“It is one of life’s most self-evident truths that everything fades, that we fear the fading, and that we must live, nonetheless, in the face of the fear.” – Irvin D. Yalom, MD, Existential Psychotherapy, 1980

The email was titled simply, “A sorrowful note,” and I knew that someone had died. I held my breath and read as Dr. Jimmy Potash informed our entire department that Dr. Cait McFarland died in a car accident on December 7 while driving to work at West Cecil Health Center, Conowingo, Md., where she was director of psychiatry.

Sadness swelled as I remembered the outspoken resident who was interested in LGBTQ issues. Cait graduated from the Johns Hopkins residency program in 2020, she had recently married a social worker in the department, and the plan was for her to return to Hopkins full-time in July 2023 to be director of a clinic focused on mental health for people who are transgendered.

Sudden deaths are tragic and jarring and they call to the surface our losses from the past. These deaths don’t stand alone – I found myself thinking of my editor at Medscape, Dr. Bret Stetka, who died unexpectedly in August 2022, and then of Dr. Lidia Palcan Wenz, a psychiatrist I trained with, who died in a motor vehicle accident in 2004. Lidia’s husband also died in the accident, while their two young children in the back seat survived – this tragedy haunted me for some time. None of these people was close to me, but I am no stranger to the impact of unexpected death: My parents and brother all died from cardiac events, and any sudden death is a reminder of those losses.

Julia Riddle, MD, trained with Cait McFarland and was her close friend for years. “I don’t have a belief in ‘the afterlife’ but do like to think of the people that I have lost together in my memory – as if they are all suddenly in a new room together. And, with each loss, all the other occupants of that room come freshly to life again,” Dr. Riddle said.

Death is our shared destination in life, but sudden and unexpected deaths carry their own weight. There is no chance to tie up loose ends, to repair riffs, to say goodbye. Nothing is put in order, and the life that was to be lived goes on for some time as bills arrive, social and work events go unattended, vacations are canceled, and there is the awkward moment of running into someone who didn’t know your loved one has died.

Roger Lewin, MD, is a psychiatrist and writer in Towson, Md. He has both personal and professional experience with sudden death. “There is no way to prepare beforehand, so we have to get ready for what has already happened, and that is hard,” he said. “We invent a life for ourselves and others that extends into the future, and that gets interrupted.”

Most people become ill and die on a vaguely predictable schedule. There may be a chance to plan, to know and honor the wishes of the individual, and often there is the opportunity for loved ones to begin the grieving process gradually as death approaches. For those who are elderly, there may be a sense that this is the natural order of things – which may or may not temper the intensity of the grief for those who remain. If the person has suffered, the end may come with relief.

Still, I sometimes find myself surprised at the length and intensity of anguish that some people experience after losing a loved one who has lived a long and full life, who declined and suffered, but whose absence remains a gaping wound that takes years to form a scar.

Sudden death is not rare; accidents, homicide, and suicide are the top killers among young people, and cardiovascular deaths are number one among those who are older. Natural disasters and terrorist attacks can cause catastrophic numbers of sudden deaths and leave survivors to grieve not only the dead, but the loss of all that was familiar to them.

Psychiatry has been a bit lost as to how we approach grief. We often hear patients talk about anxiety surrounding death and illness, be it a fear of death or a longing for it. These fears can seem irrational – I am reminded of a patient who was afraid to eat romaine because of news reports that it was responsible for food poisoning in other states, but not Maryland, where the person lived. I found it odd that he worried about eating lettuce, but not about smoking two packs of cigarettes a day.

But our fears are like that – they move to what the media sensationalizes, or to what may be remote, because otherwise no one would get in a car or clear their walkway of snow. Life is most easily lived with a bit of denial: We shut out the reality that we can be here one moment, overscheduled and overwhelmed, with deadlines, mortgage payments, and summer vacation plans, oblivious to the fact that life may end at any moment. The early months of COVID-19 felt like a global game of Russian roulette, with each venture out a pull of the trigger and everyone’s defenses stripped bare.

While death belongs to us all, we relegate it to the disciplines of religion, philosophy, the arts, and psychology. Religion offers answers – whether a heaven, a hell, or continual reincarnation until the individual attains enlightenment, there is a destination. Perhaps it will be pleasant, perhaps not, and for some there is the hope that one gets to be the driver by having the right beliefs or doing good deeds, while others are comforted by the hope of being reunited with loved ones.

“The suddenness endures and the shock lasts – it’s like a meteor that creates a crater and we revisit it in different ways from different angles,” Dr. Lewin said. “It may leap on us unexpectedly, often many years later.”

Patients talk about death, and when their fears seem unrealistic we may long to reassure them, yet there is no reassurance and psychiatry grasps for how to help. Psychiatry has looked to draw lines for when normal grief crosses to abnormal. Is it an adjustment disorder, complicated grief, “prolonged” grief, pathology in need of medication and medicalization, or something one experiences individually, sometimes for a very long time even with treatment?

One justification for pathologizing “prolonged” reactions includes the fact that insurers will pay for treatment only if there is a diagnosis code, and shouldn’t people in distress be entitled to psychotherapy or medication? Yet there is something offensive about telling someone that they are mentally ill if they don’t grieve along a prescribed timeline, as much as there is about denying them the possible benefits of therapy or medication if they seek it, but are suffering in all the “right” ways. Psychiatry’s approach to death is inelegant at best.

In his poignant podcast series, All There Is, Anderson Cooper is tasked with sorting through his mother’s apartment after her death at age 95. In the course of packing up her belongings, he brings on other guests to talk about their emotional reactions to death. Mr. Cooper’s mother, Gloria Vanderbilt, died at an advanced age, but his father died after a brief cardiac illness when Mr. Cooper was a child, and his brother died by suicide when he was 21. He uses these experiences as a springboard to examine childhood losses, the aftermath of suicide, and the loneliness of grief.

“Loss and grief is this universal experience that we will all go through multiple times in our lives,” Mr. Cooper says, “And yet it leaves us feeling so alone and so separated from other people. At least it does me and has my entire life.”

When we talk about grief and loss, we talk about “getting over it,” or “moving on.” But loss doesn’t work that way – time usually eases the pain, leaving scars that are part of the road map for who we are on the journey that defines us.

Sudden death is hard, and the unexpected death of a young person is tragic. For Cait McFarland, there are the decades she won’t get to experience. For her family and friends, it may be excruciating, and for all the patients who have lost a psychiatrist, may time bring healing and peace.

The Dr. Caitlin McFarland Educational Fund for LGBTQI+ Mental Health is being established, and donations are being accepted at https://www.gofundme.com/f/in-memory-of-cait-mcfarland.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

“It is one of life’s most self-evident truths that everything fades, that we fear the fading, and that we must live, nonetheless, in the face of the fear.” – Irvin D. Yalom, MD, Existential Psychotherapy, 1980

The email was titled simply, “A sorrowful note,” and I knew that someone had died. I held my breath and read as Dr. Jimmy Potash informed our entire department that Dr. Cait McFarland died in a car accident on December 7 while driving to work at West Cecil Health Center, Conowingo, Md., where she was director of psychiatry.

Sadness swelled as I remembered the outspoken resident who was interested in LGBTQ issues. Cait graduated from the Johns Hopkins residency program in 2020, she had recently married a social worker in the department, and the plan was for her to return to Hopkins full-time in July 2023 to be director of a clinic focused on mental health for people who are transgendered.

Sudden deaths are tragic and jarring and they call to the surface our losses from the past. These deaths don’t stand alone – I found myself thinking of my editor at Medscape, Dr. Bret Stetka, who died unexpectedly in August 2022, and then of Dr. Lidia Palcan Wenz, a psychiatrist I trained with, who died in a motor vehicle accident in 2004. Lidia’s husband also died in the accident, while their two young children in the back seat survived – this tragedy haunted me for some time. None of these people was close to me, but I am no stranger to the impact of unexpected death: My parents and brother all died from cardiac events, and any sudden death is a reminder of those losses.

Julia Riddle, MD, trained with Cait McFarland and was her close friend for years. “I don’t have a belief in ‘the afterlife’ but do like to think of the people that I have lost together in my memory – as if they are all suddenly in a new room together. And, with each loss, all the other occupants of that room come freshly to life again,” Dr. Riddle said.

Death is our shared destination in life, but sudden and unexpected deaths carry their own weight. There is no chance to tie up loose ends, to repair riffs, to say goodbye. Nothing is put in order, and the life that was to be lived goes on for some time as bills arrive, social and work events go unattended, vacations are canceled, and there is the awkward moment of running into someone who didn’t know your loved one has died.

Roger Lewin, MD, is a psychiatrist and writer in Towson, Md. He has both personal and professional experience with sudden death. “There is no way to prepare beforehand, so we have to get ready for what has already happened, and that is hard,” he said. “We invent a life for ourselves and others that extends into the future, and that gets interrupted.”

Most people become ill and die on a vaguely predictable schedule. There may be a chance to plan, to know and honor the wishes of the individual, and often there is the opportunity for loved ones to begin the grieving process gradually as death approaches. For those who are elderly, there may be a sense that this is the natural order of things – which may or may not temper the intensity of the grief for those who remain. If the person has suffered, the end may come with relief.

Still, I sometimes find myself surprised at the length and intensity of anguish that some people experience after losing a loved one who has lived a long and full life, who declined and suffered, but whose absence remains a gaping wound that takes years to form a scar.

Sudden death is not rare; accidents, homicide, and suicide are the top killers among young people, and cardiovascular deaths are number one among those who are older. Natural disasters and terrorist attacks can cause catastrophic numbers of sudden deaths and leave survivors to grieve not only the dead, but the loss of all that was familiar to them.

Psychiatry has been a bit lost as to how we approach grief. We often hear patients talk about anxiety surrounding death and illness, be it a fear of death or a longing for it. These fears can seem irrational – I am reminded of a patient who was afraid to eat romaine because of news reports that it was responsible for food poisoning in other states, but not Maryland, where the person lived. I found it odd that he worried about eating lettuce, but not about smoking two packs of cigarettes a day.

But our fears are like that – they move to what the media sensationalizes, or to what may be remote, because otherwise no one would get in a car or clear their walkway of snow. Life is most easily lived with a bit of denial: We shut out the reality that we can be here one moment, overscheduled and overwhelmed, with deadlines, mortgage payments, and summer vacation plans, oblivious to the fact that life may end at any moment. The early months of COVID-19 felt like a global game of Russian roulette, with each venture out a pull of the trigger and everyone’s defenses stripped bare.

While death belongs to us all, we relegate it to the disciplines of religion, philosophy, the arts, and psychology. Religion offers answers – whether a heaven, a hell, or continual reincarnation until the individual attains enlightenment, there is a destination. Perhaps it will be pleasant, perhaps not, and for some there is the hope that one gets to be the driver by having the right beliefs or doing good deeds, while others are comforted by the hope of being reunited with loved ones.

“The suddenness endures and the shock lasts – it’s like a meteor that creates a crater and we revisit it in different ways from different angles,” Dr. Lewin said. “It may leap on us unexpectedly, often many years later.”

Patients talk about death, and when their fears seem unrealistic we may long to reassure them, yet there is no reassurance and psychiatry grasps for how to help. Psychiatry has looked to draw lines for when normal grief crosses to abnormal. Is it an adjustment disorder, complicated grief, “prolonged” grief, pathology in need of medication and medicalization, or something one experiences individually, sometimes for a very long time even with treatment?

One justification for pathologizing “prolonged” reactions includes the fact that insurers will pay for treatment only if there is a diagnosis code, and shouldn’t people in distress be entitled to psychotherapy or medication? Yet there is something offensive about telling someone that they are mentally ill if they don’t grieve along a prescribed timeline, as much as there is about denying them the possible benefits of therapy or medication if they seek it, but are suffering in all the “right” ways. Psychiatry’s approach to death is inelegant at best.

In his poignant podcast series, All There Is, Anderson Cooper is tasked with sorting through his mother’s apartment after her death at age 95. In the course of packing up her belongings, he brings on other guests to talk about their emotional reactions to death. Mr. Cooper’s mother, Gloria Vanderbilt, died at an advanced age, but his father died after a brief cardiac illness when Mr. Cooper was a child, and his brother died by suicide when he was 21. He uses these experiences as a springboard to examine childhood losses, the aftermath of suicide, and the loneliness of grief.

“Loss and grief is this universal experience that we will all go through multiple times in our lives,” Mr. Cooper says, “And yet it leaves us feeling so alone and so separated from other people. At least it does me and has my entire life.”

When we talk about grief and loss, we talk about “getting over it,” or “moving on.” But loss doesn’t work that way – time usually eases the pain, leaving scars that are part of the road map for who we are on the journey that defines us.

Sudden death is hard, and the unexpected death of a young person is tragic. For Cait McFarland, there are the decades she won’t get to experience. For her family and friends, it may be excruciating, and for all the patients who have lost a psychiatrist, may time bring healing and peace.

The Dr. Caitlin McFarland Educational Fund for LGBTQI+ Mental Health is being established, and donations are being accepted at https://www.gofundme.com/f/in-memory-of-cait-mcfarland.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

“It is one of life’s most self-evident truths that everything fades, that we fear the fading, and that we must live, nonetheless, in the face of the fear.” – Irvin D. Yalom, MD, Existential Psychotherapy, 1980

The email was titled simply, “A sorrowful note,” and I knew that someone had died. I held my breath and read as Dr. Jimmy Potash informed our entire department that Dr. Cait McFarland died in a car accident on December 7 while driving to work at West Cecil Health Center, Conowingo, Md., where she was director of psychiatry.

Sadness swelled as I remembered the outspoken resident who was interested in LGBTQ issues. Cait graduated from the Johns Hopkins residency program in 2020, she had recently married a social worker in the department, and the plan was for her to return to Hopkins full-time in July 2023 to be director of a clinic focused on mental health for people who are transgendered.

Sudden deaths are tragic and jarring and they call to the surface our losses from the past. These deaths don’t stand alone – I found myself thinking of my editor at Medscape, Dr. Bret Stetka, who died unexpectedly in August 2022, and then of Dr. Lidia Palcan Wenz, a psychiatrist I trained with, who died in a motor vehicle accident in 2004. Lidia’s husband also died in the accident, while their two young children in the back seat survived – this tragedy haunted me for some time. None of these people was close to me, but I am no stranger to the impact of unexpected death: My parents and brother all died from cardiac events, and any sudden death is a reminder of those losses.

Julia Riddle, MD, trained with Cait McFarland and was her close friend for years. “I don’t have a belief in ‘the afterlife’ but do like to think of the people that I have lost together in my memory – as if they are all suddenly in a new room together. And, with each loss, all the other occupants of that room come freshly to life again,” Dr. Riddle said.

Death is our shared destination in life, but sudden and unexpected deaths carry their own weight. There is no chance to tie up loose ends, to repair riffs, to say goodbye. Nothing is put in order, and the life that was to be lived goes on for some time as bills arrive, social and work events go unattended, vacations are canceled, and there is the awkward moment of running into someone who didn’t know your loved one has died.

Roger Lewin, MD, is a psychiatrist and writer in Towson, Md. He has both personal and professional experience with sudden death. “There is no way to prepare beforehand, so we have to get ready for what has already happened, and that is hard,” he said. “We invent a life for ourselves and others that extends into the future, and that gets interrupted.”

Most people become ill and die on a vaguely predictable schedule. There may be a chance to plan, to know and honor the wishes of the individual, and often there is the opportunity for loved ones to begin the grieving process gradually as death approaches. For those who are elderly, there may be a sense that this is the natural order of things – which may or may not temper the intensity of the grief for those who remain. If the person has suffered, the end may come with relief.

Still, I sometimes find myself surprised at the length and intensity of anguish that some people experience after losing a loved one who has lived a long and full life, who declined and suffered, but whose absence remains a gaping wound that takes years to form a scar.

Sudden death is not rare; accidents, homicide, and suicide are the top killers among young people, and cardiovascular deaths are number one among those who are older. Natural disasters and terrorist attacks can cause catastrophic numbers of sudden deaths and leave survivors to grieve not only the dead, but the loss of all that was familiar to them.

Psychiatry has been a bit lost as to how we approach grief. We often hear patients talk about anxiety surrounding death and illness, be it a fear of death or a longing for it. These fears can seem irrational – I am reminded of a patient who was afraid to eat romaine because of news reports that it was responsible for food poisoning in other states, but not Maryland, where the person lived. I found it odd that he worried about eating lettuce, but not about smoking two packs of cigarettes a day.

But our fears are like that – they move to what the media sensationalizes, or to what may be remote, because otherwise no one would get in a car or clear their walkway of snow. Life is most easily lived with a bit of denial: We shut out the reality that we can be here one moment, overscheduled and overwhelmed, with deadlines, mortgage payments, and summer vacation plans, oblivious to the fact that life may end at any moment. The early months of COVID-19 felt like a global game of Russian roulette, with each venture out a pull of the trigger and everyone’s defenses stripped bare.

While death belongs to us all, we relegate it to the disciplines of religion, philosophy, the arts, and psychology. Religion offers answers – whether a heaven, a hell, or continual reincarnation until the individual attains enlightenment, there is a destination. Perhaps it will be pleasant, perhaps not, and for some there is the hope that one gets to be the driver by having the right beliefs or doing good deeds, while others are comforted by the hope of being reunited with loved ones.

“The suddenness endures and the shock lasts – it’s like a meteor that creates a crater and we revisit it in different ways from different angles,” Dr. Lewin said. “It may leap on us unexpectedly, often many years later.”

Patients talk about death, and when their fears seem unrealistic we may long to reassure them, yet there is no reassurance and psychiatry grasps for how to help. Psychiatry has looked to draw lines for when normal grief crosses to abnormal. Is it an adjustment disorder, complicated grief, “prolonged” grief, pathology in need of medication and medicalization, or something one experiences individually, sometimes for a very long time even with treatment?

One justification for pathologizing “prolonged” reactions includes the fact that insurers will pay for treatment only if there is a diagnosis code, and shouldn’t people in distress be entitled to psychotherapy or medication? Yet there is something offensive about telling someone that they are mentally ill if they don’t grieve along a prescribed timeline, as much as there is about denying them the possible benefits of therapy or medication if they seek it, but are suffering in all the “right” ways. Psychiatry’s approach to death is inelegant at best.

In his poignant podcast series, All There Is, Anderson Cooper is tasked with sorting through his mother’s apartment after her death at age 95. In the course of packing up her belongings, he brings on other guests to talk about their emotional reactions to death. Mr. Cooper’s mother, Gloria Vanderbilt, died at an advanced age, but his father died after a brief cardiac illness when Mr. Cooper was a child, and his brother died by suicide when he was 21. He uses these experiences as a springboard to examine childhood losses, the aftermath of suicide, and the loneliness of grief.

“Loss and grief is this universal experience that we will all go through multiple times in our lives,” Mr. Cooper says, “And yet it leaves us feeling so alone and so separated from other people. At least it does me and has my entire life.”

When we talk about grief and loss, we talk about “getting over it,” or “moving on.” But loss doesn’t work that way – time usually eases the pain, leaving scars that are part of the road map for who we are on the journey that defines us.

Sudden death is hard, and the unexpected death of a young person is tragic. For Cait McFarland, there are the decades she won’t get to experience. For her family and friends, it may be excruciating, and for all the patients who have lost a psychiatrist, may time bring healing and peace.

The Dr. Caitlin McFarland Educational Fund for LGBTQI+ Mental Health is being established, and donations are being accepted at https://www.gofundme.com/f/in-memory-of-cait-mcfarland.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

In this era of efficacious treatments for mantle cell lymphoma (MCL), patients who survive 2 years sans disease recurrence or progression live nearly as long as age- and sex-matched individuals in the general population, a recent study showed.

Patients with MCL who achieved this endpoint – event-free survival at 24 months (EFS24) – also had a low risk of lymphoma-related death, and most often died from unrelated causes, according to results of the prospective cohort study.

Although longer follow-up and confirmation from other study groups are needed, these findings demonstrated a prognostic role for EFS24 in patients with mantle cell lymphoma, according to the lead author, Yucai Wang, MD, PhD, a hematologist/oncologist with Mayo Clinic in Rochester, Minn.

As more effective therapies emerge, overall survival (OS) will likely continue to improve, such that EFS24 will may become an important clinical endpoint in MCL frontline therapy, according to Dr. Wang.

“When we counseled patients with newly diagnosed MCL, we used to tell them that this is an aggressive and incurable disease, and patients would feel bad about it, “ Dr. Wang said in an interview.

“Now that we have better therapy, and outcomes are improving,” he continued, “I think it’s important to tell our patients now that we have improved outcomes for patients with this disease, and things are probably going to get better in the future, to always remain hopeful. That’s powerful for our patients to know.”
 

Two eras of treatment

The current analysis by Dr. Wang and colleagues was based on patients identified in the Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource Cohort Study, a prospective observational study of lymphoma patients evaluated at the Mayo Clinic and the University of Iowa.

The patients were divided into two “eras” of treatment, based on the date of enrollment. Era 1 of enrollment was 2002 to 2009, and Era 2 was 2010 to 2015.

Patients in Era 2 had a substantially improved EFS and OS compared with those in Era 1, according to a previous report from Dr. Wang and coauthors.

Those improved treatment outcomes were likely due to advances in frontline immunochemotherapy, the authors said in that report. In particular, they pointed to the use of highly effective induction regimens containing high-dose cytarabine in patients who were eligible for autologous stem cell transplantation, and the combined use of rituximab-bendamustine in patients who were not eligible for transplant.

In addition, the increased use of salvage treatments such as lenalidomide and Bruton’s tyrosine kinase inhibitors has likely contributed to improvements in outcomes across eras, Dr. Wang and coauthors said in the present report, which looks more closely at the prognostic role of the EFS24 endpoint in Era 1 and Era 2 patients.

The five-year OS for patients diagnosed in Era 2 was 68.4%, compared with 59.2% in Era 1, the authors reported.

Achieving 2 years of EFS had no impact on OS in the earlier era, their findings further show.

In Era 1, the 98 patients who achieved EFS24 went on to have inferior OS compared with the general population, while in Era 2, the 99 patients achieving EFS24 had similar OS compared with the general population.

This was reported as a standardized mortality ratio (SMR) in Era 1 of 2.23 (95% confidence interval, 1.67-2.92; P < .001). By contrast, the SMR in Era 2 was just 1.31 (95% CI, 0.78-2.07; P = .31).

The risk of dying from lymphoma was lower among patients achieving EFS24 in the more recent Era 2, the results showed.

Among patients in Era 1 achieving EFS24, the primary cause of death was lymphoma-related, and the 5-year rate of lymphoma-related death was 19.8%, versus 6.2% for causes of death unrelated to lymphoma.

By contrast, among patients in Era 2 achieving EFS24, the 5-year rate of lymphoma-related death was 2.1% and 5.5% for other causes.
 

Favorable prognosis

These findings clearly showed that in one cohort of patients with MCL treated in the recent past, those patients going 2 years without evidence of disease progression or events “have a great prognosis,” said Matthew Matasar, MD, MS, chief of blood disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health.

However, there are limitations to describing the role of EFS24 in MCL based solely on this single-cohort study, Dr. Matasar said in an interview.

“There’s a lot of heterogeneity in how we treat mantle cell lymphoma,” he said, “so I would just caution generalizing out of a patient population treated one way to populations that may receive quite different therapeutic approaches.”

Dr. Wang said he and his coinvestigators have several confirmatory studies in the works that are focused on other groups of patients both inside and outside the United States, to validate of EFS24 as an endpoint.

“We have at least four cohorts to look into this and see whether we can see the same or similar results,” he said in the interview.

Dr. Wang disclosed ties with Incyte, InnoCare, LOXO Oncology, Novartis, Genentech, Eli Lilly, TG Therapeutics, MorphoSys, Genmab, and Kite.

In this era of efficacious treatments for mantle cell lymphoma (MCL), patients who survive 2 years sans disease recurrence or progression live nearly as long as age- and sex-matched individuals in the general population, a recent study showed.

Patients with MCL who achieved this endpoint – event-free survival at 24 months (EFS24) – also had a low risk of lymphoma-related death, and most often died from unrelated causes, according to results of the prospective cohort study.

Although longer follow-up and confirmation from other study groups are needed, these findings demonstrated a prognostic role for EFS24 in patients with mantle cell lymphoma, according to the lead author, Yucai Wang, MD, PhD, a hematologist/oncologist with Mayo Clinic in Rochester, Minn.

As more effective therapies emerge, overall survival (OS) will likely continue to improve, such that EFS24 will may become an important clinical endpoint in MCL frontline therapy, according to Dr. Wang.

“When we counseled patients with newly diagnosed MCL, we used to tell them that this is an aggressive and incurable disease, and patients would feel bad about it, “ Dr. Wang said in an interview.

“Now that we have better therapy, and outcomes are improving,” he continued, “I think it’s important to tell our patients now that we have improved outcomes for patients with this disease, and things are probably going to get better in the future, to always remain hopeful. That’s powerful for our patients to know.”
 

Two eras of treatment

The current analysis by Dr. Wang and colleagues was based on patients identified in the Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource Cohort Study, a prospective observational study of lymphoma patients evaluated at the Mayo Clinic and the University of Iowa.

The patients were divided into two “eras” of treatment, based on the date of enrollment. Era 1 of enrollment was 2002 to 2009, and Era 2 was 2010 to 2015.

Patients in Era 2 had a substantially improved EFS and OS compared with those in Era 1, according to a previous report from Dr. Wang and coauthors.

Those improved treatment outcomes were likely due to advances in frontline immunochemotherapy, the authors said in that report. In particular, they pointed to the use of highly effective induction regimens containing high-dose cytarabine in patients who were eligible for autologous stem cell transplantation, and the combined use of rituximab-bendamustine in patients who were not eligible for transplant.

In addition, the increased use of salvage treatments such as lenalidomide and Bruton’s tyrosine kinase inhibitors has likely contributed to improvements in outcomes across eras, Dr. Wang and coauthors said in the present report, which looks more closely at the prognostic role of the EFS24 endpoint in Era 1 and Era 2 patients.

The five-year OS for patients diagnosed in Era 2 was 68.4%, compared with 59.2% in Era 1, the authors reported.

Achieving 2 years of EFS had no impact on OS in the earlier era, their findings further show.

In Era 1, the 98 patients who achieved EFS24 went on to have inferior OS compared with the general population, while in Era 2, the 99 patients achieving EFS24 had similar OS compared with the general population.

This was reported as a standardized mortality ratio (SMR) in Era 1 of 2.23 (95% confidence interval, 1.67-2.92; P < .001). By contrast, the SMR in Era 2 was just 1.31 (95% CI, 0.78-2.07; P = .31).

The risk of dying from lymphoma was lower among patients achieving EFS24 in the more recent Era 2, the results showed.

Among patients in Era 1 achieving EFS24, the primary cause of death was lymphoma-related, and the 5-year rate of lymphoma-related death was 19.8%, versus 6.2% for causes of death unrelated to lymphoma.

By contrast, among patients in Era 2 achieving EFS24, the 5-year rate of lymphoma-related death was 2.1% and 5.5% for other causes.
 

Favorable prognosis

These findings clearly showed that in one cohort of patients with MCL treated in the recent past, those patients going 2 years without evidence of disease progression or events “have a great prognosis,” said Matthew Matasar, MD, MS, chief of blood disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health.

However, there are limitations to describing the role of EFS24 in MCL based solely on this single-cohort study, Dr. Matasar said in an interview.

“There’s a lot of heterogeneity in how we treat mantle cell lymphoma,” he said, “so I would just caution generalizing out of a patient population treated one way to populations that may receive quite different therapeutic approaches.”

Dr. Wang said he and his coinvestigators have several confirmatory studies in the works that are focused on other groups of patients both inside and outside the United States, to validate of EFS24 as an endpoint.

“We have at least four cohorts to look into this and see whether we can see the same or similar results,” he said in the interview.

Dr. Wang disclosed ties with Incyte, InnoCare, LOXO Oncology, Novartis, Genentech, Eli Lilly, TG Therapeutics, MorphoSys, Genmab, and Kite.

In this era of efficacious treatments for mantle cell lymphoma (MCL), patients who survive 2 years sans disease recurrence or progression live nearly as long as age- and sex-matched individuals in the general population, a recent study showed.

Patients with MCL who achieved this endpoint – event-free survival at 24 months (EFS24) – also had a low risk of lymphoma-related death, and most often died from unrelated causes, according to results of the prospective cohort study.

Although longer follow-up and confirmation from other study groups are needed, these findings demonstrated a prognostic role for EFS24 in patients with mantle cell lymphoma, according to the lead author, Yucai Wang, MD, PhD, a hematologist/oncologist with Mayo Clinic in Rochester, Minn.

As more effective therapies emerge, overall survival (OS) will likely continue to improve, such that EFS24 will may become an important clinical endpoint in MCL frontline therapy, according to Dr. Wang.

“When we counseled patients with newly diagnosed MCL, we used to tell them that this is an aggressive and incurable disease, and patients would feel bad about it, “ Dr. Wang said in an interview.

“Now that we have better therapy, and outcomes are improving,” he continued, “I think it’s important to tell our patients now that we have improved outcomes for patients with this disease, and things are probably going to get better in the future, to always remain hopeful. That’s powerful for our patients to know.”
 

Two eras of treatment

The current analysis by Dr. Wang and colleagues was based on patients identified in the Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource Cohort Study, a prospective observational study of lymphoma patients evaluated at the Mayo Clinic and the University of Iowa.

The patients were divided into two “eras” of treatment, based on the date of enrollment. Era 1 of enrollment was 2002 to 2009, and Era 2 was 2010 to 2015.

Patients in Era 2 had a substantially improved EFS and OS compared with those in Era 1, according to a previous report from Dr. Wang and coauthors.

Those improved treatment outcomes were likely due to advances in frontline immunochemotherapy, the authors said in that report. In particular, they pointed to the use of highly effective induction regimens containing high-dose cytarabine in patients who were eligible for autologous stem cell transplantation, and the combined use of rituximab-bendamustine in patients who were not eligible for transplant.

In addition, the increased use of salvage treatments such as lenalidomide and Bruton’s tyrosine kinase inhibitors has likely contributed to improvements in outcomes across eras, Dr. Wang and coauthors said in the present report, which looks more closely at the prognostic role of the EFS24 endpoint in Era 1 and Era 2 patients.

The five-year OS for patients diagnosed in Era 2 was 68.4%, compared with 59.2% in Era 1, the authors reported.

Achieving 2 years of EFS had no impact on OS in the earlier era, their findings further show.

In Era 1, the 98 patients who achieved EFS24 went on to have inferior OS compared with the general population, while in Era 2, the 99 patients achieving EFS24 had similar OS compared with the general population.

This was reported as a standardized mortality ratio (SMR) in Era 1 of 2.23 (95% confidence interval, 1.67-2.92; P < .001). By contrast, the SMR in Era 2 was just 1.31 (95% CI, 0.78-2.07; P = .31).

The risk of dying from lymphoma was lower among patients achieving EFS24 in the more recent Era 2, the results showed.

Among patients in Era 1 achieving EFS24, the primary cause of death was lymphoma-related, and the 5-year rate of lymphoma-related death was 19.8%, versus 6.2% for causes of death unrelated to lymphoma.

By contrast, among patients in Era 2 achieving EFS24, the 5-year rate of lymphoma-related death was 2.1% and 5.5% for other causes.
 

Favorable prognosis

These findings clearly showed that in one cohort of patients with MCL treated in the recent past, those patients going 2 years without evidence of disease progression or events “have a great prognosis,” said Matthew Matasar, MD, MS, chief of blood disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health.

However, there are limitations to describing the role of EFS24 in MCL based solely on this single-cohort study, Dr. Matasar said in an interview.

“There’s a lot of heterogeneity in how we treat mantle cell lymphoma,” he said, “so I would just caution generalizing out of a patient population treated one way to populations that may receive quite different therapeutic approaches.”

Dr. Wang said he and his coinvestigators have several confirmatory studies in the works that are focused on other groups of patients both inside and outside the United States, to validate of EFS24 as an endpoint.

“We have at least four cohorts to look into this and see whether we can see the same or similar results,” he said in the interview.

Dr. Wang disclosed ties with Incyte, InnoCare, LOXO Oncology, Novartis, Genentech, Eli Lilly, TG Therapeutics, MorphoSys, Genmab, and Kite.

Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.

Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.

However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.

In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.

Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).

Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.

Notably, after adjusting for multiple variables, FFM was independently associated with improved scores on the 6-minute walk test for UW patients; NW and PO patients had no such association after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.

However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).

Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.

The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.

However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.

The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.

Mr. Machado disclosed financial support from ZonMW.  

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

Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.

Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.

However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.

In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.

Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).

Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.

Notably, after adjusting for multiple variables, FFM was independently associated with improved scores on the 6-minute walk test for UW patients; NW and PO patients had no such association after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.

However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).

Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.

The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.

However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.

The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.

Mr. Machado disclosed financial support from ZonMW.  

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

Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.

Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.

However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.

In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.

Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).

Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.

Notably, after adjusting for multiple variables, FFM was independently associated with improved scores on the 6-minute walk test for UW patients; NW and PO patients had no such association after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.

However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).

Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.

The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.

However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.

The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.

Mr. Machado disclosed financial support from ZonMW.  

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

In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).

“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”

The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.

And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.

A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.

“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.

Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.

“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”

The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.

Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.

“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”

“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”

Other important clues of bipolarity in depressed patients include:

• Family history: Most cases are genetically driven.
• Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
• Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
• Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.

Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.

“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”

“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
 

Treatment resistance

When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.

“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.

There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.

Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.

“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.

“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”

Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).

“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”

The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.

And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.

A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.

“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.

Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.

“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”

The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.

Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.

“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”

“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”

Other important clues of bipolarity in depressed patients include:

• Family history: Most cases are genetically driven.
• Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
• Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
• Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.

Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.

“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”

“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
 

Treatment resistance

When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.

“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.

There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.

Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.

“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.

“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”

Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).

“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”

The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.

And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.

A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.

“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.

Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.

“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”

The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.

Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.

“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”

“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”

Other important clues of bipolarity in depressed patients include:

• Family history: Most cases are genetically driven.
• Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
• Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
• Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.

Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.

“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”

“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
 

Treatment resistance

When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.

“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.

There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.

Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.

“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.

“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”

Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

Higher concentrations of serum zinc, alone and in combination with copper, and selenium, were inversely related to an increased risk of sleep disorders in adults, based on data from 3,660 individuals.

Previous research has shown an association between trace metals and sleep and sleep patterns, but data on the impact of serum trace metals on sleep disorders have been limited, wrote Ming-Gang Deng, MD, of Wuhan (China) University and colleagues.

In a study published in the Journal of Affective Disorders, the researchers reviewed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to calculate the odds ratios of sleep disorders and serum zinc (Zn), copper (Cu), and selenium (Se). The study population included adults aged 18 years and older, with an average age of 47.6 years. Approximately half of the participants were men, and the majority was non-Hispanic white. Serum Zn, Cu, and Se were identified at the Environmental Health Sciences Laboratory of the Centers for Disease Control and Prevention National Center for Environmental Health. The lower limits of detection for Zn, Cu, and Se were 2.9 mcg/dL, 2.5 mcg/dL, and 4.5 mcg/L, respectively. Sleep disorders were assessed based on self-reports of discussions with health professionals about sleep disorders, and via the Sleep Disorder Questionnaire.

After adjusting for sociodemographic, behavioral characteristics, and health characteristics, adults in the highest tertiles of serum Zn had a 30% reduced risk of sleep disorders, compared with those in the lowest tertiles of serum Zn (odds ratio, 0.70; P = .035). In measures of trace metals ratios, serum Zn/Cu and Zn/Se also were significantly associated with reduced risk of sleep disorders for individuals in the highest tertiles, compared with those in the lowest tertiles (OR, 0.62 and OR, 0.68, respectively).

However, serum Cu, Se and Cu/Se were not associated with sleep disorder risk.

Sociodemographic factors included age, sex, race, education level, family income level; behavioral characteristics included smoking, alcohol consumption, physical activity, and caffeine intake.

The researchers also used a restricted cubic spline model to examine the dose-response relationships between serum trace metals, serum trace metals ratios, and sleep disorders. In this analysis, higher levels of serum Zn, Zn/Cu, and Zn/Se were related to reduced risk of sleep disorders, while no significant association appeared between serum Cu, Se, or Cu/Se and sleep disorders risk.

The findings showing a lack of association between Se and sleep disorders were not consistent with previous studies, the researchers wrote in their discussion. Previous research has shown that a higher Se was less likely to be associated with trouble falling asleep, and has shown a potential treatment effect of Se on obstructive sleep apnea, they said.

“Although serum Cu and Se levels were not correlated to sleep disorders in our study, the Zn/Cu and Zn/Se may provide some novel insights,” they wrote. For example, Zn/Cu has been used as a predictor of several clinical complications related to an increased risk of sleep disorders including cardiovascular disease, cancer, and major depressive disorder, they noted.

The findings were limited by several factors including the cross-sectional design, use of self-reports, and the inability to examine relationships between trace metals and specific sleep disorder symptoms, such as restless legs syndrome, insomnia, and obstructive sleep apnea, the researchers noted.

However, the results were strengthened by the large national sample, and support data from previous studies, they said.

“The inverse associations of serum Zn, and Zn/Cu, Zn/Se with sleep disorders enlightened us that increasing Zn intake may be an excellent approach to prevent sleep disorders due to its benefits from these three aspects,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Higher concentrations of serum zinc, alone and in combination with copper, and selenium, were inversely related to an increased risk of sleep disorders in adults, based on data from 3,660 individuals.

Previous research has shown an association between trace metals and sleep and sleep patterns, but data on the impact of serum trace metals on sleep disorders have been limited, wrote Ming-Gang Deng, MD, of Wuhan (China) University and colleagues.

In a study published in the Journal of Affective Disorders, the researchers reviewed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to calculate the odds ratios of sleep disorders and serum zinc (Zn), copper (Cu), and selenium (Se). The study population included adults aged 18 years and older, with an average age of 47.6 years. Approximately half of the participants were men, and the majority was non-Hispanic white. Serum Zn, Cu, and Se were identified at the Environmental Health Sciences Laboratory of the Centers for Disease Control and Prevention National Center for Environmental Health. The lower limits of detection for Zn, Cu, and Se were 2.9 mcg/dL, 2.5 mcg/dL, and 4.5 mcg/L, respectively. Sleep disorders were assessed based on self-reports of discussions with health professionals about sleep disorders, and via the Sleep Disorder Questionnaire.

After adjusting for sociodemographic, behavioral characteristics, and health characteristics, adults in the highest tertiles of serum Zn had a 30% reduced risk of sleep disorders, compared with those in the lowest tertiles of serum Zn (odds ratio, 0.70; P = .035). In measures of trace metals ratios, serum Zn/Cu and Zn/Se also were significantly associated with reduced risk of sleep disorders for individuals in the highest tertiles, compared with those in the lowest tertiles (OR, 0.62 and OR, 0.68, respectively).

However, serum Cu, Se and Cu/Se were not associated with sleep disorder risk.

Sociodemographic factors included age, sex, race, education level, family income level; behavioral characteristics included smoking, alcohol consumption, physical activity, and caffeine intake.

The researchers also used a restricted cubic spline model to examine the dose-response relationships between serum trace metals, serum trace metals ratios, and sleep disorders. In this analysis, higher levels of serum Zn, Zn/Cu, and Zn/Se were related to reduced risk of sleep disorders, while no significant association appeared between serum Cu, Se, or Cu/Se and sleep disorders risk.

The findings showing a lack of association between Se and sleep disorders were not consistent with previous studies, the researchers wrote in their discussion. Previous research has shown that a higher Se was less likely to be associated with trouble falling asleep, and has shown a potential treatment effect of Se on obstructive sleep apnea, they said.

“Although serum Cu and Se levels were not correlated to sleep disorders in our study, the Zn/Cu and Zn/Se may provide some novel insights,” they wrote. For example, Zn/Cu has been used as a predictor of several clinical complications related to an increased risk of sleep disorders including cardiovascular disease, cancer, and major depressive disorder, they noted.

The findings were limited by several factors including the cross-sectional design, use of self-reports, and the inability to examine relationships between trace metals and specific sleep disorder symptoms, such as restless legs syndrome, insomnia, and obstructive sleep apnea, the researchers noted.

However, the results were strengthened by the large national sample, and support data from previous studies, they said.

“The inverse associations of serum Zn, and Zn/Cu, Zn/Se with sleep disorders enlightened us that increasing Zn intake may be an excellent approach to prevent sleep disorders due to its benefits from these three aspects,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Higher concentrations of serum zinc, alone and in combination with copper, and selenium, were inversely related to an increased risk of sleep disorders in adults, based on data from 3,660 individuals.

Previous research has shown an association between trace metals and sleep and sleep patterns, but data on the impact of serum trace metals on sleep disorders have been limited, wrote Ming-Gang Deng, MD, of Wuhan (China) University and colleagues.

In a study published in the Journal of Affective Disorders, the researchers reviewed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to calculate the odds ratios of sleep disorders and serum zinc (Zn), copper (Cu), and selenium (Se). The study population included adults aged 18 years and older, with an average age of 47.6 years. Approximately half of the participants were men, and the majority was non-Hispanic white. Serum Zn, Cu, and Se were identified at the Environmental Health Sciences Laboratory of the Centers for Disease Control and Prevention National Center for Environmental Health. The lower limits of detection for Zn, Cu, and Se were 2.9 mcg/dL, 2.5 mcg/dL, and 4.5 mcg/L, respectively. Sleep disorders were assessed based on self-reports of discussions with health professionals about sleep disorders, and via the Sleep Disorder Questionnaire.

After adjusting for sociodemographic, behavioral characteristics, and health characteristics, adults in the highest tertiles of serum Zn had a 30% reduced risk of sleep disorders, compared with those in the lowest tertiles of serum Zn (odds ratio, 0.70; P = .035). In measures of trace metals ratios, serum Zn/Cu and Zn/Se also were significantly associated with reduced risk of sleep disorders for individuals in the highest tertiles, compared with those in the lowest tertiles (OR, 0.62 and OR, 0.68, respectively).

However, serum Cu, Se and Cu/Se were not associated with sleep disorder risk.

Sociodemographic factors included age, sex, race, education level, family income level; behavioral characteristics included smoking, alcohol consumption, physical activity, and caffeine intake.

The researchers also used a restricted cubic spline model to examine the dose-response relationships between serum trace metals, serum trace metals ratios, and sleep disorders. In this analysis, higher levels of serum Zn, Zn/Cu, and Zn/Se were related to reduced risk of sleep disorders, while no significant association appeared between serum Cu, Se, or Cu/Se and sleep disorders risk.

The findings showing a lack of association between Se and sleep disorders were not consistent with previous studies, the researchers wrote in their discussion. Previous research has shown that a higher Se was less likely to be associated with trouble falling asleep, and has shown a potential treatment effect of Se on obstructive sleep apnea, they said.

“Although serum Cu and Se levels were not correlated to sleep disorders in our study, the Zn/Cu and Zn/Se may provide some novel insights,” they wrote. For example, Zn/Cu has been used as a predictor of several clinical complications related to an increased risk of sleep disorders including cardiovascular disease, cancer, and major depressive disorder, they noted.

The findings were limited by several factors including the cross-sectional design, use of self-reports, and the inability to examine relationships between trace metals and specific sleep disorder symptoms, such as restless legs syndrome, insomnia, and obstructive sleep apnea, the researchers noted.

However, the results were strengthened by the large national sample, and support data from previous studies, they said.

“The inverse associations of serum Zn, and Zn/Cu, Zn/Se with sleep disorders enlightened us that increasing Zn intake may be an excellent approach to prevent sleep disorders due to its benefits from these three aspects,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A year ago in December, mapping specialist Whitney Tyshynski, 35, was working out 5 days a week with a personal trainer near her home in Alberta, Canada, doing 5k trail runs, lifting heavy weights, and feeling good. Then, in January she got COVID-19. The symptoms never went away.
 

Nowadays, Ms. Tyshynski needs a walker to retrieve her mail, a half-block trip she can’t make without fear of fainting. Because she gets dizzy when she drives, she rarely goes anywhere in her car. Going for a dog walk with a friend means sitting in a car and watching the friend and the dogs in an open field. And since fainting at Costco during the summer, she’s afraid to shop by herself.

Because she lives alone and her closest relatives are an hour and a half away, Ms. Tyshynski is dependent on friends. But she’s reluctant to lean on them because they already have trouble understanding how debilitating her lingering symptoms can be.

“I’ve had people pretty much insinuate that I’m lazy,” she says.

There’s no question that COVID-19 cut people off from one another. But for those like Ms. Tyshynski who have long COVID, that disconnect has never ended. It’s not just that symptoms including extreme fatigue and brain fog make it difficult to socialize; it’s that people who had COVID-19 and recovered are often skeptical that the condition is real.

At worst, as Ms. Tyshynski has discovered, people don’t take it seriously and accuse those who have it of exaggerating their health woes. In that way, long COVID can be as isolating as the original illness.

“Isolation in long COVID comes in various forms and it’s not primarily just that physical isolation,” says Yochai Re’em, MD, a psychiatrist in private practice in New York who has experienced long COVID and blogs about the condition for Psychology Today. “A different yet equally challenging type of isolation is the emotional isolation, where you need more emotional support, connection with other people who can appreciate what it is you are going through without putting their own needs and desires onto you – and that can be hard to find.”

It’s hard to find in part because of what Dr. Re’em sees as a collective belief that anyone who feels bad should be able to get better by exercising, researching, or going to a doctor.

“Society thinks you need to take some kind of action and usually that’s a physical action,” he says. “And that attitude is tremendously problematic in this illness because of the postexertional malaise that people experience: When people exert themselves, their symptoms get worse. And so the action that people take can’t be that traditional action that we’re used to taking in our society.”

Long COVID patients often have their feelings invalidated not just by friends, loved ones, and extended family, but by health care providers. That can heighten feelings of isolation, particularly for people who live alone, says Jordan Anderson, DO, a neuropsychiatrist and assistant professor of psychiatry at Oregon Health & Science University in Portland.

The first patients Dr. Anderson saw as part of OHSU’s long COVID program contracted the virus in February 2020. Because the program addresses both the physical and mental health components of the condition, Dr. Anderson has seen a lot of people whose emotional challenges are similar to those Ms. Tyshynski faces.

“I think there’s a lack of understanding that leads to people just not necessarily taking it seriously,” he says. “Plus, the symptoms of long COVID do wax and wane. They’re not static. So people can be feeling pretty good one day and be feeling terrible the next. There’s some predictability to it, but it’s not absolutely predictable. It can be difficult for people to understand.”

Both Dr. Anderson and Dr. Re’em stress that long COVID patients need to prioritize their own energy regardless of what they’re being told by those who don’t understand the illness. Dr. Anderson offers to speak to his patients’ spouses to educate them about the realities of the condition because, he says, “any kind of lack of awareness or understanding in a family member or close support could potentially isolate the person struggling with long COVID.”

Depending on how open-minded and motivated a friend or relative is, they might develop more empathy with time and education, Dr. Re’em says. But for others, dealing with a confusing, unfamiliar chronic illness can be overwhelming and provoke anxiety.

“The hopelessness is too much for them to sit with, so instead they say things like ‘just push through it,’ or ‘just do X, Y, and Z,’ because psychologically it’s too much for them to take on that burden,” he says.

The good news is that there are plenty of web-based support groups for people with long COVID, including Body Politic (which Dr. Re’em is affiliated with), Survivor Corps, and on Facebook. “The patient community with this illness is tremendous, absolutely tremendous,” Dr. Re’em says. “Those people can be found and they can support each other.”

Some long COVID clinics run groups, as do individual practitioners such as Dr. Re’em, although those can be challenging to join. For instance, Dr. Re’em’s are only for New York state residents.

The key to finding a group is to be patient, because finding the right one takes time and energy.

“There are support groups that exist, but they are not as prevalent as I would like them to be,” Dr. Anderson says.

OHSU had an educational support group run by a social worker affiliated with the long COVID hub, but when the social worker left the program, the program was put on hold.

There’s a psychotherapy group operating out of the psychiatry department, but the patients are recruited exclusively from Dr. Anderson’s clinic and access is limited.

“The services exist, but I think that generally they’re sparse and pretty geographically dependent,” Dr. Anderson says. “I think you’d probably more likely be able to find something like this in a city or an area that has an academic institution or a place with a lot of resources rather than out in a rural community.”

Ms. Tyshynski opted not to join a group for fear it would increase the depression and anxiety that she had even before developing long COVID. When she and her family joined a cancer support group when her father was ill, she found it more depressing than helpful. Where she has found support is from the cofounder of the animal rescue society where she volunteers, a woman who has had long COVID for more than 2 years and has been a source of comfort and advice.

It’s one of the rare reminders Ms. Tyshynski has that even though she may live alone, she’s not completely alone. “Other people are going through this, too,” she says. “It helps to remember that.”

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

A year ago in December, mapping specialist Whitney Tyshynski, 35, was working out 5 days a week with a personal trainer near her home in Alberta, Canada, doing 5k trail runs, lifting heavy weights, and feeling good. Then, in January she got COVID-19. The symptoms never went away.
 

Nowadays, Ms. Tyshynski needs a walker to retrieve her mail, a half-block trip she can’t make without fear of fainting. Because she gets dizzy when she drives, she rarely goes anywhere in her car. Going for a dog walk with a friend means sitting in a car and watching the friend and the dogs in an open field. And since fainting at Costco during the summer, she’s afraid to shop by herself.

Because she lives alone and her closest relatives are an hour and a half away, Ms. Tyshynski is dependent on friends. But she’s reluctant to lean on them because they already have trouble understanding how debilitating her lingering symptoms can be.

“I’ve had people pretty much insinuate that I’m lazy,” she says.

There’s no question that COVID-19 cut people off from one another. But for those like Ms. Tyshynski who have long COVID, that disconnect has never ended. It’s not just that symptoms including extreme fatigue and brain fog make it difficult to socialize; it’s that people who had COVID-19 and recovered are often skeptical that the condition is real.

At worst, as Ms. Tyshynski has discovered, people don’t take it seriously and accuse those who have it of exaggerating their health woes. In that way, long COVID can be as isolating as the original illness.

“Isolation in long COVID comes in various forms and it’s not primarily just that physical isolation,” says Yochai Re’em, MD, a psychiatrist in private practice in New York who has experienced long COVID and blogs about the condition for Psychology Today. “A different yet equally challenging type of isolation is the emotional isolation, where you need more emotional support, connection with other people who can appreciate what it is you are going through without putting their own needs and desires onto you – and that can be hard to find.”

It’s hard to find in part because of what Dr. Re’em sees as a collective belief that anyone who feels bad should be able to get better by exercising, researching, or going to a doctor.

“Society thinks you need to take some kind of action and usually that’s a physical action,” he says. “And that attitude is tremendously problematic in this illness because of the postexertional malaise that people experience: When people exert themselves, their symptoms get worse. And so the action that people take can’t be that traditional action that we’re used to taking in our society.”

Long COVID patients often have their feelings invalidated not just by friends, loved ones, and extended family, but by health care providers. That can heighten feelings of isolation, particularly for people who live alone, says Jordan Anderson, DO, a neuropsychiatrist and assistant professor of psychiatry at Oregon Health & Science University in Portland.

The first patients Dr. Anderson saw as part of OHSU’s long COVID program contracted the virus in February 2020. Because the program addresses both the physical and mental health components of the condition, Dr. Anderson has seen a lot of people whose emotional challenges are similar to those Ms. Tyshynski faces.

“I think there’s a lack of understanding that leads to people just not necessarily taking it seriously,” he says. “Plus, the symptoms of long COVID do wax and wane. They’re not static. So people can be feeling pretty good one day and be feeling terrible the next. There’s some predictability to it, but it’s not absolutely predictable. It can be difficult for people to understand.”

Both Dr. Anderson and Dr. Re’em stress that long COVID patients need to prioritize their own energy regardless of what they’re being told by those who don’t understand the illness. Dr. Anderson offers to speak to his patients’ spouses to educate them about the realities of the condition because, he says, “any kind of lack of awareness or understanding in a family member or close support could potentially isolate the person struggling with long COVID.”

Depending on how open-minded and motivated a friend or relative is, they might develop more empathy with time and education, Dr. Re’em says. But for others, dealing with a confusing, unfamiliar chronic illness can be overwhelming and provoke anxiety.

“The hopelessness is too much for them to sit with, so instead they say things like ‘just push through it,’ or ‘just do X, Y, and Z,’ because psychologically it’s too much for them to take on that burden,” he says.

The good news is that there are plenty of web-based support groups for people with long COVID, including Body Politic (which Dr. Re’em is affiliated with), Survivor Corps, and on Facebook. “The patient community with this illness is tremendous, absolutely tremendous,” Dr. Re’em says. “Those people can be found and they can support each other.”

Some long COVID clinics run groups, as do individual practitioners such as Dr. Re’em, although those can be challenging to join. For instance, Dr. Re’em’s are only for New York state residents.

The key to finding a group is to be patient, because finding the right one takes time and energy.

“There are support groups that exist, but they are not as prevalent as I would like them to be,” Dr. Anderson says.

OHSU had an educational support group run by a social worker affiliated with the long COVID hub, but when the social worker left the program, the program was put on hold.

There’s a psychotherapy group operating out of the psychiatry department, but the patients are recruited exclusively from Dr. Anderson’s clinic and access is limited.

“The services exist, but I think that generally they’re sparse and pretty geographically dependent,” Dr. Anderson says. “I think you’d probably more likely be able to find something like this in a city or an area that has an academic institution or a place with a lot of resources rather than out in a rural community.”

Ms. Tyshynski opted not to join a group for fear it would increase the depression and anxiety that she had even before developing long COVID. When she and her family joined a cancer support group when her father was ill, she found it more depressing than helpful. Where she has found support is from the cofounder of the animal rescue society where she volunteers, a woman who has had long COVID for more than 2 years and has been a source of comfort and advice.

It’s one of the rare reminders Ms. Tyshynski has that even though she may live alone, she’s not completely alone. “Other people are going through this, too,” she says. “It helps to remember that.”

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

A year ago in December, mapping specialist Whitney Tyshynski, 35, was working out 5 days a week with a personal trainer near her home in Alberta, Canada, doing 5k trail runs, lifting heavy weights, and feeling good. Then, in January she got COVID-19. The symptoms never went away.
 

Nowadays, Ms. Tyshynski needs a walker to retrieve her mail, a half-block trip she can’t make without fear of fainting. Because she gets dizzy when she drives, she rarely goes anywhere in her car. Going for a dog walk with a friend means sitting in a car and watching the friend and the dogs in an open field. And since fainting at Costco during the summer, she’s afraid to shop by herself.

Because she lives alone and her closest relatives are an hour and a half away, Ms. Tyshynski is dependent on friends. But she’s reluctant to lean on them because they already have trouble understanding how debilitating her lingering symptoms can be.

“I’ve had people pretty much insinuate that I’m lazy,” she says.

There’s no question that COVID-19 cut people off from one another. But for those like Ms. Tyshynski who have long COVID, that disconnect has never ended. It’s not just that symptoms including extreme fatigue and brain fog make it difficult to socialize; it’s that people who had COVID-19 and recovered are often skeptical that the condition is real.

At worst, as Ms. Tyshynski has discovered, people don’t take it seriously and accuse those who have it of exaggerating their health woes. In that way, long COVID can be as isolating as the original illness.

“Isolation in long COVID comes in various forms and it’s not primarily just that physical isolation,” says Yochai Re’em, MD, a psychiatrist in private practice in New York who has experienced long COVID and blogs about the condition for Psychology Today. “A different yet equally challenging type of isolation is the emotional isolation, where you need more emotional support, connection with other people who can appreciate what it is you are going through without putting their own needs and desires onto you – and that can be hard to find.”

It’s hard to find in part because of what Dr. Re’em sees as a collective belief that anyone who feels bad should be able to get better by exercising, researching, or going to a doctor.

“Society thinks you need to take some kind of action and usually that’s a physical action,” he says. “And that attitude is tremendously problematic in this illness because of the postexertional malaise that people experience: When people exert themselves, their symptoms get worse. And so the action that people take can’t be that traditional action that we’re used to taking in our society.”

Long COVID patients often have their feelings invalidated not just by friends, loved ones, and extended family, but by health care providers. That can heighten feelings of isolation, particularly for people who live alone, says Jordan Anderson, DO, a neuropsychiatrist and assistant professor of psychiatry at Oregon Health & Science University in Portland.

The first patients Dr. Anderson saw as part of OHSU’s long COVID program contracted the virus in February 2020. Because the program addresses both the physical and mental health components of the condition, Dr. Anderson has seen a lot of people whose emotional challenges are similar to those Ms. Tyshynski faces.

“I think there’s a lack of understanding that leads to people just not necessarily taking it seriously,” he says. “Plus, the symptoms of long COVID do wax and wane. They’re not static. So people can be feeling pretty good one day and be feeling terrible the next. There’s some predictability to it, but it’s not absolutely predictable. It can be difficult for people to understand.”

Both Dr. Anderson and Dr. Re’em stress that long COVID patients need to prioritize their own energy regardless of what they’re being told by those who don’t understand the illness. Dr. Anderson offers to speak to his patients’ spouses to educate them about the realities of the condition because, he says, “any kind of lack of awareness or understanding in a family member or close support could potentially isolate the person struggling with long COVID.”

Depending on how open-minded and motivated a friend or relative is, they might develop more empathy with time and education, Dr. Re’em says. But for others, dealing with a confusing, unfamiliar chronic illness can be overwhelming and provoke anxiety.

“The hopelessness is too much for them to sit with, so instead they say things like ‘just push through it,’ or ‘just do X, Y, and Z,’ because psychologically it’s too much for them to take on that burden,” he says.

The good news is that there are plenty of web-based support groups for people with long COVID, including Body Politic (which Dr. Re’em is affiliated with), Survivor Corps, and on Facebook. “The patient community with this illness is tremendous, absolutely tremendous,” Dr. Re’em says. “Those people can be found and they can support each other.”

Some long COVID clinics run groups, as do individual practitioners such as Dr. Re’em, although those can be challenging to join. For instance, Dr. Re’em’s are only for New York state residents.

The key to finding a group is to be patient, because finding the right one takes time and energy.

“There are support groups that exist, but they are not as prevalent as I would like them to be,” Dr. Anderson says.

OHSU had an educational support group run by a social worker affiliated with the long COVID hub, but when the social worker left the program, the program was put on hold.

There’s a psychotherapy group operating out of the psychiatry department, but the patients are recruited exclusively from Dr. Anderson’s clinic and access is limited.

“The services exist, but I think that generally they’re sparse and pretty geographically dependent,” Dr. Anderson says. “I think you’d probably more likely be able to find something like this in a city or an area that has an academic institution or a place with a lot of resources rather than out in a rural community.”

Ms. Tyshynski opted not to join a group for fear it would increase the depression and anxiety that she had even before developing long COVID. When she and her family joined a cancer support group when her father was ill, she found it more depressing than helpful. Where she has found support is from the cofounder of the animal rescue society where she volunteers, a woman who has had long COVID for more than 2 years and has been a source of comfort and advice.

It’s one of the rare reminders Ms. Tyshynski has that even though she may live alone, she’s not completely alone. “Other people are going through this, too,” she says. “It helps to remember that.”

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

The U.S. Food and Drug Administration has approved the medication lenacapavir (Sunlenca) for adults living with multidrug resistant HIV-1 infection. After the initial doses are completed – given both orally and via subcutaneous injection – the drug is administered by injection every 6 months.
 

“Following today’s decision from the FDA, lenacapavir helps to fill a critical unmet need for people with complex prior treatment histories and offers physicians a long-awaited twice-yearly option for these patients who otherwise have limited therapy choices,” said site principal investigator Sorana Segal-Maurer, MD, a professor of clinical medicine at Weill Cornell Medicine, New York, in a statement.

HIV drug regimens generally consist of two or three HIV medicines combined in a daily pill. In 2021, the FDA approved the first injectable complete drug regimen for HIV-1, Cabenuva, which can be administered monthly or every other month. Lenacapavir is administered only twice annually, but it is also combined with other antiretrovirals. The injections and oral tablets of lenacapavir are estimated to cost $42,250 in the first year of treatment and then $39,000 annually in the subsequent years, Reuters reported.

Lenacapavir is the first of a new class of drug called capsid inhibitors to be FDA-approved for treating HIV-1. The drug blocks the HIV-1 virus’s protein shell and interferes with essential steps of the virus’s evolution. The approval, announced today, was based on a multicenter clinical trial of 72 patients with multidrug resistant HIV-1 infection. After a year of the medication, 30 (83%) of the 36 patients randomly assigned to take lenacapavir, in combination with other HIV medications, had undetectable viral loads.

“Today’s approval ushers in a new class of antiretroviral drugs that may help patients with HIV who have run out of treatment options,” said Debra Birnkrant, MD, director of the division of antivirals in the FDA’s Center for Drug Evaluation and Research, in a press release. “The availability of new classes of antiretroviral medications may possibly help these patients live longer, healthier lives.”

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

The U.S. Food and Drug Administration has approved the medication lenacapavir (Sunlenca) for adults living with multidrug resistant HIV-1 infection. After the initial doses are completed – given both orally and via subcutaneous injection – the drug is administered by injection every 6 months.
 

“Following today’s decision from the FDA, lenacapavir helps to fill a critical unmet need for people with complex prior treatment histories and offers physicians a long-awaited twice-yearly option for these patients who otherwise have limited therapy choices,” said site principal investigator Sorana Segal-Maurer, MD, a professor of clinical medicine at Weill Cornell Medicine, New York, in a statement.

HIV drug regimens generally consist of two or three HIV medicines combined in a daily pill. In 2021, the FDA approved the first injectable complete drug regimen for HIV-1, Cabenuva, which can be administered monthly or every other month. Lenacapavir is administered only twice annually, but it is also combined with other antiretrovirals. The injections and oral tablets of lenacapavir are estimated to cost $42,250 in the first year of treatment and then $39,000 annually in the subsequent years, Reuters reported.

Lenacapavir is the first of a new class of drug called capsid inhibitors to be FDA-approved for treating HIV-1. The drug blocks the HIV-1 virus’s protein shell and interferes with essential steps of the virus’s evolution. The approval, announced today, was based on a multicenter clinical trial of 72 patients with multidrug resistant HIV-1 infection. After a year of the medication, 30 (83%) of the 36 patients randomly assigned to take lenacapavir, in combination with other HIV medications, had undetectable viral loads.

“Today’s approval ushers in a new class of antiretroviral drugs that may help patients with HIV who have run out of treatment options,” said Debra Birnkrant, MD, director of the division of antivirals in the FDA’s Center for Drug Evaluation and Research, in a press release. “The availability of new classes of antiretroviral medications may possibly help these patients live longer, healthier lives.”

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

The U.S. Food and Drug Administration has approved the medication lenacapavir (Sunlenca) for adults living with multidrug resistant HIV-1 infection. After the initial doses are completed – given both orally and via subcutaneous injection – the drug is administered by injection every 6 months.
 

“Following today’s decision from the FDA, lenacapavir helps to fill a critical unmet need for people with complex prior treatment histories and offers physicians a long-awaited twice-yearly option for these patients who otherwise have limited therapy choices,” said site principal investigator Sorana Segal-Maurer, MD, a professor of clinical medicine at Weill Cornell Medicine, New York, in a statement.

HIV drug regimens generally consist of two or three HIV medicines combined in a daily pill. In 2021, the FDA approved the first injectable complete drug regimen for HIV-1, Cabenuva, which can be administered monthly or every other month. Lenacapavir is administered only twice annually, but it is also combined with other antiretrovirals. The injections and oral tablets of lenacapavir are estimated to cost $42,250 in the first year of treatment and then $39,000 annually in the subsequent years, Reuters reported.

Lenacapavir is the first of a new class of drug called capsid inhibitors to be FDA-approved for treating HIV-1. The drug blocks the HIV-1 virus’s protein shell and interferes with essential steps of the virus’s evolution. The approval, announced today, was based on a multicenter clinical trial of 72 patients with multidrug resistant HIV-1 infection. After a year of the medication, 30 (83%) of the 36 patients randomly assigned to take lenacapavir, in combination with other HIV medications, had undetectable viral loads.

“Today’s approval ushers in a new class of antiretroviral drugs that may help patients with HIV who have run out of treatment options,” said Debra Birnkrant, MD, director of the division of antivirals in the FDA’s Center for Drug Evaluation and Research, in a press release. “The availability of new classes of antiretroviral medications may possibly help these patients live longer, healthier lives.”

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

NEW ORLEANS – Addressing an audience of hematologists, an immunologist and a thrombosis specialist presented insights on two hot COVID-19 topics: strategies the virus uses to breach the immune system and the diagnosis and treatment of vaccine-related blood clots.

In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”

The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”

The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.

“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”

How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”

Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”

What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)

The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.

Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”

The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.

The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”

“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”

Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.

NEW ORLEANS – Addressing an audience of hematologists, an immunologist and a thrombosis specialist presented insights on two hot COVID-19 topics: strategies the virus uses to breach the immune system and the diagnosis and treatment of vaccine-related blood clots.

In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”

The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”

The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.

“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”

How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”

Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”

What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)

The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.

Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”

The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.

The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”

“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”

Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.

NEW ORLEANS – Addressing an audience of hematologists, an immunologist and a thrombosis specialist presented insights on two hot COVID-19 topics: strategies the virus uses to breach the immune system and the diagnosis and treatment of vaccine-related blood clots.

In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”

The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”

The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.

“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”

How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”

Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”

What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)

The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.

Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”

The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.

The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”

“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”

Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.

This patient's clinical presentation and endoscopy findings are consistent with a diagnosis of recurrent MCL presenting as a colonic mass.

MCL is an aggressive type of non-Hodgkin lymphoma that accounts for approximately 5%-7% of all lymphomas. Nearly 80% of patients have extranodal involvement at initial presentation, occurring in sites such as the bone marrow, spleen, Waldeyer ring, and the gastrointestinal (GI) tract. Secondary GI involvement in MCL (involving nodal and/or other extranodal tissue) is common and may be detected at diagnosis and/or relapse. In several retrospective studies, the prevalence of secondary GI involvement in MCL ranged from 15% to 30%. However, in later studies, routine endoscopies in patients with untreated MCL showed GI involvement in up to 90% of patients, despite most patients not reporting GI symptoms.

The colon is the most commonly involved GI site; however, both the upper and lower GI tract from the stomach to the colon can be involved. Lymphomatous polyposis is the most common endoscopic presentation of MCL, but polyp, mass, or even normal-appearing mucosa may also be seen. 

New and emerging treatment options are helping to improve survival in patients with relapsed/refractory MCL. According to National Comprehensive Cancer Network guidelines, the preferred second-line and subsequent regimens are:

•    Bruton tyrosine kinase (BTK) inhibitors:

o    Acalabrutinib
o    Ibrutinib ± rituximab
o    Zanubrutinib

•    Lenalidomide + rituximab (if BTK inhibitor is contraindicated)

Other regimens that may be useful in certain circumstances are:

•    Bendamustine + rituximab (if not previously given)
•    Bendamustine + rituximab + cytarabine (RBAC500) (if not previously given)
•    Bortezomib ± rituximab
•    RDHA (rituximab, dexamethasone, cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) (if not previously given)
•    GemOx (gemcitabine, oxaliplatin) + rituximab
•    Ibrutinib, lenalidomide, rituximab (category 2B)
•    Ibrutinib + venetoclax
•    Venetoclax, lenalidomide, rituximab (category 2B)
•    Venetoclax ± rituximab

Brexucabtagene autoleucel is suggested as third-line therapy, after chemoimmunotherapy and treatment with a BTK inhibitor. 

Timothy J. Voorhees, MD, MSCR, Assistant Professor of Internal Medicine - Clinical, Division of Hematology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH.

Timothy J. Voorhees, MD, MSCR, has disclosed the following relevant financial relationships:
Received research grant from: AstraZeneca; Morphosys; Incyte; Recordati.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's clinical presentation and endoscopy findings are consistent with a diagnosis of recurrent MCL presenting as a colonic mass.

MCL is an aggressive type of non-Hodgkin lymphoma that accounts for approximately 5%-7% of all lymphomas. Nearly 80% of patients have extranodal involvement at initial presentation, occurring in sites such as the bone marrow, spleen, Waldeyer ring, and the gastrointestinal (GI) tract. Secondary GI involvement in MCL (involving nodal and/or other extranodal tissue) is common and may be detected at diagnosis and/or relapse. In several retrospective studies, the prevalence of secondary GI involvement in MCL ranged from 15% to 30%. However, in later studies, routine endoscopies in patients with untreated MCL showed GI involvement in up to 90% of patients, despite most patients not reporting GI symptoms.

The colon is the most commonly involved GI site; however, both the upper and lower GI tract from the stomach to the colon can be involved. Lymphomatous polyposis is the most common endoscopic presentation of MCL, but polyp, mass, or even normal-appearing mucosa may also be seen. 

New and emerging treatment options are helping to improve survival in patients with relapsed/refractory MCL. According to National Comprehensive Cancer Network guidelines, the preferred second-line and subsequent regimens are:

•    Bruton tyrosine kinase (BTK) inhibitors:

o    Acalabrutinib
o    Ibrutinib ± rituximab
o    Zanubrutinib

•    Lenalidomide + rituximab (if BTK inhibitor is contraindicated)

Other regimens that may be useful in certain circumstances are:

•    Bendamustine + rituximab (if not previously given)
•    Bendamustine + rituximab + cytarabine (RBAC500) (if not previously given)
•    Bortezomib ± rituximab
•    RDHA (rituximab, dexamethasone, cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) (if not previously given)
•    GemOx (gemcitabine, oxaliplatin) + rituximab
•    Ibrutinib, lenalidomide, rituximab (category 2B)
•    Ibrutinib + venetoclax
•    Venetoclax, lenalidomide, rituximab (category 2B)
•    Venetoclax ± rituximab

Brexucabtagene autoleucel is suggested as third-line therapy, after chemoimmunotherapy and treatment with a BTK inhibitor. 

Timothy J. Voorhees, MD, MSCR, Assistant Professor of Internal Medicine - Clinical, Division of Hematology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH.

Timothy J. Voorhees, MD, MSCR, has disclosed the following relevant financial relationships:
Received research grant from: AstraZeneca; Morphosys; Incyte; Recordati.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's clinical presentation and endoscopy findings are consistent with a diagnosis of recurrent MCL presenting as a colonic mass.

MCL is an aggressive type of non-Hodgkin lymphoma that accounts for approximately 5%-7% of all lymphomas. Nearly 80% of patients have extranodal involvement at initial presentation, occurring in sites such as the bone marrow, spleen, Waldeyer ring, and the gastrointestinal (GI) tract. Secondary GI involvement in MCL (involving nodal and/or other extranodal tissue) is common and may be detected at diagnosis and/or relapse. In several retrospective studies, the prevalence of secondary GI involvement in MCL ranged from 15% to 30%. However, in later studies, routine endoscopies in patients with untreated MCL showed GI involvement in up to 90% of patients, despite most patients not reporting GI symptoms.

The colon is the most commonly involved GI site; however, both the upper and lower GI tract from the stomach to the colon can be involved. Lymphomatous polyposis is the most common endoscopic presentation of MCL, but polyp, mass, or even normal-appearing mucosa may also be seen. 

New and emerging treatment options are helping to improve survival in patients with relapsed/refractory MCL. According to National Comprehensive Cancer Network guidelines, the preferred second-line and subsequent regimens are:

•    Bruton tyrosine kinase (BTK) inhibitors:

o    Acalabrutinib
o    Ibrutinib ± rituximab
o    Zanubrutinib

•    Lenalidomide + rituximab (if BTK inhibitor is contraindicated)

Other regimens that may be useful in certain circumstances are:

•    Bendamustine + rituximab (if not previously given)
•    Bendamustine + rituximab + cytarabine (RBAC500) (if not previously given)
•    Bortezomib ± rituximab
•    RDHA (rituximab, dexamethasone, cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) (if not previously given)
•    GemOx (gemcitabine, oxaliplatin) + rituximab
•    Ibrutinib, lenalidomide, rituximab (category 2B)
•    Ibrutinib + venetoclax
•    Venetoclax, lenalidomide, rituximab (category 2B)
•    Venetoclax ± rituximab

Brexucabtagene autoleucel is suggested as third-line therapy, after chemoimmunotherapy and treatment with a BTK inhibitor. 

Timothy J. Voorhees, MD, MSCR, Assistant Professor of Internal Medicine - Clinical, Division of Hematology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH.

Timothy J. Voorhees, MD, MSCR, has disclosed the following relevant financial relationships:
Received research grant from: AstraZeneca; Morphosys; Incyte; Recordati.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.