Federal Practitioner

Left atrial appendage closure was noninferior to use of direct oral anticoagulants for the prevention of atrial fibrillation (AFib)–related events in high-risk patients, based on data from 402 adults.

Given the limitations of vitamin K antagonists for preventing stroke in AFib, “a novel site-specific therapeutic alternative, mechanical left atrial appendage occlusion [LAAO], entered clinical practice,” but has not been compared with current safe and effective oral anticoagulants, wrote Pavel Osmancik, MD, of University Hospital Kralovske Vinohrady, Prague, and colleagues.

In a study published in the Journal of the American College of Cardiology, the researchers randomized 201 moderate- or high-risk adults with nonvalvular AFib to LAAO and another 201 to direct oral anticoagulants (DOAC).

Patients in the LAAO group underwent transesophageal echocardiography to exclude left atrial thrombi and underwent implantation with Boston Scientific’s Watchman, Watchman-FLX, or Abbott’s Amulet devices. Patients in the DOAC group received rivaroxaban, apixaban, or dabigatran at the manufacturer-recommended dose.

The primary outcome was a composite of complications related to procedures or devices, thromboembolic events (including stroke), and clinically significant bleeding. After an average of 20 months follow-up, 35 patients in the LAAO group and 41 in the DOAC group met the primary outcome (11% per 100 patient-years vs. 13% per 100 patient-years).

In addition, no differences appeared between the groups for the endpoint components of all-stroke/transient ischemic attack event (subdistribution hazard ratio, 1.00), clinically significantly bleeding (sHR, 0.81), or cardiovascular death (sHR, 0.75).

Nine patients experienced major complications related to LAAO, including clinically significant bleeding (sHR, 0.81; 95% CI, 0.44-1.52) and cardiovascular death (sHR, 0.75; 95% CI, 0.34-1.62). Major LAAO-related complications occurred in nine (4.5%) patients, with a short-term (up to 7 days or hospital discharge) complication rate of 2.1% and a 2.7% late complication rate. The late complications included three pericardial effusions, one of which resulted in death, the researchers wrote.

The study findings were limited by several factors, including the inability to assess the differences among the components of the composite primary endpoint. For example, “Regarding the primary endpoint, stroke reduction may be more important than bleeding reduction,” the investigators wrote.

The results were strengthened, however, by the enrollment of a high-risk AF population and is the first known randomized trial to compare percutaneous LAAO and DOACs for stroke prevention in this group. But the late complication rate of 2.7% is “suboptimal” and safety issues reinforce the need for refinement of operator technique and device technology with LAAO, they concluded.

‘Important step forward,’ with caveats

“How LAAO might stack up against DOAC therapy has remained an open question: Compared with warfarin, DOACs are easier to use and are associated with a reduction in mortality, driven by a substantially lower risk of intracranial hemorrhage and fatal bleeding,” wrote Matthew J. Price, MD, of the Scripps Clinic in La Jolla, Calif., and Jacqueline Saw, MD, of Vancouver General Hospital, in an accompanying editorial.

Bruce Jancin/Frontline Medical News

SOURCES: Osmancik P et al. J Am Coll Cardiol. 2020;75:3122-35; Price MJ, Saw J. J Am Coll Cardiol. 2020;75:3136-9.

Left atrial appendage closure was noninferior to use of direct oral anticoagulants for the prevention of atrial fibrillation (AFib)–related events in high-risk patients, based on data from 402 adults.

Given the limitations of vitamin K antagonists for preventing stroke in AFib, “a novel site-specific therapeutic alternative, mechanical left atrial appendage occlusion [LAAO], entered clinical practice,” but has not been compared with current safe and effective oral anticoagulants, wrote Pavel Osmancik, MD, of University Hospital Kralovske Vinohrady, Prague, and colleagues.

In a study published in the Journal of the American College of Cardiology, the researchers randomized 201 moderate- or high-risk adults with nonvalvular AFib to LAAO and another 201 to direct oral anticoagulants (DOAC).

Patients in the LAAO group underwent transesophageal echocardiography to exclude left atrial thrombi and underwent implantation with Boston Scientific’s Watchman, Watchman-FLX, or Abbott’s Amulet devices. Patients in the DOAC group received rivaroxaban, apixaban, or dabigatran at the manufacturer-recommended dose.

The primary outcome was a composite of complications related to procedures or devices, thromboembolic events (including stroke), and clinically significant bleeding. After an average of 20 months follow-up, 35 patients in the LAAO group and 41 in the DOAC group met the primary outcome (11% per 100 patient-years vs. 13% per 100 patient-years).

In addition, no differences appeared between the groups for the endpoint components of all-stroke/transient ischemic attack event (subdistribution hazard ratio, 1.00), clinically significantly bleeding (sHR, 0.81), or cardiovascular death (sHR, 0.75).

Nine patients experienced major complications related to LAAO, including clinically significant bleeding (sHR, 0.81; 95% CI, 0.44-1.52) and cardiovascular death (sHR, 0.75; 95% CI, 0.34-1.62). Major LAAO-related complications occurred in nine (4.5%) patients, with a short-term (up to 7 days or hospital discharge) complication rate of 2.1% and a 2.7% late complication rate. The late complications included three pericardial effusions, one of which resulted in death, the researchers wrote.

The study findings were limited by several factors, including the inability to assess the differences among the components of the composite primary endpoint. For example, “Regarding the primary endpoint, stroke reduction may be more important than bleeding reduction,” the investigators wrote.

The results were strengthened, however, by the enrollment of a high-risk AF population and is the first known randomized trial to compare percutaneous LAAO and DOACs for stroke prevention in this group. But the late complication rate of 2.7% is “suboptimal” and safety issues reinforce the need for refinement of operator technique and device technology with LAAO, they concluded.

‘Important step forward,’ with caveats

“How LAAO might stack up against DOAC therapy has remained an open question: Compared with warfarin, DOACs are easier to use and are associated with a reduction in mortality, driven by a substantially lower risk of intracranial hemorrhage and fatal bleeding,” wrote Matthew J. Price, MD, of the Scripps Clinic in La Jolla, Calif., and Jacqueline Saw, MD, of Vancouver General Hospital, in an accompanying editorial.

Bruce Jancin/Frontline Medical News

SOURCES: Osmancik P et al. J Am Coll Cardiol. 2020;75:3122-35; Price MJ, Saw J. J Am Coll Cardiol. 2020;75:3136-9.

Left atrial appendage closure was noninferior to use of direct oral anticoagulants for the prevention of atrial fibrillation (AFib)–related events in high-risk patients, based on data from 402 adults.

Given the limitations of vitamin K antagonists for preventing stroke in AFib, “a novel site-specific therapeutic alternative, mechanical left atrial appendage occlusion [LAAO], entered clinical practice,” but has not been compared with current safe and effective oral anticoagulants, wrote Pavel Osmancik, MD, of University Hospital Kralovske Vinohrady, Prague, and colleagues.

In a study published in the Journal of the American College of Cardiology, the researchers randomized 201 moderate- or high-risk adults with nonvalvular AFib to LAAO and another 201 to direct oral anticoagulants (DOAC).

Patients in the LAAO group underwent transesophageal echocardiography to exclude left atrial thrombi and underwent implantation with Boston Scientific’s Watchman, Watchman-FLX, or Abbott’s Amulet devices. Patients in the DOAC group received rivaroxaban, apixaban, or dabigatran at the manufacturer-recommended dose.

The primary outcome was a composite of complications related to procedures or devices, thromboembolic events (including stroke), and clinically significant bleeding. After an average of 20 months follow-up, 35 patients in the LAAO group and 41 in the DOAC group met the primary outcome (11% per 100 patient-years vs. 13% per 100 patient-years).

In addition, no differences appeared between the groups for the endpoint components of all-stroke/transient ischemic attack event (subdistribution hazard ratio, 1.00), clinically significantly bleeding (sHR, 0.81), or cardiovascular death (sHR, 0.75).

Nine patients experienced major complications related to LAAO, including clinically significant bleeding (sHR, 0.81; 95% CI, 0.44-1.52) and cardiovascular death (sHR, 0.75; 95% CI, 0.34-1.62). Major LAAO-related complications occurred in nine (4.5%) patients, with a short-term (up to 7 days or hospital discharge) complication rate of 2.1% and a 2.7% late complication rate. The late complications included three pericardial effusions, one of which resulted in death, the researchers wrote.

The study findings were limited by several factors, including the inability to assess the differences among the components of the composite primary endpoint. For example, “Regarding the primary endpoint, stroke reduction may be more important than bleeding reduction,” the investigators wrote.

The results were strengthened, however, by the enrollment of a high-risk AF population and is the first known randomized trial to compare percutaneous LAAO and DOACs for stroke prevention in this group. But the late complication rate of 2.7% is “suboptimal” and safety issues reinforce the need for refinement of operator technique and device technology with LAAO, they concluded.

‘Important step forward,’ with caveats

“How LAAO might stack up against DOAC therapy has remained an open question: Compared with warfarin, DOACs are easier to use and are associated with a reduction in mortality, driven by a substantially lower risk of intracranial hemorrhage and fatal bleeding,” wrote Matthew J. Price, MD, of the Scripps Clinic in La Jolla, Calif., and Jacqueline Saw, MD, of Vancouver General Hospital, in an accompanying editorial.

Bruce Jancin/Frontline Medical News

SOURCES: Osmancik P et al. J Am Coll Cardiol. 2020;75:3122-35; Price MJ, Saw J. J Am Coll Cardiol. 2020;75:3136-9.

Prominent female physicians are handing over their social media platforms today to black female physicians as part of a campaign called #ShareTheMicNowMed.

The social media event, which will play out on both Twitter and Instagram, is an offshoot of #ShareTheMicNow, held earlier this month. For that event, more than 90 women, including A-list celebrities like Ellen DeGeneres, Julia Roberts, and Senator Elizabeth Warren, swapped accounts with women of color, such as “I’m Still Here” author Austin Channing Brown, Olympic fencer Ibtihaj Muhammad, and #MeToo founder Tarana Burke.

The physician event will feature 10 teams of two, with one physician handing over her account to her black female counterpart for the day. The takeover will allow the black physician to share her thoughts about the successes and challenges she faces as a woman of color in medicine.

“It was such an honor to be contacted by Arghavan Salles, MD, PhD, to participate in an event that has a goal of connecting like-minded women from various backgrounds to share a diverse perspective with a different audience,” Minnesota family medicine physician Jay-Sheree Allen, MD, told Medscape Medical News. “This event is not only incredibly important but timely.”

Participants say the goal of the takeovers is to amplify the reach and voice of black women in medicine while crossing boundaries and empowering others to do the same. Only about 5% of all active physicians in 2018 identified as Black or African American, according to a report by the Association of American Medical Colleges. And of those, just over a third are female, the report found.

“I think that as we hear those small numbers we often celebrate the success of those people without looking back and understanding where all of the barriers are that are limiting talented black women from entering medicine at every stage,” another campaign participant, Chicago pediatrician Rebekah Fenton, MD, told Medscape Medical News.

Allen says that, amid continuing worldwide protests over racial injustice, prompted by the death of George Floyd while in Minneapolis police custody last month, the online event is very timely and an important way to advocate for black lives and engage in a productive conversation.

Prominent female physicians are handing over their social media platforms today to black female physicians as part of a campaign called #ShareTheMicNowMed.

The social media event, which will play out on both Twitter and Instagram, is an offshoot of #ShareTheMicNow, held earlier this month. For that event, more than 90 women, including A-list celebrities like Ellen DeGeneres, Julia Roberts, and Senator Elizabeth Warren, swapped accounts with women of color, such as “I’m Still Here” author Austin Channing Brown, Olympic fencer Ibtihaj Muhammad, and #MeToo founder Tarana Burke.

The physician event will feature 10 teams of two, with one physician handing over her account to her black female counterpart for the day. The takeover will allow the black physician to share her thoughts about the successes and challenges she faces as a woman of color in medicine.

“It was such an honor to be contacted by Arghavan Salles, MD, PhD, to participate in an event that has a goal of connecting like-minded women from various backgrounds to share a diverse perspective with a different audience,” Minnesota family medicine physician Jay-Sheree Allen, MD, told Medscape Medical News. “This event is not only incredibly important but timely.”

Participants say the goal of the takeovers is to amplify the reach and voice of black women in medicine while crossing boundaries and empowering others to do the same. Only about 5% of all active physicians in 2018 identified as Black or African American, according to a report by the Association of American Medical Colleges. And of those, just over a third are female, the report found.

“I think that as we hear those small numbers we often celebrate the success of those people without looking back and understanding where all of the barriers are that are limiting talented black women from entering medicine at every stage,” another campaign participant, Chicago pediatrician Rebekah Fenton, MD, told Medscape Medical News.

Allen says that, amid continuing worldwide protests over racial injustice, prompted by the death of George Floyd while in Minneapolis police custody last month, the online event is very timely and an important way to advocate for black lives and engage in a productive conversation.

Prominent female physicians are handing over their social media platforms today to black female physicians as part of a campaign called #ShareTheMicNowMed.

The social media event, which will play out on both Twitter and Instagram, is an offshoot of #ShareTheMicNow, held earlier this month. For that event, more than 90 women, including A-list celebrities like Ellen DeGeneres, Julia Roberts, and Senator Elizabeth Warren, swapped accounts with women of color, such as “I’m Still Here” author Austin Channing Brown, Olympic fencer Ibtihaj Muhammad, and #MeToo founder Tarana Burke.

The physician event will feature 10 teams of two, with one physician handing over her account to her black female counterpart for the day. The takeover will allow the black physician to share her thoughts about the successes and challenges she faces as a woman of color in medicine.

“It was such an honor to be contacted by Arghavan Salles, MD, PhD, to participate in an event that has a goal of connecting like-minded women from various backgrounds to share a diverse perspective with a different audience,” Minnesota family medicine physician Jay-Sheree Allen, MD, told Medscape Medical News. “This event is not only incredibly important but timely.”

Participants say the goal of the takeovers is to amplify the reach and voice of black women in medicine while crossing boundaries and empowering others to do the same. Only about 5% of all active physicians in 2018 identified as Black or African American, according to a report by the Association of American Medical Colleges. And of those, just over a third are female, the report found.

“I think that as we hear those small numbers we often celebrate the success of those people without looking back and understanding where all of the barriers are that are limiting talented black women from entering medicine at every stage,” another campaign participant, Chicago pediatrician Rebekah Fenton, MD, told Medscape Medical News.

Allen says that, amid continuing worldwide protests over racial injustice, prompted by the death of George Floyd while in Minneapolis police custody last month, the online event is very timely and an important way to advocate for black lives and engage in a productive conversation.

I was recently interviewed, as a gay psychiatrist treating gay patients who lived through the AIDS epidemic, about my perspectives on living through a COVID pandemic: Were there parallels and contrasts between the two? A month later, listening to patients remotely via teletherapy, I’m experiencing an unsettling similarity to serosorting, a phenomenon that emerged during the AIDS epidemic.

Serosorting is the practice of choosing a sexual partner based on their HIV serostatus. Sorting out who was positive from who was negative allowed people to give themselves permission to have unprotected sex without risk of getting HIV. However, it was not uncommon to make those decisions without really knowing a potential partner’s actual serostatus. In fact, a lot of people serosorted by guessing.

Why not just ask a potential partner, “What’s your serostatus?” Apparently, for some, introducing the subject of HIV was deemed a sexual buzzkill. Instead, assumptions were made based on outer appearances.

Did someone look healthy? Were they well built? Were they overweight, meaning not emaciated from AIDS? If so, they were presumed negative and safe to have risky, unprotected sex with them.

Some imagined age correlated with serostatus. Since anyone older than some arbitrary age – like 30, to pull a number out of a hat – was expected to be more likely to have HIV than someone under 30, they would use that guideline in choosing sexual partners. However, these decisions were made without factual knowledge, like a blood test, but using some internal reasoning process.

Which brings us to what might be called “COVID-sorting.”

Some of my patients believe they had COVID-19, although they’d not been tested to either confirm or disprove that belief. Others had positive COVID-19 antibody tests, which they believe provides immunity. Among that group, some had symptoms, others did not.

Yet regardless of what they actually know or don’t know, patients are making calculations about managing physical distancing using their own internal formulas. They make risk calculations having little to do with actual knowledge of public health precautions on preventing COVID’s spread.

For example, one patient was planning a Memorial Day weekend in a shared Fire Island house with five friends and acquaintances. All six live alone and, as far as he knows, all are physically distancing. Consequently, my patient doesn’t think house-sharing is anything to worry about, even though he doesn’t know how scrupulously others have followed distancing guidelines.

Another patient, recovering at home after being ill with COVID-19, felt safe inviting someone over for sex who had also been ill and recovered. He didn’t think they could infect each other, presuming, not altogether unreasonably, they were both immune.

Finally, there are those who don’t know whether they had COVID-19, but think they did because they experienced influenza-like symptoms. They are giving themselves permission to meet up with others who feel the same.

Yet a Mount Sinai study, which has not yet been peer-reviewed, raises fascinating issues about immunity. The study included 719 people who suspected they had COVID-19 based on some respiratory symptoms. The majority, 62%, had no antibodies. Researchers believe they mistook influenza, another viral infection, or allergies for COVID-19 (medRxiv. 2020 May 5. doi: 10.1101/2020.04.04.2008516).

The study also included 624 people who tested positive for the virus and recovered. All but three developed antibodies. Many assume those who are antibody-positive are now immune. They may be right. However, we don’t know definitively that they are, and if they are, we do not yet know how long immunity may last. Further, as reported in the New York Times, just because you test positive for antibodies, doesn’t mean you have them.

It should be underscored that COVID-sorting is not limited to gay men or psychiatric patients. Central Park, these days, is filled with many unmasked, nonsocially isolating people of all sexual orientations and genders who are making their own questionable decisions. And as many states have begun opening up restrictions on social gatherings, we are seeing an all-too-human psychological mindset with wider implications – rising numbers of cases. As we move forward, all of us will have to decide for ourselves, and not only in sexual situations, how to get on with our lives in a post–COVID-19 era.

Given how much is still unknown, it is likely each of us will come up with our own algorithm of risk assessment. It is likely that the formulas used will not necessarily be based on scientific facts, although that would be ideal. If past epidemic and recent pandemic behaviors are any indicators, people’s actions will reflect some combination of their own needs and desires, their own comfort level with risk-taking, and their relative understanding of complex subjects like virology, immunology, epidemiology, and public health. The challenge faced by public health officials today is to translate complex scientific and medical issues into messages average people can understand.

What exactly can be done? I’m not exactly sure, but I hope that improved education and communication can help. In the first 2 decades of the AIDS epidemic, efforts were made to change and tailor HIV-prevention messages to specific, at-risk demographic groups. Today, public health messages aimed at preventing COVID-19’s spread that resonate with older people can fall on a younger person’s deaf ears. One message size does not fit all. Hopefully, public health officials and government leaders will act on this sooner rather than later.
 

Dr. Drescher, a psychoanalyst, is clinical professor of psychiatry at Columbia University, and training and supervising analyst at the William A. White Institute, both in New York. He also is emeritus editor of the Journal of Gay & Lesbian Mental Health. Dr. Drescher has no other disclosures.

I was recently interviewed, as a gay psychiatrist treating gay patients who lived through the AIDS epidemic, about my perspectives on living through a COVID pandemic: Were there parallels and contrasts between the two? A month later, listening to patients remotely via teletherapy, I’m experiencing an unsettling similarity to serosorting, a phenomenon that emerged during the AIDS epidemic.

Serosorting is the practice of choosing a sexual partner based on their HIV serostatus. Sorting out who was positive from who was negative allowed people to give themselves permission to have unprotected sex without risk of getting HIV. However, it was not uncommon to make those decisions without really knowing a potential partner’s actual serostatus. In fact, a lot of people serosorted by guessing.

Why not just ask a potential partner, “What’s your serostatus?” Apparently, for some, introducing the subject of HIV was deemed a sexual buzzkill. Instead, assumptions were made based on outer appearances.

Did someone look healthy? Were they well built? Were they overweight, meaning not emaciated from AIDS? If so, they were presumed negative and safe to have risky, unprotected sex with them.

Some imagined age correlated with serostatus. Since anyone older than some arbitrary age – like 30, to pull a number out of a hat – was expected to be more likely to have HIV than someone under 30, they would use that guideline in choosing sexual partners. However, these decisions were made without factual knowledge, like a blood test, but using some internal reasoning process.

Which brings us to what might be called “COVID-sorting.”

Some of my patients believe they had COVID-19, although they’d not been tested to either confirm or disprove that belief. Others had positive COVID-19 antibody tests, which they believe provides immunity. Among that group, some had symptoms, others did not.

Yet regardless of what they actually know or don’t know, patients are making calculations about managing physical distancing using their own internal formulas. They make risk calculations having little to do with actual knowledge of public health precautions on preventing COVID’s spread.

For example, one patient was planning a Memorial Day weekend in a shared Fire Island house with five friends and acquaintances. All six live alone and, as far as he knows, all are physically distancing. Consequently, my patient doesn’t think house-sharing is anything to worry about, even though he doesn’t know how scrupulously others have followed distancing guidelines.

Another patient, recovering at home after being ill with COVID-19, felt safe inviting someone over for sex who had also been ill and recovered. He didn’t think they could infect each other, presuming, not altogether unreasonably, they were both immune.

Finally, there are those who don’t know whether they had COVID-19, but think they did because they experienced influenza-like symptoms. They are giving themselves permission to meet up with others who feel the same.

Yet a Mount Sinai study, which has not yet been peer-reviewed, raises fascinating issues about immunity. The study included 719 people who suspected they had COVID-19 based on some respiratory symptoms. The majority, 62%, had no antibodies. Researchers believe they mistook influenza, another viral infection, or allergies for COVID-19 (medRxiv. 2020 May 5. doi: 10.1101/2020.04.04.2008516).

The study also included 624 people who tested positive for the virus and recovered. All but three developed antibodies. Many assume those who are antibody-positive are now immune. They may be right. However, we don’t know definitively that they are, and if they are, we do not yet know how long immunity may last. Further, as reported in the New York Times, just because you test positive for antibodies, doesn’t mean you have them.

It should be underscored that COVID-sorting is not limited to gay men or psychiatric patients. Central Park, these days, is filled with many unmasked, nonsocially isolating people of all sexual orientations and genders who are making their own questionable decisions. And as many states have begun opening up restrictions on social gatherings, we are seeing an all-too-human psychological mindset with wider implications – rising numbers of cases. As we move forward, all of us will have to decide for ourselves, and not only in sexual situations, how to get on with our lives in a post–COVID-19 era.

Given how much is still unknown, it is likely each of us will come up with our own algorithm of risk assessment. It is likely that the formulas used will not necessarily be based on scientific facts, although that would be ideal. If past epidemic and recent pandemic behaviors are any indicators, people’s actions will reflect some combination of their own needs and desires, their own comfort level with risk-taking, and their relative understanding of complex subjects like virology, immunology, epidemiology, and public health. The challenge faced by public health officials today is to translate complex scientific and medical issues into messages average people can understand.

What exactly can be done? I’m not exactly sure, but I hope that improved education and communication can help. In the first 2 decades of the AIDS epidemic, efforts were made to change and tailor HIV-prevention messages to specific, at-risk demographic groups. Today, public health messages aimed at preventing COVID-19’s spread that resonate with older people can fall on a younger person’s deaf ears. One message size does not fit all. Hopefully, public health officials and government leaders will act on this sooner rather than later.
 

Dr. Drescher, a psychoanalyst, is clinical professor of psychiatry at Columbia University, and training and supervising analyst at the William A. White Institute, both in New York. He also is emeritus editor of the Journal of Gay & Lesbian Mental Health. Dr. Drescher has no other disclosures.

I was recently interviewed, as a gay psychiatrist treating gay patients who lived through the AIDS epidemic, about my perspectives on living through a COVID pandemic: Were there parallels and contrasts between the two? A month later, listening to patients remotely via teletherapy, I’m experiencing an unsettling similarity to serosorting, a phenomenon that emerged during the AIDS epidemic.

Serosorting is the practice of choosing a sexual partner based on their HIV serostatus. Sorting out who was positive from who was negative allowed people to give themselves permission to have unprotected sex without risk of getting HIV. However, it was not uncommon to make those decisions without really knowing a potential partner’s actual serostatus. In fact, a lot of people serosorted by guessing.

Why not just ask a potential partner, “What’s your serostatus?” Apparently, for some, introducing the subject of HIV was deemed a sexual buzzkill. Instead, assumptions were made based on outer appearances.

Did someone look healthy? Were they well built? Were they overweight, meaning not emaciated from AIDS? If so, they were presumed negative and safe to have risky, unprotected sex with them.

Some imagined age correlated with serostatus. Since anyone older than some arbitrary age – like 30, to pull a number out of a hat – was expected to be more likely to have HIV than someone under 30, they would use that guideline in choosing sexual partners. However, these decisions were made without factual knowledge, like a blood test, but using some internal reasoning process.

Which brings us to what might be called “COVID-sorting.”

Some of my patients believe they had COVID-19, although they’d not been tested to either confirm or disprove that belief. Others had positive COVID-19 antibody tests, which they believe provides immunity. Among that group, some had symptoms, others did not.

Yet regardless of what they actually know or don’t know, patients are making calculations about managing physical distancing using their own internal formulas. They make risk calculations having little to do with actual knowledge of public health precautions on preventing COVID’s spread.

For example, one patient was planning a Memorial Day weekend in a shared Fire Island house with five friends and acquaintances. All six live alone and, as far as he knows, all are physically distancing. Consequently, my patient doesn’t think house-sharing is anything to worry about, even though he doesn’t know how scrupulously others have followed distancing guidelines.

Another patient, recovering at home after being ill with COVID-19, felt safe inviting someone over for sex who had also been ill and recovered. He didn’t think they could infect each other, presuming, not altogether unreasonably, they were both immune.

Finally, there are those who don’t know whether they had COVID-19, but think they did because they experienced influenza-like symptoms. They are giving themselves permission to meet up with others who feel the same.

Yet a Mount Sinai study, which has not yet been peer-reviewed, raises fascinating issues about immunity. The study included 719 people who suspected they had COVID-19 based on some respiratory symptoms. The majority, 62%, had no antibodies. Researchers believe they mistook influenza, another viral infection, or allergies for COVID-19 (medRxiv. 2020 May 5. doi: 10.1101/2020.04.04.2008516).

The study also included 624 people who tested positive for the virus and recovered. All but three developed antibodies. Many assume those who are antibody-positive are now immune. They may be right. However, we don’t know definitively that they are, and if they are, we do not yet know how long immunity may last. Further, as reported in the New York Times, just because you test positive for antibodies, doesn’t mean you have them.

It should be underscored that COVID-sorting is not limited to gay men or psychiatric patients. Central Park, these days, is filled with many unmasked, nonsocially isolating people of all sexual orientations and genders who are making their own questionable decisions. And as many states have begun opening up restrictions on social gatherings, we are seeing an all-too-human psychological mindset with wider implications – rising numbers of cases. As we move forward, all of us will have to decide for ourselves, and not only in sexual situations, how to get on with our lives in a post–COVID-19 era.

Given how much is still unknown, it is likely each of us will come up with our own algorithm of risk assessment. It is likely that the formulas used will not necessarily be based on scientific facts, although that would be ideal. If past epidemic and recent pandemic behaviors are any indicators, people’s actions will reflect some combination of their own needs and desires, their own comfort level with risk-taking, and their relative understanding of complex subjects like virology, immunology, epidemiology, and public health. The challenge faced by public health officials today is to translate complex scientific and medical issues into messages average people can understand.

What exactly can be done? I’m not exactly sure, but I hope that improved education and communication can help. In the first 2 decades of the AIDS epidemic, efforts were made to change and tailor HIV-prevention messages to specific, at-risk demographic groups. Today, public health messages aimed at preventing COVID-19’s spread that resonate with older people can fall on a younger person’s deaf ears. One message size does not fit all. Hopefully, public health officials and government leaders will act on this sooner rather than later.
 

Dr. Drescher, a psychoanalyst, is clinical professor of psychiatry at Columbia University, and training and supervising analyst at the William A. White Institute, both in New York. He also is emeritus editor of the Journal of Gay & Lesbian Mental Health. Dr. Drescher has no other disclosures.

There is concern that the COVID-19 pandemic may be inflicting collateral damage on vulnerable patients with chronic conditions, in particular, those with COPD, according to a commentary published in CHEST (2020 May 28. doi: 10.1016/j.chest.2020.05.549) by a group of physicians who study COPD.

Not only is COPD among the most prevalent underlying diseases among hospitalized COVID-19 patients (Clin Microbiol Infect. 2020 Jun 8. doi: 10.1016/j.cmi.2020.05.041), but other unanticipated factors of treatment put these patients at extra risk. Valerie Press, MD, assistant professor of medicine and pediatrics at the University of Chicago, and colleagues aimed to alert physicians to be aware of potential negative effects, or collateral damage, that the pandemic can have on their patients with COPD, even those without a COVID-19 diagnosis.

These concerns include that patients may delay presenting to the ED with acute exacerbations of COPD and once they present they may be at later stages of the exacerbation. Further, evaluation for COVID-19 as a possible trigger of acute exacerbations of COPD (AECOPD) is essential; however, implementing proven AECOPD therapies remains challenging. For instance, routine therapy with corticosteroids for AECOPD may be delayed due to diagnostic uncertainty and hesitation to treat COVID-19 with steroids while COVID-19 testing is pending,” Dr. Press and her colleagues stated.

Shortages and scarcity of medications such as albuterol inhalers to treat COPD have been reported. In addition, patients with COPD are currently less likely to access their health care providers because of fear of COVID-19 infection. This barrier to care and the current higher threshold for presenting to the hospital may to lead to more cases of AECOPD and worsening health in these patients, according to the authors.

Dr. Press said in an interview: “Access to medications delivered through inhalers is challenging even without the pandemic due to high cost of medications. Generic medications are key to improving access for patients with chronic lung disease, so once the generic albuterol becomes available, this should help with access. In the meantime, some companies help provide medications at reduced cost, but usually only on a short time basis. In addition, some pharmacies have lower-cost albuterol inhalers, but these are often not supplied with a full month of dosing.”

In addition to all these concerns is the economic toll this pandemic is taking on patients. The association between COPD and socioeconomic status has been studied in depth (Am J Respir Crit Care Med. 2019; 199[8]:961-69) and would indicate that low-income patients with COPD would face an increased burden during an economic downturn. The authors noted, “Historic rapid job loss and unemployment in the U.S., coupled with a health system of employment-integrated health insurance coverage, makes it more likely that people with COPD will not be able to afford their medication.”

Dr. Press stressed that the COVID pandemic has highlighted critically important disparities in access to health care and disparities in health. “Many of the recommendations regarding stay-at-home and other safety mechanisms to prevent contracting and spreading COVID-19 have not been feasible for all sub-populations in the United States. Those that were essential workers did not have the ability to stay home. Further, those that rely on public transportation had less opportunities to social distance. Finally, while telemedicine opportunities have advanced for clinical care, not all patients have equal access to these capabilities and health disparities could widen in this regard as well. Clinicians have a responsibility to identify social determinants of health that increase risks to our patients’ health and limit their safety.”*

The authors offer some concrete suggestions of how physicians can address some of these concerns, including the following:

• Be alert to potential barriers to accessing medication and be aware of generic albuterol inhaler recently approved by the FDA in response to COVID-19–related shortages.
• Use telemedicine to monitor patients and improvement of home self-management. Clinicians should help patients “seek care with worsening symptoms and have clear management guidelines regarding seeking phone/video visits; implementing therapy with corticosteroids, antibiotics, or inhalers and nebulizers; COVID-19 testing recommendations; and thresholds for seeking emergent, urgent, or outpatient care in person,” Dr. Press added, “Building on the work of nurse advice lines and case management and other support services for high-risk patients with COPD may continue via telehealth and telephone visits.”
• Ensure that untried therapy for COVID-19 “does not displace proven and necessary treatments for patients with COPD, hence placing them at increased risk for poor outcomes.”

Dr. Press is also concerned about the post–COVID-19 period for patients with COPD. “It is too early to know if there are specific after effects of the COVID infection on patients with COPD, but given the damage the virus does to even healthy lungs, there is reason to have concern that COVID could cause worsening damage to the lungs of individuals with COPD.”

She noted, “Post-ICU [PICU] syndrome has been recognized in patients with ARDS generally, and patients who recover from critical illness may have long-lasting (and permanent) effects on strength, cognition, disability, and pulmonary function. Whether the PICU syndrome in patients with ARDS due to COVID-19 specifically is different from the PICU syndrome due to other causes remains unknown. But clinicians whose patients with COPD survive COVID-19 may expect long-lasting effects and slow recovery in cases where COVID-19 led to severe ARDS and a prolonged ICU stay. Assessment of overall patient recovery and functional capacity (beyond lung function and dyspnea symptoms) including deconditioning, anxiety, PTSD, weakness, and malnutrition will need to be addressed. Additionally, clinicians may help patients and their families understand the expected recovery and help facilitate family conversations about residual effects of COVID-19.”

The authors had no disclosures.

SOURCE: Press V et al. Chest. 2020 May 28. doi:10.1016/j.chest.2020.05.549.

CORRECTION: *This story was updated with further comments and clarifications from Dr. Press. 6/23/2020

There is concern that the COVID-19 pandemic may be inflicting collateral damage on vulnerable patients with chronic conditions, in particular, those with COPD, according to a commentary published in CHEST (2020 May 28. doi: 10.1016/j.chest.2020.05.549) by a group of physicians who study COPD.

Not only is COPD among the most prevalent underlying diseases among hospitalized COVID-19 patients (Clin Microbiol Infect. 2020 Jun 8. doi: 10.1016/j.cmi.2020.05.041), but other unanticipated factors of treatment put these patients at extra risk. Valerie Press, MD, assistant professor of medicine and pediatrics at the University of Chicago, and colleagues aimed to alert physicians to be aware of potential negative effects, or collateral damage, that the pandemic can have on their patients with COPD, even those without a COVID-19 diagnosis.

These concerns include that patients may delay presenting to the ED with acute exacerbations of COPD and once they present they may be at later stages of the exacerbation. Further, evaluation for COVID-19 as a possible trigger of acute exacerbations of COPD (AECOPD) is essential; however, implementing proven AECOPD therapies remains challenging. For instance, routine therapy with corticosteroids for AECOPD may be delayed due to diagnostic uncertainty and hesitation to treat COVID-19 with steroids while COVID-19 testing is pending,” Dr. Press and her colleagues stated.

Shortages and scarcity of medications such as albuterol inhalers to treat COPD have been reported. In addition, patients with COPD are currently less likely to access their health care providers because of fear of COVID-19 infection. This barrier to care and the current higher threshold for presenting to the hospital may to lead to more cases of AECOPD and worsening health in these patients, according to the authors.

Dr. Press said in an interview: “Access to medications delivered through inhalers is challenging even without the pandemic due to high cost of medications. Generic medications are key to improving access for patients with chronic lung disease, so once the generic albuterol becomes available, this should help with access. In the meantime, some companies help provide medications at reduced cost, but usually only on a short time basis. In addition, some pharmacies have lower-cost albuterol inhalers, but these are often not supplied with a full month of dosing.”

In addition to all these concerns is the economic toll this pandemic is taking on patients. The association between COPD and socioeconomic status has been studied in depth (Am J Respir Crit Care Med. 2019; 199[8]:961-69) and would indicate that low-income patients with COPD would face an increased burden during an economic downturn. The authors noted, “Historic rapid job loss and unemployment in the U.S., coupled with a health system of employment-integrated health insurance coverage, makes it more likely that people with COPD will not be able to afford their medication.”

Dr. Press stressed that the COVID pandemic has highlighted critically important disparities in access to health care and disparities in health. “Many of the recommendations regarding stay-at-home and other safety mechanisms to prevent contracting and spreading COVID-19 have not been feasible for all sub-populations in the United States. Those that were essential workers did not have the ability to stay home. Further, those that rely on public transportation had less opportunities to social distance. Finally, while telemedicine opportunities have advanced for clinical care, not all patients have equal access to these capabilities and health disparities could widen in this regard as well. Clinicians have a responsibility to identify social determinants of health that increase risks to our patients’ health and limit their safety.”*

The authors offer some concrete suggestions of how physicians can address some of these concerns, including the following:

• Be alert to potential barriers to accessing medication and be aware of generic albuterol inhaler recently approved by the FDA in response to COVID-19–related shortages.
• Use telemedicine to monitor patients and improvement of home self-management. Clinicians should help patients “seek care with worsening symptoms and have clear management guidelines regarding seeking phone/video visits; implementing therapy with corticosteroids, antibiotics, or inhalers and nebulizers; COVID-19 testing recommendations; and thresholds for seeking emergent, urgent, or outpatient care in person,” Dr. Press added, “Building on the work of nurse advice lines and case management and other support services for high-risk patients with COPD may continue via telehealth and telephone visits.”
• Ensure that untried therapy for COVID-19 “does not displace proven and necessary treatments for patients with COPD, hence placing them at increased risk for poor outcomes.”

Dr. Press is also concerned about the post–COVID-19 period for patients with COPD. “It is too early to know if there are specific after effects of the COVID infection on patients with COPD, but given the damage the virus does to even healthy lungs, there is reason to have concern that COVID could cause worsening damage to the lungs of individuals with COPD.”

She noted, “Post-ICU [PICU] syndrome has been recognized in patients with ARDS generally, and patients who recover from critical illness may have long-lasting (and permanent) effects on strength, cognition, disability, and pulmonary function. Whether the PICU syndrome in patients with ARDS due to COVID-19 specifically is different from the PICU syndrome due to other causes remains unknown. But clinicians whose patients with COPD survive COVID-19 may expect long-lasting effects and slow recovery in cases where COVID-19 led to severe ARDS and a prolonged ICU stay. Assessment of overall patient recovery and functional capacity (beyond lung function and dyspnea symptoms) including deconditioning, anxiety, PTSD, weakness, and malnutrition will need to be addressed. Additionally, clinicians may help patients and their families understand the expected recovery and help facilitate family conversations about residual effects of COVID-19.”

The authors had no disclosures.

SOURCE: Press V et al. Chest. 2020 May 28. doi:10.1016/j.chest.2020.05.549.

CORRECTION: *This story was updated with further comments and clarifications from Dr. Press. 6/23/2020

There is concern that the COVID-19 pandemic may be inflicting collateral damage on vulnerable patients with chronic conditions, in particular, those with COPD, according to a commentary published in CHEST (2020 May 28. doi: 10.1016/j.chest.2020.05.549) by a group of physicians who study COPD.

Not only is COPD among the most prevalent underlying diseases among hospitalized COVID-19 patients (Clin Microbiol Infect. 2020 Jun 8. doi: 10.1016/j.cmi.2020.05.041), but other unanticipated factors of treatment put these patients at extra risk. Valerie Press, MD, assistant professor of medicine and pediatrics at the University of Chicago, and colleagues aimed to alert physicians to be aware of potential negative effects, or collateral damage, that the pandemic can have on their patients with COPD, even those without a COVID-19 diagnosis.

These concerns include that patients may delay presenting to the ED with acute exacerbations of COPD and once they present they may be at later stages of the exacerbation. Further, evaluation for COVID-19 as a possible trigger of acute exacerbations of COPD (AECOPD) is essential; however, implementing proven AECOPD therapies remains challenging. For instance, routine therapy with corticosteroids for AECOPD may be delayed due to diagnostic uncertainty and hesitation to treat COVID-19 with steroids while COVID-19 testing is pending,” Dr. Press and her colleagues stated.

Shortages and scarcity of medications such as albuterol inhalers to treat COPD have been reported. In addition, patients with COPD are currently less likely to access their health care providers because of fear of COVID-19 infection. This barrier to care and the current higher threshold for presenting to the hospital may to lead to more cases of AECOPD and worsening health in these patients, according to the authors.

Dr. Press said in an interview: “Access to medications delivered through inhalers is challenging even without the pandemic due to high cost of medications. Generic medications are key to improving access for patients with chronic lung disease, so once the generic albuterol becomes available, this should help with access. In the meantime, some companies help provide medications at reduced cost, but usually only on a short time basis. In addition, some pharmacies have lower-cost albuterol inhalers, but these are often not supplied with a full month of dosing.”

In addition to all these concerns is the economic toll this pandemic is taking on patients. The association between COPD and socioeconomic status has been studied in depth (Am J Respir Crit Care Med. 2019; 199[8]:961-69) and would indicate that low-income patients with COPD would face an increased burden during an economic downturn. The authors noted, “Historic rapid job loss and unemployment in the U.S., coupled with a health system of employment-integrated health insurance coverage, makes it more likely that people with COPD will not be able to afford their medication.”

Dr. Press stressed that the COVID pandemic has highlighted critically important disparities in access to health care and disparities in health. “Many of the recommendations regarding stay-at-home and other safety mechanisms to prevent contracting and spreading COVID-19 have not been feasible for all sub-populations in the United States. Those that were essential workers did not have the ability to stay home. Further, those that rely on public transportation had less opportunities to social distance. Finally, while telemedicine opportunities have advanced for clinical care, not all patients have equal access to these capabilities and health disparities could widen in this regard as well. Clinicians have a responsibility to identify social determinants of health that increase risks to our patients’ health and limit their safety.”*

The authors offer some concrete suggestions of how physicians can address some of these concerns, including the following:

• Be alert to potential barriers to accessing medication and be aware of generic albuterol inhaler recently approved by the FDA in response to COVID-19–related shortages.
• Use telemedicine to monitor patients and improvement of home self-management. Clinicians should help patients “seek care with worsening symptoms and have clear management guidelines regarding seeking phone/video visits; implementing therapy with corticosteroids, antibiotics, or inhalers and nebulizers; COVID-19 testing recommendations; and thresholds for seeking emergent, urgent, or outpatient care in person,” Dr. Press added, “Building on the work of nurse advice lines and case management and other support services for high-risk patients with COPD may continue via telehealth and telephone visits.”
• Ensure that untried therapy for COVID-19 “does not displace proven and necessary treatments for patients with COPD, hence placing them at increased risk for poor outcomes.”

Dr. Press is also concerned about the post–COVID-19 period for patients with COPD. “It is too early to know if there are specific after effects of the COVID infection on patients with COPD, but given the damage the virus does to even healthy lungs, there is reason to have concern that COVID could cause worsening damage to the lungs of individuals with COPD.”

She noted, “Post-ICU [PICU] syndrome has been recognized in patients with ARDS generally, and patients who recover from critical illness may have long-lasting (and permanent) effects on strength, cognition, disability, and pulmonary function. Whether the PICU syndrome in patients with ARDS due to COVID-19 specifically is different from the PICU syndrome due to other causes remains unknown. But clinicians whose patients with COPD survive COVID-19 may expect long-lasting effects and slow recovery in cases where COVID-19 led to severe ARDS and a prolonged ICU stay. Assessment of overall patient recovery and functional capacity (beyond lung function and dyspnea symptoms) including deconditioning, anxiety, PTSD, weakness, and malnutrition will need to be addressed. Additionally, clinicians may help patients and their families understand the expected recovery and help facilitate family conversations about residual effects of COVID-19.”

The authors had no disclosures.

SOURCE: Press V et al. Chest. 2020 May 28. doi:10.1016/j.chest.2020.05.549.

CORRECTION: *This story was updated with further comments and clarifications from Dr. Press. 6/23/2020

Headache may be a key symptom of COVID-19 that predicts the disease’s clinical evolution in individual patients, new research suggests. An observational study of more than 100 patients showed that headache onset could occur during the presymptomatic or symptomatic phase of COVID-19 and could resemble tension-type or migraine headache.

Headache itself was associated with a shorter symptomatic period, while headache and anosmia were associated with a shorter hospitalization period. In a subgroup of participants, headache persisted even after the symptoms of COVID-19 had been resolved.

Investigators noted that understanding the pathophysiology of headache in COVID-19 could improve understanding of migraine and other headache disorders. “It seems that those patients who start early on, during the asymptomatic or early symptomatic period of COVID-19, with headache have a more localized inflammatory response that may reflect the ability of the body to better control and respond to the infection by SARS-CoV-2,” lead investigator Patricia Pozo-Rosich, MD, PhD, head of the headache and craniofacial pain unit at Vall d’Hebron University Hospital, Barcelona, said in an interview.

She presented the findings at the virtual annual meeting of the American Headache Society.

Systemic inflammation

Headache is one of the main symptoms of COVID-19. A recent study of 214 patients with COVID-19 showed that approximately 13% of the participants had headache and 5% had anosmia.

SARS-CoV-2 penetrates the cells through the ACE2 receptor, which is present throughout the body. “SARS-CoV-2 enters the body through the nasal cavity and it probably penetrates the nervous system in the periphery through afferent branches of the olfactory and trigeminal nerve,” Dr. Pozo-Rosich said. It travels to the lungs and, later, the bloodstream. This generates systemic inflammation that may turn into a cytokine storm. Evidence has identified cortical hyperintensities and olfactory bulb hyperintensities in patients with COVID-19, suggesting that the virus directly infects the CNS.

Interleukin-6, one of the main inflammatory molecules, has been proven to be related to COVID-19 and has become a therapeutic target. Levels of IL-6 may be lower and tend to be more stable in patients with both COVID-19 and headache than in patients with COVID-19 only.

The researchers observed 130 patients (51% women; mean age, 54 years) with COVID-19 who were attended by neurologists at Vall d’Hebron. In this group, 74.4% had headache. Patients with headache tended to be younger than those without headache (mean age, 50 years vs. 63 years, respectively) and tended to be women (58.6% vs. 29.4%).

Approximately one-third of patients with headache had a history of migraine. Most reported mild to moderate pain that resembled tension-type headache. In participants with severe pain and migraine-like features, headache more often began during the asymptomatic phase of COVID-19.

Disease evolution predictor?

The investigators followed up on 100 of the 130 patients with COVID-19, of whom 74 had headache. About 38% of these patients had ongoing headache after 6 weeks, which suggests that some patients may develop a new daily persistent headache once a 3-month period has elapsed. Half of this group had no previous headache history. Headache had been the prodromal symptom of COVID-19 for 21.4% of these patients.

Results showed that headache predicted the clinical evolution of COVID-19. The symptomatic phase of COVID-19 was 7 days shorter for patients with headache than for those without headache. In addition, the period of hospitalization was 7 days shorter for patients with headache and anosmia, compared with patients who had neither headache nor anosmia.

Most therapies, including ibuprofen, candesartan, and anti–calcitonin gene–related peptide (CGRP) monoclonal antibodies, are safe for treating headache in COVID-19, the investigators noted. “We should just try to initially avoid steroids to avoid interference with the body’s reaction to SARS-CoV-2,” Dr. Pozo-Rosich said.

Researchers at Sidney Kimmel Medical College, Philadelphia, are currently studying intranasal vazegepant, an anti-CGRP therapy, as a way to potentially blunt the severe inflammatory response in the lungs of patients with COVID-19, she noted, adding that this peptide may have a future role not only in headache, but also in COVID-19.

Historical link to viral infections

Commenting on the study, Matthew S. Robbins, MD, associate professor of neurology at Weill Cornell Medicine, New York, said the findings associating headache with a shorter symptomatic phase of COVID-19 were “interesting.”

“Headache is common with mild viral infections. More severe viral infections may simply feature more overwhelming respiratory symptoms and fever that lead to underreporting or underascertainment of headache,” said Dr. Robbins, who was not involved with the research.

He noted that the finding showing an association of headache and COVID-19 with a younger age and in women “may be related to a higher prevalence of migraine biology in such patients, and being triggered by the virus or the psychological stress associated with it.”

Dr. Robbins added that viral illnesses have long been associated with new daily persistent headache, “dating back to the early 1980s,” when it was first described in association with Epstein-Barr virus. These infections have also been implicated in the progression of migraine to chronic migraine in adolescents.

“In my view, treatment should be aimed at the symptomatic headache type for which new daily persistent headache resembles, regardless of the potential inciting factor,” Dr. Robbins said.

Dr. Pozo-Rosich has received consulting fees from Allergan, Amgen, Almirall, Biohaven, Chiesi, Eli Lilly, Medscape, Novartis, and Teva Pharmaceuticals. Dr. Robbins has disclosed no relevant financial relationships.

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

Headache may be a key symptom of COVID-19 that predicts the disease’s clinical evolution in individual patients, new research suggests. An observational study of more than 100 patients showed that headache onset could occur during the presymptomatic or symptomatic phase of COVID-19 and could resemble tension-type or migraine headache.

Headache itself was associated with a shorter symptomatic period, while headache and anosmia were associated with a shorter hospitalization period. In a subgroup of participants, headache persisted even after the symptoms of COVID-19 had been resolved.

Investigators noted that understanding the pathophysiology of headache in COVID-19 could improve understanding of migraine and other headache disorders. “It seems that those patients who start early on, during the asymptomatic or early symptomatic period of COVID-19, with headache have a more localized inflammatory response that may reflect the ability of the body to better control and respond to the infection by SARS-CoV-2,” lead investigator Patricia Pozo-Rosich, MD, PhD, head of the headache and craniofacial pain unit at Vall d’Hebron University Hospital, Barcelona, said in an interview.

She presented the findings at the virtual annual meeting of the American Headache Society.

Systemic inflammation

Headache is one of the main symptoms of COVID-19. A recent study of 214 patients with COVID-19 showed that approximately 13% of the participants had headache and 5% had anosmia.

SARS-CoV-2 penetrates the cells through the ACE2 receptor, which is present throughout the body. “SARS-CoV-2 enters the body through the nasal cavity and it probably penetrates the nervous system in the periphery through afferent branches of the olfactory and trigeminal nerve,” Dr. Pozo-Rosich said. It travels to the lungs and, later, the bloodstream. This generates systemic inflammation that may turn into a cytokine storm. Evidence has identified cortical hyperintensities and olfactory bulb hyperintensities in patients with COVID-19, suggesting that the virus directly infects the CNS.

Interleukin-6, one of the main inflammatory molecules, has been proven to be related to COVID-19 and has become a therapeutic target. Levels of IL-6 may be lower and tend to be more stable in patients with both COVID-19 and headache than in patients with COVID-19 only.

The researchers observed 130 patients (51% women; mean age, 54 years) with COVID-19 who were attended by neurologists at Vall d’Hebron. In this group, 74.4% had headache. Patients with headache tended to be younger than those without headache (mean age, 50 years vs. 63 years, respectively) and tended to be women (58.6% vs. 29.4%).

Approximately one-third of patients with headache had a history of migraine. Most reported mild to moderate pain that resembled tension-type headache. In participants with severe pain and migraine-like features, headache more often began during the asymptomatic phase of COVID-19.

Disease evolution predictor?

The investigators followed up on 100 of the 130 patients with COVID-19, of whom 74 had headache. About 38% of these patients had ongoing headache after 6 weeks, which suggests that some patients may develop a new daily persistent headache once a 3-month period has elapsed. Half of this group had no previous headache history. Headache had been the prodromal symptom of COVID-19 for 21.4% of these patients.

Results showed that headache predicted the clinical evolution of COVID-19. The symptomatic phase of COVID-19 was 7 days shorter for patients with headache than for those without headache. In addition, the period of hospitalization was 7 days shorter for patients with headache and anosmia, compared with patients who had neither headache nor anosmia.

Most therapies, including ibuprofen, candesartan, and anti–calcitonin gene–related peptide (CGRP) monoclonal antibodies, are safe for treating headache in COVID-19, the investigators noted. “We should just try to initially avoid steroids to avoid interference with the body’s reaction to SARS-CoV-2,” Dr. Pozo-Rosich said.

Researchers at Sidney Kimmel Medical College, Philadelphia, are currently studying intranasal vazegepant, an anti-CGRP therapy, as a way to potentially blunt the severe inflammatory response in the lungs of patients with COVID-19, she noted, adding that this peptide may have a future role not only in headache, but also in COVID-19.

Historical link to viral infections

Commenting on the study, Matthew S. Robbins, MD, associate professor of neurology at Weill Cornell Medicine, New York, said the findings associating headache with a shorter symptomatic phase of COVID-19 were “interesting.”

“Headache is common with mild viral infections. More severe viral infections may simply feature more overwhelming respiratory symptoms and fever that lead to underreporting or underascertainment of headache,” said Dr. Robbins, who was not involved with the research.

He noted that the finding showing an association of headache and COVID-19 with a younger age and in women “may be related to a higher prevalence of migraine biology in such patients, and being triggered by the virus or the psychological stress associated with it.”

Dr. Robbins added that viral illnesses have long been associated with new daily persistent headache, “dating back to the early 1980s,” when it was first described in association with Epstein-Barr virus. These infections have also been implicated in the progression of migraine to chronic migraine in adolescents.

“In my view, treatment should be aimed at the symptomatic headache type for which new daily persistent headache resembles, regardless of the potential inciting factor,” Dr. Robbins said.

Dr. Pozo-Rosich has received consulting fees from Allergan, Amgen, Almirall, Biohaven, Chiesi, Eli Lilly, Medscape, Novartis, and Teva Pharmaceuticals. Dr. Robbins has disclosed no relevant financial relationships.

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

Headache may be a key symptom of COVID-19 that predicts the disease’s clinical evolution in individual patients, new research suggests. An observational study of more than 100 patients showed that headache onset could occur during the presymptomatic or symptomatic phase of COVID-19 and could resemble tension-type or migraine headache.

Headache itself was associated with a shorter symptomatic period, while headache and anosmia were associated with a shorter hospitalization period. In a subgroup of participants, headache persisted even after the symptoms of COVID-19 had been resolved.

Investigators noted that understanding the pathophysiology of headache in COVID-19 could improve understanding of migraine and other headache disorders. “It seems that those patients who start early on, during the asymptomatic or early symptomatic period of COVID-19, with headache have a more localized inflammatory response that may reflect the ability of the body to better control and respond to the infection by SARS-CoV-2,” lead investigator Patricia Pozo-Rosich, MD, PhD, head of the headache and craniofacial pain unit at Vall d’Hebron University Hospital, Barcelona, said in an interview.

She presented the findings at the virtual annual meeting of the American Headache Society.

Systemic inflammation

Headache is one of the main symptoms of COVID-19. A recent study of 214 patients with COVID-19 showed that approximately 13% of the participants had headache and 5% had anosmia.

SARS-CoV-2 penetrates the cells through the ACE2 receptor, which is present throughout the body. “SARS-CoV-2 enters the body through the nasal cavity and it probably penetrates the nervous system in the periphery through afferent branches of the olfactory and trigeminal nerve,” Dr. Pozo-Rosich said. It travels to the lungs and, later, the bloodstream. This generates systemic inflammation that may turn into a cytokine storm. Evidence has identified cortical hyperintensities and olfactory bulb hyperintensities in patients with COVID-19, suggesting that the virus directly infects the CNS.

Interleukin-6, one of the main inflammatory molecules, has been proven to be related to COVID-19 and has become a therapeutic target. Levels of IL-6 may be lower and tend to be more stable in patients with both COVID-19 and headache than in patients with COVID-19 only.

The researchers observed 130 patients (51% women; mean age, 54 years) with COVID-19 who were attended by neurologists at Vall d’Hebron. In this group, 74.4% had headache. Patients with headache tended to be younger than those without headache (mean age, 50 years vs. 63 years, respectively) and tended to be women (58.6% vs. 29.4%).

Approximately one-third of patients with headache had a history of migraine. Most reported mild to moderate pain that resembled tension-type headache. In participants with severe pain and migraine-like features, headache more often began during the asymptomatic phase of COVID-19.

Disease evolution predictor?

The investigators followed up on 100 of the 130 patients with COVID-19, of whom 74 had headache. About 38% of these patients had ongoing headache after 6 weeks, which suggests that some patients may develop a new daily persistent headache once a 3-month period has elapsed. Half of this group had no previous headache history. Headache had been the prodromal symptom of COVID-19 for 21.4% of these patients.

Results showed that headache predicted the clinical evolution of COVID-19. The symptomatic phase of COVID-19 was 7 days shorter for patients with headache than for those without headache. In addition, the period of hospitalization was 7 days shorter for patients with headache and anosmia, compared with patients who had neither headache nor anosmia.

Most therapies, including ibuprofen, candesartan, and anti–calcitonin gene–related peptide (CGRP) monoclonal antibodies, are safe for treating headache in COVID-19, the investigators noted. “We should just try to initially avoid steroids to avoid interference with the body’s reaction to SARS-CoV-2,” Dr. Pozo-Rosich said.

Researchers at Sidney Kimmel Medical College, Philadelphia, are currently studying intranasal vazegepant, an anti-CGRP therapy, as a way to potentially blunt the severe inflammatory response in the lungs of patients with COVID-19, she noted, adding that this peptide may have a future role not only in headache, but also in COVID-19.

Historical link to viral infections

Commenting on the study, Matthew S. Robbins, MD, associate professor of neurology at Weill Cornell Medicine, New York, said the findings associating headache with a shorter symptomatic phase of COVID-19 were “interesting.”

“Headache is common with mild viral infections. More severe viral infections may simply feature more overwhelming respiratory symptoms and fever that lead to underreporting or underascertainment of headache,” said Dr. Robbins, who was not involved with the research.

He noted that the finding showing an association of headache and COVID-19 with a younger age and in women “may be related to a higher prevalence of migraine biology in such patients, and being triggered by the virus or the psychological stress associated with it.”

Dr. Robbins added that viral illnesses have long been associated with new daily persistent headache, “dating back to the early 1980s,” when it was first described in association with Epstein-Barr virus. These infections have also been implicated in the progression of migraine to chronic migraine in adolescents.

“In my view, treatment should be aimed at the symptomatic headache type for which new daily persistent headache resembles, regardless of the potential inciting factor,” Dr. Robbins said.

Dr. Pozo-Rosich has received consulting fees from Allergan, Amgen, Almirall, Biohaven, Chiesi, Eli Lilly, Medscape, Novartis, and Teva Pharmaceuticals. Dr. Robbins has disclosed no relevant financial relationships.

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

Presented during the ASCO 2020 plenary session, the results of the phase 3 ADAURA trial will prove practice-changing, according to Dr. Mark Kris of Memorial Sloan Kettering Cancer Center. Over 600 patients whose resected tumors were found to have EGFR mutations were treated with osimertinib. The results more than doubled disease-free survival rates, from 44% to 90% at 2 years.

Among other adjuvant trials, the phase 2 VISION study looked at tepotinib, a once-daily, highly selective oral MET inhibitor. The study showed durable responses coupled with acceptable side effects. The drug has been given fast-track status by the US Food and Drug Administration.

Dr. Kris notes that the DESTINY study introduces trastuzumab deruxtecan, an antibody-drug conjugate, as a promising new class of drugs for lung cancer patients. Interim results presented at ASCO further support the HER2 mutation as another potential target for patients with lung cancer.

Finally, the phase 2 CITYSCAPE study provides preliminary evidence for a new checkpoint inhibitor. The monoclonal antibody tiragolumab was developed to block TIGIT. The study showed that the combination of tiragolumab and atezolizumab can improve both rates of response and time to disease recurrence — results Dr. Kris considers encouraging for patients with advanced lung cancer.

Mark G. Kris, MD

Mark G. Kris, MD, Professor, Department of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Presented during the ASCO 2020 plenary session, the results of the phase 3 ADAURA trial will prove practice-changing, according to Dr. Mark Kris of Memorial Sloan Kettering Cancer Center. Over 600 patients whose resected tumors were found to have EGFR mutations were treated with osimertinib. The results more than doubled disease-free survival rates, from 44% to 90% at 2 years.

Among other adjuvant trials, the phase 2 VISION study looked at tepotinib, a once-daily, highly selective oral MET inhibitor. The study showed durable responses coupled with acceptable side effects. The drug has been given fast-track status by the US Food and Drug Administration.

Dr. Kris notes that the DESTINY study introduces trastuzumab deruxtecan, an antibody-drug conjugate, as a promising new class of drugs for lung cancer patients. Interim results presented at ASCO further support the HER2 mutation as another potential target for patients with lung cancer.

Finally, the phase 2 CITYSCAPE study provides preliminary evidence for a new checkpoint inhibitor. The monoclonal antibody tiragolumab was developed to block TIGIT. The study showed that the combination of tiragolumab and atezolizumab can improve both rates of response and time to disease recurrence — results Dr. Kris considers encouraging for patients with advanced lung cancer.

Mark G. Kris, MD

Mark G. Kris, MD, Professor, Department of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Presented during the ASCO 2020 plenary session, the results of the phase 3 ADAURA trial will prove practice-changing, according to Dr. Mark Kris of Memorial Sloan Kettering Cancer Center. Over 600 patients whose resected tumors were found to have EGFR mutations were treated with osimertinib. The results more than doubled disease-free survival rates, from 44% to 90% at 2 years.

Among other adjuvant trials, the phase 2 VISION study looked at tepotinib, a once-daily, highly selective oral MET inhibitor. The study showed durable responses coupled with acceptable side effects. The drug has been given fast-track status by the US Food and Drug Administration.

Dr. Kris notes that the DESTINY study introduces trastuzumab deruxtecan, an antibody-drug conjugate, as a promising new class of drugs for lung cancer patients. Interim results presented at ASCO further support the HER2 mutation as another potential target for patients with lung cancer.

Finally, the phase 2 CITYSCAPE study provides preliminary evidence for a new checkpoint inhibitor. The monoclonal antibody tiragolumab was developed to block TIGIT. The study showed that the combination of tiragolumab and atezolizumab can improve both rates of response and time to disease recurrence — results Dr. Kris considers encouraging for patients with advanced lung cancer.

Mark G. Kris, MD

Mark G. Kris, MD, Professor, Department of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

A new article in the Journal of Clinical Endocrinology & Metabolism (JCEM) addresses unique concerns and considerations regarding diabetic ketoacidosis (DKA) in the setting of COVID-19.

Corresponding author Marie E. McDonnell, MD, director of the diabetes program at Brigham and Women’s Hospital, Boston, Massachusetts, discussed the recommendations with Medscape Medical News and also spoke about the news this week that the corticosteroid dexamethasone reduced death rates in severely ill patients with COVID-19.

The full JCEM article, by lead author Nadine E. Palermo, DO, Division of Endocrinology, Diabetes, and Hypertension, also at Brigham and Women’s Hospital, covers DKA diagnosis and triage, and emphasizes that usual hospital protocols for DKA management may need to be adjusted during COVID-19 to help preserve personal protective equipment and ICU beds.

“Hospitals and clinicians need to be able to quickly identify and manage DKA in COVID patients to save lives. This involves determining the options for management, including when less intensive subcutaneous insulin is indicated, and understanding how to guide patients on avoiding this serious complication,” McDonnell said in an Endocrine Society statement.
 

What about dexamethasone for severe COVID-19 in diabetes?

The new article briefly touches on the fact that upward adjustments to intensive intravenous insulin therapy for DKA may be necessary in patients with COVID-19 who are receiving concomitant corticosteroids or vasopressors.

But it was written prior to the June 16 announcement of the “RECOVERY” trial results with dexamethasone. The UK National Health Service immediately approved the drug’s use in the COVID-19 setting, despite the fact that there has been no published article on the findings yet.

McDonnell told Medscape Medical News that she would need to see formal results to better understand exactly which patients were studied and which ones benefited.

“The peer review will be critical. It looks as if it only benefits people who need respiratory support, but I want to understand that in much more detail,” she said. “If they all had acute respiratory distress syndrome [ARDS],” that’s different.

“There are already some data supporting steroid use in ARDS,” she noted, but added that not all of it suggests benefit.

She pointed to one of several studies now showing that diabetes, and hyperglycemia among people without a prior diabetes diagnosis, are both strong predictors of mortality in hospitalized patients with COVID-19.

“There was a very clear relationship between hyperglycemia and outcomes. We really shouldn’t put people at risk until we have clear data,” she said.

If, once the data are reviewed and appropriate dexamethasone becomes an established treatment for severe COVID-19, hyperglycemia would be a concern among all patients, not just those with previously diagnosed diabetes, she noted.

“We know a good number of people with prediabetes develop hyperglycemia when put on steroids. They can push people over the edge. We’re not going to miss anybody, but treating steroid-induced hyperglycemia is really hard,” McDonnell explained.

She also recommended 2014 guidance from Diabetes UK and the Association of British Clinical Diabetologists, which addresses management of inpatient steroid-induced DKA in patients with and without pre-existing diabetes.

Another major concern, she said, is “patients trying to get dexamethasone when they start to get sick” because this is not the right population to use this agent.

“We worry about people who do not need this drug. If they have diabetes, they put themselves at risk of hyperglycemia, which then increases the risk of severe COVID-19. And then they’re also putting themselves at risk of DKA. It would just be bad medicine,” she said.

Managing DKA in the face of COVID-19: Flexibility is key

In the JCEM article, Palermo and colleagues emphasize that the usual hospital protocols for DKA management may need to be adjusted during COVID-19 in the interest of reducing transmission risk and preserving scare resources.

They provide evidence for alternative treatment strategies, such as the use of subcutaneous rather than intravenous insulin when appropriate.

“We wanted to outline when exactly you should consider nonintensive management strategies for DKA,” McDonnell further explained to Medscape Medical News.

“That would include those with mild or some with moderate DKA. ... The idea is to remind our colleagues about that because hospitals tend to operate on a protocol-driven algorithmic methodology, they can forget to step off the usual care pathway even if evidence supports that,” she said.   

But on the other hand, she also said that, in some very complex or severely ill patients with COVID-19, classical intravenous insulin therapy makes the most sense even if their DKA is mild.
 

The outpatient setting: Prevention and preparation

The new article also addresses several concerns regarding DKA prevention in the outpatient setting.

As with other guidelines, it includes a reminder that patients with diabetes should be advised to discontinue sodium-glucose cotransporter 2 (SGLT2) inhibitors if they become ill with COVID-19, especially if they’re not eating or drinking normally, because they raise the risk for DKA.

Also, for patients with type 1 diabetes, particularly those with a history of repeated DKA, “this is the time to make sure we reach out to patients to refill their insulin prescriptions and address issues related to cost and other access difficulties,” McDonnell said.

The authors also emphasize that insulin starts and education should not be postponed during the pandemic. “Patients identified as meeting criteria to start insulin should be referred for urgent education, either in person or, whenever possible and practical, via video teleconferencing,” they urge.

McDonnell has reported receiving research funding from Novo Nordisk. The other two authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

A new article in the Journal of Clinical Endocrinology & Metabolism (JCEM) addresses unique concerns and considerations regarding diabetic ketoacidosis (DKA) in the setting of COVID-19.

Corresponding author Marie E. McDonnell, MD, director of the diabetes program at Brigham and Women’s Hospital, Boston, Massachusetts, discussed the recommendations with Medscape Medical News and also spoke about the news this week that the corticosteroid dexamethasone reduced death rates in severely ill patients with COVID-19.

The full JCEM article, by lead author Nadine E. Palermo, DO, Division of Endocrinology, Diabetes, and Hypertension, also at Brigham and Women’s Hospital, covers DKA diagnosis and triage, and emphasizes that usual hospital protocols for DKA management may need to be adjusted during COVID-19 to help preserve personal protective equipment and ICU beds.

“Hospitals and clinicians need to be able to quickly identify and manage DKA in COVID patients to save lives. This involves determining the options for management, including when less intensive subcutaneous insulin is indicated, and understanding how to guide patients on avoiding this serious complication,” McDonnell said in an Endocrine Society statement.
 

What about dexamethasone for severe COVID-19 in diabetes?

The new article briefly touches on the fact that upward adjustments to intensive intravenous insulin therapy for DKA may be necessary in patients with COVID-19 who are receiving concomitant corticosteroids or vasopressors.

But it was written prior to the June 16 announcement of the “RECOVERY” trial results with dexamethasone. The UK National Health Service immediately approved the drug’s use in the COVID-19 setting, despite the fact that there has been no published article on the findings yet.

McDonnell told Medscape Medical News that she would need to see formal results to better understand exactly which patients were studied and which ones benefited.

“The peer review will be critical. It looks as if it only benefits people who need respiratory support, but I want to understand that in much more detail,” she said. “If they all had acute respiratory distress syndrome [ARDS],” that’s different.

“There are already some data supporting steroid use in ARDS,” she noted, but added that not all of it suggests benefit.

She pointed to one of several studies now showing that diabetes, and hyperglycemia among people without a prior diabetes diagnosis, are both strong predictors of mortality in hospitalized patients with COVID-19.

“There was a very clear relationship between hyperglycemia and outcomes. We really shouldn’t put people at risk until we have clear data,” she said.

If, once the data are reviewed and appropriate dexamethasone becomes an established treatment for severe COVID-19, hyperglycemia would be a concern among all patients, not just those with previously diagnosed diabetes, she noted.

“We know a good number of people with prediabetes develop hyperglycemia when put on steroids. They can push people over the edge. We’re not going to miss anybody, but treating steroid-induced hyperglycemia is really hard,” McDonnell explained.

She also recommended 2014 guidance from Diabetes UK and the Association of British Clinical Diabetologists, which addresses management of inpatient steroid-induced DKA in patients with and without pre-existing diabetes.

Another major concern, she said, is “patients trying to get dexamethasone when they start to get sick” because this is not the right population to use this agent.

“We worry about people who do not need this drug. If they have diabetes, they put themselves at risk of hyperglycemia, which then increases the risk of severe COVID-19. And then they’re also putting themselves at risk of DKA. It would just be bad medicine,” she said.

Managing DKA in the face of COVID-19: Flexibility is key

In the JCEM article, Palermo and colleagues emphasize that the usual hospital protocols for DKA management may need to be adjusted during COVID-19 in the interest of reducing transmission risk and preserving scare resources.

They provide evidence for alternative treatment strategies, such as the use of subcutaneous rather than intravenous insulin when appropriate.

“We wanted to outline when exactly you should consider nonintensive management strategies for DKA,” McDonnell further explained to Medscape Medical News.

“That would include those with mild or some with moderate DKA. ... The idea is to remind our colleagues about that because hospitals tend to operate on a protocol-driven algorithmic methodology, they can forget to step off the usual care pathway even if evidence supports that,” she said.   

But on the other hand, she also said that, in some very complex or severely ill patients with COVID-19, classical intravenous insulin therapy makes the most sense even if their DKA is mild.
 

The outpatient setting: Prevention and preparation

The new article also addresses several concerns regarding DKA prevention in the outpatient setting.

As with other guidelines, it includes a reminder that patients with diabetes should be advised to discontinue sodium-glucose cotransporter 2 (SGLT2) inhibitors if they become ill with COVID-19, especially if they’re not eating or drinking normally, because they raise the risk for DKA.

Also, for patients with type 1 diabetes, particularly those with a history of repeated DKA, “this is the time to make sure we reach out to patients to refill their insulin prescriptions and address issues related to cost and other access difficulties,” McDonnell said.

The authors also emphasize that insulin starts and education should not be postponed during the pandemic. “Patients identified as meeting criteria to start insulin should be referred for urgent education, either in person or, whenever possible and practical, via video teleconferencing,” they urge.

McDonnell has reported receiving research funding from Novo Nordisk. The other two authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

A new article in the Journal of Clinical Endocrinology & Metabolism (JCEM) addresses unique concerns and considerations regarding diabetic ketoacidosis (DKA) in the setting of COVID-19.

Corresponding author Marie E. McDonnell, MD, director of the diabetes program at Brigham and Women’s Hospital, Boston, Massachusetts, discussed the recommendations with Medscape Medical News and also spoke about the news this week that the corticosteroid dexamethasone reduced death rates in severely ill patients with COVID-19.

The full JCEM article, by lead author Nadine E. Palermo, DO, Division of Endocrinology, Diabetes, and Hypertension, also at Brigham and Women’s Hospital, covers DKA diagnosis and triage, and emphasizes that usual hospital protocols for DKA management may need to be adjusted during COVID-19 to help preserve personal protective equipment and ICU beds.

“Hospitals and clinicians need to be able to quickly identify and manage DKA in COVID patients to save lives. This involves determining the options for management, including when less intensive subcutaneous insulin is indicated, and understanding how to guide patients on avoiding this serious complication,” McDonnell said in an Endocrine Society statement.
 

What about dexamethasone for severe COVID-19 in diabetes?

The new article briefly touches on the fact that upward adjustments to intensive intravenous insulin therapy for DKA may be necessary in patients with COVID-19 who are receiving concomitant corticosteroids or vasopressors.

But it was written prior to the June 16 announcement of the “RECOVERY” trial results with dexamethasone. The UK National Health Service immediately approved the drug’s use in the COVID-19 setting, despite the fact that there has been no published article on the findings yet.

McDonnell told Medscape Medical News that she would need to see formal results to better understand exactly which patients were studied and which ones benefited.

“The peer review will be critical. It looks as if it only benefits people who need respiratory support, but I want to understand that in much more detail,” she said. “If they all had acute respiratory distress syndrome [ARDS],” that’s different.

“There are already some data supporting steroid use in ARDS,” she noted, but added that not all of it suggests benefit.

She pointed to one of several studies now showing that diabetes, and hyperglycemia among people without a prior diabetes diagnosis, are both strong predictors of mortality in hospitalized patients with COVID-19.

“There was a very clear relationship between hyperglycemia and outcomes. We really shouldn’t put people at risk until we have clear data,” she said.

If, once the data are reviewed and appropriate dexamethasone becomes an established treatment for severe COVID-19, hyperglycemia would be a concern among all patients, not just those with previously diagnosed diabetes, she noted.

“We know a good number of people with prediabetes develop hyperglycemia when put on steroids. They can push people over the edge. We’re not going to miss anybody, but treating steroid-induced hyperglycemia is really hard,” McDonnell explained.

She also recommended 2014 guidance from Diabetes UK and the Association of British Clinical Diabetologists, which addresses management of inpatient steroid-induced DKA in patients with and without pre-existing diabetes.

Another major concern, she said, is “patients trying to get dexamethasone when they start to get sick” because this is not the right population to use this agent.

“We worry about people who do not need this drug. If they have diabetes, they put themselves at risk of hyperglycemia, which then increases the risk of severe COVID-19. And then they’re also putting themselves at risk of DKA. It would just be bad medicine,” she said.

Managing DKA in the face of COVID-19: Flexibility is key

In the JCEM article, Palermo and colleagues emphasize that the usual hospital protocols for DKA management may need to be adjusted during COVID-19 in the interest of reducing transmission risk and preserving scare resources.

They provide evidence for alternative treatment strategies, such as the use of subcutaneous rather than intravenous insulin when appropriate.

“We wanted to outline when exactly you should consider nonintensive management strategies for DKA,” McDonnell further explained to Medscape Medical News.

“That would include those with mild or some with moderate DKA. ... The idea is to remind our colleagues about that because hospitals tend to operate on a protocol-driven algorithmic methodology, they can forget to step off the usual care pathway even if evidence supports that,” she said.   

But on the other hand, she also said that, in some very complex or severely ill patients with COVID-19, classical intravenous insulin therapy makes the most sense even if their DKA is mild.
 

The outpatient setting: Prevention and preparation

The new article also addresses several concerns regarding DKA prevention in the outpatient setting.

As with other guidelines, it includes a reminder that patients with diabetes should be advised to discontinue sodium-glucose cotransporter 2 (SGLT2) inhibitors if they become ill with COVID-19, especially if they’re not eating or drinking normally, because they raise the risk for DKA.

Also, for patients with type 1 diabetes, particularly those with a history of repeated DKA, “this is the time to make sure we reach out to patients to refill their insulin prescriptions and address issues related to cost and other access difficulties,” McDonnell said.

The authors also emphasize that insulin starts and education should not be postponed during the pandemic. “Patients identified as meeting criteria to start insulin should be referred for urgent education, either in person or, whenever possible and practical, via video teleconferencing,” they urge.

McDonnell has reported receiving research funding from Novo Nordisk. The other two authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Maryland psychiatrist Annette Hanson, MD, hasn’t changed her morning routine much since the coronavirus pandemic began. She still avoids putting on a necklace or earrings, which could be torn away or used as a ligature, and heads to work.

The only difference is that Dr. Hanson wears easy-to-clean scrubs instead of business attire. “That way I can strip down and shower as soon as I get home. I’m not sure that’s necessary, but I’m being cautious,” said Dr. Hanson, a forensic psychiatrist who is an assistant professor of psychiatry at the University of Maryland and at Johns Hopkins University, both in Baltimore.

As many of her colleagues shelter in place and work from home with the help of telemedicine, prison psychiatrists such as Dr. Hanson continue to evaluate and treat patients in person – behind bars. That hasn’t changed. But so much else has, from the elimination of family visits to the suspension of many court hearings, leaving already vulnerable inmates in limbo.

“Prisons continue to be a poor place to receive mental health care. The setting is destructive to physical and mental health, and the pandemic has made it worse,” said Bandy X. Lee, MD, MDiv, of Yale University, New Haven, Conn., who treats inmates in several states.

Like the inmates they treat, prison psychiatrists are facing unique challenges that test their powers of creativity and resilience. “The most challenging part is to continue care in a system that has essentially been frozen in place,” Dr. Hanson said.

As of June 9, nearly 44,000 inmates in federal and state prisons had tested positive for coronavirus, according to the Associated Press and the Marshall Project. At least 500 people have died. Those numbers do not include inmates and staff members in local jails or juvenile detention centers.

Statistics about COVID-19 in prison staff members are incomplete since only 20 states reported them, and it’s not clear where they contracted the virus. Even so, at least 9,180 cases in staff members were reported, along with 38 deaths, the AP/Marshall Project report.

Using telemedicine is impossible at many jails and prisons, forcing many psychiatrists to protect themselves and their patients as best they can. At the Los Angeles County Jail, which does not use telemedicine, group sessions have been greatly reduced. Instead, psychiatrists are spending more time talking to inmates at the doors to cells or modules, said supervising psychiatrist Joseph R. Simpson, MD, PhD.

The risk of transmission still exists, he said. “Our health system has a comprehensive testing, monitoring, and isolation system in place now to slow the spread and flatten the curve,” Dr. Simpson said. “However, once COVID enters any correctional facility, preventing it from spreading entirely is difficult or impossible given the nature of the living arrangements.”

In interviews, psychiatrists said inmates are more stressed by the limitations spawned by the pandemic than the risk of infection. Many facilities have banned in-person visits, and telephone calls are an expensive alternative, said Nicolas Badre, MD, who treats inmates at jails in the San Diego region.

“That one lifeline you had is no longer there. The second lifeline is that your public defender will get you a plea deal, but they’ve postponed hearings,” he said. “I’ve seen cases of folks who are more anxious and more depressed because COVID is delaying their case or because they’re unable to speak with their families and friends.”

Restrictions on contact with people on the outside are especially difficult for inmates at risk of psychosis, Dr. Badre said. “You add those two [limitations], and how does that not sound to someone with schizophrenia like the government is out to get you? And when someone asks you to wear a mask, how do you trust them?”

According to Dr. Lee, some patients with severe mental illness are unable to comprehend the risk of the pandemic, and they fail to protect themselves. While she’s begun to rely on telemedicine, “it’s a very blunt instrument. Many of my patients are very sick and less able to interact with a screen. And sometimes you’re exhausted at the end of the day because you’ve been yelling at the screen and trying different ways to gain the attention of individuals who are responding to external stimuli and can’t engage.”

The pandemic has improved conditions in prisons and jails on one front: Many are releasing inmates to lower the risk of spreading infection. And Dr. Badre said, “a lot of people are doing just fine, finding themselves to be completely resilient and finding meaning at this time.”

Other than anxiety, the psychiatrists did not report seeing higher percentages of any specific conditions. And they said they are not prescribing any more medications than before COVID-19. But many of the perennial treatments for anxiety – improving the diet, getting out and exercising, developing a hobby, reaching out to others – can be difficult at the best of times behind bars. Those treatments might be impossible now.

At the juvenile justice system in the Chicago area, for example, the pandemic has forced the cancellation of activities such as writing, taking art classes, and barber training. In-person visits are banned, too. “For a lot of them, seeing their family relieves stress, makes them feel more hopeful. It gives them a sense of normalcy to hug their mom,” said Yana Oskin, MD.

But it’s still possible to urge the young people to read, write, work with puzzles, and exercise daily even if it’s just in their rooms, she said. “While their movements have been limited, they do still get to go outside. If they can’t go to the gym, the recreation specialist comes to their pod.”

And while some psychiatrists and older inmates might not be thrilled to have to adjust to therapy via screen during the pandemic, young people are a different story. Dr. Oskin is working with them via telemedicine, which allowed at least one inmate to gain a kind of victory.

“We have an assistant who sets up Skype visits, and the camera was not angled properly,” she recalled. “She couldn’t figure out. The kid sat down and fixed it in 2 seconds.”

Dr. Hanson is the coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has no other disclosures. Dr. Lee is the author of “Violence: An Interdisciplinary Approach to Causes, Consequences and Cures” (Wiley Blackwell, 2019). She has no other disclosures. Dr. Simpson is coauthor of “Neuroimaging in Forensic Psychiatry: From the Clinic to the Courtroom” (Wiley Blackwell, 2012). He has no other disclosures. Dr. Badre and Dr. Oskin reported no disclosures.

Maryland psychiatrist Annette Hanson, MD, hasn’t changed her morning routine much since the coronavirus pandemic began. She still avoids putting on a necklace or earrings, which could be torn away or used as a ligature, and heads to work.

The only difference is that Dr. Hanson wears easy-to-clean scrubs instead of business attire. “That way I can strip down and shower as soon as I get home. I’m not sure that’s necessary, but I’m being cautious,” said Dr. Hanson, a forensic psychiatrist who is an assistant professor of psychiatry at the University of Maryland and at Johns Hopkins University, both in Baltimore.

As many of her colleagues shelter in place and work from home with the help of telemedicine, prison psychiatrists such as Dr. Hanson continue to evaluate and treat patients in person – behind bars. That hasn’t changed. But so much else has, from the elimination of family visits to the suspension of many court hearings, leaving already vulnerable inmates in limbo.

“Prisons continue to be a poor place to receive mental health care. The setting is destructive to physical and mental health, and the pandemic has made it worse,” said Bandy X. Lee, MD, MDiv, of Yale University, New Haven, Conn., who treats inmates in several states.

Like the inmates they treat, prison psychiatrists are facing unique challenges that test their powers of creativity and resilience. “The most challenging part is to continue care in a system that has essentially been frozen in place,” Dr. Hanson said.

As of June 9, nearly 44,000 inmates in federal and state prisons had tested positive for coronavirus, according to the Associated Press and the Marshall Project. At least 500 people have died. Those numbers do not include inmates and staff members in local jails or juvenile detention centers.

Statistics about COVID-19 in prison staff members are incomplete since only 20 states reported them, and it’s not clear where they contracted the virus. Even so, at least 9,180 cases in staff members were reported, along with 38 deaths, the AP/Marshall Project report.

Using telemedicine is impossible at many jails and prisons, forcing many psychiatrists to protect themselves and their patients as best they can. At the Los Angeles County Jail, which does not use telemedicine, group sessions have been greatly reduced. Instead, psychiatrists are spending more time talking to inmates at the doors to cells or modules, said supervising psychiatrist Joseph R. Simpson, MD, PhD.

The risk of transmission still exists, he said. “Our health system has a comprehensive testing, monitoring, and isolation system in place now to slow the spread and flatten the curve,” Dr. Simpson said. “However, once COVID enters any correctional facility, preventing it from spreading entirely is difficult or impossible given the nature of the living arrangements.”

In interviews, psychiatrists said inmates are more stressed by the limitations spawned by the pandemic than the risk of infection. Many facilities have banned in-person visits, and telephone calls are an expensive alternative, said Nicolas Badre, MD, who treats inmates at jails in the San Diego region.

“That one lifeline you had is no longer there. The second lifeline is that your public defender will get you a plea deal, but they’ve postponed hearings,” he said. “I’ve seen cases of folks who are more anxious and more depressed because COVID is delaying their case or because they’re unable to speak with their families and friends.”

Restrictions on contact with people on the outside are especially difficult for inmates at risk of psychosis, Dr. Badre said. “You add those two [limitations], and how does that not sound to someone with schizophrenia like the government is out to get you? And when someone asks you to wear a mask, how do you trust them?”

According to Dr. Lee, some patients with severe mental illness are unable to comprehend the risk of the pandemic, and they fail to protect themselves. While she’s begun to rely on telemedicine, “it’s a very blunt instrument. Many of my patients are very sick and less able to interact with a screen. And sometimes you’re exhausted at the end of the day because you’ve been yelling at the screen and trying different ways to gain the attention of individuals who are responding to external stimuli and can’t engage.”

The pandemic has improved conditions in prisons and jails on one front: Many are releasing inmates to lower the risk of spreading infection. And Dr. Badre said, “a lot of people are doing just fine, finding themselves to be completely resilient and finding meaning at this time.”

Other than anxiety, the psychiatrists did not report seeing higher percentages of any specific conditions. And they said they are not prescribing any more medications than before COVID-19. But many of the perennial treatments for anxiety – improving the diet, getting out and exercising, developing a hobby, reaching out to others – can be difficult at the best of times behind bars. Those treatments might be impossible now.

At the juvenile justice system in the Chicago area, for example, the pandemic has forced the cancellation of activities such as writing, taking art classes, and barber training. In-person visits are banned, too. “For a lot of them, seeing their family relieves stress, makes them feel more hopeful. It gives them a sense of normalcy to hug their mom,” said Yana Oskin, MD.

But it’s still possible to urge the young people to read, write, work with puzzles, and exercise daily even if it’s just in their rooms, she said. “While their movements have been limited, they do still get to go outside. If they can’t go to the gym, the recreation specialist comes to their pod.”

And while some psychiatrists and older inmates might not be thrilled to have to adjust to therapy via screen during the pandemic, young people are a different story. Dr. Oskin is working with them via telemedicine, which allowed at least one inmate to gain a kind of victory.

“We have an assistant who sets up Skype visits, and the camera was not angled properly,” she recalled. “She couldn’t figure out. The kid sat down and fixed it in 2 seconds.”

Dr. Hanson is the coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has no other disclosures. Dr. Lee is the author of “Violence: An Interdisciplinary Approach to Causes, Consequences and Cures” (Wiley Blackwell, 2019). She has no other disclosures. Dr. Simpson is coauthor of “Neuroimaging in Forensic Psychiatry: From the Clinic to the Courtroom” (Wiley Blackwell, 2012). He has no other disclosures. Dr. Badre and Dr. Oskin reported no disclosures.

Maryland psychiatrist Annette Hanson, MD, hasn’t changed her morning routine much since the coronavirus pandemic began. She still avoids putting on a necklace or earrings, which could be torn away or used as a ligature, and heads to work.

The only difference is that Dr. Hanson wears easy-to-clean scrubs instead of business attire. “That way I can strip down and shower as soon as I get home. I’m not sure that’s necessary, but I’m being cautious,” said Dr. Hanson, a forensic psychiatrist who is an assistant professor of psychiatry at the University of Maryland and at Johns Hopkins University, both in Baltimore.

As many of her colleagues shelter in place and work from home with the help of telemedicine, prison psychiatrists such as Dr. Hanson continue to evaluate and treat patients in person – behind bars. That hasn’t changed. But so much else has, from the elimination of family visits to the suspension of many court hearings, leaving already vulnerable inmates in limbo.

“Prisons continue to be a poor place to receive mental health care. The setting is destructive to physical and mental health, and the pandemic has made it worse,” said Bandy X. Lee, MD, MDiv, of Yale University, New Haven, Conn., who treats inmates in several states.

Like the inmates they treat, prison psychiatrists are facing unique challenges that test their powers of creativity and resilience. “The most challenging part is to continue care in a system that has essentially been frozen in place,” Dr. Hanson said.

As of June 9, nearly 44,000 inmates in federal and state prisons had tested positive for coronavirus, according to the Associated Press and the Marshall Project. At least 500 people have died. Those numbers do not include inmates and staff members in local jails or juvenile detention centers.

Statistics about COVID-19 in prison staff members are incomplete since only 20 states reported them, and it’s not clear where they contracted the virus. Even so, at least 9,180 cases in staff members were reported, along with 38 deaths, the AP/Marshall Project report.

Using telemedicine is impossible at many jails and prisons, forcing many psychiatrists to protect themselves and their patients as best they can. At the Los Angeles County Jail, which does not use telemedicine, group sessions have been greatly reduced. Instead, psychiatrists are spending more time talking to inmates at the doors to cells or modules, said supervising psychiatrist Joseph R. Simpson, MD, PhD.

The risk of transmission still exists, he said. “Our health system has a comprehensive testing, monitoring, and isolation system in place now to slow the spread and flatten the curve,” Dr. Simpson said. “However, once COVID enters any correctional facility, preventing it from spreading entirely is difficult or impossible given the nature of the living arrangements.”

In interviews, psychiatrists said inmates are more stressed by the limitations spawned by the pandemic than the risk of infection. Many facilities have banned in-person visits, and telephone calls are an expensive alternative, said Nicolas Badre, MD, who treats inmates at jails in the San Diego region.

“That one lifeline you had is no longer there. The second lifeline is that your public defender will get you a plea deal, but they’ve postponed hearings,” he said. “I’ve seen cases of folks who are more anxious and more depressed because COVID is delaying their case or because they’re unable to speak with their families and friends.”

Restrictions on contact with people on the outside are especially difficult for inmates at risk of psychosis, Dr. Badre said. “You add those two [limitations], and how does that not sound to someone with schizophrenia like the government is out to get you? And when someone asks you to wear a mask, how do you trust them?”

According to Dr. Lee, some patients with severe mental illness are unable to comprehend the risk of the pandemic, and they fail to protect themselves. While she’s begun to rely on telemedicine, “it’s a very blunt instrument. Many of my patients are very sick and less able to interact with a screen. And sometimes you’re exhausted at the end of the day because you’ve been yelling at the screen and trying different ways to gain the attention of individuals who are responding to external stimuli and can’t engage.”

The pandemic has improved conditions in prisons and jails on one front: Many are releasing inmates to lower the risk of spreading infection. And Dr. Badre said, “a lot of people are doing just fine, finding themselves to be completely resilient and finding meaning at this time.”

Other than anxiety, the psychiatrists did not report seeing higher percentages of any specific conditions. And they said they are not prescribing any more medications than before COVID-19. But many of the perennial treatments for anxiety – improving the diet, getting out and exercising, developing a hobby, reaching out to others – can be difficult at the best of times behind bars. Those treatments might be impossible now.

At the juvenile justice system in the Chicago area, for example, the pandemic has forced the cancellation of activities such as writing, taking art classes, and barber training. In-person visits are banned, too. “For a lot of them, seeing their family relieves stress, makes them feel more hopeful. It gives them a sense of normalcy to hug their mom,” said Yana Oskin, MD.

But it’s still possible to urge the young people to read, write, work with puzzles, and exercise daily even if it’s just in their rooms, she said. “While their movements have been limited, they do still get to go outside. If they can’t go to the gym, the recreation specialist comes to their pod.”

And while some psychiatrists and older inmates might not be thrilled to have to adjust to therapy via screen during the pandemic, young people are a different story. Dr. Oskin is working with them via telemedicine, which allowed at least one inmate to gain a kind of victory.

“We have an assistant who sets up Skype visits, and the camera was not angled properly,” she recalled. “She couldn’t figure out. The kid sat down and fixed it in 2 seconds.”

Dr. Hanson is the coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has no other disclosures. Dr. Lee is the author of “Violence: An Interdisciplinary Approach to Causes, Consequences and Cures” (Wiley Blackwell, 2019). She has no other disclosures. Dr. Simpson is coauthor of “Neuroimaging in Forensic Psychiatry: From the Clinic to the Courtroom” (Wiley Blackwell, 2012). He has no other disclosures. Dr. Badre and Dr. Oskin reported no disclosures.

Adding tiragolumab to first-line treatment with atezolizumab improves outcomes in patients with PD-L1–positive non–small cell lung cancer (NSCLC), according to updated results from the phase 2 CITYSCAPE study.

Patients who received tiragolumab, an anti-TIGIT antibody, in combination with atezolizumab, a PD-L1 inhibitor, had superior overall response rates (ORR) and progression-free survival (PFS), when compared with results of patients who received placebo with atezolizumab.

Melissa L. Johnson, MD, of the Sarah Cannon Research Institute in Nashville, Tenn., presented these results as part of the American Society of Clinical Oncology virtual scientific program.

Dr. Johnson explained that TIGIT is an immunomodulatory receptor present on activated T cells and natural killer cells in multiple cancers, including NSCLC.

“TIGIT inhibits T cells and natural killer cells by binding to its ligand PVR on tumor cells and antigen-presenting cells,” she said. “TIGIT expression strongly correlates with PD-1 expression, sometimes on the same tumor-infiltrating T cells in lung cancer. So the hypothesis of this trial was that anti-TIGIT antibodies, which prevent TIGIT from binding to its ligand, could restore the antitumor response and could complement the activity of anti–PD-L1/PD-1 antibodies.”

Dr. Johnson noted that combination anti–TIGIT/PD-L1 antibody treatment synergistically improved tumor control and prolonged survival over either antibody alone in preclinical models (Cancer Cell. 2014 Dec 8;26[6]:923-937). In addition, tiragolumab has been evaluated in a phase 1 study, both as monotherapy and in combination with atezolizumab, in multiple solid tumors (NCT02794571).

The phase 2 CITYSCAPE study (NCT03563716) was initiated to confirm the efficacy and safety of tiragolumab plus atezolizumab versus placebo plus atezolizumab for the first-line treatment of NSCLC, Dr. Johnson said.

CITYSCAPE enrolled 135 patients with chemotherapy-naive, PD-L1–positive, locally advanced or metastatic NSCLC. Patients did not have EGFR or ALK alterations.

Half of patients (n = 68) were randomized to receive tiragolumab at 600 mg plus atezolizumab at 1,200 mg, both given on day 1 of every 3-week cycle. The other half of patients (n = 67) were randomized to receive atezolizumab at the same dose and schedule plus placebo.
 

ORR and PFS

The study’s primary analysis was conducted in June 2019 at a median follow-up of 5.9 months. At that time, the ORR and PFS data showed an early benefit with tiragolumab. The ORR was 31% in the tiragolumab arm and 16% in the placebo arm. The median PFS was 5.42 months and 3.58 months, respectively (hazard ratio, 0.57).

With an additional 6 months of follow-up, the tiragolumab benefit persisted, Dr. Johnson said. The updated ORR in the intent-to-treat population was 37% in the tiragolumab arm and 21% in the placebo arm. The median PFS was 5.6 months and 3.9 months, respectively (HR, 0.58).

The tiragolumab combination showed “clinically meaningful” improvements in ORR and PFS, Dr. Johnson said. She also noted “a greater magnitude of improvement” was seen in patients with a PD-L1 tumor proportion score of 50% or greater.

There were 29 patients in each treatment arm with a PD-L1 tumor proportion score of 50% or greater. Among these patients, the ORR was 66% in the tiragolumab arm and 24% in the placebo arm. The median PFS was not reached and 4.1 months, respectively (HR, 0.30).

There were no significant differences in ORR or PFS among patients with PD-L1 tumor proportion scores below 50%, Dr. Johnson noted.

She added that duration of response and overall survival data are not yet mature and will be presented at a future conference.
 

Adverse events

As reported in the primary analysis, tiragolumab plus atezolizumab had a tolerable safety profile, Dr. Johnson said.

“Despite a near doubling of the median treatment duration [at the updated analysis], there were similar numbers of any-cause adverse events, grade 3-5 adverse events, and serious adverse events,” she said.

Overall, adverse events occurred in 99% of patients in the tiragolumab arm and 96% of those in the placebo arm. Rates of grade 3-5 adverse events were 48% and 44%, respectively. Rates of serious adverse events were 37% and 35%, respectively.

A higher frequency of adverse events in the tiragolumab arm was related to an increase in immune-related events, including infusion reactions, pruritus, rash, arthralgia, and nephritis. This makes sense because the patients in that group were receiving two active immunotherapies, Dr. Johnson said.
 

Data inspire cautious optimism

The safety and activity of tiragolumab plus atezolizumab are “to be confirmed in an ongoing phase 3 study called SKYSCRAPER-01 [NCT04294810],” Dr. Johnson said.

Invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., said the ORRs in CITYSCAPE have “generated a lot of buzz,” but she urged caution pending phase 3 results.

“While we are all excited by the data and want to see a winner, we should be careful, as speed can also crash and burn,” she said. “We have plenty of examples of promising studies that collapsed in later phase trials.”

There is room, however, for cautious optimism that the combination is a promising advance “as long as no prognostic or confounding variable is determined later on to be nonrandomly distributed between the groups to account for the difference seen,” Dr. Dy said.

She also noted that “the distribution of favorable or unfavorable mutations between the groups is unknown, and understanding this will be relevant.”

Preclinical data suggest the presence of DNM1 expression is crucial for maximizing the effect of TIGIT blockade, and tumor MHC class 1 expression appears to be reduced alongside reductions in DNM1 expression in the intratumoral natural kill cells in lung cancer specimens, Dr. Dy explained.

“Assessment of these biomarkers will be instructive,” she said. “More recent data also appear to implicate a paradoxical role of soluble CD155 or PVR ligand in actually inhibiting DNM1, so the effect of systemic TIGIT blockade may be mitigated if there is rebound increase of counterbalancing signals by increased secretion of soluble CD155, and we look forward to more data in the future regarding this.”

CITYSCAPE was sponsored by Genentech. Dr. Johnson disclosed relationships with Genentech and numerous other companies. Dr. Dy disclosed relationships with AstraZeneca, GlaxoSmithKline, Takeda, Amgen, Bristol-Myers Squibb, Regeneron, and Tesaro.

[email protected]

SOURCE: Rodriguez-Abreu D et al. ASCO 2020, Abstract 9503.

Adding tiragolumab to first-line treatment with atezolizumab improves outcomes in patients with PD-L1–positive non–small cell lung cancer (NSCLC), according to updated results from the phase 2 CITYSCAPE study.

Patients who received tiragolumab, an anti-TIGIT antibody, in combination with atezolizumab, a PD-L1 inhibitor, had superior overall response rates (ORR) and progression-free survival (PFS), when compared with results of patients who received placebo with atezolizumab.

Melissa L. Johnson, MD, of the Sarah Cannon Research Institute in Nashville, Tenn., presented these results as part of the American Society of Clinical Oncology virtual scientific program.

Dr. Johnson explained that TIGIT is an immunomodulatory receptor present on activated T cells and natural killer cells in multiple cancers, including NSCLC.

“TIGIT inhibits T cells and natural killer cells by binding to its ligand PVR on tumor cells and antigen-presenting cells,” she said. “TIGIT expression strongly correlates with PD-1 expression, sometimes on the same tumor-infiltrating T cells in lung cancer. So the hypothesis of this trial was that anti-TIGIT antibodies, which prevent TIGIT from binding to its ligand, could restore the antitumor response and could complement the activity of anti–PD-L1/PD-1 antibodies.”

Dr. Johnson noted that combination anti–TIGIT/PD-L1 antibody treatment synergistically improved tumor control and prolonged survival over either antibody alone in preclinical models (Cancer Cell. 2014 Dec 8;26[6]:923-937). In addition, tiragolumab has been evaluated in a phase 1 study, both as monotherapy and in combination with atezolizumab, in multiple solid tumors (NCT02794571).

The phase 2 CITYSCAPE study (NCT03563716) was initiated to confirm the efficacy and safety of tiragolumab plus atezolizumab versus placebo plus atezolizumab for the first-line treatment of NSCLC, Dr. Johnson said.

CITYSCAPE enrolled 135 patients with chemotherapy-naive, PD-L1–positive, locally advanced or metastatic NSCLC. Patients did not have EGFR or ALK alterations.

Half of patients (n = 68) were randomized to receive tiragolumab at 600 mg plus atezolizumab at 1,200 mg, both given on day 1 of every 3-week cycle. The other half of patients (n = 67) were randomized to receive atezolizumab at the same dose and schedule plus placebo.
 

ORR and PFS

The study’s primary analysis was conducted in June 2019 at a median follow-up of 5.9 months. At that time, the ORR and PFS data showed an early benefit with tiragolumab. The ORR was 31% in the tiragolumab arm and 16% in the placebo arm. The median PFS was 5.42 months and 3.58 months, respectively (hazard ratio, 0.57).

With an additional 6 months of follow-up, the tiragolumab benefit persisted, Dr. Johnson said. The updated ORR in the intent-to-treat population was 37% in the tiragolumab arm and 21% in the placebo arm. The median PFS was 5.6 months and 3.9 months, respectively (HR, 0.58).

The tiragolumab combination showed “clinically meaningful” improvements in ORR and PFS, Dr. Johnson said. She also noted “a greater magnitude of improvement” was seen in patients with a PD-L1 tumor proportion score of 50% or greater.

There were 29 patients in each treatment arm with a PD-L1 tumor proportion score of 50% or greater. Among these patients, the ORR was 66% in the tiragolumab arm and 24% in the placebo arm. The median PFS was not reached and 4.1 months, respectively (HR, 0.30).

There were no significant differences in ORR or PFS among patients with PD-L1 tumor proportion scores below 50%, Dr. Johnson noted.

She added that duration of response and overall survival data are not yet mature and will be presented at a future conference.
 

Adverse events

As reported in the primary analysis, tiragolumab plus atezolizumab had a tolerable safety profile, Dr. Johnson said.

“Despite a near doubling of the median treatment duration [at the updated analysis], there were similar numbers of any-cause adverse events, grade 3-5 adverse events, and serious adverse events,” she said.

Overall, adverse events occurred in 99% of patients in the tiragolumab arm and 96% of those in the placebo arm. Rates of grade 3-5 adverse events were 48% and 44%, respectively. Rates of serious adverse events were 37% and 35%, respectively.

A higher frequency of adverse events in the tiragolumab arm was related to an increase in immune-related events, including infusion reactions, pruritus, rash, arthralgia, and nephritis. This makes sense because the patients in that group were receiving two active immunotherapies, Dr. Johnson said.
 

Data inspire cautious optimism

The safety and activity of tiragolumab plus atezolizumab are “to be confirmed in an ongoing phase 3 study called SKYSCRAPER-01 [NCT04294810],” Dr. Johnson said.

Invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., said the ORRs in CITYSCAPE have “generated a lot of buzz,” but she urged caution pending phase 3 results.

“While we are all excited by the data and want to see a winner, we should be careful, as speed can also crash and burn,” she said. “We have plenty of examples of promising studies that collapsed in later phase trials.”

There is room, however, for cautious optimism that the combination is a promising advance “as long as no prognostic or confounding variable is determined later on to be nonrandomly distributed between the groups to account for the difference seen,” Dr. Dy said.

She also noted that “the distribution of favorable or unfavorable mutations between the groups is unknown, and understanding this will be relevant.”

Preclinical data suggest the presence of DNM1 expression is crucial for maximizing the effect of TIGIT blockade, and tumor MHC class 1 expression appears to be reduced alongside reductions in DNM1 expression in the intratumoral natural kill cells in lung cancer specimens, Dr. Dy explained.

“Assessment of these biomarkers will be instructive,” she said. “More recent data also appear to implicate a paradoxical role of soluble CD155 or PVR ligand in actually inhibiting DNM1, so the effect of systemic TIGIT blockade may be mitigated if there is rebound increase of counterbalancing signals by increased secretion of soluble CD155, and we look forward to more data in the future regarding this.”

CITYSCAPE was sponsored by Genentech. Dr. Johnson disclosed relationships with Genentech and numerous other companies. Dr. Dy disclosed relationships with AstraZeneca, GlaxoSmithKline, Takeda, Amgen, Bristol-Myers Squibb, Regeneron, and Tesaro.

[email protected]

SOURCE: Rodriguez-Abreu D et al. ASCO 2020, Abstract 9503.

Adding tiragolumab to first-line treatment with atezolizumab improves outcomes in patients with PD-L1–positive non–small cell lung cancer (NSCLC), according to updated results from the phase 2 CITYSCAPE study.

Patients who received tiragolumab, an anti-TIGIT antibody, in combination with atezolizumab, a PD-L1 inhibitor, had superior overall response rates (ORR) and progression-free survival (PFS), when compared with results of patients who received placebo with atezolizumab.

Melissa L. Johnson, MD, of the Sarah Cannon Research Institute in Nashville, Tenn., presented these results as part of the American Society of Clinical Oncology virtual scientific program.

Dr. Johnson explained that TIGIT is an immunomodulatory receptor present on activated T cells and natural killer cells in multiple cancers, including NSCLC.

“TIGIT inhibits T cells and natural killer cells by binding to its ligand PVR on tumor cells and antigen-presenting cells,” she said. “TIGIT expression strongly correlates with PD-1 expression, sometimes on the same tumor-infiltrating T cells in lung cancer. So the hypothesis of this trial was that anti-TIGIT antibodies, which prevent TIGIT from binding to its ligand, could restore the antitumor response and could complement the activity of anti–PD-L1/PD-1 antibodies.”

Dr. Johnson noted that combination anti–TIGIT/PD-L1 antibody treatment synergistically improved tumor control and prolonged survival over either antibody alone in preclinical models (Cancer Cell. 2014 Dec 8;26[6]:923-937). In addition, tiragolumab has been evaluated in a phase 1 study, both as monotherapy and in combination with atezolizumab, in multiple solid tumors (NCT02794571).

The phase 2 CITYSCAPE study (NCT03563716) was initiated to confirm the efficacy and safety of tiragolumab plus atezolizumab versus placebo plus atezolizumab for the first-line treatment of NSCLC, Dr. Johnson said.

CITYSCAPE enrolled 135 patients with chemotherapy-naive, PD-L1–positive, locally advanced or metastatic NSCLC. Patients did not have EGFR or ALK alterations.

Half of patients (n = 68) were randomized to receive tiragolumab at 600 mg plus atezolizumab at 1,200 mg, both given on day 1 of every 3-week cycle. The other half of patients (n = 67) were randomized to receive atezolizumab at the same dose and schedule plus placebo.