news organization. “I always wanted to be in a field to help people [before they hit] rock bottom, when no one else could be there for them.”

Dr. Goodman’s personal battle with mental health didn’t arise until he started residency. “I was not really myself.” He said he felt numb and burned out. “I was not getting as much enjoyment out of things.” A friend pointed out that he might be depressed, so he went to see a therapist and then a psychiatrist and started on medication. “It had a profound impact on how I felt.”

Still, it took a while before Dr. Goodman was comfortable sharing his story with the 1.6 million followers he had already built across his social media platforms.

“I started on social media in 2020 with the goal of advocating for mental health and inspiring future doctors.” He said the message seemed to resonate with people struggling during the early part of the pandemic. On his social media accounts, he also talks about medical school, residency, and being a health care provider. His fiancé is also a resident doctor, in internal medicine.

Dr. Goodman is also trying to create a more realistic image of doctors than the superheroes he believed they were growing up. He wants those who grow up wanting to be doctors and who look up to him to see him as a human being with vulnerabilities, such as mental health.

“You can be a doctor and have mental health issues. Seeking treatment for mental health makes you a better doctor, and for other health care workers suffering in the midst of the pandemic, I want to let them know they are not alone.”

He pointed to the statistic that doctors have one of the highest suicide rates of any professions. “It’s better to talk about that in the early stages of training.”

Students, residents, or attending physicians who have mental health challenges shouldn’t allow their symptoms to go untreated, Dr. Goodman added. “Holding in all the stress and anxiety and feelings in a very traumatic field may be dangerous. Opening up and seeking treatment, that’s the brave thing to do.”

One of his goals is to campaign for the removal of a question on state medical licensing forms requiring doctors to report any mental health diagnosis. It’s why doctors may be afraid to admit that they are struggling. “I’m still here. It didn’t ruin my career.”

Doctors who seek treatment for mental health are theoretically protected under the Americans With Disabilities Act from being refused a license on the basis of that diagnosis. Dr. Goodman hopes to advocate at the state level to reduce discrimination and increase accessibility for doctors to seek mental health care.

Still, Dr. Goodman concedes he was initially fearful of the repercussions. “I opened up about it because this post could save lives. I was doing what I believed in.”

So if he runs into barriers to receive his medical license because of his admission, “that’s a serious problem,” he said. “There is already a shortage of doctors. We’ll see what happens in a few years. I am not the only one who will answer ‘yes’ to having sought treatment for a mental illness. The questions do not really need to be there.”

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

First-year psychiatry resident Jake Goodman, MD, knew he was taking a chance when he opened up on his popular social media platforms about his personal mental health battle. He mulled over the decision for several weeks before deciding to take the plunge.

As he voiced recently on his TikTok page, his biggest social media fanbase, with 1.3 million followers, it felt freeing to get his personal struggle off his chest.

“I’m a doctor in training, and most doctors would advise me not to post this,” the 29-year-old from Miami said in the video last month, which garnered 1.2 million views on TikTok alone. “They would say it’s risky for my career. But I didn’t join the medical field to continue the toxic status quo. I’m part of a new generation of health care professionals that are not afraid to be vulnerable and talk about mental health.”

“Dr. Jake,” as he calls himself on social media, admitted he was a physician who treats mental illness and also takes medication for it. “It felt good to say that. And by the way, I’m proud of it,” he said in the TikTok post.

A champion of mental health throughout the pandemic, Dr. Goodman called attention to the illness in the medical field. In a message on Instagram, he stated, “Opening up about your mental health as a medical professional, especially as a doctor who treats mental illness, can be taboo ... So here’s me leading by example.”

He also cited statistics on the challenge: “1 in 2 people will be diagnosed with a mental health illness at some point in their life. Yet many of us will never take medication that can help correct the chemical imbalance in our brains due to medication stigma: the fear that taking medications for our mental health somehow makes us weak.”

Mental health remains an issue among residents. Nearly 70% of residents polled by Medscape in its 2021 Residents Lifestyle & Happiness Report said they strongly or somewhat agree there’s a stigma against seeking mental health help. And nearly half, or 47% of those polled, said they sometimes (36%) or always/most of the time (11%) were depressed. The latter category rose in the past year.

Dr. Goodman told this news organization that he became passionate about mental health when he lost a college friend to suicide. “It really exposed the stigma” of mental health, he said. “I always knew it was there, but it took me seeing someone lose his life and [asking] why didn’t he feel comfortable talking to us, and why didn’t I feel comfortable talking to him?”
 

Stress of medical training

The decision to pursue psychiatry as his specialty came after a rotation in a clinic for people struggling with substance use disorders. “I was enthralled to see people change their life ... just by mental health care.” It’s why he went into medicine, he tells this news organization. “I always wanted to be in a field to help people [before they hit] rock bottom, when no one else could be there for them.”

Dr. Goodman’s personal battle with mental health didn’t arise until he started residency. “I was not really myself.” He said he felt numb and burned out. “I was not getting as much enjoyment out of things.” A friend pointed out that he might be depressed, so he went to see a therapist and then a psychiatrist and started on medication. “It had a profound impact on how I felt.”

Still, it took a while before Dr. Goodman was comfortable sharing his story with the 1.6 million followers he had already built across his social media platforms.

“I started on social media in 2020 with the goal of advocating for mental health and inspiring future doctors.” He said the message seemed to resonate with people struggling during the early part of the pandemic. On his social media accounts, he also talks about medical school, residency, and being a health care provider. His fiancé is also a resident doctor, in internal medicine.

Dr. Goodman is also trying to create a more realistic image of doctors than the superheroes he believed they were growing up. He wants those who grow up wanting to be doctors and who look up to him to see him as a human being with vulnerabilities, such as mental health.

“You can be a doctor and have mental health issues. Seeking treatment for mental health makes you a better doctor, and for other health care workers suffering in the midst of the pandemic, I want to let them know they are not alone.”

He pointed to the statistic that doctors have one of the highest suicide rates of any professions. “It’s better to talk about that in the early stages of training.”

Students, residents, or attending physicians who have mental health challenges shouldn’t allow their symptoms to go untreated, Dr. Goodman added. “Holding in all the stress and anxiety and feelings in a very traumatic field may be dangerous. Opening up and seeking treatment, that’s the brave thing to do.”

One of his goals is to campaign for the removal of a question on state medical licensing forms requiring doctors to report any mental health diagnosis. It’s why doctors may be afraid to admit that they are struggling. “I’m still here. It didn’t ruin my career.”

Doctors who seek treatment for mental health are theoretically protected under the Americans With Disabilities Act from being refused a license on the basis of that diagnosis. Dr. Goodman hopes to advocate at the state level to reduce discrimination and increase accessibility for doctors to seek mental health care.

Still, Dr. Goodman concedes he was initially fearful of the repercussions. “I opened up about it because this post could save lives. I was doing what I believed in.”

So if he runs into barriers to receive his medical license because of his admission, “that’s a serious problem,” he said. “There is already a shortage of doctors. We’ll see what happens in a few years. I am not the only one who will answer ‘yes’ to having sought treatment for a mental illness. The questions do not really need to be there.”

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

Most children with multisystem inflammatory syndrome related to COVID-19 infection show recovery of cardiac function by 3 months, but longer term follow-up is still needed, suggests a new retrospective longitudinal cohort study.

While 80%-85% of children with multisystem inflammatory syndrome have cardiovascular involvement, “lack of knowledge about the short-term consequences of MIS-C has led to uncertainty among physicians in making recommendations about follow-up,” Daisuke Matsubara, MD, PhD, and colleagues wrote in their paper, which was published in the Journal of the American Heart Association.

Dr. Matsubara, of the department of pediatrics at the Children’s Hospital of Philadelphia, and colleagues examined cardiac outcomes among 60 patients aged 18 years or under admitted to two Philadelphia hospitals with MIS-C between April 2020 and January 2021. They compared those with outcomes in 60 age-matched healthy children who had undergone echocardiography for a range of non–COVID-related conditions such as chest pain or syncope.

The study used echocardiography, MRI, biochemistry, and functional and clinical parameters to assess the degree of change and damage to the heart at 3 months after admission.

When the patients first presented to a hospital, 42 had biochemical signs of myocardial injury, such as elevated brain-type natriuretic peptide and troponin levels. However, most patients’ symptoms were no longer present by the time they were discharged from hospital.

The researchers found that 81% of patients who presented with myocardial injury had lost the left atrial contraction phase. This dropped to 51% during the subacute phase, then 30% at 1 month. By 3-4 months, all patients achieved normal left atrial contraction phase.

At 1 month after admission, all MIS-C patients had significant signs of cardiac strain, compared with controls, including changes to global longitudinal strain, global circumferential strain, circumferential early diastolic strain rate, and right ventricular free wall longitudinal strain.
 

Parameters of strain normalized by 3 months

All parameters of strain had normalized, compared with controls, by 3 months. In the case of global longitudinal strain and left atrial strain, the median time to normalization was 6 days. For left ventricular ejection fraction the median time to normalization was 8 days and for right ventricular free wall longitudinal strain it was 9 days.

A small difference persisted with global longitudinal strain, but the authors said the difference was within the range of normal published values and not clinically relevant. The dysfunction appeared to be spread evenly across the heart rather than varying between segments, they noted.

“Deformation analysis could detect subtle myocardial changes; therefore, our study suggests the absence of persistent subclinical myocardial dysfunction after 3-4 months,” Dr. Matsubara said in an interview.

Four patients experienced small coronary aneurysms during the acute phase of MIS-C, but all had resolved within 2 months and none experienced any further lesions.

Among the 14 patients who underwent cardiac MRI at presentation, 2 had evidence of myocardial edema and fibrosis during the subacute phase of illness, despite having normal left ventricular systolic function and conventional echocardiography.

At follow-up, only one patient had residual edema; this individual had no evidence of fibrosis and had normal systolic function.
 

Study provides reassurance, but longer follow-up needed

Commenting on the study, pediatric cardiologist Devyani Chowdhury, MD, director of Cardiology Care for Children in Lancaster, Pa., said that overall it provided reassurance that most children do recover from MIS-C – and fits with her own clinical experience of the condition – but cautioned that longer-term follow-up was still needed.

“Three months is really not long term for a child,” Dr. Chowdhury said in an interview. “I’ve had a couple of patients whose MRIs have not normalized even after 1 year.”

Dr. Chowdhury also noted that it was a relatively small sample size, and it was also not yet possible to work out what host factors might play a role in increasing the risk of longer-term effects of MIS-C.

“I think it is a disease in evolution and we have to give it time, but in the very short term at least these kids are not dying, they are recovering, going home, and returning to activity and the heart is getting better,” she said.

The study authors suggested their findings could provide an evidence base for recommendations on when children with MIS-C can return to sports and physical activity, given that current consensus statements on the issue treat MIS-C as being equivalent to myocarditis in adults.

Dr. Matsubara noted that the cardiac outcomes of MIS-C were very different from those in COVID-19–affected adults, where echocardiography and MRI show longer-term evidence of myocardial impairments.

“This finding is also different from that of adult COVID-19, where the high troponin is reported to be the prognostic factor,” he said, suggesting this could explain different mechanisms of myocardial injury between MIS-C and COVID-19 myocarditis.

One author was supported by the National Institutes of Health. No conflicts of interest were declared.

Most children with multisystem inflammatory syndrome related to COVID-19 infection show recovery of cardiac function by 3 months, but longer term follow-up is still needed, suggests a new retrospective longitudinal cohort study.

While 80%-85% of children with multisystem inflammatory syndrome have cardiovascular involvement, “lack of knowledge about the short-term consequences of MIS-C has led to uncertainty among physicians in making recommendations about follow-up,” Daisuke Matsubara, MD, PhD, and colleagues wrote in their paper, which was published in the Journal of the American Heart Association.

Dr. Matsubara, of the department of pediatrics at the Children’s Hospital of Philadelphia, and colleagues examined cardiac outcomes among 60 patients aged 18 years or under admitted to two Philadelphia hospitals with MIS-C between April 2020 and January 2021. They compared those with outcomes in 60 age-matched healthy children who had undergone echocardiography for a range of non–COVID-related conditions such as chest pain or syncope.

The study used echocardiography, MRI, biochemistry, and functional and clinical parameters to assess the degree of change and damage to the heart at 3 months after admission.

When the patients first presented to a hospital, 42 had biochemical signs of myocardial injury, such as elevated brain-type natriuretic peptide and troponin levels. However, most patients’ symptoms were no longer present by the time they were discharged from hospital.

The researchers found that 81% of patients who presented with myocardial injury had lost the left atrial contraction phase. This dropped to 51% during the subacute phase, then 30% at 1 month. By 3-4 months, all patients achieved normal left atrial contraction phase.

At 1 month after admission, all MIS-C patients had significant signs of cardiac strain, compared with controls, including changes to global longitudinal strain, global circumferential strain, circumferential early diastolic strain rate, and right ventricular free wall longitudinal strain.
 

Parameters of strain normalized by 3 months

All parameters of strain had normalized, compared with controls, by 3 months. In the case of global longitudinal strain and left atrial strain, the median time to normalization was 6 days. For left ventricular ejection fraction the median time to normalization was 8 days and for right ventricular free wall longitudinal strain it was 9 days.

A small difference persisted with global longitudinal strain, but the authors said the difference was within the range of normal published values and not clinically relevant. The dysfunction appeared to be spread evenly across the heart rather than varying between segments, they noted.

“Deformation analysis could detect subtle myocardial changes; therefore, our study suggests the absence of persistent subclinical myocardial dysfunction after 3-4 months,” Dr. Matsubara said in an interview.

Four patients experienced small coronary aneurysms during the acute phase of MIS-C, but all had resolved within 2 months and none experienced any further lesions.

Among the 14 patients who underwent cardiac MRI at presentation, 2 had evidence of myocardial edema and fibrosis during the subacute phase of illness, despite having normal left ventricular systolic function and conventional echocardiography.

At follow-up, only one patient had residual edema; this individual had no evidence of fibrosis and had normal systolic function.
 

Study provides reassurance, but longer follow-up needed

Commenting on the study, pediatric cardiologist Devyani Chowdhury, MD, director of Cardiology Care for Children in Lancaster, Pa., said that overall it provided reassurance that most children do recover from MIS-C – and fits with her own clinical experience of the condition – but cautioned that longer-term follow-up was still needed.

“Three months is really not long term for a child,” Dr. Chowdhury said in an interview. “I’ve had a couple of patients whose MRIs have not normalized even after 1 year.”

Dr. Chowdhury also noted that it was a relatively small sample size, and it was also not yet possible to work out what host factors might play a role in increasing the risk of longer-term effects of MIS-C.

“I think it is a disease in evolution and we have to give it time, but in the very short term at least these kids are not dying, they are recovering, going home, and returning to activity and the heart is getting better,” she said.

The study authors suggested their findings could provide an evidence base for recommendations on when children with MIS-C can return to sports and physical activity, given that current consensus statements on the issue treat MIS-C as being equivalent to myocarditis in adults.

Dr. Matsubara noted that the cardiac outcomes of MIS-C were very different from those in COVID-19–affected adults, where echocardiography and MRI show longer-term evidence of myocardial impairments.

“This finding is also different from that of adult COVID-19, where the high troponin is reported to be the prognostic factor,” he said, suggesting this could explain different mechanisms of myocardial injury between MIS-C and COVID-19 myocarditis.

One author was supported by the National Institutes of Health. No conflicts of interest were declared.

Most children with multisystem inflammatory syndrome related to COVID-19 infection show recovery of cardiac function by 3 months, but longer term follow-up is still needed, suggests a new retrospective longitudinal cohort study.

While 80%-85% of children with multisystem inflammatory syndrome have cardiovascular involvement, “lack of knowledge about the short-term consequences of MIS-C has led to uncertainty among physicians in making recommendations about follow-up,” Daisuke Matsubara, MD, PhD, and colleagues wrote in their paper, which was published in the Journal of the American Heart Association.

Dr. Matsubara, of the department of pediatrics at the Children’s Hospital of Philadelphia, and colleagues examined cardiac outcomes among 60 patients aged 18 years or under admitted to two Philadelphia hospitals with MIS-C between April 2020 and January 2021. They compared those with outcomes in 60 age-matched healthy children who had undergone echocardiography for a range of non–COVID-related conditions such as chest pain or syncope.

The study used echocardiography, MRI, biochemistry, and functional and clinical parameters to assess the degree of change and damage to the heart at 3 months after admission.

When the patients first presented to a hospital, 42 had biochemical signs of myocardial injury, such as elevated brain-type natriuretic peptide and troponin levels. However, most patients’ symptoms were no longer present by the time they were discharged from hospital.

The researchers found that 81% of patients who presented with myocardial injury had lost the left atrial contraction phase. This dropped to 51% during the subacute phase, then 30% at 1 month. By 3-4 months, all patients achieved normal left atrial contraction phase.

At 1 month after admission, all MIS-C patients had significant signs of cardiac strain, compared with controls, including changes to global longitudinal strain, global circumferential strain, circumferential early diastolic strain rate, and right ventricular free wall longitudinal strain.
 

Parameters of strain normalized by 3 months

All parameters of strain had normalized, compared with controls, by 3 months. In the case of global longitudinal strain and left atrial strain, the median time to normalization was 6 days. For left ventricular ejection fraction the median time to normalization was 8 days and for right ventricular free wall longitudinal strain it was 9 days.

A small difference persisted with global longitudinal strain, but the authors said the difference was within the range of normal published values and not clinically relevant. The dysfunction appeared to be spread evenly across the heart rather than varying between segments, they noted.

“Deformation analysis could detect subtle myocardial changes; therefore, our study suggests the absence of persistent subclinical myocardial dysfunction after 3-4 months,” Dr. Matsubara said in an interview.

Four patients experienced small coronary aneurysms during the acute phase of MIS-C, but all had resolved within 2 months and none experienced any further lesions.

Among the 14 patients who underwent cardiac MRI at presentation, 2 had evidence of myocardial edema and fibrosis during the subacute phase of illness, despite having normal left ventricular systolic function and conventional echocardiography.

At follow-up, only one patient had residual edema; this individual had no evidence of fibrosis and had normal systolic function.
 

Study provides reassurance, but longer follow-up needed

Commenting on the study, pediatric cardiologist Devyani Chowdhury, MD, director of Cardiology Care for Children in Lancaster, Pa., said that overall it provided reassurance that most children do recover from MIS-C – and fits with her own clinical experience of the condition – but cautioned that longer-term follow-up was still needed.

“Three months is really not long term for a child,” Dr. Chowdhury said in an interview. “I’ve had a couple of patients whose MRIs have not normalized even after 1 year.”

Dr. Chowdhury also noted that it was a relatively small sample size, and it was also not yet possible to work out what host factors might play a role in increasing the risk of longer-term effects of MIS-C.

“I think it is a disease in evolution and we have to give it time, but in the very short term at least these kids are not dying, they are recovering, going home, and returning to activity and the heart is getting better,” she said.

The study authors suggested their findings could provide an evidence base for recommendations on when children with MIS-C can return to sports and physical activity, given that current consensus statements on the issue treat MIS-C as being equivalent to myocarditis in adults.

Dr. Matsubara noted that the cardiac outcomes of MIS-C were very different from those in COVID-19–affected adults, where echocardiography and MRI show longer-term evidence of myocardial impairments.

“This finding is also different from that of adult COVID-19, where the high troponin is reported to be the prognostic factor,” he said, suggesting this could explain different mechanisms of myocardial injury between MIS-C and COVID-19 myocarditis.

One author was supported by the National Institutes of Health. No conflicts of interest were declared.