COVID-19 Updates

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19-era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome which was strengthened by every “there is nothing else we can offer your loved one at this time,” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic, Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today, you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician.
 

Dr. Persampiere is a 2nd-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at [email protected] or via [email protected].

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19-era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome which was strengthened by every “there is nothing else we can offer your loved one at this time,” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic, Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today, you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician.
 

Dr. Persampiere is a 2nd-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at [email protected] or via [email protected].

I graduated medical school in May 2020, right as COVID was taking over the country, and the specter of the virus has hung over every aspect of my residency education thus far.

I did not get a medical school graduation; I was one of the many thousands of newly graduated students who simply left their 4th-year rotation sites one chilly day in March 2020 and just never went back. My medical school education didn’t end with me walking triumphantly across the stage – a first-generation college student finally achieving the greatest dream in her life. Instead, it ended with a Zoom “graduation” and a cross-country move from Georgia to Pennsylvania amidst the greatest pandemic in recent memory. To say my impostor syndrome was bad would be an understatement.
 

Residency in the COVID-19-era

The joy and the draw to family medicine for me has always been the broad scope of conditions that we see and treat. From day 1, however, much of my residency has been devoted to one very small subset of patients – those with COVID-19. At one point, our hospital was so strained that our family medicine program had to run a second inpatient service alongside our usual five-resident service team just to provide care to everybody. Patients were in the hallways. The ER was packed to the gills. We were sleepless, terrified, unvaccinated, and desperate to help our patients survive a disease that was incompletely understood, with very few tools in our toolbox to combat it.

I distinctly remember sitting in the workroom with a coresident of mine, our faces seemingly permanently lined from wearing N95s all shift, and saying to him, “I worry I will be a bad family medicine physician. I worry I haven’t seen enough, other than COVID.” It was midway through my intern year; the days were short, so I was driving to and from the hospital in chilly darkness. My patients, like many around the country, were doing poorly. Vaccines seemed like a promise too good to be true. Worst of all: Those of us who were interns, who had no triumphant podium moment to end our medical school education, were suffering with an intense sense of impostor syndrome which was strengthened by every “there is nothing else we can offer your loved one at this time,” conversation we had. My apprehension about not having seen a wider breadth of medicine during my training is a sentiment still widely shared by COVID-era residents.

Luckily, my coresident was supportive.

“We’re going to be great family medicine physicians,” he said. “We’re learning the hard stuff – the bread and butter of FM – up-front. You’ll see.”

In some ways, I think he was right. Clinical skills, empathy, humility, and forging strong relationships are at the center of every family medicine physician’s heart; my generation has had to learn these skills early and under pressure. Sometimes, there are no answers. Sometimes, the best thing a family doctor can do for a patient is to hear them, understand them, and hold their hand.
 

‘We watched Cinderella together’

Shortly after that conversation with my coresident, I had a particular case which moved me. This gentleman with intellectual disability and COVID had been declining steadily since his admission to the hospital. He was isolated from everybody he knew and loved, but it did not dampen his spirits. He was cheerful to every person who entered his room, clad in their shrouds of PPE, which more often than not felt more like mourning garb than protective wear. I remember very little about this patient’s clinical picture – the COVID, the superimposed pneumonia, the repeated intubations. What I do remember is he loved the Disney classic, Cinderella. I knew this because I developed a very close relationship with his family during the course of his hospitalization. Amidst the torrential onslaught of patients, I made sure to call families every day – not because I wanted to, but because my mentors and attendings and coresidents had all drilled into me from day 1 that we are family medicine, and a large part of our role is to advocate for our patients, and to communicate with their loved ones. So I called. I learned a lot about him; his likes, his dislikes, his close bond with his siblings, and of course his lifelong love for Cinderella. On the last week of my ICU rotation, my patient passed peacefully. His nurse and I were bedside. We held his hand. We told him his family loved him. We watched Cinderella together on an iPad encased in protective plastic.

My next rotation was an outpatient one and it looked more like the “bread and butter” of family medicine. But as I whisked in and out of patient rooms, attending to patients with diabetes, with depression, with pain, I could not stop thinking about my hospitalized patients who my coresidents had assumed care of. Each exam room I entered, I rather morbidly thought “this patient could be next on our hospital service.” Without realizing it, I made more of an effort to get to know each patient holistically. I learned who they were as people. I found myself writing small, medically low-yield details in the chart: “Margaret loves to sing in her church choir;” “Katherine is a self-published author.”

I learned from my attendings. As I sat at the precepting table with them, observing their conversations about patients, their collective decades of experience were apparent.

“I’ve been seeing this patient every few weeks since I was a resident,” said one of my attendings.

“I don’t even see my parents that often,” I thought.

The depth of her relationship with, understanding of, and compassion for this patient struck me deeply. This was why I went into family medicine. My attending knew her patients; they were not faceless unknowns in a hospital gown to her. She would have known to play Cinderella for them in the end.

This is a unique time for trainees. We have been challenged, terrified, overwhelmed, and heartbroken. But at no point have we been isolated. We’ve had the generations of doctors before us to lead the way, to teach us the “hard stuff.” We’ve had senior residents to lean on, who have taken us aside and told us, “I can do the goals-of-care talk today, you need a break.” While the plague seems to have passed over our hospital for now, it has left behind a class of family medicine residents who are proud to carry on our specialty’s long tradition of compassionate, empathetic, lifelong care. “We care for all life stages, from cradle to grave,” says every family medicine physician.

My class, for better or for worse, has cared more often for patients in the twilight of their lives, and while it has been hard, I believe it has made us all better doctors. Now, when I hold a newborn in my arms for a well-child check, I am exceptionally grateful – for the opportunities I have been given, for new beginnings amidst so much sadness, and for the great privilege of being a family medicine physician.
 

Dr. Persampiere is a 2nd-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. You can contact her directly at [email protected] or via [email protected].

Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.

Bruce Jancin/MDedge News

Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.

“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”

The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.

The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.

The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.

Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.

The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.

The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.

The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.

The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.

The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.

Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.

The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.

No major bleeding events were reported.

The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.

Safety and efficacy results were similar in all randomly assigned patients.

The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.

“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”

“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.

Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
 

Robust evidence

“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.

“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.

The ACTIV-4B trial has immediate implications for clinical practice, he added.

“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”

ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.

“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.

The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.

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

Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.

Bruce Jancin/MDedge News

Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.

“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”

The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.

The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.

The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.

Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.

The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.

The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.

The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.

The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.

The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.

Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.

The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.

No major bleeding events were reported.

The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.

Safety and efficacy results were similar in all randomly assigned patients.

The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.

“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”

“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.

Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
 

Robust evidence

“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.

“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.

The ACTIV-4B trial has immediate implications for clinical practice, he added.

“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”

ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.

“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.

The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.

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

Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.

Bruce Jancin/MDedge News

Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.

“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”

The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.

The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.

The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.

Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.

The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.

The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.

The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.

The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.

The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.

Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.

The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.

No major bleeding events were reported.

The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.

Safety and efficacy results were similar in all randomly assigned patients.

The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.

“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”

“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.

Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
 

Robust evidence

“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.

“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.

The ACTIV-4B trial has immediate implications for clinical practice, he added.

“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”

ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.

“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.

The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.

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

COVID-19 vaccination rates vary dramatically by astrological sign, with Leos at the top of the list and Scorpios at the bottom, according to The Salt Lake Tribune.

The Salt Lake County Health Department calculated the rates based on anonymous birth dates from the county’s vaccination data and then compared those figures to national estimates for the overall population represented by each sign.

“Now that Mercury is not in retrograde, we’re just going to leave this here … (and yes, this is based on data),” the Health Department wrote in a Twitter post on Tuesday.

“The COVID-19 vaccine is backed by science and is no way influenced by horoscopes,” the department continued. “But come on Scorpios!”

According to the graphic, 70% of those with the Leo sign are fully vaccinated, followed by Aquarius at 67%, and Aries and Sagittarius both at 59%. The other signs range from 58% to 50%, in descending order: Cancer, Taurus, Gemini, Libra, Pisces, Capricorn, and Virgo. Scorpio sits at the bottom of the list, with 46% fully vaccinated.

Notably, three of the top four signs are elemental fire signs, The Salt Lake Tribune noted.

“We are overachievers,” Jeff Eason, an Aries and the department’s bureau manager of population health and informatics, who did the analysis, told the newspaper.

The Health Department’s post sparked positive and negative feedback across social media, with some musing about their own sign’s inclinations and others scoffing at astrology altogether.

“What we’re really doing is finding new and different ways to keep our community talking about vaccination when there is significant message fatigue around this topic,” the department wrote in the comments.

The range of vaccination rates was startlingly wide, Mr. Eason told The Salt Lake Tribune. But he noted that the difference “could all come down to denominators.”

Each sign’s vaccination rate was ranked almost exactly inverse to its share of the overall population, the newspaper reported. Scorpios and Virgos make up 9.4% and 9.3% of the U.S. population, respectively, as compared with 7.1% for Leos and 6.3% for Aquarians.

If the 12 astrological signs were more evenly distributed in Salt Lake County than nationally, Mr. Eason said, the range of vaccinations rates wouldn’t be as wide as the analysis shows.

“Obviously, it’s not super scientific because we are talking astrology,” Nicholas Rupp, a spokesman for the health department and a vaccinated Scorpio, told the newspaper.

Still, health department officials wanted to do the analysis as a fun way to start conversations and promote vaccinations. About 59% of Salt Lake County residents are fully vaccinated, and about 54% of Utah residents are fully vaccinated.

“We do have message fatigue around vaccines,” Mr. Rupp said.

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

COVID-19 vaccination rates vary dramatically by astrological sign, with Leos at the top of the list and Scorpios at the bottom, according to The Salt Lake Tribune.

The Salt Lake County Health Department calculated the rates based on anonymous birth dates from the county’s vaccination data and then compared those figures to national estimates for the overall population represented by each sign.

“Now that Mercury is not in retrograde, we’re just going to leave this here … (and yes, this is based on data),” the Health Department wrote in a Twitter post on Tuesday.

“The COVID-19 vaccine is backed by science and is no way influenced by horoscopes,” the department continued. “But come on Scorpios!”

According to the graphic, 70% of those with the Leo sign are fully vaccinated, followed by Aquarius at 67%, and Aries and Sagittarius both at 59%. The other signs range from 58% to 50%, in descending order: Cancer, Taurus, Gemini, Libra, Pisces, Capricorn, and Virgo. Scorpio sits at the bottom of the list, with 46% fully vaccinated.

Notably, three of the top four signs are elemental fire signs, The Salt Lake Tribune noted.

“We are overachievers,” Jeff Eason, an Aries and the department’s bureau manager of population health and informatics, who did the analysis, told the newspaper.

The Health Department’s post sparked positive and negative feedback across social media, with some musing about their own sign’s inclinations and others scoffing at astrology altogether.

“What we’re really doing is finding new and different ways to keep our community talking about vaccination when there is significant message fatigue around this topic,” the department wrote in the comments.

The range of vaccination rates was startlingly wide, Mr. Eason told The Salt Lake Tribune. But he noted that the difference “could all come down to denominators.”

Each sign’s vaccination rate was ranked almost exactly inverse to its share of the overall population, the newspaper reported. Scorpios and Virgos make up 9.4% and 9.3% of the U.S. population, respectively, as compared with 7.1% for Leos and 6.3% for Aquarians.

If the 12 astrological signs were more evenly distributed in Salt Lake County than nationally, Mr. Eason said, the range of vaccinations rates wouldn’t be as wide as the analysis shows.

“Obviously, it’s not super scientific because we are talking astrology,” Nicholas Rupp, a spokesman for the health department and a vaccinated Scorpio, told the newspaper.

Still, health department officials wanted to do the analysis as a fun way to start conversations and promote vaccinations. About 59% of Salt Lake County residents are fully vaccinated, and about 54% of Utah residents are fully vaccinated.

“We do have message fatigue around vaccines,” Mr. Rupp said.

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

COVID-19 vaccination rates vary dramatically by astrological sign, with Leos at the top of the list and Scorpios at the bottom, according to The Salt Lake Tribune.

The Salt Lake County Health Department calculated the rates based on anonymous birth dates from the county’s vaccination data and then compared those figures to national estimates for the overall population represented by each sign.

“Now that Mercury is not in retrograde, we’re just going to leave this here … (and yes, this is based on data),” the Health Department wrote in a Twitter post on Tuesday.

“The COVID-19 vaccine is backed by science and is no way influenced by horoscopes,” the department continued. “But come on Scorpios!”

According to the graphic, 70% of those with the Leo sign are fully vaccinated, followed by Aquarius at 67%, and Aries and Sagittarius both at 59%. The other signs range from 58% to 50%, in descending order: Cancer, Taurus, Gemini, Libra, Pisces, Capricorn, and Virgo. Scorpio sits at the bottom of the list, with 46% fully vaccinated.

Notably, three of the top four signs are elemental fire signs, The Salt Lake Tribune noted.

“We are overachievers,” Jeff Eason, an Aries and the department’s bureau manager of population health and informatics, who did the analysis, told the newspaper.

The Health Department’s post sparked positive and negative feedback across social media, with some musing about their own sign’s inclinations and others scoffing at astrology altogether.

“What we’re really doing is finding new and different ways to keep our community talking about vaccination when there is significant message fatigue around this topic,” the department wrote in the comments.

The range of vaccination rates was startlingly wide, Mr. Eason told The Salt Lake Tribune. But he noted that the difference “could all come down to denominators.”

Each sign’s vaccination rate was ranked almost exactly inverse to its share of the overall population, the newspaper reported. Scorpios and Virgos make up 9.4% and 9.3% of the U.S. population, respectively, as compared with 7.1% for Leos and 6.3% for Aquarians.

If the 12 astrological signs were more evenly distributed in Salt Lake County than nationally, Mr. Eason said, the range of vaccinations rates wouldn’t be as wide as the analysis shows.

“Obviously, it’s not super scientific because we are talking astrology,” Nicholas Rupp, a spokesman for the health department and a vaccinated Scorpio, told the newspaper.

Still, health department officials wanted to do the analysis as a fun way to start conversations and promote vaccinations. About 59% of Salt Lake County residents are fully vaccinated, and about 54% of Utah residents are fully vaccinated.

“We do have message fatigue around vaccines,” Mr. Rupp said.

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

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

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

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

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

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

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

Editor’s note: This story was updated with the CDC director’s endorsement.

Centers for Disease Control and Prevention (CDC) Director Rochelle Walensky, MD, has signed off on an advisory panel’s earlier unanimous vote to recommend boosters for the Moderna and Johnson and Johnson COVID vaccines.

The decision now means that millions of Americans are eligible to get a booster shot for either the Pfizer, Moderna, or J&J COVID vaccines.

“The evidence shows that all three COVID-19 vaccines authorized in the United States are safe – as demonstrated by the over 400 million vaccine doses already given. And, they are all highly effective in reducing the risk of severe disease, hospitalization, and death, even in the midst of the widely circulating Delta variant,” Dr. Walensky said in a CDC news release.

She also signed off on the panel’s suggestion that individuals can mix or match the booster from any one of the three available COVID-19 vaccines.

The Advisory Committee on Immunization Practices (ACIP) recommended in a late afternoon 15-0 vote that everyone over age 18 who are at least 2 months past their Johnson & Johnson vaccine should get a booster, an endorsement that affects an estimated 13 million Americans.

Those eligible for a booster at least 6 months after their last Moderna shot are the same groups who can get a Pfizer booster.

They are:

• Anyone over age 65.
• Those over age 18 with an underlying health condition that puts them at risk of severe COVID-19.
• Those over age 18 who may be at higher risk of a COVID-19 infection because they live or work in a risky setting.

These recommendations are in line with the Food and Drug Administration’s Oct. 20 authorization of the boosters, along with the ability to mix-and-match vaccines.

There are an estimated 47 million Pfizer recipients and 39 million people vaccinated with Moderna who are now eligible for a booster dose, according to data presented by the CDC.
 

Questions, concerns

Before voting, some committee members expressed discomfort in broadly recommending boosters, stressing that there is very little evidence supporting the need for boosters in people younger than age 50.

“I can’t say that I am comfortable that anybody under 50 – an otherwise healthy individual – needs a booster vaccine at this time with either Moderna or Pfizer,” said ACIP member Sarah Long, MD, professor of pediatrics at Drexel University in Philadelphia.

She said she would try to mitigate any potential harm by having some kind of age restriction on the otherwise worried well.

“We don’t usually have the vaccines [for] the worried well. We give it because we have a need that’s worth the risk, and there’s a burden of severity of disease,” Dr. Long said.

The evidence to date shows that all the vaccines authorized for use in the U.S. continue to protect people well against severe COVID-19 outcomes, including hospitalization and death.

But breakthrough infections are on the rise, especially for people who initially received the Johnson and Johnson one-dose vaccine.

On Oct. 21, Pfizer released data from a study of more than 10,000 fully vaccinated people. Half were randomly assigned to get a booster of their Comirnaty vaccine, the other half were given a placebo.

Over the ensuing 2.5 months, there were 5 COVID-19 cases in the boosted group, and 109 in the group that got a placebo.

The data were posted in a press release and have not yet been peer reviewed, but are the first to show clinical effectiveness of boosters at preventing COVID-19 infections.

Data recently considered by the FDA and CDC for booster doses come from studies that were mostly shorter and smaller. These studies looked at biomarkers of immunity like the concentration of antibodies in a person’s blood and the percentage of study participants who saw a boost to those antibodies.

The studies demonstrated that boosters indeed restore high levels of antibodies, but unlike the newest Pfizer data they were not able to show that these antibodies prevented COVID-19.

These studies also weren’t powered to pick up on any less common safety problems that might arise after another dose of the shots.
 

“Real world” recommendations

In the end, however, the panel felt it was more important to be permissive in allowing boosters so that individuals and their doctors could be free to make their own decisions.

“The decision made by the FDA and the ACIP recommendations, I think, reflects the real world. The public is going to do what they feel driven to do. This at least adds a scientific review of the currently available data,” said Jay Varkey, MD, an infectious disease physician and associate professor at Emory University in Atlanta, who was not involved in the ACIP’s deliberations.

Dr. Varkey said he would recommend that anyone who is younger than 65, and who has no underlying medical conditions such as diabetes or obesity, speak with their doctor about their individual benefits and risks before getting a booster.

The CDC is planning to release a detailed suite of clinical considerations to help people weigh the risks and benefits of getting a booster.

Safety updates presented at the meeting show that serious adverse events after vaccination are extremely rare, but in some cases, they may rise above the risk for those problems generally seen in the population.

Those rare events include the disabling autoimmune condition Guillain-Barré syndrome and the platelet disorder thrombosis with thrombocytopenia (TTS), which causes blood clots along with the risk of excess bleeding because of a low platelet count.

Both can occur after the J&J vaccine. Out of 15.3 million doses of the vaccine given to date, there have been 47 cases of TTS and five deaths. These events are more common in younger women.

The mRNA vaccines, such as those from Pfizer and Moderna, can cause heart inflammation called myocarditis or pericarditis. This side effect is more common in men 18-24 years old. The reported rate of myocarditis after vaccination is 39 cases for every 1 million doses.

In voting to permit boosters, committee member Wilbur Chen, MD, professor at the University of Maryland’s Center for Vaccine Development, said he hoped boosters wouldn’t give Americans false confidence.

Dr. Chen stressed that ending the pandemic would depend on “a multilayered approach” that includes masking, social distancing, avoiding large crowds indoors, and convincing more Americans to take their first doses of the vaccines.

“We’re not just going to vaccinate ourselves out of this situation,” Dr. Chen said.
 

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

Editor’s note: This story was updated with the CDC director’s endorsement.

Centers for Disease Control and Prevention (CDC) Director Rochelle Walensky, MD, has signed off on an advisory panel’s earlier unanimous vote to recommend boosters for the Moderna and Johnson and Johnson COVID vaccines.

The decision now means that millions of Americans are eligible to get a booster shot for either the Pfizer, Moderna, or J&J COVID vaccines.

“The evidence shows that all three COVID-19 vaccines authorized in the United States are safe – as demonstrated by the over 400 million vaccine doses already given. And, they are all highly effective in reducing the risk of severe disease, hospitalization, and death, even in the midst of the widely circulating Delta variant,” Dr. Walensky said in a CDC news release.

She also signed off on the panel’s suggestion that individuals can mix or match the booster from any one of the three available COVID-19 vaccines.

The Advisory Committee on Immunization Practices (ACIP) recommended in a late afternoon 15-0 vote that everyone over age 18 who are at least 2 months past their Johnson & Johnson vaccine should get a booster, an endorsement that affects an estimated 13 million Americans.

Those eligible for a booster at least 6 months after their last Moderna shot are the same groups who can get a Pfizer booster.

They are:

• Anyone over age 65.
• Those over age 18 with an underlying health condition that puts them at risk of severe COVID-19.
• Those over age 18 who may be at higher risk of a COVID-19 infection because they live or work in a risky setting.

These recommendations are in line with the Food and Drug Administration’s Oct. 20 authorization of the boosters, along with the ability to mix-and-match vaccines.

There are an estimated 47 million Pfizer recipients and 39 million people vaccinated with Moderna who are now eligible for a booster dose, according to data presented by the CDC.
 

Questions, concerns

Before voting, some committee members expressed discomfort in broadly recommending boosters, stressing that there is very little evidence supporting the need for boosters in people younger than age 50.

“I can’t say that I am comfortable that anybody under 50 – an otherwise healthy individual – needs a booster vaccine at this time with either Moderna or Pfizer,” said ACIP member Sarah Long, MD, professor of pediatrics at Drexel University in Philadelphia.

She said she would try to mitigate any potential harm by having some kind of age restriction on the otherwise worried well.

“We don’t usually have the vaccines [for] the worried well. We give it because we have a need that’s worth the risk, and there’s a burden of severity of disease,” Dr. Long said.

The evidence to date shows that all the vaccines authorized for use in the U.S. continue to protect people well against severe COVID-19 outcomes, including hospitalization and death.

But breakthrough infections are on the rise, especially for people who initially received the Johnson and Johnson one-dose vaccine.

On Oct. 21, Pfizer released data from a study of more than 10,000 fully vaccinated people. Half were randomly assigned to get a booster of their Comirnaty vaccine, the other half were given a placebo.

Over the ensuing 2.5 months, there were 5 COVID-19 cases in the boosted group, and 109 in the group that got a placebo.

The data were posted in a press release and have not yet been peer reviewed, but are the first to show clinical effectiveness of boosters at preventing COVID-19 infections.

Data recently considered by the FDA and CDC for booster doses come from studies that were mostly shorter and smaller. These studies looked at biomarkers of immunity like the concentration of antibodies in a person’s blood and the percentage of study participants who saw a boost to those antibodies.

The studies demonstrated that boosters indeed restore high levels of antibodies, but unlike the newest Pfizer data they were not able to show that these antibodies prevented COVID-19.

These studies also weren’t powered to pick up on any less common safety problems that might arise after another dose of the shots.
 

“Real world” recommendations

In the end, however, the panel felt it was more important to be permissive in allowing boosters so that individuals and their doctors could be free to make their own decisions.

“The decision made by the FDA and the ACIP recommendations, I think, reflects the real world. The public is going to do what they feel driven to do. This at least adds a scientific review of the currently available data,” said Jay Varkey, MD, an infectious disease physician and associate professor at Emory University in Atlanta, who was not involved in the ACIP’s deliberations.

Dr. Varkey said he would recommend that anyone who is younger than 65, and who has no underlying medical conditions such as diabetes or obesity, speak with their doctor about their individual benefits and risks before getting a booster.

The CDC is planning to release a detailed suite of clinical considerations to help people weigh the risks and benefits of getting a booster.

Safety updates presented at the meeting show that serious adverse events after vaccination are extremely rare, but in some cases, they may rise above the risk for those problems generally seen in the population.

Those rare events include the disabling autoimmune condition Guillain-Barré syndrome and the platelet disorder thrombosis with thrombocytopenia (TTS), which causes blood clots along with the risk of excess bleeding because of a low platelet count.

Both can occur after the J&J vaccine. Out of 15.3 million doses of the vaccine given to date, there have been 47 cases of TTS and five deaths. These events are more common in younger women.

The mRNA vaccines, such as those from Pfizer and Moderna, can cause heart inflammation called myocarditis or pericarditis. This side effect is more common in men 18-24 years old. The reported rate of myocarditis after vaccination is 39 cases for every 1 million doses.

In voting to permit boosters, committee member Wilbur Chen, MD, professor at the University of Maryland’s Center for Vaccine Development, said he hoped boosters wouldn’t give Americans false confidence.

Dr. Chen stressed that ending the pandemic would depend on “a multilayered approach” that includes masking, social distancing, avoiding large crowds indoors, and convincing more Americans to take their first doses of the vaccines.

“We’re not just going to vaccinate ourselves out of this situation,” Dr. Chen said.
 

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

Editor’s note: This story was updated with the CDC director’s endorsement.

Centers for Disease Control and Prevention (CDC) Director Rochelle Walensky, MD, has signed off on an advisory panel’s earlier unanimous vote to recommend boosters for the Moderna and Johnson and Johnson COVID vaccines.

The decision now means that millions of Americans are eligible to get a booster shot for either the Pfizer, Moderna, or J&J COVID vaccines.

“The evidence shows that all three COVID-19 vaccines authorized in the United States are safe – as demonstrated by the over 400 million vaccine doses already given. And, they are all highly effective in reducing the risk of severe disease, hospitalization, and death, even in the midst of the widely circulating Delta variant,” Dr. Walensky said in a CDC news release.

She also signed off on the panel’s suggestion that individuals can mix or match the booster from any one of the three available COVID-19 vaccines.

The Advisory Committee on Immunization Practices (ACIP) recommended in a late afternoon 15-0 vote that everyone over age 18 who are at least 2 months past their Johnson & Johnson vaccine should get a booster, an endorsement that affects an estimated 13 million Americans.

Those eligible for a booster at least 6 months after their last Moderna shot are the same groups who can get a Pfizer booster.

They are:

• Anyone over age 65.
• Those over age 18 with an underlying health condition that puts them at risk of severe COVID-19.
• Those over age 18 who may be at higher risk of a COVID-19 infection because they live or work in a risky setting.

These recommendations are in line with the Food and Drug Administration’s Oct. 20 authorization of the boosters, along with the ability to mix-and-match vaccines.

There are an estimated 47 million Pfizer recipients and 39 million people vaccinated with Moderna who are now eligible for a booster dose, according to data presented by the CDC.
 

Questions, concerns

Before voting, some committee members expressed discomfort in broadly recommending boosters, stressing that there is very little evidence supporting the need for boosters in people younger than age 50.

“I can’t say that I am comfortable that anybody under 50 – an otherwise healthy individual – needs a booster vaccine at this time with either Moderna or Pfizer,” said ACIP member Sarah Long, MD, professor of pediatrics at Drexel University in Philadelphia.

She said she would try to mitigate any potential harm by having some kind of age restriction on the otherwise worried well.

“We don’t usually have the vaccines [for] the worried well. We give it because we have a need that’s worth the risk, and there’s a burden of severity of disease,” Dr. Long said.

The evidence to date shows that all the vaccines authorized for use in the U.S. continue to protect people well against severe COVID-19 outcomes, including hospitalization and death.

But breakthrough infections are on the rise, especially for people who initially received the Johnson and Johnson one-dose vaccine.

On Oct. 21, Pfizer released data from a study of more than 10,000 fully vaccinated people. Half were randomly assigned to get a booster of their Comirnaty vaccine, the other half were given a placebo.

Over the ensuing 2.5 months, there were 5 COVID-19 cases in the boosted group, and 109 in the group that got a placebo.

The data were posted in a press release and have not yet been peer reviewed, but are the first to show clinical effectiveness of boosters at preventing COVID-19 infections.

Data recently considered by the FDA and CDC for booster doses come from studies that were mostly shorter and smaller. These studies looked at biomarkers of immunity like the concentration of antibodies in a person’s blood and the percentage of study participants who saw a boost to those antibodies.

The studies demonstrated that boosters indeed restore high levels of antibodies, but unlike the newest Pfizer data they were not able to show that these antibodies prevented COVID-19.

These studies also weren’t powered to pick up on any less common safety problems that might arise after another dose of the shots.
 

“Real world” recommendations

In the end, however, the panel felt it was more important to be permissive in allowing boosters so that individuals and their doctors could be free to make their own decisions.

“The decision made by the FDA and the ACIP recommendations, I think, reflects the real world. The public is going to do what they feel driven to do. This at least adds a scientific review of the currently available data,” said Jay Varkey, MD, an infectious disease physician and associate professor at Emory University in Atlanta, who was not involved in the ACIP’s deliberations.

Dr. Varkey said he would recommend that anyone who is younger than 65, and who has no underlying medical conditions such as diabetes or obesity, speak with their doctor about their individual benefits and risks before getting a booster.

The CDC is planning to release a detailed suite of clinical considerations to help people weigh the risks and benefits of getting a booster.

Safety updates presented at the meeting show that serious adverse events after vaccination are extremely rare, but in some cases, they may rise above the risk for those problems generally seen in the population.

Those rare events include the disabling autoimmune condition Guillain-Barré syndrome and the platelet disorder thrombosis with thrombocytopenia (TTS), which causes blood clots along with the risk of excess bleeding because of a low platelet count.

Both can occur after the J&J vaccine. Out of 15.3 million doses of the vaccine given to date, there have been 47 cases of TTS and five deaths. These events are more common in younger women.

The mRNA vaccines, such as those from Pfizer and Moderna, can cause heart inflammation called myocarditis or pericarditis. This side effect is more common in men 18-24 years old. The reported rate of myocarditis after vaccination is 39 cases for every 1 million doses.

In voting to permit boosters, committee member Wilbur Chen, MD, professor at the University of Maryland’s Center for Vaccine Development, said he hoped boosters wouldn’t give Americans false confidence.

Dr. Chen stressed that ending the pandemic would depend on “a multilayered approach” that includes masking, social distancing, avoiding large crowds indoors, and convincing more Americans to take their first doses of the vaccines.

“We’re not just going to vaccinate ourselves out of this situation,” Dr. Chen said.
 

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

During the COVID-19 pandemic, visitation in intensive care units has been restricted for obvious safety reasons, but such restrictions have contributed to the already serious strains on staff, results of a survey indicate.

Among 91 residents, nurse practitioners, and physician assistants who work in ICUs in the Emory Healthcare system, in Atlanta, two-thirds agreed that visitation restrictions were necessary, but nearly three-fourths said that the restrictions had a negative effect on their job satisfaction, and slightly more than half reported experiencing symptoms of burnout, wrote Nicole Herbst, MD, and Joanne Kuntz, MD, from Emory University School of Medicine.

“Because families are not present at bedside, restrictive visitation policies have necessitated that communication with families be more intentional and planned than before the COVID-19 pandemic. Understanding the ways these restrictions impact providers and patients can help guide future interventions to improve communication with families and reduce provider burnout,” the authors wrote in a poster presentation at the American College of Chest Physicians (CHEST) 2021 Annual Meeting.
 

Valid concerns, negative effects

“During the COVID pandemic, we fell back into old ways of doing things, where parents were restricted from the bedsides of patients in the intensive care unit. And I think we have shown over the last decade that family presence at the bedside significantly improves outcomes for patients and also helps clinicians caring for those patients,” commented Christopher Carroll, MD, FCCP, from Connecticut Children’s Medical Center, Hartford, in an interview.

“We had good reason to exclude visitors because we were worried about their own safety and their own health, but now 18 months into this pandemic, we know how to prevent COVID. We know now how to safely walk into the room of a patient who has COVID and walk out of it and not get infected. There’s no reason why we can’t relax these restrictions and allow families to be there with their loved ones,” continued Dr. Carroll, who was not involved in the study.

With visitation limited or banned outright, ICU staff have had to replace face-to-face discussion with more intentional, planned, and time-consuming methods, such as telephone calls and online video.

At the time of the survey, only two visitors were allowed to see patients in end-of-life situations in Emory ICUs. Exceptions to this rule were rare.
 

Study details

ICU staff members were asked about their communication practices, their attitudes about the effect of the restrictions on communication with families and job satisfaction, and about symptoms of burnout, using a validated single-item measure.

A total of 91 practitioners completed most of the survey questions. The results showed that more than half of all respondents (57.9%) reported spending more time communicating with families than they had the previous year.

A large majority (90.5%) also said that video communication (for example, with a tablet, personal device, or computer) was as effective or more effective than telephone communication.

In all, 64.3% of practitioners agreed that visitation restrictions were appropriate, but 71.4% said that the restrictions had a negative effect on their job satisfaction, and 51.8% reported experiencing symptoms of burnout, such as stress, low energy, exhaustion, or lack of motivation.

Casey Cable, MD, a pulmonary disease and critical care specialist at Virginia Commonwealth Medical Center, Richmond, Virginia, who was not involved in the study, did her fellowship at Emory. She told this news organization that the study findings might be skewed a bit by subjective impressions.

“I work in a level I trauma unit providing tertiary medical care, and we’re using more video to communicate with family members, more iPads,” she said. “Their finding is interesting that people felt that they were communicating more with family members, and I wonder if that’s a type of recall bias, because at the bedside, you can have a conversation, as opposed to actively talking to family members by calling them, videoing them, or whatnot, and I think that sticks in our head more, about putting in more effort. I don’t know if we are spending more time communicating with family or if that’s what we just recall.”

She agreed with the authors that visitation restrictions have a definite negative effect on job satisfaction and that they cause feelings of burnout.

“It’s tough not having families at bedside and offering them support. When visitors are not able to see how sick their family members are, it complicates discussions about end-of-life care, transitioning to comfort care, or maybe not doing everything,” she said.

No funding source for the study was reported. Dr. Herbst, Dr. Kuntz, Dr. Carroll, and Dr. Cable have disclosed no relevant financial relationships.

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

During the COVID-19 pandemic, visitation in intensive care units has been restricted for obvious safety reasons, but such restrictions have contributed to the already serious strains on staff, results of a survey indicate.

Among 91 residents, nurse practitioners, and physician assistants who work in ICUs in the Emory Healthcare system, in Atlanta, two-thirds agreed that visitation restrictions were necessary, but nearly three-fourths said that the restrictions had a negative effect on their job satisfaction, and slightly more than half reported experiencing symptoms of burnout, wrote Nicole Herbst, MD, and Joanne Kuntz, MD, from Emory University School of Medicine.

“Because families are not present at bedside, restrictive visitation policies have necessitated that communication with families be more intentional and planned than before the COVID-19 pandemic. Understanding the ways these restrictions impact providers and patients can help guide future interventions to improve communication with families and reduce provider burnout,” the authors wrote in a poster presentation at the American College of Chest Physicians (CHEST) 2021 Annual Meeting.
 

Valid concerns, negative effects

“During the COVID pandemic, we fell back into old ways of doing things, where parents were restricted from the bedsides of patients in the intensive care unit. And I think we have shown over the last decade that family presence at the bedside significantly improves outcomes for patients and also helps clinicians caring for those patients,” commented Christopher Carroll, MD, FCCP, from Connecticut Children’s Medical Center, Hartford, in an interview.

“We had good reason to exclude visitors because we were worried about their own safety and their own health, but now 18 months into this pandemic, we know how to prevent COVID. We know now how to safely walk into the room of a patient who has COVID and walk out of it and not get infected. There’s no reason why we can’t relax these restrictions and allow families to be there with their loved ones,” continued Dr. Carroll, who was not involved in the study.

With visitation limited or banned outright, ICU staff have had to replace face-to-face discussion with more intentional, planned, and time-consuming methods, such as telephone calls and online video.

At the time of the survey, only two visitors were allowed to see patients in end-of-life situations in Emory ICUs. Exceptions to this rule were rare.
 

Study details

ICU staff members were asked about their communication practices, their attitudes about the effect of the restrictions on communication with families and job satisfaction, and about symptoms of burnout, using a validated single-item measure.

A total of 91 practitioners completed most of the survey questions. The results showed that more than half of all respondents (57.9%) reported spending more time communicating with families than they had the previous year.

A large majority (90.5%) also said that video communication (for example, with a tablet, personal device, or computer) was as effective or more effective than telephone communication.

In all, 64.3% of practitioners agreed that visitation restrictions were appropriate, but 71.4% said that the restrictions had a negative effect on their job satisfaction, and 51.8% reported experiencing symptoms of burnout, such as stress, low energy, exhaustion, or lack of motivation.

Casey Cable, MD, a pulmonary disease and critical care specialist at Virginia Commonwealth Medical Center, Richmond, Virginia, who was not involved in the study, did her fellowship at Emory. She told this news organization that the study findings might be skewed a bit by subjective impressions.

“I work in a level I trauma unit providing tertiary medical care, and we’re using more video to communicate with family members, more iPads,” she said. “Their finding is interesting that people felt that they were communicating more with family members, and I wonder if that’s a type of recall bias, because at the bedside, you can have a conversation, as opposed to actively talking to family members by calling them, videoing them, or whatnot, and I think that sticks in our head more, about putting in more effort. I don’t know if we are spending more time communicating with family or if that’s what we just recall.”

She agreed with the authors that visitation restrictions have a definite negative effect on job satisfaction and that they cause feelings of burnout.

“It’s tough not having families at bedside and offering them support. When visitors are not able to see how sick their family members are, it complicates discussions about end-of-life care, transitioning to comfort care, or maybe not doing everything,” she said.

No funding source for the study was reported. Dr. Herbst, Dr. Kuntz, Dr. Carroll, and Dr. Cable have disclosed no relevant financial relationships.

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

During the COVID-19 pandemic, visitation in intensive care units has been restricted for obvious safety reasons, but such restrictions have contributed to the already serious strains on staff, results of a survey indicate.

Among 91 residents, nurse practitioners, and physician assistants who work in ICUs in the Emory Healthcare system, in Atlanta, two-thirds agreed that visitation restrictions were necessary, but nearly three-fourths said that the restrictions had a negative effect on their job satisfaction, and slightly more than half reported experiencing symptoms of burnout, wrote Nicole Herbst, MD, and Joanne Kuntz, MD, from Emory University School of Medicine.

“Because families are not present at bedside, restrictive visitation policies have necessitated that communication with families be more intentional and planned than before the COVID-19 pandemic. Understanding the ways these restrictions impact providers and patients can help guide future interventions to improve communication with families and reduce provider burnout,” the authors wrote in a poster presentation at the American College of Chest Physicians (CHEST) 2021 Annual Meeting.
 

Valid concerns, negative effects

“During the COVID pandemic, we fell back into old ways of doing things, where parents were restricted from the bedsides of patients in the intensive care unit. And I think we have shown over the last decade that family presence at the bedside significantly improves outcomes for patients and also helps clinicians caring for those patients,” commented Christopher Carroll, MD, FCCP, from Connecticut Children’s Medical Center, Hartford, in an interview.

“We had good reason to exclude visitors because we were worried about their own safety and their own health, but now 18 months into this pandemic, we know how to prevent COVID. We know now how to safely walk into the room of a patient who has COVID and walk out of it and not get infected. There’s no reason why we can’t relax these restrictions and allow families to be there with their loved ones,” continued Dr. Carroll, who was not involved in the study.

With visitation limited or banned outright, ICU staff have had to replace face-to-face discussion with more intentional, planned, and time-consuming methods, such as telephone calls and online video.

At the time of the survey, only two visitors were allowed to see patients in end-of-life situations in Emory ICUs. Exceptions to this rule were rare.
 

Study details

ICU staff members were asked about their communication practices, their attitudes about the effect of the restrictions on communication with families and job satisfaction, and about symptoms of burnout, using a validated single-item measure.

A total of 91 practitioners completed most of the survey questions. The results showed that more than half of all respondents (57.9%) reported spending more time communicating with families than they had the previous year.

A large majority (90.5%) also said that video communication (for example, with a tablet, personal device, or computer) was as effective or more effective than telephone communication.

In all, 64.3% of practitioners agreed that visitation restrictions were appropriate, but 71.4% said that the restrictions had a negative effect on their job satisfaction, and 51.8% reported experiencing symptoms of burnout, such as stress, low energy, exhaustion, or lack of motivation.

Casey Cable, MD, a pulmonary disease and critical care specialist at Virginia Commonwealth Medical Center, Richmond, Virginia, who was not involved in the study, did her fellowship at Emory. She told this news organization that the study findings might be skewed a bit by subjective impressions.

“I work in a level I trauma unit providing tertiary medical care, and we’re using more video to communicate with family members, more iPads,” she said. “Their finding is interesting that people felt that they were communicating more with family members, and I wonder if that’s a type of recall bias, because at the bedside, you can have a conversation, as opposed to actively talking to family members by calling them, videoing them, or whatnot, and I think that sticks in our head more, about putting in more effort. I don’t know if we are spending more time communicating with family or if that’s what we just recall.”

She agreed with the authors that visitation restrictions have a definite negative effect on job satisfaction and that they cause feelings of burnout.

“It’s tough not having families at bedside and offering them support. When visitors are not able to see how sick their family members are, it complicates discussions about end-of-life care, transitioning to comfort care, or maybe not doing everything,” she said.

No funding source for the study was reported. Dr. Herbst, Dr. Kuntz, Dr. Carroll, and Dr. Cable have disclosed no relevant financial relationships.

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

Background: A large proportion of Italian patients with COVID-19 presented with symptoms, most commonly cough, fever, dyspnea, myalgias, anosmia, and gastrointestinal symptoms. Information is lacking on persistent symptoms after recovery.

From April 21 to May 29, 2020, 179 patients were potentially eligible; 143 ultimately were included. During hospitalization, 72.7% of participants had evidence of interstitial pneumonia. Patients were assessed a mean of 60.3 days after onset of the first COVID-19 symptom. Only 18 (12.6%) were completely free of any COVID-19–related symptoms, 32% had one or two symptoms, and 55% had three or more. Worsened quality of life was observed among 44.1% of patients.

Bottom line: 87.4% of patients who had recovered from COVID-19 reported persistence of at least one symptom, particularly fatigue and dyspnea.

Citation: Carfi A et al. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603-5.

Dr. Walker is a hospitalist at the Lexington (Ky.) VA Health Care System.

Background: A large proportion of Italian patients with COVID-19 presented with symptoms, most commonly cough, fever, dyspnea, myalgias, anosmia, and gastrointestinal symptoms. Information is lacking on persistent symptoms after recovery.

From April 21 to May 29, 2020, 179 patients were potentially eligible; 143 ultimately were included. During hospitalization, 72.7% of participants had evidence of interstitial pneumonia. Patients were assessed a mean of 60.3 days after onset of the first COVID-19 symptom. Only 18 (12.6%) were completely free of any COVID-19–related symptoms, 32% had one or two symptoms, and 55% had three or more. Worsened quality of life was observed among 44.1% of patients.

Bottom line: 87.4% of patients who had recovered from COVID-19 reported persistence of at least one symptom, particularly fatigue and dyspnea.

Citation: Carfi A et al. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603-5.

Dr. Walker is a hospitalist at the Lexington (Ky.) VA Health Care System.

Background: A large proportion of Italian patients with COVID-19 presented with symptoms, most commonly cough, fever, dyspnea, myalgias, anosmia, and gastrointestinal symptoms. Information is lacking on persistent symptoms after recovery.

From April 21 to May 29, 2020, 179 patients were potentially eligible; 143 ultimately were included. During hospitalization, 72.7% of participants had evidence of interstitial pneumonia. Patients were assessed a mean of 60.3 days after onset of the first COVID-19 symptom. Only 18 (12.6%) were completely free of any COVID-19–related symptoms, 32% had one or two symptoms, and 55% had three or more. Worsened quality of life was observed among 44.1% of patients.

Bottom line: 87.4% of patients who had recovered from COVID-19 reported persistence of at least one symptom, particularly fatigue and dyspnea.

Citation: Carfi A et al. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603-5.

Dr. Walker is a hospitalist at the Lexington (Ky.) VA Health Care System.

Racial/ethnic disparities in COVID-19 mortality rates may be related more to comorbidities than to demographics, suggest authors of a new study.

Researchers compared the length of stay in intensive care units in two suburban hospitals for patients with severe SARS-CoV-2 infections. Their study shows that although the incidence of comorbidities and rates of use of mechanical ventilation and death were higher among Black patients than among patients of other races, length of stay in the ICU was generally similar for patients of all races. The study was conducted by Tripti Kumar, DO, from Lankenau Medical Center, Wynnewood, Pennsylvania, and colleagues.

“Racial disparities are observed in the United States concerning COVID-19, and studies have discovered that minority populations are at ongoing risk for health inequity,” Dr. Kumar said in a narrated e-poster presented during the American College of Chest Physicians (CHEST) 2021 Annual Meeting.

“Primary prevention initiatives should take precedence in mitigating the effect that comorbidities have on these vulnerable populations to help reduce necessity for mechanical ventilation, hospital length of stay, and overall mortality,” she said.
 

Higher death rates for Black patients

At the time the study was conducted, the COVID-19 death rate in the United States had topped 500,000 (as of this writing, it stands at 726,000). Of those who died, 22.4% were Black, 18.1% were Hispanic, and 3.6% were of Asian descent. The numbers of COVID-19 diagnoses and deaths were significantly higher in U.S. counties where the proportions of Black residents were higher, the authors note.

To see whether differences in COVID-19 outcomes were reflected in ICU length of stay, the researchers conducted a retrospective chart review of data on 162 patients admitted to ICUs at Paoli Hospital and Lankenau Medical Center, both in the suburban Philadelphia town of Wynnewood.

All patients were diagnosed with COVID-19 from March through June 2020.

In all, 60% of the study population were Black, 35% were White, 3% were Asian, and 2% were Hispanic. Women composed 46% of the sample.

The average length of ICU stay, which was the primary endpoint, was similar among Black patients (15.4 days), White patients (15.5 days), and Asians (16 days). The shortest average hospital stay was among Hispanic patients, at 11.3 days.

The investigators determined that among all races, the prevalence of type 2 diabetes, obesity, hypertension, and smoking was highest among Black patients.

Overall, nearly 85% of patients required mechanical ventilation. Among the patients who required it, 86% were Black, 84% were White, 66% were Hispanic, and 75% were Asian.

Overall mortality was 62%. It was higher among Black patients, at 60%, than among White patients, at 33%. The investigators did not report mortality rates for Hispanic or Asian patients.
 

Missing data

Demondes Haynes, MD, FCCP, professor of medicine in the Division of Pulmonary and Critical Care and associate dean for admissions at the University of Mississippi Medical Center and School of Medicine, Jackson, who was not involved in the study, told this news organization that there are some gaps in the study that make it difficult to draw strong conclusions about the findings.

“For sure, comorbidities contribute a great deal to mortality, but is there something else going on? I think this poster is incomplete in that it cannot answer that question,” he said in an interview.

He noted that the use of retrospective rather than prospective data makes it hard to account for potential confounders.

“I agree that these findings show the potential contribution of comorbidities, but to me, this is a little incomplete to make that a definitive statement,” he said.

“I can’t argue with their recommendation for primary prevention – we definitely want to do primary prevention to decrease comorbidities. Would it decrease overall mortality? It might, it sure might, for just COVID-19 I’d say no, we need more information.”

No funding source for the study was reported. Dr. Kumar and colleagues and Dr. Haynes reported no relevant financial relationships.

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

Racial/ethnic disparities in COVID-19 mortality rates may be related more to comorbidities than to demographics, suggest authors of a new study.

Researchers compared the length of stay in intensive care units in two suburban hospitals for patients with severe SARS-CoV-2 infections. Their study shows that although the incidence of comorbidities and rates of use of mechanical ventilation and death were higher among Black patients than among patients of other races, length of stay in the ICU was generally similar for patients of all races. The study was conducted by Tripti Kumar, DO, from Lankenau Medical Center, Wynnewood, Pennsylvania, and colleagues.

“Racial disparities are observed in the United States concerning COVID-19, and studies have discovered that minority populations are at ongoing risk for health inequity,” Dr. Kumar said in a narrated e-poster presented during the American College of Chest Physicians (CHEST) 2021 Annual Meeting.

“Primary prevention initiatives should take precedence in mitigating the effect that comorbidities have on these vulnerable populations to help reduce necessity for mechanical ventilation, hospital length of stay, and overall mortality,” she said.
 

Higher death rates for Black patients

At the time the study was conducted, the COVID-19 death rate in the United States had topped 500,000 (as of this writing, it stands at 726,000). Of those who died, 22.4% were Black, 18.1% were Hispanic, and 3.6% were of Asian descent. The numbers of COVID-19 diagnoses and deaths were significantly higher in U.S. counties where the proportions of Black residents were higher, the authors note.

To see whether differences in COVID-19 outcomes were reflected in ICU length of stay, the researchers conducted a retrospective chart review of data on 162 patients admitted to ICUs at Paoli Hospital and Lankenau Medical Center, both in the suburban Philadelphia town of Wynnewood.

All patients were diagnosed with COVID-19 from March through June 2020.

In all, 60% of the study population were Black, 35% were White, 3% were Asian, and 2% were Hispanic. Women composed 46% of the sample.

The average length of ICU stay, which was the primary endpoint, was similar among Black patients (15.4 days), White patients (15.5 days), and Asians (16 days). The shortest average hospital stay was among Hispanic patients, at 11.3 days.

The investigators determined that among all races, the prevalence of type 2 diabetes, obesity, hypertension, and smoking was highest among Black patients.

Overall, nearly 85% of patients required mechanical ventilation. Among the patients who required it, 86% were Black, 84% were White, 66% were Hispanic, and 75% were Asian.

Overall mortality was 62%. It was higher among Black patients, at 60%, than among White patients, at 33%. The investigators did not report mortality rates for Hispanic or Asian patients.
 

Missing data

Demondes Haynes, MD, FCCP, professor of medicine in the Division of Pulmonary and Critical Care and associate dean for admissions at the University of Mississippi Medical Center and School of Medicine, Jackson, who was not involved in the study, told this news organization that there are some gaps in the study that make it difficult to draw strong conclusions about the findings.

“For sure, comorbidities contribute a great deal to mortality, but is there something else going on? I think this poster is incomplete in that it cannot answer that question,” he said in an interview.

He noted that the use of retrospective rather than prospective data makes it hard to account for potential confounders.

“I agree that these findings show the potential contribution of comorbidities, but to me, this is a little incomplete to make that a definitive statement,” he said.

“I can’t argue with their recommendation for primary prevention – we definitely want to do primary prevention to decrease comorbidities. Would it decrease overall mortality? It might, it sure might, for just COVID-19 I’d say no, we need more information.”

No funding source for the study was reported. Dr. Kumar and colleagues and Dr. Haynes reported no relevant financial relationships.

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

Racial/ethnic disparities in COVID-19 mortality rates may be related more to comorbidities than to demographics, suggest authors of a new study.

Researchers compared the length of stay in intensive care units in two suburban hospitals for patients with severe SARS-CoV-2 infections. Their study shows that although the incidence of comorbidities and rates of use of mechanical ventilation and death were higher among Black patients than among patients of other races, length of stay in the ICU was generally similar for patients of all races. The study was conducted by Tripti Kumar, DO, from Lankenau Medical Center, Wynnewood, Pennsylvania, and colleagues.

“Racial disparities are observed in the United States concerning COVID-19, and studies have discovered that minority populations are at ongoing risk for health inequity,” Dr. Kumar said in a narrated e-poster presented during the American College of Chest Physicians (CHEST) 2021 Annual Meeting.

“Primary prevention initiatives should take precedence in mitigating the effect that comorbidities have on these vulnerable populations to help reduce necessity for mechanical ventilation, hospital length of stay, and overall mortality,” she said.
 

Higher death rates for Black patients

At the time the study was conducted, the COVID-19 death rate in the United States had topped 500,000 (as of this writing, it stands at 726,000). Of those who died, 22.4% were Black, 18.1% were Hispanic, and 3.6% were of Asian descent. The numbers of COVID-19 diagnoses and deaths were significantly higher in U.S. counties where the proportions of Black residents were higher, the authors note.

To see whether differences in COVID-19 outcomes were reflected in ICU length of stay, the researchers conducted a retrospective chart review of data on 162 patients admitted to ICUs at Paoli Hospital and Lankenau Medical Center, both in the suburban Philadelphia town of Wynnewood.

All patients were diagnosed with COVID-19 from March through June 2020.

In all, 60% of the study population were Black, 35% were White, 3% were Asian, and 2% were Hispanic. Women composed 46% of the sample.

The average length of ICU stay, which was the primary endpoint, was similar among Black patients (15.4 days), White patients (15.5 days), and Asians (16 days). The shortest average hospital stay was among Hispanic patients, at 11.3 days.

The investigators determined that among all races, the prevalence of type 2 diabetes, obesity, hypertension, and smoking was highest among Black patients.

Overall, nearly 85% of patients required mechanical ventilation. Among the patients who required it, 86% were Black, 84% were White, 66% were Hispanic, and 75% were Asian.

Overall mortality was 62%. It was higher among Black patients, at 60%, than among White patients, at 33%. The investigators did not report mortality rates for Hispanic or Asian patients.
 

Missing data

Demondes Haynes, MD, FCCP, professor of medicine in the Division of Pulmonary and Critical Care and associate dean for admissions at the University of Mississippi Medical Center and School of Medicine, Jackson, who was not involved in the study, told this news organization that there are some gaps in the study that make it difficult to draw strong conclusions about the findings.

“For sure, comorbidities contribute a great deal to mortality, but is there something else going on? I think this poster is incomplete in that it cannot answer that question,” he said in an interview.

He noted that the use of retrospective rather than prospective data makes it hard to account for potential confounders.

“I agree that these findings show the potential contribution of comorbidities, but to me, this is a little incomplete to make that a definitive statement,” he said.

“I can’t argue with their recommendation for primary prevention – we definitely want to do primary prevention to decrease comorbidities. Would it decrease overall mortality? It might, it sure might, for just COVID-19 I’d say no, we need more information.”

No funding source for the study was reported. Dr. Kumar and colleagues and Dr. Haynes reported no relevant financial relationships.

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

The new breakfast of champions

We love a good ranking system here at LOTME world headquarters, especially the food-based ones. Luckily for us (and our readers), a new study published in Nature Food offers a food-based ranking system.

PxHere

Sadly, unlike the last food-related ranking we covered, the Food Compass doesn’t tell you how much life you gain or lose from each food you eat down to the precise minute. Instead, it favors a more simple rating system from 1 to 100, with healthier foods scoring higher, and even incorporates mixed foods, not just single ingredients. This makes it better at assessing and comparing food combinations, rather than trying to mix and match the many ingredients that go into even relatively simple recipes.

The top and bottom of the rankings contain the usual suspects. Legumes and nuts, at 78.6, had the highest average score among the broad food groups, followed by fruits and then vegetables. Rounding out the bottom were sweets and savory snacks at 16.4. Among the individual foods, there were perfect scores in both directions: 100 for raw raspberries, while instant noodle soup and nonchocolate, ready-to-eat, nonfat pudding (very specific there) each earned a 1.

There are a few surprises in between. Nonfat cappuccino received a green light from the investigators, great news for the coffee drinkers out there. A serving of sweet potato chips scored better than a simple grilled chicken breast, and a slice of pizza, loaded up with extra meat and a thick crust, is still more nutritious than a bowl of corn flakes.

Neither is good for you, of course, but we’re still going to take this as a sign that pizza is the ideal breakfast food. Add that to your morning coffee, and you’re ready to start the day. Move over Wheaties, there’s a new breakfast of champions.
 

COVID-19 resisters, please step forward

Some people have all the luck with good genes, both inside and out.

ktsimage/Thinkstock

Genetically speaking, humans are 99.9% the same, but that 0.1% is where things get interesting. Because of that 0.1% difference, some people are more likely to contract diseases such as HIV, while others might be more resistant. These small differences in genetic code could be the key to finding treatments for COVID-19.

“The introduction of SARS-CoV-2 to a naive population, on a global scale, has provided yet another demonstration of the remarkable clinical variability between individuals in the course of infection, ranging from asymptomatic infections to life-threatening disease,” the researchers said in Nature Immunology.

The investigators have been scouring the world to find people who might be resistant to SARS-CoV-2 and have enrolled over 400 individuals in a “dedicated resistance study cohort,” according to ScienceAlert.

The investigators are looking at households in which families were infected but one member did not show severe symptoms, or for individuals who have been around the virus multiple times and haven’t contracted it. They are also looking at blood types.

Enrollment is ongoing, so if you’ve been in contact with COVID-19 multiple times and have not gotten sick, scientists would like to hear from you.
 

Better living through parasitization

How would you like to triple your life span, while maintaining a youthful appearance and gaining special social standing and privileges?

pxfuel

Sounds pretty good, right, so what’s the catch? Well, you have to be infected with a tapeworm ... and you have to be an ant.

If you are an ant, here’s the deal: Workers of the species Temnothorax nylanderi that have tapeworms live much longer than uninfected workers, and while living out those longer lives they do less work and receive gifts of food.

In a study conducted at Johannes Gutenberg University in Mainz, Germany, infected ants’ metabolic rates and lipid levels were similar to those of younger ants, and they appeared to remain in a permanent juvenile stage as a result of the infection, the investigators reported.

They tracked Temnothorax colonies for 3 years, at which point 95% of the uninfected workers had died but over half of the infected ants were still alive. Pretty great, right? Wrong. There was no joy in antville, for the uninfected workers had struck out. “Strained by the additional burden of their wormed-up nestmates, they seemed to be shunting care away from their queen. They were dying sooner than they might have if the colonies had remained parasite-free,” according to an article in the Atlantic.

Does this situation seem just a wee bit familiar? A small group lives longer, healthier lives and enjoys special privileges while the majority of that society works harder to support them? We’ll put it into the form of a chicken-and-egg argument: Which came first, the tapeworms or the one-percenters?
 

Laughing the pandemic stress away

Doomscrolling on social media has become one of the world’s favorite pastimes during the pandemic, but research shows that those memes about COVID-19 might combat the doom and gloom of the outside world.

littlehenrabi/Getty Images

A study recently published in Psychology of Popular Media showed that viewing memes, specifically those that were COVID-19 related, actually lessened the stress of the pandemic.

The researchers conducted a survey of 748 people aged 18-88 years. Each participant viewed three memes with text or three memes with text but no images. All three memes had similar cuteness levels (baby or adult), subject (animal or human), and caption (COVID-19–related or not). The participants were then asked to report on their stress levels and feelings before and after the memes.

The people who looked at memes felt less stressed and a higher humor level, especially the participants who received the COVID-19 memes. Study Finds said that they had more “pandemic-coping confidence” than those who got regular memes.

“While the World Health Organization recommended that people avoid too much COVID-related media for the benefit of their mental health, our research reveals that memes about COVID-19 could help people feel more confident in their ability to deal with the pandemic,” lead author Jessica Gall Myrick, PhD, said in a written statement. “The positive emotions associated with this type of content may make people feel psychologically safer and therefore better able to pay attention to the underlying messages related to health threats.”

So if you think you’ve been wasting time looking at memes during this pandemic, think again. It actually might keep you sane. Keep on scrolling!
 

Giving the gift of stress reduction

It’s a big week here at LOTME. You’ve just read our 100th edition, and to help celebrate that milestone – along with Count Your Buttons Day, Celebration of the Mind Day, and the International Day of the Nacho – we’re presenting an extra-special bonus feature, courtesy of Sad and Useless: The most depressive humor site on the Internet.

Sadanduseless.com

We hope you’ll stop your doomscrolling long enough to enjoy this stress-reducing meme. Thanks for reading!

The new breakfast of champions

We love a good ranking system here at LOTME world headquarters, especially the food-based ones. Luckily for us (and our readers), a new study published in Nature Food offers a food-based ranking system.

PxHere

Sadly, unlike the last food-related ranking we covered, the Food Compass doesn’t tell you how much life you gain or lose from each food you eat down to the precise minute. Instead, it favors a more simple rating system from 1 to 100, with healthier foods scoring higher, and even incorporates mixed foods, not just single ingredients. This makes it better at assessing and comparing food combinations, rather than trying to mix and match the many ingredients that go into even relatively simple recipes.

The top and bottom of the rankings contain the usual suspects. Legumes and nuts, at 78.6, had the highest average score among the broad food groups, followed by fruits and then vegetables. Rounding out the bottom were sweets and savory snacks at 16.4. Among the individual foods, there were perfect scores in both directions: 100 for raw raspberries, while instant noodle soup and nonchocolate, ready-to-eat, nonfat pudding (very specific there) each earned a 1.

There are a few surprises in between. Nonfat cappuccino received a green light from the investigators, great news for the coffee drinkers out there. A serving of sweet potato chips scored better than a simple grilled chicken breast, and a slice of pizza, loaded up with extra meat and a thick crust, is still more nutritious than a bowl of corn flakes.

Neither is good for you, of course, but we’re still going to take this as a sign that pizza is the ideal breakfast food. Add that to your morning coffee, and you’re ready to start the day. Move over Wheaties, there’s a new breakfast of champions.
 

COVID-19 resisters, please step forward

Some people have all the luck with good genes, both inside and out.

ktsimage/Thinkstock

Genetically speaking, humans are 99.9% the same, but that 0.1% is where things get interesting. Because of that 0.1% difference, some people are more likely to contract diseases such as HIV, while others might be more resistant. These small differences in genetic code could be the key to finding treatments for COVID-19.

“The introduction of SARS-CoV-2 to a naive population, on a global scale, has provided yet another demonstration of the remarkable clinical variability between individuals in the course of infection, ranging from asymptomatic infections to life-threatening disease,” the researchers said in Nature Immunology.

The investigators have been scouring the world to find people who might be resistant to SARS-CoV-2 and have enrolled over 400 individuals in a “dedicated resistance study cohort,” according to ScienceAlert.

The investigators are looking at households in which families were infected but one member did not show severe symptoms, or for individuals who have been around the virus multiple times and haven’t contracted it. They are also looking at blood types.

Enrollment is ongoing, so if you’ve been in contact with COVID-19 multiple times and have not gotten sick, scientists would like to hear from you.
 

Better living through parasitization

How would you like to triple your life span, while maintaining a youthful appearance and gaining special social standing and privileges?

pxfuel

Sounds pretty good, right, so what’s the catch? Well, you have to be infected with a tapeworm ... and you have to be an ant.

If you are an ant, here’s the deal: Workers of the species Temnothorax nylanderi that have tapeworms live much longer than uninfected workers, and while living out those longer lives they do less work and receive gifts of food.

In a study conducted at Johannes Gutenberg University in Mainz, Germany, infected ants’ metabolic rates and lipid levels were similar to those of younger ants, and they appeared to remain in a permanent juvenile stage as a result of the infection, the investigators reported.

They tracked Temnothorax colonies for 3 years, at which point 95% of the uninfected workers had died but over half of the infected ants were still alive. Pretty great, right? Wrong. There was no joy in antville, for the uninfected workers had struck out. “Strained by the additional burden of their wormed-up nestmates, they seemed to be shunting care away from their queen. They were dying sooner than they might have if the colonies had remained parasite-free,” according to an article in the Atlantic.

Does this situation seem just a wee bit familiar? A small group lives longer, healthier lives and enjoys special privileges while the majority of that society works harder to support them? We’ll put it into the form of a chicken-and-egg argument: Which came first, the tapeworms or the one-percenters?
 

Laughing the pandemic stress away

Doomscrolling on social media has become one of the world’s favorite pastimes during the pandemic, but research shows that those memes about COVID-19 might combat the doom and gloom of the outside world.

littlehenrabi/Getty Images

A study recently published in Psychology of Popular Media showed that viewing memes, specifically those that were COVID-19 related, actually lessened the stress of the pandemic.

The researchers conducted a survey of 748 people aged 18-88 years. Each participant viewed three memes with text or three memes with text but no images. All three memes had similar cuteness levels (baby or adult), subject (animal or human), and caption (COVID-19–related or not). The participants were then asked to report on their stress levels and feelings before and after the memes.

The people who looked at memes felt less stressed and a higher humor level, especially the participants who received the COVID-19 memes. Study Finds said that they had more “pandemic-coping confidence” than those who got regular memes.

“While the World Health Organization recommended that people avoid too much COVID-related media for the benefit of their mental health, our research reveals that memes about COVID-19 could help people feel more confident in their ability to deal with the pandemic,” lead author Jessica Gall Myrick, PhD, said in a written statement. “The positive emotions associated with this type of content may make people feel psychologically safer and therefore better able to pay attention to the underlying messages related to health threats.”

So if you think you’ve been wasting time looking at memes during this pandemic, think again. It actually might keep you sane. Keep on scrolling!
 

Giving the gift of stress reduction

It’s a big week here at LOTME. You’ve just read our 100th edition, and to help celebrate that milestone – along with Count Your Buttons Day, Celebration of the Mind Day, and the International Day of the Nacho – we’re presenting an extra-special bonus feature, courtesy of Sad and Useless: The most depressive humor site on the Internet.

Sadanduseless.com

We hope you’ll stop your doomscrolling long enough to enjoy this stress-reducing meme. Thanks for reading!

The new breakfast of champions

We love a good ranking system here at LOTME world headquarters, especially the food-based ones. Luckily for us (and our readers), a new study published in Nature Food offers a food-based ranking system.

PxHere

Sadly, unlike the last food-related ranking we covered, the Food Compass doesn’t tell you how much life you gain or lose from each food you eat down to the precise minute. Instead, it favors a more simple rating system from 1 to 100, with healthier foods scoring higher, and even incorporates mixed foods, not just single ingredients. This makes it better at assessing and comparing food combinations, rather than trying to mix and match the many ingredients that go into even relatively simple recipes.

The top and bottom of the rankings contain the usual suspects. Legumes and nuts, at 78.6, had the highest average score among the broad food groups, followed by fruits and then vegetables. Rounding out the bottom were sweets and savory snacks at 16.4. Among the individual foods, there were perfect scores in both directions: 100 for raw raspberries, while instant noodle soup and nonchocolate, ready-to-eat, nonfat pudding (very specific there) each earned a 1.

There are a few surprises in between. Nonfat cappuccino received a green light from the investigators, great news for the coffee drinkers out there. A serving of sweet potato chips scored better than a simple grilled chicken breast, and a slice of pizza, loaded up with extra meat and a thick crust, is still more nutritious than a bowl of corn flakes.

Neither is good for you, of course, but we’re still going to take this as a sign that pizza is the ideal breakfast food. Add that to your morning coffee, and you’re ready to start the day. Move over Wheaties, there’s a new breakfast of champions.
 

COVID-19 resisters, please step forward

Some people have all the luck with good genes, both inside and out.

ktsimage/Thinkstock

Genetically speaking, humans are 99.9% the same, but that 0.1% is where things get interesting. Because of that 0.1% difference, some people are more likely to contract diseases such as HIV, while others might be more resistant. These small differences in genetic code could be the key to finding treatments for COVID-19.

“The introduction of SARS-CoV-2 to a naive population, on a global scale, has provided yet another demonstration of the remarkable clinical variability between individuals in the course of infection, ranging from asymptomatic infections to life-threatening disease,” the researchers said in Nature Immunology.

The investigators have been scouring the world to find people who might be resistant to SARS-CoV-2 and have enrolled over 400 individuals in a “dedicated resistance study cohort,” according to ScienceAlert.

The investigators are looking at households in which families were infected but one member did not show severe symptoms, or for individuals who have been around the virus multiple times and haven’t contracted it. They are also looking at blood types.

Enrollment is ongoing, so if you’ve been in contact with COVID-19 multiple times and have not gotten sick, scientists would like to hear from you.
 

Better living through parasitization

How would you like to triple your life span, while maintaining a youthful appearance and gaining special social standing and privileges?

pxfuel

Sounds pretty good, right, so what’s the catch? Well, you have to be infected with a tapeworm ... and you have to be an ant.

If you are an ant, here’s the deal: Workers of the species Temnothorax nylanderi that have tapeworms live much longer than uninfected workers, and while living out those longer lives they do less work and receive gifts of food.

In a study conducted at Johannes Gutenberg University in Mainz, Germany, infected ants’ metabolic rates and lipid levels were similar to those of younger ants, and they appeared to remain in a permanent juvenile stage as a result of the infection, the investigators reported.

They tracked Temnothorax colonies for 3 years, at which point 95% of the uninfected workers had died but over half of the infected ants were still alive. Pretty great, right? Wrong. There was no joy in antville, for the uninfected workers had struck out. “Strained by the additional burden of their wormed-up nestmates, they seemed to be shunting care away from their queen. They were dying sooner than they might have if the colonies had remained parasite-free,” according to an article in the Atlantic.

Does this situation seem just a wee bit familiar? A small group lives longer, healthier lives and enjoys special privileges while the majority of that society works harder to support them? We’ll put it into the form of a chicken-and-egg argument: Which came first, the tapeworms or the one-percenters?
 

Laughing the pandemic stress away

Doomscrolling on social media has become one of the world’s favorite pastimes during the pandemic, but research shows that those memes about COVID-19 might combat the doom and gloom of the outside world.

littlehenrabi/Getty Images

A study recently published in Psychology of Popular Media showed that viewing memes, specifically those that were COVID-19 related, actually lessened the stress of the pandemic.

The researchers conducted a survey of 748 people aged 18-88 years. Each participant viewed three memes with text or three memes with text but no images. All three memes had similar cuteness levels (baby or adult), subject (animal or human), and caption (COVID-19–related or not). The participants were then asked to report on their stress levels and feelings before and after the memes.

The people who looked at memes felt less stressed and a higher humor level, especially the participants who received the COVID-19 memes. Study Finds said that they had more “pandemic-coping confidence” than those who got regular memes.

“While the World Health Organization recommended that people avoid too much COVID-related media for the benefit of their mental health, our research reveals that memes about COVID-19 could help people feel more confident in their ability to deal with the pandemic,” lead author Jessica Gall Myrick, PhD, said in a written statement. “The positive emotions associated with this type of content may make people feel psychologically safer and therefore better able to pay attention to the underlying messages related to health threats.”

So if you think you’ve been wasting time looking at memes during this pandemic, think again. It actually might keep you sane. Keep on scrolling!
 

Giving the gift of stress reduction

It’s a big week here at LOTME. You’ve just read our 100th edition, and to help celebrate that milestone – along with Count Your Buttons Day, Celebration of the Mind Day, and the International Day of the Nacho – we’re presenting an extra-special bonus feature, courtesy of Sad and Useless: The most depressive humor site on the Internet.

Sadanduseless.com

We hope you’ll stop your doomscrolling long enough to enjoy this stress-reducing meme. Thanks for reading!

The U.S. Food and Drug Administration (FDA) has authorized booster doses for the Moderna and Johnson & Johnson COVID-19 vaccines, while also allowing boosters to be given interchangeably with any of the other vaccines, in people who are eligible to get them.

The move to amend the Emergency Use Authorization for these vaccines gives the vaccine experts on the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices latitude to recommend a mix-and-match strategy if they feel the science supports it.

The committee convenes Oct. 21 for a day-long meeting to make its recommendations for additional doses.

People who’ve previously received two doses of the Moderna mRNA vaccine, which is now called Spikevax, are eligible for a third dose of any COVID-19 vaccine if they are 6 months past their second dose and are:

• 65 years of age or older
• 18 to 64 years of age, but at high risk for severe COVID-19 because of an underlying health condition
• 18 to 64 years of age and at high risk for exposure to the SARS-CoV-2 virus because they live in a group setting, such as a prison or care home, or work in a risky occupation, such as healthcare

People who’ve previously received a dose of the Johnson & Johnson vaccine are eligible for a second dose of any COVID-19 vaccine if they are over the age of 18 and at least 2 months past their vaccination.

“Today’s actions demonstrate our commitment to public health in proactively fighting against the COVID-19 pandemic,” said Acting FDA Commissioner Janet Woodcock, MD, in a news release. “As the pandemic continues to impact the country, science has shown that vaccination continues to be the safest and most effective way to prevent COVID-19, including the most serious consequences of the disease, such as hospitalization and death.

“The available data suggest waning immunity in some populations who are fully vaccinated. The availability of these authorized boosters is important for continued protection against COVID-19 disease.”

A version of this article was first published on Medscape.com.

The U.S. Food and Drug Administration (FDA) has authorized booster doses for the Moderna and Johnson & Johnson COVID-19 vaccines, while also allowing boosters to be given interchangeably with any of the other vaccines, in people who are eligible to get them.

The move to amend the Emergency Use Authorization for these vaccines gives the vaccine experts on the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices latitude to recommend a mix-and-match strategy if they feel the science supports it.

The committee convenes Oct. 21 for a day-long meeting to make its recommendations for additional doses.

People who’ve previously received two doses of the Moderna mRNA vaccine, which is now called Spikevax, are eligible for a third dose of any COVID-19 vaccine if they are 6 months past their second dose and are:

• 65 years of age or older
• 18 to 64 years of age, but at high risk for severe COVID-19 because of an underlying health condition
• 18 to 64 years of age and at high risk for exposure to the SARS-CoV-2 virus because they live in a group setting, such as a prison or care home, or work in a risky occupation, such as healthcare

People who’ve previously received a dose of the Johnson & Johnson vaccine are eligible for a second dose of any COVID-19 vaccine if they are over the age of 18 and at least 2 months past their vaccination.

“Today’s actions demonstrate our commitment to public health in proactively fighting against the COVID-19 pandemic,” said Acting FDA Commissioner Janet Woodcock, MD, in a news release. “As the pandemic continues to impact the country, science has shown that vaccination continues to be the safest and most effective way to prevent COVID-19, including the most serious consequences of the disease, such as hospitalization and death.

“The available data suggest waning immunity in some populations who are fully vaccinated. The availability of these authorized boosters is important for continued protection against COVID-19 disease.”

A version of this article was first published on Medscape.com.

The U.S. Food and Drug Administration (FDA) has authorized booster doses for the Moderna and Johnson & Johnson COVID-19 vaccines, while also allowing boosters to be given interchangeably with any of the other vaccines, in people who are eligible to get them.

The move to amend the Emergency Use Authorization for these vaccines gives the vaccine experts on the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices latitude to recommend a mix-and-match strategy if they feel the science supports it.

The committee convenes Oct. 21 for a day-long meeting to make its recommendations for additional doses.

People who’ve previously received two doses of the Moderna mRNA vaccine, which is now called Spikevax, are eligible for a third dose of any COVID-19 vaccine if they are 6 months past their second dose and are:

• 65 years of age or older
• 18 to 64 years of age, but at high risk for severe COVID-19 because of an underlying health condition
• 18 to 64 years of age and at high risk for exposure to the SARS-CoV-2 virus because they live in a group setting, such as a prison or care home, or work in a risky occupation, such as healthcare

People who’ve previously received a dose of the Johnson & Johnson vaccine are eligible for a second dose of any COVID-19 vaccine if they are over the age of 18 and at least 2 months past their vaccination.

“Today’s actions demonstrate our commitment to public health in proactively fighting against the COVID-19 pandemic,” said Acting FDA Commissioner Janet Woodcock, MD, in a news release. “As the pandemic continues to impact the country, science has shown that vaccination continues to be the safest and most effective way to prevent COVID-19, including the most serious consequences of the disease, such as hospitalization and death.

“The available data suggest waning immunity in some populations who are fully vaccinated. The availability of these authorized boosters is important for continued protection against COVID-19 disease.”

A version of this article was first published on Medscape.com.