The Food and Drug Administration has approved pembrolizumab (Keytruda) monotherapy for locally advanced cutaneous squamous cell carcinoma (cSCC) that can’t be cured by surgery or radiation.

The July 6 approval for the programmed death–1 inhibitor follows a June FDA approval for pembrolizumab monotherapy in patients with recurrent or metastatic cSCC disease not curable by surgery or radiation. Both approvals, pembrolizumab’s first for cSCC, are based on findings from the second interim analysis of the phase 2, multicenter, open-label KEYNOTE-629 trial.

The objective response rate in the cohort of 54 patients with locally advanced disease was 50%, including a complete response rate of 17% and a partial response rate of 33%. Duration of response was 6 months or longer in 81% of the 27 responders, and 12 months or longer in 37% of responders. After a median follow-up of 13.4 months, median duration of response had not yet been reached.

Pembrolizumab has previously received FDA approvals, either as monotherapy or in combination with other agents, for the treatment of numerous cancer types, including certain melanomas, non–small cell lung cancers, head and neck SCCs, classical Hodgkin lymphomas, primary mediastinal large B-cell lymphomas, urothelial carcinomas, microsatellite instability–high or mismatch repair–deficient cancers, and gastric, esophageal, cervical, hepatocellular, Merkel cell, renal cell, tumor mutational burden–high, and triple-negative breast cancers.

Patients in the KEYNOTE-629 trial received pembrolizumab at a dose of 200 mg IV every 3 weeks for 24 months or until documented disease progression or unacceptable toxicity.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC in KEYNOTE-629 were similar to those observed in patients with melanoma or non–small cell lung cancer who were treated with pembrolizumab monotherapy in previous trials.

The checkpoint inhibitor can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation,” Merck explained in a press release, noting that “early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda.”

Depending on the severity of any reaction, treatment should be withheld or permanently discontinued, and corticosteroids administered if appropriate, Merck stated.

[email protected]

The Food and Drug Administration has approved pembrolizumab (Keytruda) monotherapy for locally advanced cutaneous squamous cell carcinoma (cSCC) that can’t be cured by surgery or radiation.

The July 6 approval for the programmed death–1 inhibitor follows a June FDA approval for pembrolizumab monotherapy in patients with recurrent or metastatic cSCC disease not curable by surgery or radiation. Both approvals, pembrolizumab’s first for cSCC, are based on findings from the second interim analysis of the phase 2, multicenter, open-label KEYNOTE-629 trial.

The objective response rate in the cohort of 54 patients with locally advanced disease was 50%, including a complete response rate of 17% and a partial response rate of 33%. Duration of response was 6 months or longer in 81% of the 27 responders, and 12 months or longer in 37% of responders. After a median follow-up of 13.4 months, median duration of response had not yet been reached.

Pembrolizumab has previously received FDA approvals, either as monotherapy or in combination with other agents, for the treatment of numerous cancer types, including certain melanomas, non–small cell lung cancers, head and neck SCCs, classical Hodgkin lymphomas, primary mediastinal large B-cell lymphomas, urothelial carcinomas, microsatellite instability–high or mismatch repair–deficient cancers, and gastric, esophageal, cervical, hepatocellular, Merkel cell, renal cell, tumor mutational burden–high, and triple-negative breast cancers.

Patients in the KEYNOTE-629 trial received pembrolizumab at a dose of 200 mg IV every 3 weeks for 24 months or until documented disease progression or unacceptable toxicity.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC in KEYNOTE-629 were similar to those observed in patients with melanoma or non–small cell lung cancer who were treated with pembrolizumab monotherapy in previous trials.

The checkpoint inhibitor can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation,” Merck explained in a press release, noting that “early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda.”

Depending on the severity of any reaction, treatment should be withheld or permanently discontinued, and corticosteroids administered if appropriate, Merck stated.

[email protected]

The Food and Drug Administration has approved pembrolizumab (Keytruda) monotherapy for locally advanced cutaneous squamous cell carcinoma (cSCC) that can’t be cured by surgery or radiation.

The July 6 approval for the programmed death–1 inhibitor follows a June FDA approval for pembrolizumab monotherapy in patients with recurrent or metastatic cSCC disease not curable by surgery or radiation. Both approvals, pembrolizumab’s first for cSCC, are based on findings from the second interim analysis of the phase 2, multicenter, open-label KEYNOTE-629 trial.

The objective response rate in the cohort of 54 patients with locally advanced disease was 50%, including a complete response rate of 17% and a partial response rate of 33%. Duration of response was 6 months or longer in 81% of the 27 responders, and 12 months or longer in 37% of responders. After a median follow-up of 13.4 months, median duration of response had not yet been reached.

Pembrolizumab has previously received FDA approvals, either as monotherapy or in combination with other agents, for the treatment of numerous cancer types, including certain melanomas, non–small cell lung cancers, head and neck SCCs, classical Hodgkin lymphomas, primary mediastinal large B-cell lymphomas, urothelial carcinomas, microsatellite instability–high or mismatch repair–deficient cancers, and gastric, esophageal, cervical, hepatocellular, Merkel cell, renal cell, tumor mutational burden–high, and triple-negative breast cancers.

Patients in the KEYNOTE-629 trial received pembrolizumab at a dose of 200 mg IV every 3 weeks for 24 months or until documented disease progression or unacceptable toxicity.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC in KEYNOTE-629 were similar to those observed in patients with melanoma or non–small cell lung cancer who were treated with pembrolizumab monotherapy in previous trials.

The checkpoint inhibitor can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation,” Merck explained in a press release, noting that “early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda.”

Depending on the severity of any reaction, treatment should be withheld or permanently discontinued, and corticosteroids administered if appropriate, Merck stated.

[email protected]

With only a quarter of all children aged 12-15 years fully vaccinated against COVID-19, first vaccinations continued to drop and new cases for all children rose for the second consecutive week.

Just under 25% of children aged 12-15 had completed the vaccine regimen as of July 12, and just over one-third (33.5%) had received at least one dose. Meanwhile, that age group represented 11.5% of people who initiated vaccination during the 2 weeks ending July 12, down from 12.1% a week earlier, the Centers for Disease Control and Prevention said. The total number of new vaccinations for the week ending July 12 was just over 201,000, compared with 307,000 for the previous week.

New cases of COVID-19, however, were on the rise in children. The 19,000 new cases reported for the week ending July 8 were up from 12,000 a week earlier and 8,000 the week before that, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

That report also shows that children made up 22.3% of all new cases during the week of July 2-8, compared with 16.8% the previous week, and that there were nine deaths in children that same week, the most since March. COVID-related deaths among children total 344 in the 46 jurisdictions (43 states, New York City, Puerto Rico, and Guam) that are reporting such data by age. “It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states,” the two groups noted.

Such data are available from the CDC’s COVID Data Tracker, however, and they show that children aged 16-17 years, who became eligible for COVID vaccination before the younger age group, are further ahead in the process. Among the older children, almost 46% had gotten at least one dose and 37% were fully vaccinated by July 12.

[email protected]

With only a quarter of all children aged 12-15 years fully vaccinated against COVID-19, first vaccinations continued to drop and new cases for all children rose for the second consecutive week.

Just under 25% of children aged 12-15 had completed the vaccine regimen as of July 12, and just over one-third (33.5%) had received at least one dose. Meanwhile, that age group represented 11.5% of people who initiated vaccination during the 2 weeks ending July 12, down from 12.1% a week earlier, the Centers for Disease Control and Prevention said. The total number of new vaccinations for the week ending July 12 was just over 201,000, compared with 307,000 for the previous week.

New cases of COVID-19, however, were on the rise in children. The 19,000 new cases reported for the week ending July 8 were up from 12,000 a week earlier and 8,000 the week before that, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

That report also shows that children made up 22.3% of all new cases during the week of July 2-8, compared with 16.8% the previous week, and that there were nine deaths in children that same week, the most since March. COVID-related deaths among children total 344 in the 46 jurisdictions (43 states, New York City, Puerto Rico, and Guam) that are reporting such data by age. “It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states,” the two groups noted.

Such data are available from the CDC’s COVID Data Tracker, however, and they show that children aged 16-17 years, who became eligible for COVID vaccination before the younger age group, are further ahead in the process. Among the older children, almost 46% had gotten at least one dose and 37% were fully vaccinated by July 12.

[email protected]

With only a quarter of all children aged 12-15 years fully vaccinated against COVID-19, first vaccinations continued to drop and new cases for all children rose for the second consecutive week.

Just under 25% of children aged 12-15 had completed the vaccine regimen as of July 12, and just over one-third (33.5%) had received at least one dose. Meanwhile, that age group represented 11.5% of people who initiated vaccination during the 2 weeks ending July 12, down from 12.1% a week earlier, the Centers for Disease Control and Prevention said. The total number of new vaccinations for the week ending July 12 was just over 201,000, compared with 307,000 for the previous week.

New cases of COVID-19, however, were on the rise in children. The 19,000 new cases reported for the week ending July 8 were up from 12,000 a week earlier and 8,000 the week before that, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

That report also shows that children made up 22.3% of all new cases during the week of July 2-8, compared with 16.8% the previous week, and that there were nine deaths in children that same week, the most since March. COVID-related deaths among children total 344 in the 46 jurisdictions (43 states, New York City, Puerto Rico, and Guam) that are reporting such data by age. “It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states,” the two groups noted.

Such data are available from the CDC’s COVID Data Tracker, however, and they show that children aged 16-17 years, who became eligible for COVID vaccination before the younger age group, are further ahead in the process. Among the older children, almost 46% had gotten at least one dose and 37% were fully vaccinated by July 12.

[email protected]

People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.

The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.

The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.

“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.

“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”

Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.

Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.

Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.

All participants had low neutralizing titers against the alpha (B.1.1.7) variant.

The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”

A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.

‘Some protection is better than none’

These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.

It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.

“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.

“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.

“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
 

Temporarily stopping methotrexate

It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.

Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.

“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”

Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.

However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.

This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.

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

People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.

The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.

The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.

“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.

“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”

Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.

Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.

Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.

All participants had low neutralizing titers against the alpha (B.1.1.7) variant.

The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”

A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.

‘Some protection is better than none’

These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.

It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.

“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.

“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.

“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
 

Temporarily stopping methotrexate

It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.

Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.

“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”

Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.

However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.

This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.

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

People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.

The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.

The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.

“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.

“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”

Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.

Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.

Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.

All participants had low neutralizing titers against the alpha (B.1.1.7) variant.

The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”

A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.

‘Some protection is better than none’

These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.

It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.

“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.

“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.

“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
 

Temporarily stopping methotrexate

It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.

Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.

“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”

Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.

However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.

This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.

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

Asthma is a complex, heterogeneous disease with unmet treatment needs. Patients with severe asthma generally continue to have severe disease despite being on controller therapies. 

Uncontrolled asthma can result in unnecessary suffering and interfere with daily activities. It also increases the risk for exacerbations and places substantial burden on the healthcare system.

In this ReCAP, Drs Sandhya Khurana and Steve N. Georas, from the Mary H. Parkes Center for Asthma, Allergy, and Pulmonary Care in Rochester, New York, discuss current challenges in the management of severe asthma, and how advances in the understanding of phenotypes and therapeutic options guide their approaches to asthma management. 

They review key indicators of severe asthma, tools to assess asthma control, approaches to phenotyping patients, treatment options for type 2 and non–type 2 asthma, and emerging agents.
 

--

Sandhya Khurana, MD is a Professor, Department of Medicine, University of Rochester, Director, Mary H. Parkes Center for Asthma, Allergy, and Pulmonary Care, Rochester, New York.
Sandhya Khurana, MD, has disclosed the following relevant financial relationships: Received research grant from: GlaxoSmithKline.

Steve N. Georas, MD is a Professor, Department of Medicine, University of Rochester; Walter & Carmina Mary Parkes Family Endowed Professor; Director, Pulmonary Function Labs, Mary H. Parkes Center for Asthma, Allergy, and Pulmonary Care, Rochester, New York.
Steve N. Georas, MD, has disclosed no relevant financial relationships.

Asthma is a complex, heterogeneous disease with unmet treatment needs. Patients with severe asthma generally continue to have severe disease despite being on controller therapies. 

Uncontrolled asthma can result in unnecessary suffering and interfere with daily activities. It also increases the risk for exacerbations and places substantial burden on the healthcare system.

In this ReCAP, Drs Sandhya Khurana and Steve N. Georas, from the Mary H. Parkes Center for Asthma, Allergy, and Pulmonary Care in Rochester, New York, discuss current challenges in the management of severe asthma, and how advances in the understanding of phenotypes and therapeutic options guide their approaches to asthma management. 

They review key indicators of severe asthma, tools to assess asthma control, approaches to phenotyping patients, treatment options for type 2 and non–type 2 asthma, and emerging agents.
 

--

Sandhya Khurana, MD is a Professor, Department of Medicine, University of Rochester, Director, Mary H. Parkes Center for Asthma, Allergy, and Pulmonary Care, Rochester, New York.
Sandhya Khurana, MD, has disclosed the following relevant financial relationships: Received research grant from: GlaxoSmithKline.

Steve N. Georas, MD is a Professor, Department of Medicine, University of Rochester; Walter & Carmina Mary Parkes Family Endowed Professor; Director, Pulmonary Function Labs, Mary H. Parkes Center for Asthma, Allergy, and Pulmonary Care, Rochester, New York.
Steve N. Georas, MD, has disclosed no relevant financial relationships.

Asthma is a complex, heterogeneous disease with unmet treatment needs. Patients with severe asthma generally continue to have severe disease despite being on controller therapies. 

Uncontrolled asthma can result in unnecessary suffering and interfere with daily activities. It also increases the risk for exacerbations and places substantial burden on the healthcare system.

In this ReCAP, Drs Sandhya Khurana and Steve N. Georas, from the Mary H. Parkes Center for Asthma, Allergy, and Pulmonary Care in Rochester, New York, discuss current challenges in the management of severe asthma, and how advances in the understanding of phenotypes and therapeutic options guide their approaches to asthma management. 

They review key indicators of severe asthma, tools to assess asthma control, approaches to phenotyping patients, treatment options for type 2 and non–type 2 asthma, and emerging agents.
 

--

Sandhya Khurana, MD is a Professor, Department of Medicine, University of Rochester, Director, Mary H. Parkes Center for Asthma, Allergy, and Pulmonary Care, Rochester, New York.
Sandhya Khurana, MD, has disclosed the following relevant financial relationships: Received research grant from: GlaxoSmithKline.

Steve N. Georas, MD is a Professor, Department of Medicine, University of Rochester; Walter & Carmina Mary Parkes Family Endowed Professor; Director, Pulmonary Function Labs, Mary H. Parkes Center for Asthma, Allergy, and Pulmonary Care, Rochester, New York.
Steve N. Georas, MD, has disclosed no relevant financial relationships.

Salary disparities persist in academic internal medicine specialties and are most obvious in procedural specialties, such as cardiology, in which there are fewer women, research suggests.

“Substantial salary inequities persist at the highest faculty levels and specifically in procedural-based specialties,” Teresa Wang, MD, and colleagues reported in a research letter published online July 12, 2021, in JAMA Internal Medicine.

To examine the demographics and salaries of academic internal medicine physician specialists, Dr. Wang, who is with the division of cardiovascular medicine at the University of Pennsylvania, Philadelphia, and coauthors analyzed survey results from faculty at 154 U.S. medical schools.

They used data from the Association of American Medical Colleges Faculty Salary Report of 2018-2019 to assess the median annual salary, faculty rank, and gender for 21,905 faculty in 13 internal medicine specialties.

Overall, women made up less than 40% of full-time faculty across ranks. Female representation was approximately equal at the instructor and assistant ranks – 47% and 46%, respectively – but decreased to 24% at the professor level.

The authors found that women made up the majority in three specialties – general internal medicine, endocrinology, and geriatrics. In contrast, women were least represented in the procedural specialties of pulmonology, critical/intensive care, gastroenterology, and cardiology.

The greatest imbalance was in cardiology, in which only 21% were women, the researchers noted.

Across faculty ranks, the median annual salary was less for women than for men. The median salary for women was within $25,000 of that for men at all ranks except chief and was at least 90% of that for men in 10 of 13 internal medicine specialties.

Cardiology, gastroenterology, and critical/intensive care were the three specialties in which women’s median salary did not reach 90% of men’s. These specialties tended to be better paid overall, “but also demonstrated the largest gender disparities in both representation and salary, particularly within the higher ranks of cardiology and gastroenterology,” the researchers said.

The reasons for gender disparities are unclear, though internal medicine procedural specialties “have long been male dominated in composition and leadership,” the authors noted. The findings indicate that workforce gender parity may be associated with salary equity.

“Despite the growing awareness of workforce disparities in medicine, our findings suggest that women internal medicine specialists remain underpaid and are not promoted to senior level academic ranks when compared with career trajectories of their male counterparts,” study author Nosheen Reza, MD, of the division of cardiovascular medicine at the University of Pennsylvania, told this news organization.

The researchers noted that they were unable to adjust at the individual level for various factors that may influence salary, such as professional service, academic productivity, clinical volume, and supplementary funding sources, and that the results might not apply to all U.S. medical schools, in which departmental structures vary.

Procedures versus evaluation and management

Still, the research “provides an interesting snapshot of current salary disparities in academic internal medicine,” comment Rita F. Redberg, MD, and colleagues in a related editorial. Dr. Redberg, the editor of JAMA Internal Medicine, is affiliated with the department of medicine at the University of California, San Francisco.

Internal medicine has 13 specialties and dozens of subspecialties, and “procedural subspecialties are more male dominated and better paid than nonprocedural subspecialties – both topics deserving of further exploration,” the editorialists wrote.

The field needs to address various issues that drive some women to “shun male-dominated procedural-based fields – including lack of role models, macho ‘cowboy’ culture, unpredictable schedules, longer training periods, or cultural factors,” Dr. Redberg and coauthors suggested. “Concurrently, the medical profession overall, as well as specialties, should thoughtfully and frequently reassess how to distribute pay more equitably and to remove the premium currently paid for procedures over evaluation and management services.”

“Unfortunately, it is not a surprise that there continues to be a gender gap for salary in academic medicine,” Dr. Redberg said in an interview. “It was interesting to see that gender pay disparities were greatest in the procedure-intensive specialties, and we do know that procedures are much more highly reimbursed than evaluation and management time, even in the IM specialties. From a patient perspective, I think what they value most highly is having their doctor talk with them and explain treatment options and risks and benefits. Sadly, our fee-for-service–based reimbursement system values procedures more highly than talking with patients. And part of the gender gap in salary is attributed to less women being proceduralists.”

The Medicare Payment Advisory Commission “has made some excellent recommendations to Congress on helping to correct this imbalance,” Dr. Redberg added.

In a separate viewpoint article, Leah M. Marcotte, MD, of the department of medicine at the University of Washington, Seattle, and colleagues describe reasons why women physicians may have “slower promotional time lines,” compared with men, such as receiving fewer and smaller grants, being underrepresented as speakers at national conferences, and receiving fewer invitations to author editorials.

“To narrow this gap, institutions should proactively nominate women, with a greater focus on those underrepresented in medicine, for internal and external awards and speaking opportunities,” Dr. Marcotte and coauthors wrote. “Institutions should adopt policies to cover child care, breastfeeding/pumping accommodations, and dependent travel. Academic departments should continue to offer virtual speaking opportunities even after COVID-19 pandemic travel restrictions become unnecessary.”

Institutions can also assist women faculty in preparing promotion dossiers.

“Gender disparities in promotion in academic medicine have been described for decades, and yet progress to close the gap has been untenably slow,” they said. “Rather than expecting faculty to adapt to existing systems, we need to change the promotion process to work better for all.”

The authors disclosed no relevant financial relationships. Dr. Redberg has received grants from Arnold Ventures, the Greenwall Foundation, and the National Heart, Lung, and Blood Institute outside the submitted work. One viewpoint coauthor has received honoraria from the American Board of Internal Medicine, and another has received personal fees from F-Prime Capital, both outside the submitted work.

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

Salary disparities persist in academic internal medicine specialties and are most obvious in procedural specialties, such as cardiology, in which there are fewer women, research suggests.

“Substantial salary inequities persist at the highest faculty levels and specifically in procedural-based specialties,” Teresa Wang, MD, and colleagues reported in a research letter published online July 12, 2021, in JAMA Internal Medicine.

To examine the demographics and salaries of academic internal medicine physician specialists, Dr. Wang, who is with the division of cardiovascular medicine at the University of Pennsylvania, Philadelphia, and coauthors analyzed survey results from faculty at 154 U.S. medical schools.

They used data from the Association of American Medical Colleges Faculty Salary Report of 2018-2019 to assess the median annual salary, faculty rank, and gender for 21,905 faculty in 13 internal medicine specialties.

Overall, women made up less than 40% of full-time faculty across ranks. Female representation was approximately equal at the instructor and assistant ranks – 47% and 46%, respectively – but decreased to 24% at the professor level.

The authors found that women made up the majority in three specialties – general internal medicine, endocrinology, and geriatrics. In contrast, women were least represented in the procedural specialties of pulmonology, critical/intensive care, gastroenterology, and cardiology.

The greatest imbalance was in cardiology, in which only 21% were women, the researchers noted.

Across faculty ranks, the median annual salary was less for women than for men. The median salary for women was within $25,000 of that for men at all ranks except chief and was at least 90% of that for men in 10 of 13 internal medicine specialties.

Cardiology, gastroenterology, and critical/intensive care were the three specialties in which women’s median salary did not reach 90% of men’s. These specialties tended to be better paid overall, “but also demonstrated the largest gender disparities in both representation and salary, particularly within the higher ranks of cardiology and gastroenterology,” the researchers said.

The reasons for gender disparities are unclear, though internal medicine procedural specialties “have long been male dominated in composition and leadership,” the authors noted. The findings indicate that workforce gender parity may be associated with salary equity.

“Despite the growing awareness of workforce disparities in medicine, our findings suggest that women internal medicine specialists remain underpaid and are not promoted to senior level academic ranks when compared with career trajectories of their male counterparts,” study author Nosheen Reza, MD, of the division of cardiovascular medicine at the University of Pennsylvania, told this news organization.

The researchers noted that they were unable to adjust at the individual level for various factors that may influence salary, such as professional service, academic productivity, clinical volume, and supplementary funding sources, and that the results might not apply to all U.S. medical schools, in which departmental structures vary.

Procedures versus evaluation and management

Still, the research “provides an interesting snapshot of current salary disparities in academic internal medicine,” comment Rita F. Redberg, MD, and colleagues in a related editorial. Dr. Redberg, the editor of JAMA Internal Medicine, is affiliated with the department of medicine at the University of California, San Francisco.

Internal medicine has 13 specialties and dozens of subspecialties, and “procedural subspecialties are more male dominated and better paid than nonprocedural subspecialties – both topics deserving of further exploration,” the editorialists wrote.

The field needs to address various issues that drive some women to “shun male-dominated procedural-based fields – including lack of role models, macho ‘cowboy’ culture, unpredictable schedules, longer training periods, or cultural factors,” Dr. Redberg and coauthors suggested. “Concurrently, the medical profession overall, as well as specialties, should thoughtfully and frequently reassess how to distribute pay more equitably and to remove the premium currently paid for procedures over evaluation and management services.”

“Unfortunately, it is not a surprise that there continues to be a gender gap for salary in academic medicine,” Dr. Redberg said in an interview. “It was interesting to see that gender pay disparities were greatest in the procedure-intensive specialties, and we do know that procedures are much more highly reimbursed than evaluation and management time, even in the IM specialties. From a patient perspective, I think what they value most highly is having their doctor talk with them and explain treatment options and risks and benefits. Sadly, our fee-for-service–based reimbursement system values procedures more highly than talking with patients. And part of the gender gap in salary is attributed to less women being proceduralists.”

The Medicare Payment Advisory Commission “has made some excellent recommendations to Congress on helping to correct this imbalance,” Dr. Redberg added.

In a separate viewpoint article, Leah M. Marcotte, MD, of the department of medicine at the University of Washington, Seattle, and colleagues describe reasons why women physicians may have “slower promotional time lines,” compared with men, such as receiving fewer and smaller grants, being underrepresented as speakers at national conferences, and receiving fewer invitations to author editorials.

“To narrow this gap, institutions should proactively nominate women, with a greater focus on those underrepresented in medicine, for internal and external awards and speaking opportunities,” Dr. Marcotte and coauthors wrote. “Institutions should adopt policies to cover child care, breastfeeding/pumping accommodations, and dependent travel. Academic departments should continue to offer virtual speaking opportunities even after COVID-19 pandemic travel restrictions become unnecessary.”

Institutions can also assist women faculty in preparing promotion dossiers.

“Gender disparities in promotion in academic medicine have been described for decades, and yet progress to close the gap has been untenably slow,” they said. “Rather than expecting faculty to adapt to existing systems, we need to change the promotion process to work better for all.”

The authors disclosed no relevant financial relationships. Dr. Redberg has received grants from Arnold Ventures, the Greenwall Foundation, and the National Heart, Lung, and Blood Institute outside the submitted work. One viewpoint coauthor has received honoraria from the American Board of Internal Medicine, and another has received personal fees from F-Prime Capital, both outside the submitted work.

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

Salary disparities persist in academic internal medicine specialties and are most obvious in procedural specialties, such as cardiology, in which there are fewer women, research suggests.

“Substantial salary inequities persist at the highest faculty levels and specifically in procedural-based specialties,” Teresa Wang, MD, and colleagues reported in a research letter published online July 12, 2021, in JAMA Internal Medicine.

To examine the demographics and salaries of academic internal medicine physician specialists, Dr. Wang, who is with the division of cardiovascular medicine at the University of Pennsylvania, Philadelphia, and coauthors analyzed survey results from faculty at 154 U.S. medical schools.

They used data from the Association of American Medical Colleges Faculty Salary Report of 2018-2019 to assess the median annual salary, faculty rank, and gender for 21,905 faculty in 13 internal medicine specialties.

Overall, women made up less than 40% of full-time faculty across ranks. Female representation was approximately equal at the instructor and assistant ranks – 47% and 46%, respectively – but decreased to 24% at the professor level.

The authors found that women made up the majority in three specialties – general internal medicine, endocrinology, and geriatrics. In contrast, women were least represented in the procedural specialties of pulmonology, critical/intensive care, gastroenterology, and cardiology.

The greatest imbalance was in cardiology, in which only 21% were women, the researchers noted.

Across faculty ranks, the median annual salary was less for women than for men. The median salary for women was within $25,000 of that for men at all ranks except chief and was at least 90% of that for men in 10 of 13 internal medicine specialties.

Cardiology, gastroenterology, and critical/intensive care were the three specialties in which women’s median salary did not reach 90% of men’s. These specialties tended to be better paid overall, “but also demonstrated the largest gender disparities in both representation and salary, particularly within the higher ranks of cardiology and gastroenterology,” the researchers said.

The reasons for gender disparities are unclear, though internal medicine procedural specialties “have long been male dominated in composition and leadership,” the authors noted. The findings indicate that workforce gender parity may be associated with salary equity.

“Despite the growing awareness of workforce disparities in medicine, our findings suggest that women internal medicine specialists remain underpaid and are not promoted to senior level academic ranks when compared with career trajectories of their male counterparts,” study author Nosheen Reza, MD, of the division of cardiovascular medicine at the University of Pennsylvania, told this news organization.

The researchers noted that they were unable to adjust at the individual level for various factors that may influence salary, such as professional service, academic productivity, clinical volume, and supplementary funding sources, and that the results might not apply to all U.S. medical schools, in which departmental structures vary.

Procedures versus evaluation and management

Still, the research “provides an interesting snapshot of current salary disparities in academic internal medicine,” comment Rita F. Redberg, MD, and colleagues in a related editorial. Dr. Redberg, the editor of JAMA Internal Medicine, is affiliated with the department of medicine at the University of California, San Francisco.

Internal medicine has 13 specialties and dozens of subspecialties, and “procedural subspecialties are more male dominated and better paid than nonprocedural subspecialties – both topics deserving of further exploration,” the editorialists wrote.

The field needs to address various issues that drive some women to “shun male-dominated procedural-based fields – including lack of role models, macho ‘cowboy’ culture, unpredictable schedules, longer training periods, or cultural factors,” Dr. Redberg and coauthors suggested. “Concurrently, the medical profession overall, as well as specialties, should thoughtfully and frequently reassess how to distribute pay more equitably and to remove the premium currently paid for procedures over evaluation and management services.”

“Unfortunately, it is not a surprise that there continues to be a gender gap for salary in academic medicine,” Dr. Redberg said in an interview. “It was interesting to see that gender pay disparities were greatest in the procedure-intensive specialties, and we do know that procedures are much more highly reimbursed than evaluation and management time, even in the IM specialties. From a patient perspective, I think what they value most highly is having their doctor talk with them and explain treatment options and risks and benefits. Sadly, our fee-for-service–based reimbursement system values procedures more highly than talking with patients. And part of the gender gap in salary is attributed to less women being proceduralists.”

The Medicare Payment Advisory Commission “has made some excellent recommendations to Congress on helping to correct this imbalance,” Dr. Redberg added.

In a separate viewpoint article, Leah M. Marcotte, MD, of the department of medicine at the University of Washington, Seattle, and colleagues describe reasons why women physicians may have “slower promotional time lines,” compared with men, such as receiving fewer and smaller grants, being underrepresented as speakers at national conferences, and receiving fewer invitations to author editorials.

“To narrow this gap, institutions should proactively nominate women, with a greater focus on those underrepresented in medicine, for internal and external awards and speaking opportunities,” Dr. Marcotte and coauthors wrote. “Institutions should adopt policies to cover child care, breastfeeding/pumping accommodations, and dependent travel. Academic departments should continue to offer virtual speaking opportunities even after COVID-19 pandemic travel restrictions become unnecessary.”

Institutions can also assist women faculty in preparing promotion dossiers.

“Gender disparities in promotion in academic medicine have been described for decades, and yet progress to close the gap has been untenably slow,” they said. “Rather than expecting faculty to adapt to existing systems, we need to change the promotion process to work better for all.”

The authors disclosed no relevant financial relationships. Dr. Redberg has received grants from Arnold Ventures, the Greenwall Foundation, and the National Heart, Lung, and Blood Institute outside the submitted work. One viewpoint coauthor has received honoraria from the American Board of Internal Medicine, and another has received personal fees from F-Prime Capital, both outside the submitted work.

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

Patients with hepatocellular carcinoma (HCC) can be offered transarterial radioembolization (TARE) as a safe and effective first-line treatment or adjunct to other locoregional therapies, authors of a large multicenter study reported.

Among 422 patients with HCC treated with TARE in eight European countries, the median overall survival was 16.5 months, with fewer than 10% of patients experiencing grade 3 or greater adverse events, reported Frank Kolligs, MD, from Helios Hospital Berlin-Buch.

“This exploratory study evaluated factors that can influence the application and outcome of transarterial radioembolization in clinical practice. TARE is generally applied according to guideline recommendations, and randomized, controlled trials are needed to confirm the effect of personalized dosimetry on the effectiveness of TARE,” he said in an oral abstract presented at the meeting sponsored by the European Association for the Study of the Liver.

Intriguingly, the investigators found evidence suggesting that patients whose treatments were planned using a partition model had better survival outcomes than those patients who treatments were based on calculated body surface area or measured BSA (mBSA), but this finding will need to be explored in more detail, Dr. Kolligs said.

The partition model incorporates variables such as tumor volume and liver volume, shunt fractions, the ratio of radiation uptake between tumor and normal tissues, vascular anatomy and other factors to estimate the optimal dose.
 

Study design

Dr. Kolligs and colleagues looked at prospective data from the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Registry for SIR-Spheres Therapy to evaluate the real-world clinical application of TARE with yttrium Y-90 resin microspheres in Europe, clinical outcomes, safety, and quality of life.

They selected data from centers with a minimum of 10 cases performed in the previous 12 months and at least 40 total cases overall.

The patients included adults 18 years and older scheduled for treatment with Y-90 resin microspheres for primary or metastatic liver tumors, with no specific exclusion criteria. The patients were followed for at least 24 months at recommended intervals of every 3 months. The first patient was enrolled in January 2015, and the last follow-up visit was in December 2019. A total of 422 registry patients had a diagnosis of HCC and were included in the study.

The median age was 68 years (range, 60-74), 80.8% were male, 70.9% had cirrhosis, 14.5% had ascites, and 8.5% had extrahepatic disease. About 32% of patients had one tumor nodule, 33% had two to five nodules, and the remainder had either more than five or an uncountable number.

In all, 14% of patients had Barcelona Clinic Liver Cancer stage A disease, 51.4% had stage B, 33.6% had stage C, and 0.9% stage D.

About one-third of patients had portal vein occlusion. Tumors were in both left and right lobes in 35.5%, the left lobe alone in 12.1%, and the right lobe alone in 52.4%.

Half of all patients (50.2%) received TARE as first-line therapy, 44.8% had it following surgery (17.1%), ablation (14.7%), and/or transarterial chemoembolization (; 23%). In addition, 9.7% of patients received systemic therapy prior to TARE, primarily with sorafenib (Nexavar).

Treatment intent was palliative for 57.3% of patients, and tumor downsizing/downstaging in 32.5% (remainder unspecified).
 

Survival and prognostic factors

As noted before, median overall survival was 16.5 months. Median progression-free survival was 6.1 months, and median hepatic PFS was 6.7 months.

Factors prognostic for better overall survival included hepatitis B or C virus as the cirrhosis cause versus alcohol (hazard ratio for death, 0.51 for each; P = .0060 for HBV and P = .0007 for HCV); unilobar versus bilobar tumors (HR, 0.67; P = .0422 for left-lobe; HR 0.55; P < .0001 for right); prior surgery (HR, 0.67; P = .0258); prior ablation (HR, 0.65; P = .0394); and curative versus palliative intent (HR, 0.53; P < .0001).

Factors associated with worse overall survival were presence of ascites (HR 1.75, P = .001); presence of extrahepatic disease before TARE (HR, 1.81, P = .0037); tumor burden greater than 5 nodules (HR, 1.67; P = .0073); main portal vein occlusion (HR, 2.14; P = .0064); lobar portal vein occlusion (HR, 1.77; P = .0083); total bilirubin greater than 1.5 mg/dL (HR, 1.69; P = .0094); albumin-bilirubin grade A2 (HR, 1.66; P = .0005); ALB1 grade A3 (HR, 3.92; P < .0001); and BSA/mBSA versus partition-model dosimetry (HR, 1.89; P < .0001).

The safety analysis showed that 36.7% of patients had at least one adverse event, but only 7.1% had at least one grade 3 or greater event.

Grade 3 or greater events were abdominal pain (nine patients), fatigue (six), nausea (three), radioembolization-induced liver disease (three), vomiting (two), and GI ulceration (one). Fifteen additional patients had other unspecified events.

The investigators acknowledged broad inclusion criteria, relatively high rates of loss to follow-up, and differences in national guidelines and local standards of practice as potential limitations to their findings.

In the question-and-answer following the presentation, session comoderator María Varela, MD, PhD, a pathologist in the liver unit at the Hospital Universitario Central de Asturia, Oviedo, Spain, questioned why about one-third of patients received TARE for downstaging, but only 13 underwent subsequent surgical resection.

“We don’t have a detailed analysis of this subgroup of patients who received curative intent as yet, ” Dr. Kolligs said.

Pierre Nahon, MD, from the University of Paris and Hôpital Jean Verdier in Bondy, France, commented that, among this heterogenous population, one of the best indications for TARE is probably localized HCC with adjacent portal vein thrombosis.

He asked whether the investigators had examined overall survival among patients with localized unilobar HCC with adjacent small portal vein thrombosis.

“We find that patients with portal vein occlusion have a worse prognosis in the total group,” Dr. Kolligs replied. “To look into the question whether partial thrombosis with a small tumor might benefit is an interesting question, and we should look into that, but I don’t have any data on that yet.”

Another audience member asked: “According to your data, which patients are the best candidates for radioembolization?”

“According to these data, the best candidates are of course patients with good liver function, ascites should ideally not be present, and what is probably is important is that we identify or include patients without extrahepatic disease,” he said.

The study was sponsored by CIRSE. Dr. Kolligs disclosed speaking activities and consulting for several companies. Dr. Varela disclosed speaking for several companies and advisory board activity for Bayer. Dr. Nahon disclosed honoraria and consulting fees from several companies.

Patients with hepatocellular carcinoma (HCC) can be offered transarterial radioembolization (TARE) as a safe and effective first-line treatment or adjunct to other locoregional therapies, authors of a large multicenter study reported.

Among 422 patients with HCC treated with TARE in eight European countries, the median overall survival was 16.5 months, with fewer than 10% of patients experiencing grade 3 or greater adverse events, reported Frank Kolligs, MD, from Helios Hospital Berlin-Buch.

“This exploratory study evaluated factors that can influence the application and outcome of transarterial radioembolization in clinical practice. TARE is generally applied according to guideline recommendations, and randomized, controlled trials are needed to confirm the effect of personalized dosimetry on the effectiveness of TARE,” he said in an oral abstract presented at the meeting sponsored by the European Association for the Study of the Liver.

Intriguingly, the investigators found evidence suggesting that patients whose treatments were planned using a partition model had better survival outcomes than those patients who treatments were based on calculated body surface area or measured BSA (mBSA), but this finding will need to be explored in more detail, Dr. Kolligs said.

The partition model incorporates variables such as tumor volume and liver volume, shunt fractions, the ratio of radiation uptake between tumor and normal tissues, vascular anatomy and other factors to estimate the optimal dose.
 

Study design

Dr. Kolligs and colleagues looked at prospective data from the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Registry for SIR-Spheres Therapy to evaluate the real-world clinical application of TARE with yttrium Y-90 resin microspheres in Europe, clinical outcomes, safety, and quality of life.

They selected data from centers with a minimum of 10 cases performed in the previous 12 months and at least 40 total cases overall.

The patients included adults 18 years and older scheduled for treatment with Y-90 resin microspheres for primary or metastatic liver tumors, with no specific exclusion criteria. The patients were followed for at least 24 months at recommended intervals of every 3 months. The first patient was enrolled in January 2015, and the last follow-up visit was in December 2019. A total of 422 registry patients had a diagnosis of HCC and were included in the study.

The median age was 68 years (range, 60-74), 80.8% were male, 70.9% had cirrhosis, 14.5% had ascites, and 8.5% had extrahepatic disease. About 32% of patients had one tumor nodule, 33% had two to five nodules, and the remainder had either more than five or an uncountable number.

In all, 14% of patients had Barcelona Clinic Liver Cancer stage A disease, 51.4% had stage B, 33.6% had stage C, and 0.9% stage D.

About one-third of patients had portal vein occlusion. Tumors were in both left and right lobes in 35.5%, the left lobe alone in 12.1%, and the right lobe alone in 52.4%.

Half of all patients (50.2%) received TARE as first-line therapy, 44.8% had it following surgery (17.1%), ablation (14.7%), and/or transarterial chemoembolization (; 23%). In addition, 9.7% of patients received systemic therapy prior to TARE, primarily with sorafenib (Nexavar).

Treatment intent was palliative for 57.3% of patients, and tumor downsizing/downstaging in 32.5% (remainder unspecified).
 

Survival and prognostic factors

As noted before, median overall survival was 16.5 months. Median progression-free survival was 6.1 months, and median hepatic PFS was 6.7 months.

Factors prognostic for better overall survival included hepatitis B or C virus as the cirrhosis cause versus alcohol (hazard ratio for death, 0.51 for each; P = .0060 for HBV and P = .0007 for HCV); unilobar versus bilobar tumors (HR, 0.67; P = .0422 for left-lobe; HR 0.55; P < .0001 for right); prior surgery (HR, 0.67; P = .0258); prior ablation (HR, 0.65; P = .0394); and curative versus palliative intent (HR, 0.53; P < .0001).

Factors associated with worse overall survival were presence of ascites (HR 1.75, P = .001); presence of extrahepatic disease before TARE (HR, 1.81, P = .0037); tumor burden greater than 5 nodules (HR, 1.67; P = .0073); main portal vein occlusion (HR, 2.14; P = .0064); lobar portal vein occlusion (HR, 1.77; P = .0083); total bilirubin greater than 1.5 mg/dL (HR, 1.69; P = .0094); albumin-bilirubin grade A2 (HR, 1.66; P = .0005); ALB1 grade A3 (HR, 3.92; P < .0001); and BSA/mBSA versus partition-model dosimetry (HR, 1.89; P < .0001).

The safety analysis showed that 36.7% of patients had at least one adverse event, but only 7.1% had at least one grade 3 or greater event.

Grade 3 or greater events were abdominal pain (nine patients), fatigue (six), nausea (three), radioembolization-induced liver disease (three), vomiting (two), and GI ulceration (one). Fifteen additional patients had other unspecified events.

The investigators acknowledged broad inclusion criteria, relatively high rates of loss to follow-up, and differences in national guidelines and local standards of practice as potential limitations to their findings.

In the question-and-answer following the presentation, session comoderator María Varela, MD, PhD, a pathologist in the liver unit at the Hospital Universitario Central de Asturia, Oviedo, Spain, questioned why about one-third of patients received TARE for downstaging, but only 13 underwent subsequent surgical resection.

“We don’t have a detailed analysis of this subgroup of patients who received curative intent as yet, ” Dr. Kolligs said.

Pierre Nahon, MD, from the University of Paris and Hôpital Jean Verdier in Bondy, France, commented that, among this heterogenous population, one of the best indications for TARE is probably localized HCC with adjacent portal vein thrombosis.

He asked whether the investigators had examined overall survival among patients with localized unilobar HCC with adjacent small portal vein thrombosis.

“We find that patients with portal vein occlusion have a worse prognosis in the total group,” Dr. Kolligs replied. “To look into the question whether partial thrombosis with a small tumor might benefit is an interesting question, and we should look into that, but I don’t have any data on that yet.”

Another audience member asked: “According to your data, which patients are the best candidates for radioembolization?”

“According to these data, the best candidates are of course patients with good liver function, ascites should ideally not be present, and what is probably is important is that we identify or include patients without extrahepatic disease,” he said.

The study was sponsored by CIRSE. Dr. Kolligs disclosed speaking activities and consulting for several companies. Dr. Varela disclosed speaking for several companies and advisory board activity for Bayer. Dr. Nahon disclosed honoraria and consulting fees from several companies.

Patients with hepatocellular carcinoma (HCC) can be offered transarterial radioembolization (TARE) as a safe and effective first-line treatment or adjunct to other locoregional therapies, authors of a large multicenter study reported.

Among 422 patients with HCC treated with TARE in eight European countries, the median overall survival was 16.5 months, with fewer than 10% of patients experiencing grade 3 or greater adverse events, reported Frank Kolligs, MD, from Helios Hospital Berlin-Buch.

“This exploratory study evaluated factors that can influence the application and outcome of transarterial radioembolization in clinical practice. TARE is generally applied according to guideline recommendations, and randomized, controlled trials are needed to confirm the effect of personalized dosimetry on the effectiveness of TARE,” he said in an oral abstract presented at the meeting sponsored by the European Association for the Study of the Liver.

Intriguingly, the investigators found evidence suggesting that patients whose treatments were planned using a partition model had better survival outcomes than those patients who treatments were based on calculated body surface area or measured BSA (mBSA), but this finding will need to be explored in more detail, Dr. Kolligs said.

The partition model incorporates variables such as tumor volume and liver volume, shunt fractions, the ratio of radiation uptake between tumor and normal tissues, vascular anatomy and other factors to estimate the optimal dose.
 

Study design

Dr. Kolligs and colleagues looked at prospective data from the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Registry for SIR-Spheres Therapy to evaluate the real-world clinical application of TARE with yttrium Y-90 resin microspheres in Europe, clinical outcomes, safety, and quality of life.

They selected data from centers with a minimum of 10 cases performed in the previous 12 months and at least 40 total cases overall.

The patients included adults 18 years and older scheduled for treatment with Y-90 resin microspheres for primary or metastatic liver tumors, with no specific exclusion criteria. The patients were followed for at least 24 months at recommended intervals of every 3 months. The first patient was enrolled in January 2015, and the last follow-up visit was in December 2019. A total of 422 registry patients had a diagnosis of HCC and were included in the study.

The median age was 68 years (range, 60-74), 80.8% were male, 70.9% had cirrhosis, 14.5% had ascites, and 8.5% had extrahepatic disease. About 32% of patients had one tumor nodule, 33% had two to five nodules, and the remainder had either more than five or an uncountable number.

In all, 14% of patients had Barcelona Clinic Liver Cancer stage A disease, 51.4% had stage B, 33.6% had stage C, and 0.9% stage D.

About one-third of patients had portal vein occlusion. Tumors were in both left and right lobes in 35.5%, the left lobe alone in 12.1%, and the right lobe alone in 52.4%.

Half of all patients (50.2%) received TARE as first-line therapy, 44.8% had it following surgery (17.1%), ablation (14.7%), and/or transarterial chemoembolization (; 23%). In addition, 9.7% of patients received systemic therapy prior to TARE, primarily with sorafenib (Nexavar).

Treatment intent was palliative for 57.3% of patients, and tumor downsizing/downstaging in 32.5% (remainder unspecified).
 

Survival and prognostic factors

As noted before, median overall survival was 16.5 months. Median progression-free survival was 6.1 months, and median hepatic PFS was 6.7 months.

Factors prognostic for better overall survival included hepatitis B or C virus as the cirrhosis cause versus alcohol (hazard ratio for death, 0.51 for each; P = .0060 for HBV and P = .0007 for HCV); unilobar versus bilobar tumors (HR, 0.67; P = .0422 for left-lobe; HR 0.55; P < .0001 for right); prior surgery (HR, 0.67; P = .0258); prior ablation (HR, 0.65; P = .0394); and curative versus palliative intent (HR, 0.53; P < .0001).

Factors associated with worse overall survival were presence of ascites (HR 1.75, P = .001); presence of extrahepatic disease before TARE (HR, 1.81, P = .0037); tumor burden greater than 5 nodules (HR, 1.67; P = .0073); main portal vein occlusion (HR, 2.14; P = .0064); lobar portal vein occlusion (HR, 1.77; P = .0083); total bilirubin greater than 1.5 mg/dL (HR, 1.69; P = .0094); albumin-bilirubin grade A2 (HR, 1.66; P = .0005); ALB1 grade A3 (HR, 3.92; P < .0001); and BSA/mBSA versus partition-model dosimetry (HR, 1.89; P < .0001).

The safety analysis showed that 36.7% of patients had at least one adverse event, but only 7.1% had at least one grade 3 or greater event.

Grade 3 or greater events were abdominal pain (nine patients), fatigue (six), nausea (three), radioembolization-induced liver disease (three), vomiting (two), and GI ulceration (one). Fifteen additional patients had other unspecified events.

The investigators acknowledged broad inclusion criteria, relatively high rates of loss to follow-up, and differences in national guidelines and local standards of practice as potential limitations to their findings.

In the question-and-answer following the presentation, session comoderator María Varela, MD, PhD, a pathologist in the liver unit at the Hospital Universitario Central de Asturia, Oviedo, Spain, questioned why about one-third of patients received TARE for downstaging, but only 13 underwent subsequent surgical resection.

“We don’t have a detailed analysis of this subgroup of patients who received curative intent as yet, ” Dr. Kolligs said.

Pierre Nahon, MD, from the University of Paris and Hôpital Jean Verdier in Bondy, France, commented that, among this heterogenous population, one of the best indications for TARE is probably localized HCC with adjacent portal vein thrombosis.

He asked whether the investigators had examined overall survival among patients with localized unilobar HCC with adjacent small portal vein thrombosis.

“We find that patients with portal vein occlusion have a worse prognosis in the total group,” Dr. Kolligs replied. “To look into the question whether partial thrombosis with a small tumor might benefit is an interesting question, and we should look into that, but I don’t have any data on that yet.”

Another audience member asked: “According to your data, which patients are the best candidates for radioembolization?”

“According to these data, the best candidates are of course patients with good liver function, ascites should ideally not be present, and what is probably is important is that we identify or include patients without extrahepatic disease,” he said.

The study was sponsored by CIRSE. Dr. Kolligs disclosed speaking activities and consulting for several companies. Dr. Varela disclosed speaking for several companies and advisory board activity for Bayer. Dr. Nahon disclosed honoraria and consulting fees from several companies.

Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.

The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.

In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.

The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.

“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.

He presented the new data at the 2021 annual congress of the European Association of Urology.

Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”

Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.

“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
 

Registry study

The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.

At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.

The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.

The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).

All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.

Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”

No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.

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

Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.

The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.

In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.

The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.

“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.

He presented the new data at the 2021 annual congress of the European Association of Urology.

Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”

Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.

“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
 

Registry study

The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.

At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.

The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.

The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).

All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.

Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”

No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.

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

Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.

The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.

In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.

The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.

“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.

He presented the new data at the 2021 annual congress of the European Association of Urology.

Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”

Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.

“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
 

Registry study

The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.

At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.

The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.

The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).

All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.

Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”

No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.

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

People receiving the Johnson and Johnson COVID-19 vaccine could be at increased risk for developing Guillain-Barré syndrome, the Food and Drug Administration is expected to announce as early as July 13, according to multiple media reports.

Although the FDA is projected to add the new warning to the labeling for the vaccine, the agency still calculates the benefit of vaccination with the J&J product continues to outweigh the risk. Benefits include protection against the Delta variant and serious COVID-19 outcomes.

More than 100 cases of Guillain-Barré reported to the Vaccine Adverse Event Reporting System, a federal program for reporting vaccine issues, spurred the FDA to act.

Men and people older than 50 appear to be at highest risk, according to reports of a July 12 Centers for Disease Control and Prevention statement. The CDC also revealed that most cases occur about 2 weeks following immunization.

Guillain-Barré syndrome often causes muscle weakness and sometimes temporary paralysis. Most people who develop the rare syndrome recover.

Such was not the case for a 57-year-old man, the New York Times reported July 12. He had a history of both a heart attack and stroke in the previous 4 years and died in April after vaccination with the J&J vaccine and developing Guillain-Barré.

The new warning comes in the wake of a number of setbacks for the company’s COVID-19 vaccine. On April 13, the FDA and CDC both recommended a 10-day pause on administration of the J&J vaccine after reports of rare blood clot events emerged. In mid-June, the FDA requested that Johnson and Johnson discard millions of vaccine doses produced at a manufacturing facility in Baltimore.

The mRNA vaccines from Pfizer/BioNTech and Moderna are not affected by the new FDA warning.

The Biden administration is expected to make a formal announcement of the new warning for the Johnson and Johnson vaccine as early as July 13, the Times reports.

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

People receiving the Johnson and Johnson COVID-19 vaccine could be at increased risk for developing Guillain-Barré syndrome, the Food and Drug Administration is expected to announce as early as July 13, according to multiple media reports.

Although the FDA is projected to add the new warning to the labeling for the vaccine, the agency still calculates the benefit of vaccination with the J&J product continues to outweigh the risk. Benefits include protection against the Delta variant and serious COVID-19 outcomes.

More than 100 cases of Guillain-Barré reported to the Vaccine Adverse Event Reporting System, a federal program for reporting vaccine issues, spurred the FDA to act.

Men and people older than 50 appear to be at highest risk, according to reports of a July 12 Centers for Disease Control and Prevention statement. The CDC also revealed that most cases occur about 2 weeks following immunization.

Guillain-Barré syndrome often causes muscle weakness and sometimes temporary paralysis. Most people who develop the rare syndrome recover.

Such was not the case for a 57-year-old man, the New York Times reported July 12. He had a history of both a heart attack and stroke in the previous 4 years and died in April after vaccination with the J&J vaccine and developing Guillain-Barré.

The new warning comes in the wake of a number of setbacks for the company’s COVID-19 vaccine. On April 13, the FDA and CDC both recommended a 10-day pause on administration of the J&J vaccine after reports of rare blood clot events emerged. In mid-June, the FDA requested that Johnson and Johnson discard millions of vaccine doses produced at a manufacturing facility in Baltimore.

The mRNA vaccines from Pfizer/BioNTech and Moderna are not affected by the new FDA warning.

The Biden administration is expected to make a formal announcement of the new warning for the Johnson and Johnson vaccine as early as July 13, the Times reports.

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

People receiving the Johnson and Johnson COVID-19 vaccine could be at increased risk for developing Guillain-Barré syndrome, the Food and Drug Administration is expected to announce as early as July 13, according to multiple media reports.

Although the FDA is projected to add the new warning to the labeling for the vaccine, the agency still calculates the benefit of vaccination with the J&J product continues to outweigh the risk. Benefits include protection against the Delta variant and serious COVID-19 outcomes.

More than 100 cases of Guillain-Barré reported to the Vaccine Adverse Event Reporting System, a federal program for reporting vaccine issues, spurred the FDA to act.

Men and people older than 50 appear to be at highest risk, according to reports of a July 12 Centers for Disease Control and Prevention statement. The CDC also revealed that most cases occur about 2 weeks following immunization.

Guillain-Barré syndrome often causes muscle weakness and sometimes temporary paralysis. Most people who develop the rare syndrome recover.

Such was not the case for a 57-year-old man, the New York Times reported July 12. He had a history of both a heart attack and stroke in the previous 4 years and died in April after vaccination with the J&J vaccine and developing Guillain-Barré.

The new warning comes in the wake of a number of setbacks for the company’s COVID-19 vaccine. On April 13, the FDA and CDC both recommended a 10-day pause on administration of the J&J vaccine after reports of rare blood clot events emerged. In mid-June, the FDA requested that Johnson and Johnson discard millions of vaccine doses produced at a manufacturing facility in Baltimore.

The mRNA vaccines from Pfizer/BioNTech and Moderna are not affected by the new FDA warning.

The Biden administration is expected to make a formal announcement of the new warning for the Johnson and Johnson vaccine as early as July 13, the Times reports.

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

Patients with infected pancreatic necrosis (IPN) are more likely to experience organ failure and mortality, which makes identifying them as quickly as possible especially crucial. A new study aimed to make this task a bit easier by categorizing the main risk factors for IPN in a cohort of patients with severe acute pancreatitis, which included extensive spread of necrotic collections, preceding bacteremia, and preceding open abdomen treatment, as well as postinterventional pancreatitis.

In their study, published in the Journal of Gastrointestinal Surgery, Henrik L. Husu, MD, of the University of Helsinki, and colleagues noted the inherent challenges of rendering a preoperative diagnosis of IPN.

“Fever and increasing inflammation markers may indicate suspicion of IPN, but these are very common in patients with severe acute pancreatitis treated in the ICU,” and more knowledge of specific IPN risk factors is needed to improve clinical decision-making, they said.

Dr. Husu and colleagues identified 163 adults with acute pancreatitis admitted to the ICU at a single center between 2010 and 2018, approximately 68% of whom had alcoholic necrotizing pancreatitis. Pneumonia, bacteremia, and IPN occurred at an average of 4, 16, and 23 days, respectively, after ICU admission.

Forty-seven patients (28.8%) developed IPN within 90 days of ICU admission, all patients had a least one persistent organ failure, and 60% had multiple organ failure within 24 hours of ICU admission.

In a multivariate regression analysis, independent risk factors for IPN included postoperative or postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (odds ratio,13.5) and widespread necrotic collections (OR, 5.7 for unilateral paracolic or retromesenteric; OR, 21.8 for bilateral paracolic or unilateral paracolic and retromesenteric). Other risk factors were preceding bacteremia (OR, 4.8) and preceding open abdomen treatment for abdominal compartment syndrome (OR, 3.6).

After 90 days, 29 patients had died, including 7 with IPN and 22 without IPN. In addition, patients with IPN had longer overall hospital stays and ICU stays, higher rates of ICU readmission, and greater use of open necrosectomy, the researchers noted.

The study findings were limited by several factors, including the retrospective design, lack of controls, potential differences in treatment protocols, and the survival bias that prevented direct comparison of mortality in patients with and without IPN, the researchers noted. “This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself.”

However, the researchers noted that “the strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course,” and results indicate a significant morbid outcome associated with IPN. “In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential,” they emphasized. 
 

More data may prompt greater intervention

“IPN portends a poor prognosis, and can be challenging to both diagnose and treat,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview. “Identifying risk factors for development of IPN may facilitate earlier therapy that could modify the natural history of this disease.”

Dr. Ketwaroo said he was not surprised by the study findings. “This was a small single-center, retrospective study, where infection could only be ascertained among those who received interventions, and the findings should thus be interpreted within these limitations. Overall, however, I was not surprised. More extensive necrosis and opportunities for infectious seeding of necrosis such as interventions (ERCP) and bacteremia would be expected risk factors. I was surprised by the use of prophylactic antibiotics, as well as the high rate of open necrosectomy, though this should not affect the main findings of risk factors for infection.

“The studies highlight that a significant portion of patients with severe acute pancreatitis with necrosis will develop infection,” said Dr. Ketwaroo. “Being aware of the risk factors for infection, as identified in this study, can add to our clinical judgment in suspecting infection and opting for debridement. Especially with advancements in endoscopic necrosectomy, gastroenterologists may be more inclined to intervene when suspecting IPN. The next steps for research are to validate risk factors in larger, prospective studies.”

The study was supported by governmental competitive funds for medical research, a research grant from the Medical Society of Finland, and a research grant from Perkléns Foundation. The researchers had no financial conflicts to disclose. Dr. Ketwaroo had no financial conflicts to disclose but is a member of the GI & Hepatology News editorial advisory board.

Patients with infected pancreatic necrosis (IPN) are more likely to experience organ failure and mortality, which makes identifying them as quickly as possible especially crucial. A new study aimed to make this task a bit easier by categorizing the main risk factors for IPN in a cohort of patients with severe acute pancreatitis, which included extensive spread of necrotic collections, preceding bacteremia, and preceding open abdomen treatment, as well as postinterventional pancreatitis.

In their study, published in the Journal of Gastrointestinal Surgery, Henrik L. Husu, MD, of the University of Helsinki, and colleagues noted the inherent challenges of rendering a preoperative diagnosis of IPN.

“Fever and increasing inflammation markers may indicate suspicion of IPN, but these are very common in patients with severe acute pancreatitis treated in the ICU,” and more knowledge of specific IPN risk factors is needed to improve clinical decision-making, they said.

Dr. Husu and colleagues identified 163 adults with acute pancreatitis admitted to the ICU at a single center between 2010 and 2018, approximately 68% of whom had alcoholic necrotizing pancreatitis. Pneumonia, bacteremia, and IPN occurred at an average of 4, 16, and 23 days, respectively, after ICU admission.

Forty-seven patients (28.8%) developed IPN within 90 days of ICU admission, all patients had a least one persistent organ failure, and 60% had multiple organ failure within 24 hours of ICU admission.

In a multivariate regression analysis, independent risk factors for IPN included postoperative or postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (odds ratio,13.5) and widespread necrotic collections (OR, 5.7 for unilateral paracolic or retromesenteric; OR, 21.8 for bilateral paracolic or unilateral paracolic and retromesenteric). Other risk factors were preceding bacteremia (OR, 4.8) and preceding open abdomen treatment for abdominal compartment syndrome (OR, 3.6).

After 90 days, 29 patients had died, including 7 with IPN and 22 without IPN. In addition, patients with IPN had longer overall hospital stays and ICU stays, higher rates of ICU readmission, and greater use of open necrosectomy, the researchers noted.

The study findings were limited by several factors, including the retrospective design, lack of controls, potential differences in treatment protocols, and the survival bias that prevented direct comparison of mortality in patients with and without IPN, the researchers noted. “This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself.”

However, the researchers noted that “the strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course,” and results indicate a significant morbid outcome associated with IPN. “In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential,” they emphasized. 
 

More data may prompt greater intervention

“IPN portends a poor prognosis, and can be challenging to both diagnose and treat,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview. “Identifying risk factors for development of IPN may facilitate earlier therapy that could modify the natural history of this disease.”

Dr. Ketwaroo said he was not surprised by the study findings. “This was a small single-center, retrospective study, where infection could only be ascertained among those who received interventions, and the findings should thus be interpreted within these limitations. Overall, however, I was not surprised. More extensive necrosis and opportunities for infectious seeding of necrosis such as interventions (ERCP) and bacteremia would be expected risk factors. I was surprised by the use of prophylactic antibiotics, as well as the high rate of open necrosectomy, though this should not affect the main findings of risk factors for infection.

“The studies highlight that a significant portion of patients with severe acute pancreatitis with necrosis will develop infection,” said Dr. Ketwaroo. “Being aware of the risk factors for infection, as identified in this study, can add to our clinical judgment in suspecting infection and opting for debridement. Especially with advancements in endoscopic necrosectomy, gastroenterologists may be more inclined to intervene when suspecting IPN. The next steps for research are to validate risk factors in larger, prospective studies.”

The study was supported by governmental competitive funds for medical research, a research grant from the Medical Society of Finland, and a research grant from Perkléns Foundation. The researchers had no financial conflicts to disclose. Dr. Ketwaroo had no financial conflicts to disclose but is a member of the GI & Hepatology News editorial advisory board.

Patients with infected pancreatic necrosis (IPN) are more likely to experience organ failure and mortality, which makes identifying them as quickly as possible especially crucial. A new study aimed to make this task a bit easier by categorizing the main risk factors for IPN in a cohort of patients with severe acute pancreatitis, which included extensive spread of necrotic collections, preceding bacteremia, and preceding open abdomen treatment, as well as postinterventional pancreatitis.

In their study, published in the Journal of Gastrointestinal Surgery, Henrik L. Husu, MD, of the University of Helsinki, and colleagues noted the inherent challenges of rendering a preoperative diagnosis of IPN.

“Fever and increasing inflammation markers may indicate suspicion of IPN, but these are very common in patients with severe acute pancreatitis treated in the ICU,” and more knowledge of specific IPN risk factors is needed to improve clinical decision-making, they said.

Dr. Husu and colleagues identified 163 adults with acute pancreatitis admitted to the ICU at a single center between 2010 and 2018, approximately 68% of whom had alcoholic necrotizing pancreatitis. Pneumonia, bacteremia, and IPN occurred at an average of 4, 16, and 23 days, respectively, after ICU admission.

Forty-seven patients (28.8%) developed IPN within 90 days of ICU admission, all patients had a least one persistent organ failure, and 60% had multiple organ failure within 24 hours of ICU admission.

In a multivariate regression analysis, independent risk factors for IPN included postoperative or postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (odds ratio,13.5) and widespread necrotic collections (OR, 5.7 for unilateral paracolic or retromesenteric; OR, 21.8 for bilateral paracolic or unilateral paracolic and retromesenteric). Other risk factors were preceding bacteremia (OR, 4.8) and preceding open abdomen treatment for abdominal compartment syndrome (OR, 3.6).

After 90 days, 29 patients had died, including 7 with IPN and 22 without IPN. In addition, patients with IPN had longer overall hospital stays and ICU stays, higher rates of ICU readmission, and greater use of open necrosectomy, the researchers noted.

The study findings were limited by several factors, including the retrospective design, lack of controls, potential differences in treatment protocols, and the survival bias that prevented direct comparison of mortality in patients with and without IPN, the researchers noted. “This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself.”

However, the researchers noted that “the strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course,” and results indicate a significant morbid outcome associated with IPN. “In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential,” they emphasized. 
 

More data may prompt greater intervention

“IPN portends a poor prognosis, and can be challenging to both diagnose and treat,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview. “Identifying risk factors for development of IPN may facilitate earlier therapy that could modify the natural history of this disease.”

Dr. Ketwaroo said he was not surprised by the study findings. “This was a small single-center, retrospective study, where infection could only be ascertained among those who received interventions, and the findings should thus be interpreted within these limitations. Overall, however, I was not surprised. More extensive necrosis and opportunities for infectious seeding of necrosis such as interventions (ERCP) and bacteremia would be expected risk factors. I was surprised by the use of prophylactic antibiotics, as well as the high rate of open necrosectomy, though this should not affect the main findings of risk factors for infection.

“The studies highlight that a significant portion of patients with severe acute pancreatitis with necrosis will develop infection,” said Dr. Ketwaroo. “Being aware of the risk factors for infection, as identified in this study, can add to our clinical judgment in suspecting infection and opting for debridement. Especially with advancements in endoscopic necrosectomy, gastroenterologists may be more inclined to intervene when suspecting IPN. The next steps for research are to validate risk factors in larger, prospective studies.”

The study was supported by governmental competitive funds for medical research, a research grant from the Medical Society of Finland, and a research grant from Perkléns Foundation. The researchers had no financial conflicts to disclose. Dr. Ketwaroo had no financial conflicts to disclose but is a member of the GI & Hepatology News editorial advisory board.

Background

Well into its second year, the worldwide COVID-19 pandemic continues to pose substantial challenges for health care access and delivery. Regulatory agencies such as the Centers for Disease Control (CDC) do not currently have guidance related to COVID-19 specific to sleep centers and laboratories. In March 2020, within days of the World Health Organization pandemic declaration, the American Academy of Sleep Medicine (AASM) posted detailed guidance on mitigation strategies for sleep medicine practices (COVID-19 Resources).

This initial guidance has been previously reported in this publication (Sullivan S, Gurubhagavatula I. CHEST Physician 2020 May 8), and the guidance has been periodically updated during the pandemic. It was restructured in mid-2020 to include sections summarizing CDC recommendations germane for sleep practices; additional sleep medicine-specific guidance from the AASM COVID-19 Task Force (TF); and a frequently asked questions (FAQ) section. The last major update from the task force occurred on Jan. 18, 2021, though subsequent posts – especially related to recent CDC changes in masking guidelines – were made in May 2021. The purpose of this article is to summarize these updates and to call attention to areas of ongoing interest to sleep medicine. Notably, the AASM Task Force guidance is nonbinding and offered as a framework for considering best practices in this evolving situation, acknowledging the importance of weighing local factors, conditions, and regulations, as well as the interests of and risks to the patient, staff, and providers.

Key updates

Data on exposure and transmission risks specific to sleep medicine

Measures for reducing viral transmission have been central to managing the spread of the virus in clinical settings. In its last major update, the AASM TF noted that no known outbreaks of COVID-19 related to sleep center exposure have been reported. A perspective and data published in the Journal of the American Medical Association concluded that hospital transmission of the virus “in the setting of universal masking is likely rare, even during periods of high community prevalence.” It also concluded that hospital-based outbreaks are more likely to occur in small workrooms and during mealtime when staff are less adherent to masking and physical distancing (Richterman A, et al. JAMA. 2020;324[21]:2155-6). The TF elaborated on considerations to reduce transmission, which include not just telework and foundational infection control practices, but also broader workplace considerations such as optimizing ventilation, taking advantage of outdoor spaces (e.g., for breaks and eating), scheduling to reduce interactions between personnel from different teams, minimizing contact in meeting/break rooms, removing tables and chairs from lounge areas, and following CDC guidance for effective facility operations.

Vaccination

In the January update, the AASM COVID-19 TF stated that, “sleep facility leaders should encourage staff and patients to be vaccinated in accordance with CDC guidance.” The role of the sleep medicine community in encouraging healthy sleep habits before and after vaccination was emphasized, pointing to evidence linking sleep and immunity, specifically between sleep duration and vaccination response (Healthy sleep and immune response to COVID-19 vaccination. 2021 Jan.).

In an FAQ update from March 26, 2021, considering whether continued COVID-19 testing was needed following full vaccination, the AASM advised testing prior to potential aerosol-generating procedures should be made on the basis of a risk-benefit assessment by the sleep clinician. Several considerations were highlighted, including recent COVID-19 infection, vaccination status of contacts, local prevalence of newer variants, and whether individuals are receiving positive airway pressure therapy. The TF focused on the vigilance for residents and staff in long-term care facilities, which have been associated with a number of outbreaks.
 

Masking in the context of the COVID-19 vaccine

The most significant change in recommendations is the recent relaxation of masking guidance by the CDC in the setting of the approval and distribution of COVID-19 vaccinations. In May, the CDC stated that fully vaccinated individuals can resume activities without masking or physically distancing except in scenarios of travel and where required by laws, regulations, and local businesses, due to the efficacy of the vaccines, increasing evidence of reduced asymptomatic carriage and transmission after vaccination, and anticipated increased uptake of vaccination. However, the CDC also noted that these updates did not apply to health care facilities, where the recommendation remains that patients and visitors should continue to mask throughout their stay. Additionally, fully vaccinated health care workers should continue to practice infection control measures while working with patients. On May 14, the AASM TF provided a detailed FAQ acknowledging the CDC’s new guidance, emphasizing that masking guidance in health care facilities remains unchanged, and encouraging individuals to follow CDC guidance regarding vaccination, noting that emergence of newer variants continues to be monitored, and existing vaccines still appear to induce neutralizing antibodies even if to a somewhat lower degree. The situation for pediatric sleep centers has been highlighted in particular because the potential risk posed by newer variants to children remains under investigation, and children under age 12 are not approved for vaccination.
 

Important caveats to discussions around vaccination status are the lack of a centralized method to identify vaccinated individuals, the unknown duration of immunity, and reports of the use of fake vaccine cards. At this time, in health care settings, vaccination status should not exempt mask usage for any individual.
 

Sleep medicine care for those with COVID-19

Regarding the duration of isolation and precautions for adults with COVID-19, the TF highlighted the CDC’s symptom-based strategy, rather than test-based strategy, for ending isolation of these patients, availing them of sleep medicine services in person.

In line with the CDC guidance, this approach indicates that scheduling in-person care such as polysomnography for a COVID-19–positive patient may be appropriate at least 10 days after symptom onset (or after a positive test if the patient never developed symptoms); or at least 20 days after symptom onset if the illness was severe; or if at least 90 days have elapsed since symptom onset, consider preappointment COVID-19 screening. In the context of immunocompromised individuals, involvement from infectious disease specialists may be needed to help guide decisions.
 

Patient communications

For many, a repercussion of the pandemic has been delaying care or avoiding addressing medical issues, including sleep disorders. The AASM encouraged practices to consider communicating with patients that delaying needed care can increase health risks; COVID-19 transmission to patients in health care settings has been low; effective safety procedures are in place; and whether remote/telehealth services are available.

Disparities in care

In addition to the specific guidance above, there are ongoing concerns regarding disparities in care resulting from a variety of sources and becoming more evident during the pandemic. Complex factors, ranging from economic, geographic, contextual, occupational, and others contribute to disparities that health care systems – and sleep medicine - have not been able to adequately address (Jackson CL and Johnson DA. J Clin Sleep Med. 16[8]:1401-2). More specific differences may include Internet access, reduced access due to socioeconomic barriers, transportation limitations, medical mistrust, and membership in a medically vulnerable group such as children, the elderly, and those with high acuity needs. For example, in pediatric patients there exist few evidence-based alternatives and guidelines to in-lab testing and care, which may have negatively impacted access to needed sleep medicine services (Sullivan S et al. J Clin Sleep Med. 2021 Mar 1;17[3]:361-2).
 

Economics in the COVID-19 pandemic

The economic effects of COVID-19 on medical institutions and in sleep medicine is a story that continues to unfold. Reductions in patient visits and elective procedures, infection control measures limiting capacity, increased costs to maintain such measures, and variability of responses by payer and region are just a few of the issues. The Centers for Medicare & Medicaid Services has employed waivers to increased flexibility and promote safe and effective care including the use of telemedicine during the public health emergency, but the future of these waivers remains uncertain. Alarmingly, a sizeable portion of sleep practices reported financial solvency concerns related to the pandemic (Ramar K. J Clin Sleep Med. 2020;16[11]:1939-42).

Conclusion

As the COVID-19 pandemic and related public health guidance continues to evolve, sleep medicine practices continue to adapt. Vaccination, new variants, changes in mask guidance, new outbreaks around the globe, financial and staffing uncertainties, as well as addressing disparities in care and outcomes that may be augmented by the pandemic remain salient areas of ongoing development.

Dr. Lee is a Postdoctoral and Pediatric Pulmonary Fellow, Department of Pediatrics, Division of Pulmonary, Asthma, and Sleep Medicine, Stanford University School of Medicine; Dr. Sullivan is Clinical Professor, Department of Pediatrics, Division of Pulmonary, Asthma, and Sleep Medicine, and by courtesy, Division of Sleep Medicine, Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA.

Background

Well into its second year, the worldwide COVID-19 pandemic continues to pose substantial challenges for health care access and delivery. Regulatory agencies such as the Centers for Disease Control (CDC) do not currently have guidance related to COVID-19 specific to sleep centers and laboratories. In March 2020, within days of the World Health Organization pandemic declaration, the American Academy of Sleep Medicine (AASM) posted detailed guidance on mitigation strategies for sleep medicine practices (COVID-19 Resources).

This initial guidance has been previously reported in this publication (Sullivan S, Gurubhagavatula I. CHEST Physician 2020 May 8), and the guidance has been periodically updated during the pandemic. It was restructured in mid-2020 to include sections summarizing CDC recommendations germane for sleep practices; additional sleep medicine-specific guidance from the AASM COVID-19 Task Force (TF); and a frequently asked questions (FAQ) section. The last major update from the task force occurred on Jan. 18, 2021, though subsequent posts – especially related to recent CDC changes in masking guidelines – were made in May 2021. The purpose of this article is to summarize these updates and to call attention to areas of ongoing interest to sleep medicine. Notably, the AASM Task Force guidance is nonbinding and offered as a framework for considering best practices in this evolving situation, acknowledging the importance of weighing local factors, conditions, and regulations, as well as the interests of and risks to the patient, staff, and providers.

Key updates

Data on exposure and transmission risks specific to sleep medicine

Measures for reducing viral transmission have been central to managing the spread of the virus in clinical settings. In its last major update, the AASM TF noted that no known outbreaks of COVID-19 related to sleep center exposure have been reported. A perspective and data published in the Journal of the American Medical Association concluded that hospital transmission of the virus “in the setting of universal masking is likely rare, even during periods of high community prevalence.” It also concluded that hospital-based outbreaks are more likely to occur in small workrooms and during mealtime when staff are less adherent to masking and physical distancing (Richterman A, et al. JAMA. 2020;324[21]:2155-6). The TF elaborated on considerations to reduce transmission, which include not just telework and foundational infection control practices, but also broader workplace considerations such as optimizing ventilation, taking advantage of outdoor spaces (e.g., for breaks and eating), scheduling to reduce interactions between personnel from different teams, minimizing contact in meeting/break rooms, removing tables and chairs from lounge areas, and following CDC guidance for effective facility operations.

Vaccination

In the January update, the AASM COVID-19 TF stated that, “sleep facility leaders should encourage staff and patients to be vaccinated in accordance with CDC guidance.” The role of the sleep medicine community in encouraging healthy sleep habits before and after vaccination was emphasized, pointing to evidence linking sleep and immunity, specifically between sleep duration and vaccination response (Healthy sleep and immune response to COVID-19 vaccination. 2021 Jan.).

In an FAQ update from March 26, 2021, considering whether continued COVID-19 testing was needed following full vaccination, the AASM advised testing prior to potential aerosol-generating procedures should be made on the basis of a risk-benefit assessment by the sleep clinician. Several considerations were highlighted, including recent COVID-19 infection, vaccination status of contacts, local prevalence of newer variants, and whether individuals are receiving positive airway pressure therapy. The TF focused on the vigilance for residents and staff in long-term care facilities, which have been associated with a number of outbreaks.
 

Masking in the context of the COVID-19 vaccine

The most significant change in recommendations is the recent relaxation of masking guidance by the CDC in the setting of the approval and distribution of COVID-19 vaccinations. In May, the CDC stated that fully vaccinated individuals can resume activities without masking or physically distancing except in scenarios of travel and where required by laws, regulations, and local businesses, due to the efficacy of the vaccines, increasing evidence of reduced asymptomatic carriage and transmission after vaccination, and anticipated increased uptake of vaccination. However, the CDC also noted that these updates did not apply to health care facilities, where the recommendation remains that patients and visitors should continue to mask throughout their stay. Additionally, fully vaccinated health care workers should continue to practice infection control measures while working with patients. On May 14, the AASM TF provided a detailed FAQ acknowledging the CDC’s new guidance, emphasizing that masking guidance in health care facilities remains unchanged, and encouraging individuals to follow CDC guidance regarding vaccination, noting that emergence of newer variants continues to be monitored, and existing vaccines still appear to induce neutralizing antibodies even if to a somewhat lower degree. The situation for pediatric sleep centers has been highlighted in particular because the potential risk posed by newer variants to children remains under investigation, and children under age 12 are not approved for vaccination.
 

Important caveats to discussions around vaccination status are the lack of a centralized method to identify vaccinated individuals, the unknown duration of immunity, and reports of the use of fake vaccine cards. At this time, in health care settings, vaccination status should not exempt mask usage for any individual.
 

Sleep medicine care for those with COVID-19

Regarding the duration of isolation and precautions for adults with COVID-19, the TF highlighted the CDC’s symptom-based strategy, rather than test-based strategy, for ending isolation of these patients, availing them of sleep medicine services in person.

In line with the CDC guidance, this approach indicates that scheduling in-person care such as polysomnography for a COVID-19–positive patient may be appropriate at least 10 days after symptom onset (or after a positive test if the patient never developed symptoms); or at least 20 days after symptom onset if the illness was severe; or if at least 90 days have elapsed since symptom onset, consider preappointment COVID-19 screening. In the context of immunocompromised individuals, involvement from infectious disease specialists may be needed to help guide decisions.
 

Patient communications

For many, a repercussion of the pandemic has been delaying care or avoiding addressing medical issues, including sleep disorders. The AASM encouraged practices to consider communicating with patients that delaying needed care can increase health risks; COVID-19 transmission to patients in health care settings has been low; effective safety procedures are in place; and whether remote/telehealth services are available.

Disparities in care

In addition to the specific guidance above, there are ongoing concerns regarding disparities in care resulting from a variety of sources and becoming more evident during the pandemic. Complex factors, ranging from economic, geographic, contextual, occupational, and others contribute to disparities that health care systems – and sleep medicine - have not been able to adequately address (Jackson CL and Johnson DA. J Clin Sleep Med. 16[8]:1401-2). More specific differences may include Internet access, reduced access due to socioeconomic barriers, transportation limitations, medical mistrust, and membership in a medically vulnerable group such as children, the elderly, and those with high acuity needs. For example, in pediatric patients there exist few evidence-based alternatives and guidelines to in-lab testing and care, which may have negatively impacted access to needed sleep medicine services (Sullivan S et al. J Clin Sleep Med. 2021 Mar 1;17[3]:361-2).
 

Economics in the COVID-19 pandemic

The economic effects of COVID-19 on medical institutions and in sleep medicine is a story that continues to unfold. Reductions in patient visits and elective procedures, infection control measures limiting capacity, increased costs to maintain such measures, and variability of responses by payer and region are just a few of the issues. The Centers for Medicare & Medicaid Services has employed waivers to increased flexibility and promote safe and effective care including the use of telemedicine during the public health emergency, but the future of these waivers remains uncertain. Alarmingly, a sizeable portion of sleep practices reported financial solvency concerns related to the pandemic (Ramar K. J Clin Sleep Med. 2020;16[11]:1939-42).

Conclusion

As the COVID-19 pandemic and related public health guidance continues to evolve, sleep medicine practices continue to adapt. Vaccination, new variants, changes in mask guidance, new outbreaks around the globe, financial and staffing uncertainties, as well as addressing disparities in care and outcomes that may be augmented by the pandemic remain salient areas of ongoing development.

Dr. Lee is a Postdoctoral and Pediatric Pulmonary Fellow, Department of Pediatrics, Division of Pulmonary, Asthma, and Sleep Medicine, Stanford University School of Medicine; Dr. Sullivan is Clinical Professor, Department of Pediatrics, Division of Pulmonary, Asthma, and Sleep Medicine, and by courtesy, Division of Sleep Medicine, Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA.

Background

Well into its second year, the worldwide COVID-19 pandemic continues to pose substantial challenges for health care access and delivery. Regulatory agencies such as the Centers for Disease Control (CDC) do not currently have guidance related to COVID-19 specific to sleep centers and laboratories. In March 2020, within days of the World Health Organization pandemic declaration, the American Academy of Sleep Medicine (AASM) posted detailed guidance on mitigation strategies for sleep medicine practices (COVID-19 Resources).

This initial guidance has been previously reported in this publication (Sullivan S, Gurubhagavatula I. CHEST Physician 2020 May 8), and the guidance has been periodically updated during the pandemic. It was restructured in mid-2020 to include sections summarizing CDC recommendations germane for sleep practices; additional sleep medicine-specific guidance from the AASM COVID-19 Task Force (TF); and a frequently asked questions (FAQ) section. The last major update from the task force occurred on Jan. 18, 2021, though subsequent posts – especially related to recent CDC changes in masking guidelines – were made in May 2021. The purpose of this article is to summarize these updates and to call attention to areas of ongoing interest to sleep medicine. Notably, the AASM Task Force guidance is nonbinding and offered as a framework for considering best practices in this evolving situation, acknowledging the importance of weighing local factors, conditions, and regulations, as well as the interests of and risks to the patient, staff, and providers.

Key updates

Data on exposure and transmission risks specific to sleep medicine

Measures for reducing viral transmission have been central to managing the spread of the virus in clinical settings. In its last major update, the AASM TF noted that no known outbreaks of COVID-19 related to sleep center exposure have been reported. A perspective and data published in the Journal of the American Medical Association concluded that hospital transmission of the virus “in the setting of universal masking is likely rare, even during periods of high community prevalence.” It also concluded that hospital-based outbreaks are more likely to occur in small workrooms and during mealtime when staff are less adherent to masking and physical distancing (Richterman A, et al. JAMA. 2020;324[21]:2155-6). The TF elaborated on considerations to reduce transmission, which include not just telework and foundational infection control practices, but also broader workplace considerations such as optimizing ventilation, taking advantage of outdoor spaces (e.g., for breaks and eating), scheduling to reduce interactions between personnel from different teams, minimizing contact in meeting/break rooms, removing tables and chairs from lounge areas, and following CDC guidance for effective facility operations.

Vaccination

In the January update, the AASM COVID-19 TF stated that, “sleep facility leaders should encourage staff and patients to be vaccinated in accordance with CDC guidance.” The role of the sleep medicine community in encouraging healthy sleep habits before and after vaccination was emphasized, pointing to evidence linking sleep and immunity, specifically between sleep duration and vaccination response (Healthy sleep and immune response to COVID-19 vaccination. 2021 Jan.).

In an FAQ update from March 26, 2021, considering whether continued COVID-19 testing was needed following full vaccination, the AASM advised testing prior to potential aerosol-generating procedures should be made on the basis of a risk-benefit assessment by the sleep clinician. Several considerations were highlighted, including recent COVID-19 infection, vaccination status of contacts, local prevalence of newer variants, and whether individuals are receiving positive airway pressure therapy. The TF focused on the vigilance for residents and staff in long-term care facilities, which have been associated with a number of outbreaks.
 

Masking in the context of the COVID-19 vaccine

The most significant change in recommendations is the recent relaxation of masking guidance by the CDC in the setting of the approval and distribution of COVID-19 vaccinations. In May, the CDC stated that fully vaccinated individuals can resume activities without masking or physically distancing except in scenarios of travel and where required by laws, regulations, and local businesses, due to the efficacy of the vaccines, increasing evidence of reduced asymptomatic carriage and transmission after vaccination, and anticipated increased uptake of vaccination. However, the CDC also noted that these updates did not apply to health care facilities, where the recommendation remains that patients and visitors should continue to mask throughout their stay. Additionally, fully vaccinated health care workers should continue to practice infection control measures while working with patients. On May 14, the AASM TF provided a detailed FAQ acknowledging the CDC’s new guidance, emphasizing that masking guidance in health care facilities remains unchanged, and encouraging individuals to follow CDC guidance regarding vaccination, noting that emergence of newer variants continues to be monitored, and existing vaccines still appear to induce neutralizing antibodies even if to a somewhat lower degree. The situation for pediatric sleep centers has been highlighted in particular because the potential risk posed by newer variants to children remains under investigation, and children under age 12 are not approved for vaccination.
 

Important caveats to discussions around vaccination status are the lack of a centralized method to identify vaccinated individuals, the unknown duration of immunity, and reports of the use of fake vaccine cards. At this time, in health care settings, vaccination status should not exempt mask usage for any individual.
 

Sleep medicine care for those with COVID-19

Regarding the duration of isolation and precautions for adults with COVID-19, the TF highlighted the CDC’s symptom-based strategy, rather than test-based strategy, for ending isolation of these patients, availing them of sleep medicine services in person.

In line with the CDC guidance, this approach indicates that scheduling in-person care such as polysomnography for a COVID-19–positive patient may be appropriate at least 10 days after symptom onset (or after a positive test if the patient never developed symptoms); or at least 20 days after symptom onset if the illness was severe; or if at least 90 days have elapsed since symptom onset, consider preappointment COVID-19 screening. In the context of immunocompromised individuals, involvement from infectious disease specialists may be needed to help guide decisions.
 

Patient communications

For many, a repercussion of the pandemic has been delaying care or avoiding addressing medical issues, including sleep disorders. The AASM encouraged practices to consider communicating with patients that delaying needed care can increase health risks; COVID-19 transmission to patients in health care settings has been low; effective safety procedures are in place; and whether remote/telehealth services are available.

Disparities in care

In addition to the specific guidance above, there are ongoing concerns regarding disparities in care resulting from a variety of sources and becoming more evident during the pandemic. Complex factors, ranging from economic, geographic, contextual, occupational, and others contribute to disparities that health care systems – and sleep medicine - have not been able to adequately address (Jackson CL and Johnson DA. J Clin Sleep Med. 16[8]:1401-2). More specific differences may include Internet access, reduced access due to socioeconomic barriers, transportation limitations, medical mistrust, and membership in a medically vulnerable group such as children, the elderly, and those with high acuity needs. For example, in pediatric patients there exist few evidence-based alternatives and guidelines to in-lab testing and care, which may have negatively impacted access to needed sleep medicine services (Sullivan S et al. J Clin Sleep Med. 2021 Mar 1;17[3]:361-2).
 

Economics in the COVID-19 pandemic

The economic effects of COVID-19 on medical institutions and in sleep medicine is a story that continues to unfold. Reductions in patient visits and elective procedures, infection control measures limiting capacity, increased costs to maintain such measures, and variability of responses by payer and region are just a few of the issues. The Centers for Medicare & Medicaid Services has employed waivers to increased flexibility and promote safe and effective care including the use of telemedicine during the public health emergency, but the future of these waivers remains uncertain. Alarmingly, a sizeable portion of sleep practices reported financial solvency concerns related to the pandemic (Ramar K. J Clin Sleep Med. 2020;16[11]:1939-42).

Conclusion

As the COVID-19 pandemic and related public health guidance continues to evolve, sleep medicine practices continue to adapt. Vaccination, new variants, changes in mask guidance, new outbreaks around the globe, financial and staffing uncertainties, as well as addressing disparities in care and outcomes that may be augmented by the pandemic remain salient areas of ongoing development.

Dr. Lee is a Postdoctoral and Pediatric Pulmonary Fellow, Department of Pediatrics, Division of Pulmonary, Asthma, and Sleep Medicine, Stanford University School of Medicine; Dr. Sullivan is Clinical Professor, Department of Pediatrics, Division of Pulmonary, Asthma, and Sleep Medicine, and by courtesy, Division of Sleep Medicine, Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA.