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Cardiac arrest in COVID-19 pandemic: ‘Survival is possible’
In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.
A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.
Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.
Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.
“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.
“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”
Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.
“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”
“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.
“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”
“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.
“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
Out-of-hospital cardiac arrest, March 2019 vs. March 2020
Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.
In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.
They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.
There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.
The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).
Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).
The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).
In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).
This drop in survival was greater in communities with moderate to high COVID-19 mortality.
These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.
Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.
Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.
For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”
“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.
“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.
In-hospital cardiac arrest, March Through May 2020
The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.
“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”
To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.
They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).
Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.
There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).
“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”
“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.
Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”
Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.
A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.
Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.
Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.
“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.
“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”
Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.
“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”
“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.
“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”
“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.
“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
Out-of-hospital cardiac arrest, March 2019 vs. March 2020
Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.
In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.
They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.
There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.
The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).
Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).
The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).
In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).
This drop in survival was greater in communities with moderate to high COVID-19 mortality.
These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.
Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.
Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.
For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”
“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.
“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.
In-hospital cardiac arrest, March Through May 2020
The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.
“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”
To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.
They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).
Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.
There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).
“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”
“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.
Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”
Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.
A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.
Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.
Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.
“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.
“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”
Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.
“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”
“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.
“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”
“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.
“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
Out-of-hospital cardiac arrest, March 2019 vs. March 2020
Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.
In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.
They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.
There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.
The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).
Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).
The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).
In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).
This drop in survival was greater in communities with moderate to high COVID-19 mortality.
These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.
Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.
Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.
For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”
“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.
“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.
In-hospital cardiac arrest, March Through May 2020
The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.
“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”
To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.
They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).
Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.
There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).
“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”
“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.
Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”
Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AHA 2020
Escaping the daily grind
Few films have universal appeal these days, but one that comes close is the 1993 classic Groundhog Day, in which the protagonist is trapped in a time loop, doomed to living the same day over and over for many years.
One reason that this story resonates with so many, I think, is that we are all living a similar life. Not as a same-day loop, of course; but each week seems eerily similar to the last, as does each month, each year – on and on, ad infinitum. That’s why it is so important, every so often, to step out of the “loop” and reassess the bigger picture.
I write this reminder every couple of years because it’s so easy to lose sight of the overall landscape among the pressures of our daily routines. . And we are too busy to sit down and think about what we might do to break that vicious cycle. This is detrimental to our own well being, as well as that of our patients.
There are many ways to maintain your intellectual and emotional health, but here’s how I do it: I take individual days off (average of one a month) to catch up on journals or taking a CME course; or to try something new – something I’ve been thinking about doing “someday, when there is time” – such as a guitar, bass, or sailing lessons; or a long weekend away with my wife.
And until COVID-19 put a temporary stop to them earlier this year, we have embarked on at least one longer adventure each year, some of which have been shared in these pages. Our 2019 expedition to Easter Island remains among the most memorable, and fulfilled a dream I’ve had since I read Thor Heyerdahl’s Aku Aku in grade school. As we explored the giant stone moai – which are found nowhere else in the world – I didn’t have the time – or the slightest inclination – to worry about the office. But I did accumulate some great ideas – practical, medical, and literary. Original thoughts are hard to chase down during the daily grind; but in a refreshing environment, they will seek you out. When our trip was over, I returned ready to take on the world, and my practice, anew.
I know how some of you feel about “wasting” a day – or, God forbid, a week. Patients might go elsewhere while you’re gone, and every day the office is idle you “lose money.” That whole paradigm is wrong. You bring in a given amount of revenue per year – more on some days, less on other days, none on weekends and vacations; it all averages out in the end.
Besides, this is much more important than money; this is breaking the routine, clearing the cobwebs, living your life. Trust me, your practice will still be there when you return. And while COVID-19 will not last forever, there are plenty of other “sharpeners” while we wait.
More than once I’ve recounted the story of Alex Müller and J. Georg Bednorz, the Swiss Nobel Laureates whose superconductivity research ground to a halt in 1986. The harder they pressed, the more elusive progress became. So Müller decided to take a break to read a new book on ceramics – a subject that had always interested him.
Nothing could have been less relevant to his work, of course; ceramics are among the poorest conductors known. But in that lower-pressure environment, Müller realized that a unique property of ceramics might apply to their project.
Back in the lab, the team created a ceramic compound that became the first successful “high-temperature” superconductor, which in turn triggered an explosion of research leading to breakthroughs in computing, electricity transmission, magnetically-elevated trains, and many applications yet to be realized.
Sharpening your saw may not change the world, but it will change you; any nudge out of your comfort zone will give you fresh ideas and help you look at seemingly insoluble problems in completely new ways.
And to those who still can’t bear the thought of taking time off, remember the dying words that no one has spoken, ever: “I wish I had spent more time in my office!”
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.
Few films have universal appeal these days, but one that comes close is the 1993 classic Groundhog Day, in which the protagonist is trapped in a time loop, doomed to living the same day over and over for many years.
One reason that this story resonates with so many, I think, is that we are all living a similar life. Not as a same-day loop, of course; but each week seems eerily similar to the last, as does each month, each year – on and on, ad infinitum. That’s why it is so important, every so often, to step out of the “loop” and reassess the bigger picture.
I write this reminder every couple of years because it’s so easy to lose sight of the overall landscape among the pressures of our daily routines. . And we are too busy to sit down and think about what we might do to break that vicious cycle. This is detrimental to our own well being, as well as that of our patients.
There are many ways to maintain your intellectual and emotional health, but here’s how I do it: I take individual days off (average of one a month) to catch up on journals or taking a CME course; or to try something new – something I’ve been thinking about doing “someday, when there is time” – such as a guitar, bass, or sailing lessons; or a long weekend away with my wife.
And until COVID-19 put a temporary stop to them earlier this year, we have embarked on at least one longer adventure each year, some of which have been shared in these pages. Our 2019 expedition to Easter Island remains among the most memorable, and fulfilled a dream I’ve had since I read Thor Heyerdahl’s Aku Aku in grade school. As we explored the giant stone moai – which are found nowhere else in the world – I didn’t have the time – or the slightest inclination – to worry about the office. But I did accumulate some great ideas – practical, medical, and literary. Original thoughts are hard to chase down during the daily grind; but in a refreshing environment, they will seek you out. When our trip was over, I returned ready to take on the world, and my practice, anew.
I know how some of you feel about “wasting” a day – or, God forbid, a week. Patients might go elsewhere while you’re gone, and every day the office is idle you “lose money.” That whole paradigm is wrong. You bring in a given amount of revenue per year – more on some days, less on other days, none on weekends and vacations; it all averages out in the end.
Besides, this is much more important than money; this is breaking the routine, clearing the cobwebs, living your life. Trust me, your practice will still be there when you return. And while COVID-19 will not last forever, there are plenty of other “sharpeners” while we wait.
More than once I’ve recounted the story of Alex Müller and J. Georg Bednorz, the Swiss Nobel Laureates whose superconductivity research ground to a halt in 1986. The harder they pressed, the more elusive progress became. So Müller decided to take a break to read a new book on ceramics – a subject that had always interested him.
Nothing could have been less relevant to his work, of course; ceramics are among the poorest conductors known. But in that lower-pressure environment, Müller realized that a unique property of ceramics might apply to their project.
Back in the lab, the team created a ceramic compound that became the first successful “high-temperature” superconductor, which in turn triggered an explosion of research leading to breakthroughs in computing, electricity transmission, magnetically-elevated trains, and many applications yet to be realized.
Sharpening your saw may not change the world, but it will change you; any nudge out of your comfort zone will give you fresh ideas and help you look at seemingly insoluble problems in completely new ways.
And to those who still can’t bear the thought of taking time off, remember the dying words that no one has spoken, ever: “I wish I had spent more time in my office!”
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.
Few films have universal appeal these days, but one that comes close is the 1993 classic Groundhog Day, in which the protagonist is trapped in a time loop, doomed to living the same day over and over for many years.
One reason that this story resonates with so many, I think, is that we are all living a similar life. Not as a same-day loop, of course; but each week seems eerily similar to the last, as does each month, each year – on and on, ad infinitum. That’s why it is so important, every so often, to step out of the “loop” and reassess the bigger picture.
I write this reminder every couple of years because it’s so easy to lose sight of the overall landscape among the pressures of our daily routines. . And we are too busy to sit down and think about what we might do to break that vicious cycle. This is detrimental to our own well being, as well as that of our patients.
There are many ways to maintain your intellectual and emotional health, but here’s how I do it: I take individual days off (average of one a month) to catch up on journals or taking a CME course; or to try something new – something I’ve been thinking about doing “someday, when there is time” – such as a guitar, bass, or sailing lessons; or a long weekend away with my wife.
And until COVID-19 put a temporary stop to them earlier this year, we have embarked on at least one longer adventure each year, some of which have been shared in these pages. Our 2019 expedition to Easter Island remains among the most memorable, and fulfilled a dream I’ve had since I read Thor Heyerdahl’s Aku Aku in grade school. As we explored the giant stone moai – which are found nowhere else in the world – I didn’t have the time – or the slightest inclination – to worry about the office. But I did accumulate some great ideas – practical, medical, and literary. Original thoughts are hard to chase down during the daily grind; but in a refreshing environment, they will seek you out. When our trip was over, I returned ready to take on the world, and my practice, anew.
I know how some of you feel about “wasting” a day – or, God forbid, a week. Patients might go elsewhere while you’re gone, and every day the office is idle you “lose money.” That whole paradigm is wrong. You bring in a given amount of revenue per year – more on some days, less on other days, none on weekends and vacations; it all averages out in the end.
Besides, this is much more important than money; this is breaking the routine, clearing the cobwebs, living your life. Trust me, your practice will still be there when you return. And while COVID-19 will not last forever, there are plenty of other “sharpeners” while we wait.
More than once I’ve recounted the story of Alex Müller and J. Georg Bednorz, the Swiss Nobel Laureates whose superconductivity research ground to a halt in 1986. The harder they pressed, the more elusive progress became. So Müller decided to take a break to read a new book on ceramics – a subject that had always interested him.
Nothing could have been less relevant to his work, of course; ceramics are among the poorest conductors known. But in that lower-pressure environment, Müller realized that a unique property of ceramics might apply to their project.
Back in the lab, the team created a ceramic compound that became the first successful “high-temperature” superconductor, which in turn triggered an explosion of research leading to breakthroughs in computing, electricity transmission, magnetically-elevated trains, and many applications yet to be realized.
Sharpening your saw may not change the world, but it will change you; any nudge out of your comfort zone will give you fresh ideas and help you look at seemingly insoluble problems in completely new ways.
And to those who still can’t bear the thought of taking time off, remember the dying words that no one has spoken, ever: “I wish I had spent more time in my office!”
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.
Two-drug combo should be first-line standard of care in advanced endometrial cancer
The combination proved to be noninferior to paclitaxel-doxorubicin-cisplatin (TAP) in terms of response, progression-free survival, and overall survival, and with lower toxicity.
Overall survival was a median of 37 months for TC and 41 months for TAP, and there were more adverse events of grade 3 or higher with TAP.
The data were initially presented at the 2012 annual meeting of the Society of Gynecologic Oncology. In the original presentation, lead author David Scott Miller, MD, said this combination should be the standard of care in this setting. Dr. Miller is professor of obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas.
“This subsequent long-term follow-up publication confirmed that,” he said in an interview. “TAP is now rarely used.”
The results have now been published in the Journal of Clinical Oncology.
The Gynecologic Oncology Group 177 trial established TAP about a decade earlier as the standard for systemic treatment of stage III-IV and recurrent endometrial cancer. However, the regimen was associated with substantially more toxicity than doxorubicin-cisplatin.
Phase 2 trials of TC suggested that the combination was active in endometrial cancer, the authors noted. They hypothesized that doxorubicin could be omitted from the regimen and that carboplatin could be substituted for cisplatin.
Equivalent survival, lower toxicity
In the current trial, Dr. Miller and colleagues sought to determine whether TC was therapeutically equivalent or noninferior to TAP with regard to survival outcomes. Secondary endpoints involved the toxicity profile of TC, compared with TAP. The two regimens were also compared with respect to patient-reported neurotoxicity and health-related quality of life (HRQoL).
From 2003 to 2009, 1,381 women with stage III, stage IV, and recurrent endometrial cancers were enrolled in the phase 3 GOG0209 trial. Patients were treated with doxorubicin 45 mg/m2 and cisplatin 50 mg/m2 (day 1), followed by paclitaxel 160 mg/m2 (day 2) with granulocyte colony–stimulating factor or paclitaxel 175 mg/m2 and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles.
After treatment was completed, patients were followed quarterly for 2 years, semiannually for 3 years, and then annually until death. Most of the patients (61%) had measurable or recurrent disease at baseline.
In this updated analysis, with a median follow-up of 124 months, about two-thirds (>65%) of the patients had died; 28% remain alive without evidence of cancer. The adjusted ratio of death hazard of TC versus TAP was 1.002; for progression, the HR of TC to TAP was 1.032.
Median progression-free survival for TAP versus TC was 14 months versus 13 months, and for overall survival, 41 months versus 37 months.
As for adverse events, neutropenic fever was reported in 7% of patients who received TAP and in 6% of those who received TC. The rate of sensory neuropathy was greater among patients who received TAP (26% vs. 20%; P = .40), as was the rate of thrombocytopenia of grade ≥3 (23% vs. 12%), vomiting (7% vs. 4%), diarrhea (6% vs. 2%), and metabolic toxicities (14% vs. 8%). The rate of neutropenia was greater with TC (52% vs. 80%).
Data on HRQoL were collected from the first 538 patients enrolled before March 26, 2007. HRQoL was assessed at baseline and then at 6 weeks, 15 weeks, and 26 weeks. At 6 weeks, the TC group had higher scores on physical well-being and functional well-being (2.1-point difference; 0.3 to approximately 3.9 points; P = .009; effect size, 0.19). There were no statistically significant differences between groups at 15 and 26 weeks.
On the Functional Assessment of Cancer Therapy/GOG-Neurotoxicity four-item measure of sensory neuropathy (FACT/GOG-Ntx) subscale, scores were higher (indicating fewer neurotoxic symptoms) for patients in the TC group by 1.4 points (0.4 to approximately 2.5 points; P = .003; effect size, 0.64) at 26 weeks. There were no statistically significant differences between the groups at 6 and 15 weeks.
Dr. Miller noted that TC became the “backbone or control arm for most subsequent trials,” such as those evaluating immunotherapy and other agents in this setting.
The study was supported by National Cancer Institute grants to the GOG Administrative Office, the GOG Statistical Office, NRG Oncology (1 U10 CA180822), NRG Operations, and the National Cancer Institute Community Oncology Research Program. Dr. Miller has had a consulting or advisory role with Genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Alexion Pharmaceuticals, Karyopharm Therapeutics, Incyte, Guardant Health, Janssen, Alexion Pharmaceuticals, Clovis Oncology, and Merck Sharp & Dohme; has been on the speakers’ bureaus for Clovis Oncology and Genentech; and has received institutional research funding from US Biotest, Advenchen Laboratories, Millennium, Tesaro, Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, and Merck Sharp & Dohme.
A version of this article originally appeared on Medscape.com.
The combination proved to be noninferior to paclitaxel-doxorubicin-cisplatin (TAP) in terms of response, progression-free survival, and overall survival, and with lower toxicity.
Overall survival was a median of 37 months for TC and 41 months for TAP, and there were more adverse events of grade 3 or higher with TAP.
The data were initially presented at the 2012 annual meeting of the Society of Gynecologic Oncology. In the original presentation, lead author David Scott Miller, MD, said this combination should be the standard of care in this setting. Dr. Miller is professor of obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas.
“This subsequent long-term follow-up publication confirmed that,” he said in an interview. “TAP is now rarely used.”
The results have now been published in the Journal of Clinical Oncology.
The Gynecologic Oncology Group 177 trial established TAP about a decade earlier as the standard for systemic treatment of stage III-IV and recurrent endometrial cancer. However, the regimen was associated with substantially more toxicity than doxorubicin-cisplatin.
Phase 2 trials of TC suggested that the combination was active in endometrial cancer, the authors noted. They hypothesized that doxorubicin could be omitted from the regimen and that carboplatin could be substituted for cisplatin.
Equivalent survival, lower toxicity
In the current trial, Dr. Miller and colleagues sought to determine whether TC was therapeutically equivalent or noninferior to TAP with regard to survival outcomes. Secondary endpoints involved the toxicity profile of TC, compared with TAP. The two regimens were also compared with respect to patient-reported neurotoxicity and health-related quality of life (HRQoL).
From 2003 to 2009, 1,381 women with stage III, stage IV, and recurrent endometrial cancers were enrolled in the phase 3 GOG0209 trial. Patients were treated with doxorubicin 45 mg/m2 and cisplatin 50 mg/m2 (day 1), followed by paclitaxel 160 mg/m2 (day 2) with granulocyte colony–stimulating factor or paclitaxel 175 mg/m2 and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles.
After treatment was completed, patients were followed quarterly for 2 years, semiannually for 3 years, and then annually until death. Most of the patients (61%) had measurable or recurrent disease at baseline.
In this updated analysis, with a median follow-up of 124 months, about two-thirds (>65%) of the patients had died; 28% remain alive without evidence of cancer. The adjusted ratio of death hazard of TC versus TAP was 1.002; for progression, the HR of TC to TAP was 1.032.
Median progression-free survival for TAP versus TC was 14 months versus 13 months, and for overall survival, 41 months versus 37 months.
As for adverse events, neutropenic fever was reported in 7% of patients who received TAP and in 6% of those who received TC. The rate of sensory neuropathy was greater among patients who received TAP (26% vs. 20%; P = .40), as was the rate of thrombocytopenia of grade ≥3 (23% vs. 12%), vomiting (7% vs. 4%), diarrhea (6% vs. 2%), and metabolic toxicities (14% vs. 8%). The rate of neutropenia was greater with TC (52% vs. 80%).
Data on HRQoL were collected from the first 538 patients enrolled before March 26, 2007. HRQoL was assessed at baseline and then at 6 weeks, 15 weeks, and 26 weeks. At 6 weeks, the TC group had higher scores on physical well-being and functional well-being (2.1-point difference; 0.3 to approximately 3.9 points; P = .009; effect size, 0.19). There were no statistically significant differences between groups at 15 and 26 weeks.
On the Functional Assessment of Cancer Therapy/GOG-Neurotoxicity four-item measure of sensory neuropathy (FACT/GOG-Ntx) subscale, scores were higher (indicating fewer neurotoxic symptoms) for patients in the TC group by 1.4 points (0.4 to approximately 2.5 points; P = .003; effect size, 0.64) at 26 weeks. There were no statistically significant differences between the groups at 6 and 15 weeks.
Dr. Miller noted that TC became the “backbone or control arm for most subsequent trials,” such as those evaluating immunotherapy and other agents in this setting.
The study was supported by National Cancer Institute grants to the GOG Administrative Office, the GOG Statistical Office, NRG Oncology (1 U10 CA180822), NRG Operations, and the National Cancer Institute Community Oncology Research Program. Dr. Miller has had a consulting or advisory role with Genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Alexion Pharmaceuticals, Karyopharm Therapeutics, Incyte, Guardant Health, Janssen, Alexion Pharmaceuticals, Clovis Oncology, and Merck Sharp & Dohme; has been on the speakers’ bureaus for Clovis Oncology and Genentech; and has received institutional research funding from US Biotest, Advenchen Laboratories, Millennium, Tesaro, Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, and Merck Sharp & Dohme.
A version of this article originally appeared on Medscape.com.
The combination proved to be noninferior to paclitaxel-doxorubicin-cisplatin (TAP) in terms of response, progression-free survival, and overall survival, and with lower toxicity.
Overall survival was a median of 37 months for TC and 41 months for TAP, and there were more adverse events of grade 3 or higher with TAP.
The data were initially presented at the 2012 annual meeting of the Society of Gynecologic Oncology. In the original presentation, lead author David Scott Miller, MD, said this combination should be the standard of care in this setting. Dr. Miller is professor of obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas.
“This subsequent long-term follow-up publication confirmed that,” he said in an interview. “TAP is now rarely used.”
The results have now been published in the Journal of Clinical Oncology.
The Gynecologic Oncology Group 177 trial established TAP about a decade earlier as the standard for systemic treatment of stage III-IV and recurrent endometrial cancer. However, the regimen was associated with substantially more toxicity than doxorubicin-cisplatin.
Phase 2 trials of TC suggested that the combination was active in endometrial cancer, the authors noted. They hypothesized that doxorubicin could be omitted from the regimen and that carboplatin could be substituted for cisplatin.
Equivalent survival, lower toxicity
In the current trial, Dr. Miller and colleagues sought to determine whether TC was therapeutically equivalent or noninferior to TAP with regard to survival outcomes. Secondary endpoints involved the toxicity profile of TC, compared with TAP. The two regimens were also compared with respect to patient-reported neurotoxicity and health-related quality of life (HRQoL).
From 2003 to 2009, 1,381 women with stage III, stage IV, and recurrent endometrial cancers were enrolled in the phase 3 GOG0209 trial. Patients were treated with doxorubicin 45 mg/m2 and cisplatin 50 mg/m2 (day 1), followed by paclitaxel 160 mg/m2 (day 2) with granulocyte colony–stimulating factor or paclitaxel 175 mg/m2 and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles.
After treatment was completed, patients were followed quarterly for 2 years, semiannually for 3 years, and then annually until death. Most of the patients (61%) had measurable or recurrent disease at baseline.
In this updated analysis, with a median follow-up of 124 months, about two-thirds (>65%) of the patients had died; 28% remain alive without evidence of cancer. The adjusted ratio of death hazard of TC versus TAP was 1.002; for progression, the HR of TC to TAP was 1.032.
Median progression-free survival for TAP versus TC was 14 months versus 13 months, and for overall survival, 41 months versus 37 months.
As for adverse events, neutropenic fever was reported in 7% of patients who received TAP and in 6% of those who received TC. The rate of sensory neuropathy was greater among patients who received TAP (26% vs. 20%; P = .40), as was the rate of thrombocytopenia of grade ≥3 (23% vs. 12%), vomiting (7% vs. 4%), diarrhea (6% vs. 2%), and metabolic toxicities (14% vs. 8%). The rate of neutropenia was greater with TC (52% vs. 80%).
Data on HRQoL were collected from the first 538 patients enrolled before March 26, 2007. HRQoL was assessed at baseline and then at 6 weeks, 15 weeks, and 26 weeks. At 6 weeks, the TC group had higher scores on physical well-being and functional well-being (2.1-point difference; 0.3 to approximately 3.9 points; P = .009; effect size, 0.19). There were no statistically significant differences between groups at 15 and 26 weeks.
On the Functional Assessment of Cancer Therapy/GOG-Neurotoxicity four-item measure of sensory neuropathy (FACT/GOG-Ntx) subscale, scores were higher (indicating fewer neurotoxic symptoms) for patients in the TC group by 1.4 points (0.4 to approximately 2.5 points; P = .003; effect size, 0.64) at 26 weeks. There were no statistically significant differences between the groups at 6 and 15 weeks.
Dr. Miller noted that TC became the “backbone or control arm for most subsequent trials,” such as those evaluating immunotherapy and other agents in this setting.
The study was supported by National Cancer Institute grants to the GOG Administrative Office, the GOG Statistical Office, NRG Oncology (1 U10 CA180822), NRG Operations, and the National Cancer Institute Community Oncology Research Program. Dr. Miller has had a consulting or advisory role with Genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Alexion Pharmaceuticals, Karyopharm Therapeutics, Incyte, Guardant Health, Janssen, Alexion Pharmaceuticals, Clovis Oncology, and Merck Sharp & Dohme; has been on the speakers’ bureaus for Clovis Oncology and Genentech; and has received institutional research funding from US Biotest, Advenchen Laboratories, Millennium, Tesaro, Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, and Merck Sharp & Dohme.
A version of this article originally appeared on Medscape.com.
Pregnancy outcomes ‘favorable’ after BRCA breast cancer treatment
said researchers reporting a review of more than 1,000 young women with breast cancer, mostly in Europe but also Israel and North and South America.
It’s been known that pregnancy after breast cancer treatment, even for hormone receptor–positive disease, is safe overall, the team commented. However, there have been concerns about women who have BRCA mutations because of a lack of data.
The new findings “provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility” and are of “paramount importance for health care providers involved in counseling young patients,” said the researchers, led by Matteo Lambertini, MD, PhD, a medical oncologist at the University of Genoa, Italy.
The review was published in September in the Journal of Clinical Oncology.
The team reviewed reproductive outcomes among 1,252 women who were no older than 40 years when diagnosed with stage I-III BRCA-mutated invasive breast cancer between January 2000 and December 2012.
More than half (65%; n = 811) had BRCA1 mutations, 430 women (34%) had BRCA2 mutations, and 11 women had both.
Overall, 195 women became pregnant, at a median of 4.5 years after the breast cancer diagnosis and at a median age of 36 years.
The miscarriage rate was 10.3%, lower than expected in the general population.
Among the 150 patients who gave birth to 170 infants, delivery complications occurred in 13 of the 112 pregnancies with available data (11.6%), and congenital anomalies were seen in just 2 pregnancies (1.8%). This is a lower rate of anomalies than expected in the general population, the team noted. The rate of preterm delivery was 9.2%, similar to the general population.
There was no difference between the women who became pregnant and those who did not in either disease-free survival (adjusted hazard ratio, 0.87; P = .41) or overall survival (aHR, 0.88; P = .66), over a median follow-up of 8.3 years from diagnosis. In addition to BRCA mutations, the analysis adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, and breast surgery.
Over 80% of the subjects had ductal carcinoma, and over 90% of women were HER2-negative. More women in the pregnancy cohort had tumor diameters of 2 cm or less (47.2% vs. 40.9%) and a higher percentage had breast conserving surgery (59% vs. 45.9%).
Chemotherapy was administered to 95.3% of the subjects, most commonly anthracycline and taxane based, and more than 90% received endocrine therapy, most often tamoxifen alone among women who did not become pregnant and tamoxifen plus a luteinizing hormone-releasing hormone agonist among those who did. Endocrine therapy was shorter among women who became pregnant (median, 50 vs. 60 months; P < .001).
The findings held when 176 pregnant cases were matched to 528 nonpregnant controls for year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. However, disease-free survival was improved among pregnant women (HR, 0.71; P = .045) who were younger at diagnosis, with median ages of 31 years vs. 36 years (P < .001).
The study was funded by the Italian Association for Cancer Research, among others. Dr. Lambertini reports acting as a consultant for Roche and Novartis and as a speaker for Theramex, Takeda, Roche, Eli Lilly, Novartis. Several coauthors also report relationships with pharmaceutical companies, as detailed in the original article.
A version of this article originally appeared on Medscape.com.
said researchers reporting a review of more than 1,000 young women with breast cancer, mostly in Europe but also Israel and North and South America.
It’s been known that pregnancy after breast cancer treatment, even for hormone receptor–positive disease, is safe overall, the team commented. However, there have been concerns about women who have BRCA mutations because of a lack of data.
The new findings “provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility” and are of “paramount importance for health care providers involved in counseling young patients,” said the researchers, led by Matteo Lambertini, MD, PhD, a medical oncologist at the University of Genoa, Italy.
The review was published in September in the Journal of Clinical Oncology.
The team reviewed reproductive outcomes among 1,252 women who were no older than 40 years when diagnosed with stage I-III BRCA-mutated invasive breast cancer between January 2000 and December 2012.
More than half (65%; n = 811) had BRCA1 mutations, 430 women (34%) had BRCA2 mutations, and 11 women had both.
Overall, 195 women became pregnant, at a median of 4.5 years after the breast cancer diagnosis and at a median age of 36 years.
The miscarriage rate was 10.3%, lower than expected in the general population.
Among the 150 patients who gave birth to 170 infants, delivery complications occurred in 13 of the 112 pregnancies with available data (11.6%), and congenital anomalies were seen in just 2 pregnancies (1.8%). This is a lower rate of anomalies than expected in the general population, the team noted. The rate of preterm delivery was 9.2%, similar to the general population.
There was no difference between the women who became pregnant and those who did not in either disease-free survival (adjusted hazard ratio, 0.87; P = .41) or overall survival (aHR, 0.88; P = .66), over a median follow-up of 8.3 years from diagnosis. In addition to BRCA mutations, the analysis adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, and breast surgery.
Over 80% of the subjects had ductal carcinoma, and over 90% of women were HER2-negative. More women in the pregnancy cohort had tumor diameters of 2 cm or less (47.2% vs. 40.9%) and a higher percentage had breast conserving surgery (59% vs. 45.9%).
Chemotherapy was administered to 95.3% of the subjects, most commonly anthracycline and taxane based, and more than 90% received endocrine therapy, most often tamoxifen alone among women who did not become pregnant and tamoxifen plus a luteinizing hormone-releasing hormone agonist among those who did. Endocrine therapy was shorter among women who became pregnant (median, 50 vs. 60 months; P < .001).
The findings held when 176 pregnant cases were matched to 528 nonpregnant controls for year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. However, disease-free survival was improved among pregnant women (HR, 0.71; P = .045) who were younger at diagnosis, with median ages of 31 years vs. 36 years (P < .001).
The study was funded by the Italian Association for Cancer Research, among others. Dr. Lambertini reports acting as a consultant for Roche and Novartis and as a speaker for Theramex, Takeda, Roche, Eli Lilly, Novartis. Several coauthors also report relationships with pharmaceutical companies, as detailed in the original article.
A version of this article originally appeared on Medscape.com.
said researchers reporting a review of more than 1,000 young women with breast cancer, mostly in Europe but also Israel and North and South America.
It’s been known that pregnancy after breast cancer treatment, even for hormone receptor–positive disease, is safe overall, the team commented. However, there have been concerns about women who have BRCA mutations because of a lack of data.
The new findings “provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility” and are of “paramount importance for health care providers involved in counseling young patients,” said the researchers, led by Matteo Lambertini, MD, PhD, a medical oncologist at the University of Genoa, Italy.
The review was published in September in the Journal of Clinical Oncology.
The team reviewed reproductive outcomes among 1,252 women who were no older than 40 years when diagnosed with stage I-III BRCA-mutated invasive breast cancer between January 2000 and December 2012.
More than half (65%; n = 811) had BRCA1 mutations, 430 women (34%) had BRCA2 mutations, and 11 women had both.
Overall, 195 women became pregnant, at a median of 4.5 years after the breast cancer diagnosis and at a median age of 36 years.
The miscarriage rate was 10.3%, lower than expected in the general population.
Among the 150 patients who gave birth to 170 infants, delivery complications occurred in 13 of the 112 pregnancies with available data (11.6%), and congenital anomalies were seen in just 2 pregnancies (1.8%). This is a lower rate of anomalies than expected in the general population, the team noted. The rate of preterm delivery was 9.2%, similar to the general population.
There was no difference between the women who became pregnant and those who did not in either disease-free survival (adjusted hazard ratio, 0.87; P = .41) or overall survival (aHR, 0.88; P = .66), over a median follow-up of 8.3 years from diagnosis. In addition to BRCA mutations, the analysis adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, and breast surgery.
Over 80% of the subjects had ductal carcinoma, and over 90% of women were HER2-negative. More women in the pregnancy cohort had tumor diameters of 2 cm or less (47.2% vs. 40.9%) and a higher percentage had breast conserving surgery (59% vs. 45.9%).
Chemotherapy was administered to 95.3% of the subjects, most commonly anthracycline and taxane based, and more than 90% received endocrine therapy, most often tamoxifen alone among women who did not become pregnant and tamoxifen plus a luteinizing hormone-releasing hormone agonist among those who did. Endocrine therapy was shorter among women who became pregnant (median, 50 vs. 60 months; P < .001).
The findings held when 176 pregnant cases were matched to 528 nonpregnant controls for year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. However, disease-free survival was improved among pregnant women (HR, 0.71; P = .045) who were younger at diagnosis, with median ages of 31 years vs. 36 years (P < .001).
The study was funded by the Italian Association for Cancer Research, among others. Dr. Lambertini reports acting as a consultant for Roche and Novartis and as a speaker for Theramex, Takeda, Roche, Eli Lilly, Novartis. Several coauthors also report relationships with pharmaceutical companies, as detailed in the original article.
A version of this article originally appeared on Medscape.com.
Immunotherapy for ALL: Roles emerge in R/R disease, MRD+ disease
“Most of the emerging therapies in ALL are immunotherapies that have really made an impact in the relapsed and refractory setting,” he said during a presentation at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress. “Another very exciting development is that these immunotherapies are now demonstrating efficacy and increased tolerability over chemotherapy in the minimal residual disease (MRD)-positive setting up front.”
Dr. Brown, director of the pediatric leukemia program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, focused on blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T-cell therapy for ALL, and explained the rationale for their use.
Why immunotherapy?
“It turns out that in normal B cell development there are a number of proteins that are expressed on the surface of B cells and these same proteins are expressed on the surface of many B-cell malignancies,” he said, noting that ALL is “probably the least differentiated of the B-lineage malignancies,” but the vast majority of ALL cases will express CD19 and CD22, and – in adults more often than pediatric patients – CD20.
These antigens make good targets for ALL therapy because they aren’t expressed on bone marrow stem cells or other tissues in the body.
“They really are specific for B cells,” he said, explaining that inotuzumab, a CD22 antibody drug conjugate (ADC), and blinatumomab, a bi-specific T cell-engaging antibody (BiTE) that targets CD19, are antibody-based immunotherapies, whereas CAR T-cell therapies are a separate category that can be single- or multi-antigen targeted.
Inotuzumab, blinatumomab, and CAR T cells
Inotuzumab targets the CD22 immunotoxin antigen via a T-cell independent process and is delivered as a once-weekly 1-hour infusion. It is approved for adult relapsed/refractory B-ALL. Blinatumomab binds CD19 on the surface of the tumor cells and CD3 on the surface of any T cell in the vicinity of the tumor cell.
“The recognition that blinatumomab allows between the tumor cell and the T cell is independent of the specificity of the T-cell receptor. It also does not require [major histocompatibility complex] class 1 or peptide antigens on the surface of the T cell,” he said, adding that it does, however, rely on a functional endogenous cytotoxic T-cell response, unlike inotuzumab. “It’s also very difficult technically to give because it’s given as a 28-day continuous IV infusion with bag changes required every 4-7 days.”
Blinatumomab is approved for adult and pediatric Philadelphia chromosome-negative relapsed/refractory B-cell precursor ALL and MRD-positive B-cell precursor ALL.
CAR T-cell therapy, an autologous immunotherapy, is “really kind of the pinnacle of technological advances in immunotherapy in that it combine three different modalities into one: cellular therapy, gene therapy, and immunotherapy,” he said, noting that the process of genetically engineering T cells to express a CAR is complex and costly and access is limited, but expanding with about 90 centers in the U.S. now providing CAR T-cell therapy.
Response rates with each of these therapies represent a paradigm shift in the relapsed/refractory ALL setting, Dr. Brown said.
Studies have shown complete remission (CR) and minimum residual disease (MRD)-negative CR rates of 81% and 78%, respectively, with inotuzumab, and 43% and 33%, respectively, with blinatumomab.
“This depth of remission was really not seen with prior salvage therapies,” he noted, but added that neither has shown significant durable improvement in overall survival (OS) rates.
CAR T-cell therapy, however, has the highest response rates, with tisagenlecleucel – which targets CD19 and was the first CAR T-cell therapy approved for refractory or second or greater relapse in patients up to age 26 years – showing 81% CR and MRD-negative CR rates and providing a durable survival advantage without subsequent therapy in 40-50% of patients.
“So CAR T cells can represent definitive therapy in a subset of patients,” Dr. Brown said. “One thing we’re struggling with is to be able to predict which patients those are, and there are some emerging biomarkers that may help us with that, but as of now it’s very difficult to predict which patients, when you’re treating them, are going to be in [that group].”
Toxicities and limitations
Cytokine release syndrome and neurotoxicity are the primary toxicities associated with both blinatumomab and tisagenlecleucel. Hepatotoxicity is a major concern with inotuzumab.
“This is particularly important because that hepatotoxicity appears to be primarily a problem in patients who receive inotuzumab either after or prior to hematopoietic stem cell transplant, and since this therapy does not represent definitive therapy and often is really a bridge to transplant, this ... can be a significant limitation to this product,” Dr. Brown said.
A limitation of CAR T cells is failure to manufacture the product, which occurs most often in very young and heavily pretreated patients in whom it can be difficult to obtain enough functional T cells to create the product. Failure to engraft or lack of persistence of the CAR T cells can also occur.
Endogenous or CAR T-cell exhaustion is another potential limitation with blinatumomab and CAR T-cell therapy, and antigen escape can occur with both therapies, as well.
Strategies are being investigated to overcome treatment challenges, Dr. Brown noted.
Examples include efforts to develop universal “off-the-shelf” allogeneic CAR T-cell products to address failure to manufacture, working on more co-stimulatory domains that may be more effective to promote engraftment and persistence, adding immune checkpoint inhibitors to therapy to combat endogenous or CAR T-cell exhaustion, and developing multi-antigen targeted approaches to overcome antigen escape, he said.
NCCN Treatment Guidelines
Based on the currently available data, the NCCN has included these immunotherapies in guidelines for both adolescent and young adult (AYA)/adult ALL and for pediatric ALL.
Each of the treatments is listed as an option to consider in both Philadelphia chromosome-positive and -negative AYA and adult patients under age 65 years. Additionally, blinatumomab is listed as an option for up-front treatment of MRD-positive Philadelphia chromosome-negative AYA patients and older patients.
Pediatric guidelines include blinatumomab and tisagenlecleucel as options for patients with MRD-positive disease after induction and for first relapse, and they include all three therapies as options in patients with multiple relapses or refractory disease, said Dr. Brown who chairs the NCCN Clinical Practice Guidelines panel for adult and pediatric ALL.
Treatment decision making
Asked by session moderator Ranjana H. Advani, MD, how to decide between the available immunotherapies, Dr. Brown said there is no one-size-fits-all answer.
“Is it availability, insurance coverage, the patient fits better with one therapy,” asked Dr. Advani, the Saul Rosenberg Professor of Lymphoma and the Physician Leader of the Lymphoma Clinical Care Program of Stanford Cancer Institute, Palo Alto, Calif.
“All of the above,” Dr. Brown said. “In 2020 with all these options available, we are a little bit spoiled for choice ... but every patient is an individual case and the risk -benefit ratios of all these therapies differ.”
An exception is that CAR T-cell therapy is a clear stand-out for the patient who isn’t transplant eligible, he noted, adding that CAR T cells “probably give that patient the best chance of survival.”
In a patient who could potentially go to transplant, selection is a bit more challenging, but given the risks associated with inotuzumab, blinatumomab is generally the preferred non-CAR T option, he said.
“It’s a complicated question, and the answer ... is [that it is] an individualized patient-by-patient decision,” he added.
Dr. Brown reported consulting, advisory board, or expert witness activity for Novartis Pharmaceuticals Corporation and Takeda Pharmaceuticals North America Inc.
“Most of the emerging therapies in ALL are immunotherapies that have really made an impact in the relapsed and refractory setting,” he said during a presentation at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress. “Another very exciting development is that these immunotherapies are now demonstrating efficacy and increased tolerability over chemotherapy in the minimal residual disease (MRD)-positive setting up front.”
Dr. Brown, director of the pediatric leukemia program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, focused on blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T-cell therapy for ALL, and explained the rationale for their use.
Why immunotherapy?
“It turns out that in normal B cell development there are a number of proteins that are expressed on the surface of B cells and these same proteins are expressed on the surface of many B-cell malignancies,” he said, noting that ALL is “probably the least differentiated of the B-lineage malignancies,” but the vast majority of ALL cases will express CD19 and CD22, and – in adults more often than pediatric patients – CD20.
These antigens make good targets for ALL therapy because they aren’t expressed on bone marrow stem cells or other tissues in the body.
“They really are specific for B cells,” he said, explaining that inotuzumab, a CD22 antibody drug conjugate (ADC), and blinatumomab, a bi-specific T cell-engaging antibody (BiTE) that targets CD19, are antibody-based immunotherapies, whereas CAR T-cell therapies are a separate category that can be single- or multi-antigen targeted.
Inotuzumab, blinatumomab, and CAR T cells
Inotuzumab targets the CD22 immunotoxin antigen via a T-cell independent process and is delivered as a once-weekly 1-hour infusion. It is approved for adult relapsed/refractory B-ALL. Blinatumomab binds CD19 on the surface of the tumor cells and CD3 on the surface of any T cell in the vicinity of the tumor cell.
“The recognition that blinatumomab allows between the tumor cell and the T cell is independent of the specificity of the T-cell receptor. It also does not require [major histocompatibility complex] class 1 or peptide antigens on the surface of the T cell,” he said, adding that it does, however, rely on a functional endogenous cytotoxic T-cell response, unlike inotuzumab. “It’s also very difficult technically to give because it’s given as a 28-day continuous IV infusion with bag changes required every 4-7 days.”
Blinatumomab is approved for adult and pediatric Philadelphia chromosome-negative relapsed/refractory B-cell precursor ALL and MRD-positive B-cell precursor ALL.
CAR T-cell therapy, an autologous immunotherapy, is “really kind of the pinnacle of technological advances in immunotherapy in that it combine three different modalities into one: cellular therapy, gene therapy, and immunotherapy,” he said, noting that the process of genetically engineering T cells to express a CAR is complex and costly and access is limited, but expanding with about 90 centers in the U.S. now providing CAR T-cell therapy.
Response rates with each of these therapies represent a paradigm shift in the relapsed/refractory ALL setting, Dr. Brown said.
Studies have shown complete remission (CR) and minimum residual disease (MRD)-negative CR rates of 81% and 78%, respectively, with inotuzumab, and 43% and 33%, respectively, with blinatumomab.
“This depth of remission was really not seen with prior salvage therapies,” he noted, but added that neither has shown significant durable improvement in overall survival (OS) rates.
CAR T-cell therapy, however, has the highest response rates, with tisagenlecleucel – which targets CD19 and was the first CAR T-cell therapy approved for refractory or second or greater relapse in patients up to age 26 years – showing 81% CR and MRD-negative CR rates and providing a durable survival advantage without subsequent therapy in 40-50% of patients.
“So CAR T cells can represent definitive therapy in a subset of patients,” Dr. Brown said. “One thing we’re struggling with is to be able to predict which patients those are, and there are some emerging biomarkers that may help us with that, but as of now it’s very difficult to predict which patients, when you’re treating them, are going to be in [that group].”
Toxicities and limitations
Cytokine release syndrome and neurotoxicity are the primary toxicities associated with both blinatumomab and tisagenlecleucel. Hepatotoxicity is a major concern with inotuzumab.
“This is particularly important because that hepatotoxicity appears to be primarily a problem in patients who receive inotuzumab either after or prior to hematopoietic stem cell transplant, and since this therapy does not represent definitive therapy and often is really a bridge to transplant, this ... can be a significant limitation to this product,” Dr. Brown said.
A limitation of CAR T cells is failure to manufacture the product, which occurs most often in very young and heavily pretreated patients in whom it can be difficult to obtain enough functional T cells to create the product. Failure to engraft or lack of persistence of the CAR T cells can also occur.
Endogenous or CAR T-cell exhaustion is another potential limitation with blinatumomab and CAR T-cell therapy, and antigen escape can occur with both therapies, as well.
Strategies are being investigated to overcome treatment challenges, Dr. Brown noted.
Examples include efforts to develop universal “off-the-shelf” allogeneic CAR T-cell products to address failure to manufacture, working on more co-stimulatory domains that may be more effective to promote engraftment and persistence, adding immune checkpoint inhibitors to therapy to combat endogenous or CAR T-cell exhaustion, and developing multi-antigen targeted approaches to overcome antigen escape, he said.
NCCN Treatment Guidelines
Based on the currently available data, the NCCN has included these immunotherapies in guidelines for both adolescent and young adult (AYA)/adult ALL and for pediatric ALL.
Each of the treatments is listed as an option to consider in both Philadelphia chromosome-positive and -negative AYA and adult patients under age 65 years. Additionally, blinatumomab is listed as an option for up-front treatment of MRD-positive Philadelphia chromosome-negative AYA patients and older patients.
Pediatric guidelines include blinatumomab and tisagenlecleucel as options for patients with MRD-positive disease after induction and for first relapse, and they include all three therapies as options in patients with multiple relapses or refractory disease, said Dr. Brown who chairs the NCCN Clinical Practice Guidelines panel for adult and pediatric ALL.
Treatment decision making
Asked by session moderator Ranjana H. Advani, MD, how to decide between the available immunotherapies, Dr. Brown said there is no one-size-fits-all answer.
“Is it availability, insurance coverage, the patient fits better with one therapy,” asked Dr. Advani, the Saul Rosenberg Professor of Lymphoma and the Physician Leader of the Lymphoma Clinical Care Program of Stanford Cancer Institute, Palo Alto, Calif.
“All of the above,” Dr. Brown said. “In 2020 with all these options available, we are a little bit spoiled for choice ... but every patient is an individual case and the risk -benefit ratios of all these therapies differ.”
An exception is that CAR T-cell therapy is a clear stand-out for the patient who isn’t transplant eligible, he noted, adding that CAR T cells “probably give that patient the best chance of survival.”
In a patient who could potentially go to transplant, selection is a bit more challenging, but given the risks associated with inotuzumab, blinatumomab is generally the preferred non-CAR T option, he said.
“It’s a complicated question, and the answer ... is [that it is] an individualized patient-by-patient decision,” he added.
Dr. Brown reported consulting, advisory board, or expert witness activity for Novartis Pharmaceuticals Corporation and Takeda Pharmaceuticals North America Inc.
“Most of the emerging therapies in ALL are immunotherapies that have really made an impact in the relapsed and refractory setting,” he said during a presentation at the National Comprehensive Cancer Network Hematologic Malignancies Annual Congress. “Another very exciting development is that these immunotherapies are now demonstrating efficacy and increased tolerability over chemotherapy in the minimal residual disease (MRD)-positive setting up front.”
Dr. Brown, director of the pediatric leukemia program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, focused on blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T-cell therapy for ALL, and explained the rationale for their use.
Why immunotherapy?
“It turns out that in normal B cell development there are a number of proteins that are expressed on the surface of B cells and these same proteins are expressed on the surface of many B-cell malignancies,” he said, noting that ALL is “probably the least differentiated of the B-lineage malignancies,” but the vast majority of ALL cases will express CD19 and CD22, and – in adults more often than pediatric patients – CD20.
These antigens make good targets for ALL therapy because they aren’t expressed on bone marrow stem cells or other tissues in the body.
“They really are specific for B cells,” he said, explaining that inotuzumab, a CD22 antibody drug conjugate (ADC), and blinatumomab, a bi-specific T cell-engaging antibody (BiTE) that targets CD19, are antibody-based immunotherapies, whereas CAR T-cell therapies are a separate category that can be single- or multi-antigen targeted.
Inotuzumab, blinatumomab, and CAR T cells
Inotuzumab targets the CD22 immunotoxin antigen via a T-cell independent process and is delivered as a once-weekly 1-hour infusion. It is approved for adult relapsed/refractory B-ALL. Blinatumomab binds CD19 on the surface of the tumor cells and CD3 on the surface of any T cell in the vicinity of the tumor cell.
“The recognition that blinatumomab allows between the tumor cell and the T cell is independent of the specificity of the T-cell receptor. It also does not require [major histocompatibility complex] class 1 or peptide antigens on the surface of the T cell,” he said, adding that it does, however, rely on a functional endogenous cytotoxic T-cell response, unlike inotuzumab. “It’s also very difficult technically to give because it’s given as a 28-day continuous IV infusion with bag changes required every 4-7 days.”
Blinatumomab is approved for adult and pediatric Philadelphia chromosome-negative relapsed/refractory B-cell precursor ALL and MRD-positive B-cell precursor ALL.
CAR T-cell therapy, an autologous immunotherapy, is “really kind of the pinnacle of technological advances in immunotherapy in that it combine three different modalities into one: cellular therapy, gene therapy, and immunotherapy,” he said, noting that the process of genetically engineering T cells to express a CAR is complex and costly and access is limited, but expanding with about 90 centers in the U.S. now providing CAR T-cell therapy.
Response rates with each of these therapies represent a paradigm shift in the relapsed/refractory ALL setting, Dr. Brown said.
Studies have shown complete remission (CR) and minimum residual disease (MRD)-negative CR rates of 81% and 78%, respectively, with inotuzumab, and 43% and 33%, respectively, with blinatumomab.
“This depth of remission was really not seen with prior salvage therapies,” he noted, but added that neither has shown significant durable improvement in overall survival (OS) rates.
CAR T-cell therapy, however, has the highest response rates, with tisagenlecleucel – which targets CD19 and was the first CAR T-cell therapy approved for refractory or second or greater relapse in patients up to age 26 years – showing 81% CR and MRD-negative CR rates and providing a durable survival advantage without subsequent therapy in 40-50% of patients.
“So CAR T cells can represent definitive therapy in a subset of patients,” Dr. Brown said. “One thing we’re struggling with is to be able to predict which patients those are, and there are some emerging biomarkers that may help us with that, but as of now it’s very difficult to predict which patients, when you’re treating them, are going to be in [that group].”
Toxicities and limitations
Cytokine release syndrome and neurotoxicity are the primary toxicities associated with both blinatumomab and tisagenlecleucel. Hepatotoxicity is a major concern with inotuzumab.
“This is particularly important because that hepatotoxicity appears to be primarily a problem in patients who receive inotuzumab either after or prior to hematopoietic stem cell transplant, and since this therapy does not represent definitive therapy and often is really a bridge to transplant, this ... can be a significant limitation to this product,” Dr. Brown said.
A limitation of CAR T cells is failure to manufacture the product, which occurs most often in very young and heavily pretreated patients in whom it can be difficult to obtain enough functional T cells to create the product. Failure to engraft or lack of persistence of the CAR T cells can also occur.
Endogenous or CAR T-cell exhaustion is another potential limitation with blinatumomab and CAR T-cell therapy, and antigen escape can occur with both therapies, as well.
Strategies are being investigated to overcome treatment challenges, Dr. Brown noted.
Examples include efforts to develop universal “off-the-shelf” allogeneic CAR T-cell products to address failure to manufacture, working on more co-stimulatory domains that may be more effective to promote engraftment and persistence, adding immune checkpoint inhibitors to therapy to combat endogenous or CAR T-cell exhaustion, and developing multi-antigen targeted approaches to overcome antigen escape, he said.
NCCN Treatment Guidelines
Based on the currently available data, the NCCN has included these immunotherapies in guidelines for both adolescent and young adult (AYA)/adult ALL and for pediatric ALL.
Each of the treatments is listed as an option to consider in both Philadelphia chromosome-positive and -negative AYA and adult patients under age 65 years. Additionally, blinatumomab is listed as an option for up-front treatment of MRD-positive Philadelphia chromosome-negative AYA patients and older patients.
Pediatric guidelines include blinatumomab and tisagenlecleucel as options for patients with MRD-positive disease after induction and for first relapse, and they include all three therapies as options in patients with multiple relapses or refractory disease, said Dr. Brown who chairs the NCCN Clinical Practice Guidelines panel for adult and pediatric ALL.
Treatment decision making
Asked by session moderator Ranjana H. Advani, MD, how to decide between the available immunotherapies, Dr. Brown said there is no one-size-fits-all answer.
“Is it availability, insurance coverage, the patient fits better with one therapy,” asked Dr. Advani, the Saul Rosenberg Professor of Lymphoma and the Physician Leader of the Lymphoma Clinical Care Program of Stanford Cancer Institute, Palo Alto, Calif.
“All of the above,” Dr. Brown said. “In 2020 with all these options available, we are a little bit spoiled for choice ... but every patient is an individual case and the risk -benefit ratios of all these therapies differ.”
An exception is that CAR T-cell therapy is a clear stand-out for the patient who isn’t transplant eligible, he noted, adding that CAR T cells “probably give that patient the best chance of survival.”
In a patient who could potentially go to transplant, selection is a bit more challenging, but given the risks associated with inotuzumab, blinatumomab is generally the preferred non-CAR T option, he said.
“It’s a complicated question, and the answer ... is [that it is] an individualized patient-by-patient decision,” he added.
Dr. Brown reported consulting, advisory board, or expert witness activity for Novartis Pharmaceuticals Corporation and Takeda Pharmaceuticals North America Inc.
FROM NCCN HEMATOLOGIC MALIGNANCIES
Liquid biopsy captures key NASH pathology hallmarks
Large-scale scanning of serum proteins offers a potential method for noninvasive screening and monitoring of patients with nonalcoholic steatohepatitis (NASH), the technique’s developers claim.
By scanning for about 5,000 proteins in nearly 3,000 samples from patients enrolled in studies from the Clinical Research Network in NASH (NASH CRN), Rachel Ostroff, PhD, and colleagues from SomaLogic in Boulder, Colo., created four protein models that mimic results of the major pathologic findings in liver tissue biopsy.
“Concurrent positive results from the protein models had performance characteristics of ‘rule-out’ tests for pathologists’ diagnosis of NASH. These tests may assist in new drug development and medical intervention decisions,” they wrote in a late-breaking poster presented at the virtual annual meeting of the American Association for the Study of Liver Diseases.
“There is no single noninvasive method that can accurately and simultaneously capture steatosis, inflammation, hepatocyte ballooning and fibrosis, the four major pathologic components assessed by biopsy. Each of these is relevant to the multiple mechanisms targeted in drug development for NASH,” they wrote.
To see whether large-scale protemoics could serve as an alternative to invasive liver biopsy for use in clinical trials or in longitudinal studies of NASH, they used a modified aptamer proteomics platform to scan for liver-related proteins. Aptamers are olignonucleotide or peptide molecules designed to home in on a specific target.
They scanned for approximately 5,000 proteins in 2,852 serum samples from 638 patients in a NASH CRN natural history cohort, and in patients enrolled in two NASH treatment trials: the PIVENS trial, which is evaluating pioglitazone versus vitamin E and placebo in nondiabetic patients, and the FLINT trial, which is comparing obeticholic acid with placebo. All of the patients in the natural history cohort and half of all patients in the clinical trial cohorts were included in the training sets, with the remaining half included in the validation set.
The accuracy of the models, as measured by the area under the curve (AUC) of receiver operating characteristics in the training and validation sets, respectively, were as follows:
- Fibrosis: AUC 0.92/0.85.
- Steatosis: AUC 0.95/0.79.
- Inflammation: AUC 0.83/0.72.
- Hepatocyte Ballooning: AUC 0.87/0.83.
“A concurrent positive score for steatosis, inflammation and ballooning predicted the biopsy diagnosis of NASH with an accuracy of 73%,” Ostroff and colleagues wrote.
They also found that model scores applied over time showed improvements in symptoms in the patients on active therapies in the clinical trials, compared with patients on placebo.
A specialist in liver pathology and nonalcoholic fatty liver disease who was not involved in the study said in an interview that she finds the results highly promising.
Impressive results
Elizabeth M. Brunt, MD, emeritus professor of pathology and immunology at Washington University in St. Louis, was a member of the NASH CRN when SomaLogic first proposed using the groups’ data for this study.
“I was impressed with them then, and I am very impressed with what they’re presenting here, and I can’t say that about all the noninvasive tests,” she said. “I think a lot of noninvasive tests are way over-simplifying what NASH is.”
She acknowledged that, although she spent much of her career performing liver biopsies, “you can’t biopsy every single patients who you suspect of having NASH, or certainly if you want to follow them over time – it’s unrealistic,” she said in an interview.
Although the protein scanning method cannot – and is not intended to – replace a well-conducted biopsy with the interpretation of a skilled pathologist, the proteins the company investigators identified can reflect the dynamic nature of liver disease and the liver’s ability to heal itself with a high degree of accuracy and hold promise for both screening patients and for monitoring responses to therapy, Dr. Brunt said.
The study was sponsored by SomaLogic. The authors are employees of the company. Dr. Brunt had no relevant disclosures.
SOURCE: Ostroff R et al. The Liver Disease Meeting Digital Experience, Abstract LP11
Large-scale scanning of serum proteins offers a potential method for noninvasive screening and monitoring of patients with nonalcoholic steatohepatitis (NASH), the technique’s developers claim.
By scanning for about 5,000 proteins in nearly 3,000 samples from patients enrolled in studies from the Clinical Research Network in NASH (NASH CRN), Rachel Ostroff, PhD, and colleagues from SomaLogic in Boulder, Colo., created four protein models that mimic results of the major pathologic findings in liver tissue biopsy.
“Concurrent positive results from the protein models had performance characteristics of ‘rule-out’ tests for pathologists’ diagnosis of NASH. These tests may assist in new drug development and medical intervention decisions,” they wrote in a late-breaking poster presented at the virtual annual meeting of the American Association for the Study of Liver Diseases.
“There is no single noninvasive method that can accurately and simultaneously capture steatosis, inflammation, hepatocyte ballooning and fibrosis, the four major pathologic components assessed by biopsy. Each of these is relevant to the multiple mechanisms targeted in drug development for NASH,” they wrote.
To see whether large-scale protemoics could serve as an alternative to invasive liver biopsy for use in clinical trials or in longitudinal studies of NASH, they used a modified aptamer proteomics platform to scan for liver-related proteins. Aptamers are olignonucleotide or peptide molecules designed to home in on a specific target.
They scanned for approximately 5,000 proteins in 2,852 serum samples from 638 patients in a NASH CRN natural history cohort, and in patients enrolled in two NASH treatment trials: the PIVENS trial, which is evaluating pioglitazone versus vitamin E and placebo in nondiabetic patients, and the FLINT trial, which is comparing obeticholic acid with placebo. All of the patients in the natural history cohort and half of all patients in the clinical trial cohorts were included in the training sets, with the remaining half included in the validation set.
The accuracy of the models, as measured by the area under the curve (AUC) of receiver operating characteristics in the training and validation sets, respectively, were as follows:
- Fibrosis: AUC 0.92/0.85.
- Steatosis: AUC 0.95/0.79.
- Inflammation: AUC 0.83/0.72.
- Hepatocyte Ballooning: AUC 0.87/0.83.
“A concurrent positive score for steatosis, inflammation and ballooning predicted the biopsy diagnosis of NASH with an accuracy of 73%,” Ostroff and colleagues wrote.
They also found that model scores applied over time showed improvements in symptoms in the patients on active therapies in the clinical trials, compared with patients on placebo.
A specialist in liver pathology and nonalcoholic fatty liver disease who was not involved in the study said in an interview that she finds the results highly promising.
Impressive results
Elizabeth M. Brunt, MD, emeritus professor of pathology and immunology at Washington University in St. Louis, was a member of the NASH CRN when SomaLogic first proposed using the groups’ data for this study.
“I was impressed with them then, and I am very impressed with what they’re presenting here, and I can’t say that about all the noninvasive tests,” she said. “I think a lot of noninvasive tests are way over-simplifying what NASH is.”
She acknowledged that, although she spent much of her career performing liver biopsies, “you can’t biopsy every single patients who you suspect of having NASH, or certainly if you want to follow them over time – it’s unrealistic,” she said in an interview.
Although the protein scanning method cannot – and is not intended to – replace a well-conducted biopsy with the interpretation of a skilled pathologist, the proteins the company investigators identified can reflect the dynamic nature of liver disease and the liver’s ability to heal itself with a high degree of accuracy and hold promise for both screening patients and for monitoring responses to therapy, Dr. Brunt said.
The study was sponsored by SomaLogic. The authors are employees of the company. Dr. Brunt had no relevant disclosures.
SOURCE: Ostroff R et al. The Liver Disease Meeting Digital Experience, Abstract LP11
Large-scale scanning of serum proteins offers a potential method for noninvasive screening and monitoring of patients with nonalcoholic steatohepatitis (NASH), the technique’s developers claim.
By scanning for about 5,000 proteins in nearly 3,000 samples from patients enrolled in studies from the Clinical Research Network in NASH (NASH CRN), Rachel Ostroff, PhD, and colleagues from SomaLogic in Boulder, Colo., created four protein models that mimic results of the major pathologic findings in liver tissue biopsy.
“Concurrent positive results from the protein models had performance characteristics of ‘rule-out’ tests for pathologists’ diagnosis of NASH. These tests may assist in new drug development and medical intervention decisions,” they wrote in a late-breaking poster presented at the virtual annual meeting of the American Association for the Study of Liver Diseases.
“There is no single noninvasive method that can accurately and simultaneously capture steatosis, inflammation, hepatocyte ballooning and fibrosis, the four major pathologic components assessed by biopsy. Each of these is relevant to the multiple mechanisms targeted in drug development for NASH,” they wrote.
To see whether large-scale protemoics could serve as an alternative to invasive liver biopsy for use in clinical trials or in longitudinal studies of NASH, they used a modified aptamer proteomics platform to scan for liver-related proteins. Aptamers are olignonucleotide or peptide molecules designed to home in on a specific target.
They scanned for approximately 5,000 proteins in 2,852 serum samples from 638 patients in a NASH CRN natural history cohort, and in patients enrolled in two NASH treatment trials: the PIVENS trial, which is evaluating pioglitazone versus vitamin E and placebo in nondiabetic patients, and the FLINT trial, which is comparing obeticholic acid with placebo. All of the patients in the natural history cohort and half of all patients in the clinical trial cohorts were included in the training sets, with the remaining half included in the validation set.
The accuracy of the models, as measured by the area under the curve (AUC) of receiver operating characteristics in the training and validation sets, respectively, were as follows:
- Fibrosis: AUC 0.92/0.85.
- Steatosis: AUC 0.95/0.79.
- Inflammation: AUC 0.83/0.72.
- Hepatocyte Ballooning: AUC 0.87/0.83.
“A concurrent positive score for steatosis, inflammation and ballooning predicted the biopsy diagnosis of NASH with an accuracy of 73%,” Ostroff and colleagues wrote.
They also found that model scores applied over time showed improvements in symptoms in the patients on active therapies in the clinical trials, compared with patients on placebo.
A specialist in liver pathology and nonalcoholic fatty liver disease who was not involved in the study said in an interview that she finds the results highly promising.
Impressive results
Elizabeth M. Brunt, MD, emeritus professor of pathology and immunology at Washington University in St. Louis, was a member of the NASH CRN when SomaLogic first proposed using the groups’ data for this study.
“I was impressed with them then, and I am very impressed with what they’re presenting here, and I can’t say that about all the noninvasive tests,” she said. “I think a lot of noninvasive tests are way over-simplifying what NASH is.”
She acknowledged that, although she spent much of her career performing liver biopsies, “you can’t biopsy every single patients who you suspect of having NASH, or certainly if you want to follow them over time – it’s unrealistic,” she said in an interview.
Although the protein scanning method cannot – and is not intended to – replace a well-conducted biopsy with the interpretation of a skilled pathologist, the proteins the company investigators identified can reflect the dynamic nature of liver disease and the liver’s ability to heal itself with a high degree of accuracy and hold promise for both screening patients and for monitoring responses to therapy, Dr. Brunt said.
The study was sponsored by SomaLogic. The authors are employees of the company. Dr. Brunt had no relevant disclosures.
SOURCE: Ostroff R et al. The Liver Disease Meeting Digital Experience, Abstract LP11
FROM THE LIVER DISEASE MEETING DIGITAL EXPERIENCE
In those with obesity, will losing weight cut COVID-19 severity?
As study after study piles up showing that those with obesity who become infected with SARS-CoV-2 are more likely to have severe disease, several experts gave advice for clinicians and patients during the virtual ObesityWeek Interactive 2020 meeting.
Pichamol Jirapinyo, MD, MPH, associate director of bariatric endoscopy at Brigham and Women’s Hospital, Boston, presented a study on those with obesity from New England hospitals which adds to the evidence that this is “a vulnerable population for COVID-19, like elderly or immunocompromised people,” Dr. Jirapinyo said in an interview.
These findings reinforce the need for clinicians to be “more aware of complications of obesity and refer earlier for treatment,” she added.
One audience member wanted to know if there are data showing whether people with a body mass index (BMI) above 35 kg/m2 who successfully lose weight subsequently have lower rates of hospitalization, ICU admission, and death if they become infected with SARS-CoV-2.
Dr. Jirapinyo said she is not aware of any such studies, but anecdotally, two of her patients who had endoscopic sleeve gastroplasty last fall (whose BMI dropped from about 38 to 30) and later became infected with COVID-19 had mild symptoms.
But David A. Kass, MD, director, Institute of CardioScience at Johns Hopkins University, Baltimore, cautioned that
“Whether this gets reversed by weight loss is an attractive hypothesis, but at this point, it’s still a hypothesis,” he stressed.
Changes to immunity, inflammatory signaling in obesity
“There must be north of 600 or more studies by now with this message that obesity – particularly severe obesity with a BMI of 35 and higher – is a strong independent risk factor for worse COVID-19 outcome,” Dr. Kass emphasized.
“[COVID-19] revealed to the public in a somewhat dramatic fashion that being very obese does put one at higher risk of this disease being more debilitating and even fatal,” he added.
“Before this pandemic, many viewed obesity as only a problem if you have the other associated diseases – hypertension, diabetes, heart disease, atherosclerosis, obstructive sleep apnea, etc.”
“What was not as appreciated is that marked obesity changes the body in various ways all by itself – altering metabolism, inflammatory signaling, immune surveillance, and responsiveness (including a less robust response to vaccines that has been written about as well).”
“This is a bit like having a genetic abnormality that makes you at higher risk for getting, say, cancer,” he explained.
“It is there, it is real, it has an impact – but it still does take other stresses to reveal the risk potential. COVID-19 did that with obesity,” he said.
Latest study on effect of obesity, diabetes on COVID-19 severity
The study presented by Dr. Jirapinyo and colleagues identified 1,680 patients with COVID-19 at six hospitals in March 2020. Patients were a mean age of 51 years, had a mean BMI of 29.4, and 39% had obesity. Patients who required hospitalization were more likely to have obesity (46% vs. 35%; P < .0001).
Obesity was a significant risk factor for hospitalization (odds ratio, 1.7), ICU admission (OR, 1.8), and intubation (OR, 1.8; all P < .001), after controlling for age, sex, cardiovascular, pulmonary, liver, and kidney disease, and cancer.
Compared with having a normal weight, having severe obesity was also associated with roughly threefold higher risks of ICU admission and intubation – after controlling for major comorbidities.
Pandemic focuses minds on obesity prevention, treatment
Naveed Sattar, MD, PhD, said in an interview that these latest findings are “highly consistent with other studies that point to excess adiposity as a potential modifiable risk factor for more severe COVID-19.”
It “also strongly suggests that if people are worried about their risk for COVID-19 and want to improve their chances of a milder outcome, then it is reasonable to encourage them to make sustainable lifestyle changes that may lessen weight and improve their fitness levels,” said Dr. Sattar, professor of metabolic medicine, University of Glasgow.
“But of course, the big worry,” he added, “is that many are putting on weight due to lockdowns, less commuting to work, anxiety, and overeating and drinking, etc., so that many are struggling, and especially those at highest risk, such as those living in more overcrowded housing, etc. By contrast, more advantaged folk may have an easier time to improve lifestyles.”
The pandemic highlights that “we need a concerted effort on obesity prevention and treatment,” according to Dr. Sattar.
“For years we have realized links between obesity and chronic cardiometabolic conditions,” he said, “but to think excess weight may also be detrimental to acute effects of a novel virus running amok in the world has focused minds on obesity in a manner not seen before.
“Whether these new painful learnings lead to a more determined effort in countries to improve the obesogenic environment or to place more resources into prevention and management of obesity remains to be seen,” he said.
Increased inquiries about bariatric surgery following COVID-19
Meanwhile, Matthew M. Hutter, MD, MPH, president, American Society for Metabolic and Bariatric Surgery, said in an interview that “COVID-19 and studies like this are now making many aware that obesity is not just a lifestyle choice or a cosmetic issue, but “a disease that needs to be taken seriously” and treated.
“Metabolic and bariatric surgery is a very safe and effective treatment for persons with obesity with a BMI >40 kg/m2 or BMI >35 kg/m2 and related diseases like diabetes, hypertension, sleep apnea, reflux, back pain, and many others,” added Dr. Hutter, who is also professor of surgery, Harvard Medical School, Boston.
“Recently, some metabolic and bariatric centers have seen an increase in patients considering surgery,” he said. “Some say that COVID-19 has made them realize they need to do something to be healthier.”
“Currently, less than 1% of those who could benefit from surgery are actually having” it each year, Dr. Hutter noted, “and I think there are many who should seriously consider surgery to be healthier, live longer, and live better.”
This article first appeared on Medscape.com.
As study after study piles up showing that those with obesity who become infected with SARS-CoV-2 are more likely to have severe disease, several experts gave advice for clinicians and patients during the virtual ObesityWeek Interactive 2020 meeting.
Pichamol Jirapinyo, MD, MPH, associate director of bariatric endoscopy at Brigham and Women’s Hospital, Boston, presented a study on those with obesity from New England hospitals which adds to the evidence that this is “a vulnerable population for COVID-19, like elderly or immunocompromised people,” Dr. Jirapinyo said in an interview.
These findings reinforce the need for clinicians to be “more aware of complications of obesity and refer earlier for treatment,” she added.
One audience member wanted to know if there are data showing whether people with a body mass index (BMI) above 35 kg/m2 who successfully lose weight subsequently have lower rates of hospitalization, ICU admission, and death if they become infected with SARS-CoV-2.
Dr. Jirapinyo said she is not aware of any such studies, but anecdotally, two of her patients who had endoscopic sleeve gastroplasty last fall (whose BMI dropped from about 38 to 30) and later became infected with COVID-19 had mild symptoms.
But David A. Kass, MD, director, Institute of CardioScience at Johns Hopkins University, Baltimore, cautioned that
“Whether this gets reversed by weight loss is an attractive hypothesis, but at this point, it’s still a hypothesis,” he stressed.
Changes to immunity, inflammatory signaling in obesity
“There must be north of 600 or more studies by now with this message that obesity – particularly severe obesity with a BMI of 35 and higher – is a strong independent risk factor for worse COVID-19 outcome,” Dr. Kass emphasized.
“[COVID-19] revealed to the public in a somewhat dramatic fashion that being very obese does put one at higher risk of this disease being more debilitating and even fatal,” he added.
“Before this pandemic, many viewed obesity as only a problem if you have the other associated diseases – hypertension, diabetes, heart disease, atherosclerosis, obstructive sleep apnea, etc.”
“What was not as appreciated is that marked obesity changes the body in various ways all by itself – altering metabolism, inflammatory signaling, immune surveillance, and responsiveness (including a less robust response to vaccines that has been written about as well).”
“This is a bit like having a genetic abnormality that makes you at higher risk for getting, say, cancer,” he explained.
“It is there, it is real, it has an impact – but it still does take other stresses to reveal the risk potential. COVID-19 did that with obesity,” he said.
Latest study on effect of obesity, diabetes on COVID-19 severity
The study presented by Dr. Jirapinyo and colleagues identified 1,680 patients with COVID-19 at six hospitals in March 2020. Patients were a mean age of 51 years, had a mean BMI of 29.4, and 39% had obesity. Patients who required hospitalization were more likely to have obesity (46% vs. 35%; P < .0001).
Obesity was a significant risk factor for hospitalization (odds ratio, 1.7), ICU admission (OR, 1.8), and intubation (OR, 1.8; all P < .001), after controlling for age, sex, cardiovascular, pulmonary, liver, and kidney disease, and cancer.
Compared with having a normal weight, having severe obesity was also associated with roughly threefold higher risks of ICU admission and intubation – after controlling for major comorbidities.
Pandemic focuses minds on obesity prevention, treatment
Naveed Sattar, MD, PhD, said in an interview that these latest findings are “highly consistent with other studies that point to excess adiposity as a potential modifiable risk factor for more severe COVID-19.”
It “also strongly suggests that if people are worried about their risk for COVID-19 and want to improve their chances of a milder outcome, then it is reasonable to encourage them to make sustainable lifestyle changes that may lessen weight and improve their fitness levels,” said Dr. Sattar, professor of metabolic medicine, University of Glasgow.
“But of course, the big worry,” he added, “is that many are putting on weight due to lockdowns, less commuting to work, anxiety, and overeating and drinking, etc., so that many are struggling, and especially those at highest risk, such as those living in more overcrowded housing, etc. By contrast, more advantaged folk may have an easier time to improve lifestyles.”
The pandemic highlights that “we need a concerted effort on obesity prevention and treatment,” according to Dr. Sattar.
“For years we have realized links between obesity and chronic cardiometabolic conditions,” he said, “but to think excess weight may also be detrimental to acute effects of a novel virus running amok in the world has focused minds on obesity in a manner not seen before.
“Whether these new painful learnings lead to a more determined effort in countries to improve the obesogenic environment or to place more resources into prevention and management of obesity remains to be seen,” he said.
Increased inquiries about bariatric surgery following COVID-19
Meanwhile, Matthew M. Hutter, MD, MPH, president, American Society for Metabolic and Bariatric Surgery, said in an interview that “COVID-19 and studies like this are now making many aware that obesity is not just a lifestyle choice or a cosmetic issue, but “a disease that needs to be taken seriously” and treated.
“Metabolic and bariatric surgery is a very safe and effective treatment for persons with obesity with a BMI >40 kg/m2 or BMI >35 kg/m2 and related diseases like diabetes, hypertension, sleep apnea, reflux, back pain, and many others,” added Dr. Hutter, who is also professor of surgery, Harvard Medical School, Boston.
“Recently, some metabolic and bariatric centers have seen an increase in patients considering surgery,” he said. “Some say that COVID-19 has made them realize they need to do something to be healthier.”
“Currently, less than 1% of those who could benefit from surgery are actually having” it each year, Dr. Hutter noted, “and I think there are many who should seriously consider surgery to be healthier, live longer, and live better.”
This article first appeared on Medscape.com.
As study after study piles up showing that those with obesity who become infected with SARS-CoV-2 are more likely to have severe disease, several experts gave advice for clinicians and patients during the virtual ObesityWeek Interactive 2020 meeting.
Pichamol Jirapinyo, MD, MPH, associate director of bariatric endoscopy at Brigham and Women’s Hospital, Boston, presented a study on those with obesity from New England hospitals which adds to the evidence that this is “a vulnerable population for COVID-19, like elderly or immunocompromised people,” Dr. Jirapinyo said in an interview.
These findings reinforce the need for clinicians to be “more aware of complications of obesity and refer earlier for treatment,” she added.
One audience member wanted to know if there are data showing whether people with a body mass index (BMI) above 35 kg/m2 who successfully lose weight subsequently have lower rates of hospitalization, ICU admission, and death if they become infected with SARS-CoV-2.
Dr. Jirapinyo said she is not aware of any such studies, but anecdotally, two of her patients who had endoscopic sleeve gastroplasty last fall (whose BMI dropped from about 38 to 30) and later became infected with COVID-19 had mild symptoms.
But David A. Kass, MD, director, Institute of CardioScience at Johns Hopkins University, Baltimore, cautioned that
“Whether this gets reversed by weight loss is an attractive hypothesis, but at this point, it’s still a hypothesis,” he stressed.
Changes to immunity, inflammatory signaling in obesity
“There must be north of 600 or more studies by now with this message that obesity – particularly severe obesity with a BMI of 35 and higher – is a strong independent risk factor for worse COVID-19 outcome,” Dr. Kass emphasized.
“[COVID-19] revealed to the public in a somewhat dramatic fashion that being very obese does put one at higher risk of this disease being more debilitating and even fatal,” he added.
“Before this pandemic, many viewed obesity as only a problem if you have the other associated diseases – hypertension, diabetes, heart disease, atherosclerosis, obstructive sleep apnea, etc.”
“What was not as appreciated is that marked obesity changes the body in various ways all by itself – altering metabolism, inflammatory signaling, immune surveillance, and responsiveness (including a less robust response to vaccines that has been written about as well).”
“This is a bit like having a genetic abnormality that makes you at higher risk for getting, say, cancer,” he explained.
“It is there, it is real, it has an impact – but it still does take other stresses to reveal the risk potential. COVID-19 did that with obesity,” he said.
Latest study on effect of obesity, diabetes on COVID-19 severity
The study presented by Dr. Jirapinyo and colleagues identified 1,680 patients with COVID-19 at six hospitals in March 2020. Patients were a mean age of 51 years, had a mean BMI of 29.4, and 39% had obesity. Patients who required hospitalization were more likely to have obesity (46% vs. 35%; P < .0001).
Obesity was a significant risk factor for hospitalization (odds ratio, 1.7), ICU admission (OR, 1.8), and intubation (OR, 1.8; all P < .001), after controlling for age, sex, cardiovascular, pulmonary, liver, and kidney disease, and cancer.
Compared with having a normal weight, having severe obesity was also associated with roughly threefold higher risks of ICU admission and intubation – after controlling for major comorbidities.
Pandemic focuses minds on obesity prevention, treatment
Naveed Sattar, MD, PhD, said in an interview that these latest findings are “highly consistent with other studies that point to excess adiposity as a potential modifiable risk factor for more severe COVID-19.”
It “also strongly suggests that if people are worried about their risk for COVID-19 and want to improve their chances of a milder outcome, then it is reasonable to encourage them to make sustainable lifestyle changes that may lessen weight and improve their fitness levels,” said Dr. Sattar, professor of metabolic medicine, University of Glasgow.
“But of course, the big worry,” he added, “is that many are putting on weight due to lockdowns, less commuting to work, anxiety, and overeating and drinking, etc., so that many are struggling, and especially those at highest risk, such as those living in more overcrowded housing, etc. By contrast, more advantaged folk may have an easier time to improve lifestyles.”
The pandemic highlights that “we need a concerted effort on obesity prevention and treatment,” according to Dr. Sattar.
“For years we have realized links between obesity and chronic cardiometabolic conditions,” he said, “but to think excess weight may also be detrimental to acute effects of a novel virus running amok in the world has focused minds on obesity in a manner not seen before.
“Whether these new painful learnings lead to a more determined effort in countries to improve the obesogenic environment or to place more resources into prevention and management of obesity remains to be seen,” he said.
Increased inquiries about bariatric surgery following COVID-19
Meanwhile, Matthew M. Hutter, MD, MPH, president, American Society for Metabolic and Bariatric Surgery, said in an interview that “COVID-19 and studies like this are now making many aware that obesity is not just a lifestyle choice or a cosmetic issue, but “a disease that needs to be taken seriously” and treated.
“Metabolic and bariatric surgery is a very safe and effective treatment for persons with obesity with a BMI >40 kg/m2 or BMI >35 kg/m2 and related diseases like diabetes, hypertension, sleep apnea, reflux, back pain, and many others,” added Dr. Hutter, who is also professor of surgery, Harvard Medical School, Boston.
“Recently, some metabolic and bariatric centers have seen an increase in patients considering surgery,” he said. “Some say that COVID-19 has made them realize they need to do something to be healthier.”
“Currently, less than 1% of those who could benefit from surgery are actually having” it each year, Dr. Hutter noted, “and I think there are many who should seriously consider surgery to be healthier, live longer, and live better.”
This article first appeared on Medscape.com.
'Tragic' milestone: 1 million children with COVID-19
The number of new cases soared in the past week as the United States exceeded 1 million children infected with the coronavirus, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
For the first time, the number of cases in children for the week ending Nov. 12 passed 100,000, and it didn’t stop until it reached 111,946, bringing the total for the pandemic to 1,039,464 reported cases in 49 states (New York is not reporting ages), the District of Columbia, New York City, and Guam, the AAP and the CHA said in their weekly COVID-19 update.
“As a pediatrician who has practiced medicine for over 3 decades, I find this number staggering and tragic. We haven’t seen a virus flash through our communities in this way since before we had vaccines for measles and polio,” AAP President Sally Goza, MD, said in a written statement.
The previous 1-week high of almost 74,000 cases came just last week, and that number had surpassed the previous week’s new high of 61,000. The number of cumulative child cases, meanwhile, has doubled since Sept. 3, when it was just over 513,000. Children now represent 11.5% of all COVID-19 cases since the start of the pandemic in the jurisdictions reporting age distribution, the AAP and CHA said.
For the week ending Nov. 12, COVID-19 cases children made up 14% of cases nationally, rising from 13% the week before and reversing a decline that started in mid-October, the AAP/CHA data show.
The two groups continue to note the rarity of severe illness in children, but the number of deaths nationally had its biggest 1-week increase since late July, as the total rose from 123 to 133 in the 42 states reporting such data by age, as well as New York City. The cumulative hospitalization rate for children decreased slightly in the past week and is now down to 1.6% in the 23 states (and NYC) with available data, the AAP and CHA said.
The AAP called on elected leaders to enact a national strategy to combat the spread of the virus and urged health authorities to do more to collect data on longer-term impacts on children.
We’re very concerned about how this will impact all children, including toddlers who are missing key educational opportunities, as well as adolescents who may be at higher risk for anxiety and depression,” Dr. Goza said.
The number of new cases soared in the past week as the United States exceeded 1 million children infected with the coronavirus, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
For the first time, the number of cases in children for the week ending Nov. 12 passed 100,000, and it didn’t stop until it reached 111,946, bringing the total for the pandemic to 1,039,464 reported cases in 49 states (New York is not reporting ages), the District of Columbia, New York City, and Guam, the AAP and the CHA said in their weekly COVID-19 update.
“As a pediatrician who has practiced medicine for over 3 decades, I find this number staggering and tragic. We haven’t seen a virus flash through our communities in this way since before we had vaccines for measles and polio,” AAP President Sally Goza, MD, said in a written statement.
The previous 1-week high of almost 74,000 cases came just last week, and that number had surpassed the previous week’s new high of 61,000. The number of cumulative child cases, meanwhile, has doubled since Sept. 3, when it was just over 513,000. Children now represent 11.5% of all COVID-19 cases since the start of the pandemic in the jurisdictions reporting age distribution, the AAP and CHA said.
For the week ending Nov. 12, COVID-19 cases children made up 14% of cases nationally, rising from 13% the week before and reversing a decline that started in mid-October, the AAP/CHA data show.
The two groups continue to note the rarity of severe illness in children, but the number of deaths nationally had its biggest 1-week increase since late July, as the total rose from 123 to 133 in the 42 states reporting such data by age, as well as New York City. The cumulative hospitalization rate for children decreased slightly in the past week and is now down to 1.6% in the 23 states (and NYC) with available data, the AAP and CHA said.
The AAP called on elected leaders to enact a national strategy to combat the spread of the virus and urged health authorities to do more to collect data on longer-term impacts on children.
We’re very concerned about how this will impact all children, including toddlers who are missing key educational opportunities, as well as adolescents who may be at higher risk for anxiety and depression,” Dr. Goza said.
The number of new cases soared in the past week as the United States exceeded 1 million children infected with the coronavirus, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
For the first time, the number of cases in children for the week ending Nov. 12 passed 100,000, and it didn’t stop until it reached 111,946, bringing the total for the pandemic to 1,039,464 reported cases in 49 states (New York is not reporting ages), the District of Columbia, New York City, and Guam, the AAP and the CHA said in their weekly COVID-19 update.
“As a pediatrician who has practiced medicine for over 3 decades, I find this number staggering and tragic. We haven’t seen a virus flash through our communities in this way since before we had vaccines for measles and polio,” AAP President Sally Goza, MD, said in a written statement.
The previous 1-week high of almost 74,000 cases came just last week, and that number had surpassed the previous week’s new high of 61,000. The number of cumulative child cases, meanwhile, has doubled since Sept. 3, when it was just over 513,000. Children now represent 11.5% of all COVID-19 cases since the start of the pandemic in the jurisdictions reporting age distribution, the AAP and CHA said.
For the week ending Nov. 12, COVID-19 cases children made up 14% of cases nationally, rising from 13% the week before and reversing a decline that started in mid-October, the AAP/CHA data show.
The two groups continue to note the rarity of severe illness in children, but the number of deaths nationally had its biggest 1-week increase since late July, as the total rose from 123 to 133 in the 42 states reporting such data by age, as well as New York City. The cumulative hospitalization rate for children decreased slightly in the past week and is now down to 1.6% in the 23 states (and NYC) with available data, the AAP and CHA said.
The AAP called on elected leaders to enact a national strategy to combat the spread of the virus and urged health authorities to do more to collect data on longer-term impacts on children.
We’re very concerned about how this will impact all children, including toddlers who are missing key educational opportunities, as well as adolescents who may be at higher risk for anxiety and depression,” Dr. Goza said.
New-onset AFib common but unrecognized in the month after cardiac surgery
One in five patients at elevated stroke risk who underwent cardiac surgery with no history of atrial fibrillation preoperatively or at discharge developed postoperative AFib documented on a continuous cardiac rhythm monitoring device within the first 30 days after leaving the hospital in the randomized SEARCH-AF trial.
“Postoperative atrial fibrillation after cardiac surgery is not confined to the hospitalization period per se. We believe that these data should help inform on clinical practice guidelines on monitoring for postoperative atrial fibrillation in such patients,” said Subodh Verma, MD, PhD, reporting the results at the virtual American Heart Association scientific sessions.
“Guidelines provide little or no direction on optimal monitoring post cardiac surgery, particularly if patients are in sinus rhythm at discharge,” the surgeon noted.
SEARCH-AF was an open-label, multicenter study that included 336 patients at elevated stroke risk with an average CHA2DS2-VASc score of 4, no history of preoperative AFib, and none more than briefly with resolution during hospitalization. They were randomized to 30 days of postdischarge continuous cardiac rhythm monitoring with Medtronic’s SEEQ device, to Icentia’s CardioSTAT device, or to usual care, with Holter monitoring at the discretion of the treating physicians.
The primary result was a cumulative duration of AFib or atrial flutter of 6 minutes or longer during that 30-day period. This outcome occurred in 19.6% of the enhanced cardiac monitoring group and 1.7% of usual-care controls. Thus, there is an ongoing persistent occult risk of AFib that typically goes unrecognized. This 10-fold difference in the incidence of postoperative AFib translated into an absolute 17.9% between-group difference and a number-needed-to-treat of 6.
The secondary outcome of a cumulative atrial fib/flutter burden of 6 hours or more during 30 days occurred in 8.6% of the continuously monitored group and none of the controls. A cumulative AFib/flutter burden of 24 hours or greater occurred in 3.1% of the enhanced cardiac monitoring group and zero controls. These are AFib burdens that in other studies have been linked to increased risks of stroke and death, said Dr. Verma, professor of cardiovascular surgery at the University of Toronto.
“From a clinical standpoint, what this trial tells me is for my patients being discharged home tomorrow from the hospital, where they haven’t had AFib and I haven’t initiated anticoagulation, I have a low threshold to monitor these patients and to watch for periods of sustained unrecognized atrial fibrillation,” the surgeon added.
Experts: Results won’t change guidelines
Discussant Ben Freedman, MBBS, PhD, noted that the U.S. Preventive Services Task Force has stated that there are insufficient data available to recommend ECG screening for AFib to prevent stroke. Before the task force can be convinced to recommend it and for payers to cover it, a number of key questions need to be answered. And the SEARCH-AF trial doesn’t provide those answers, said Dr. Freedman, professor of cardiology and deputy director of the Heart Research Institute at the University of Sydney.
First off, it’ll be necessary to know if the risk posed by screen-detected AFib, including postoperative AFib, is similar to that of clinical AFib. Next, it must be shown that this screen-detected postoperative AFib is actionable; that is, that a screening strategy to detect postoperative AFib arising after discharge and then treat with oral anticoagulants will actually prevent more strokes than with usual care. There are large studies underway addressing that question, including HEARTLINE, STROKESTOP, and SAFERGUARD-AF, he observed.
In an interview, Rod S. Passman, MD, who gave a state-of-the-art talk on AFib detection at the meeting and wasn’t involved in SEARCH-AF, said he doesn’t consider the results practice-changing.
“It’s not guideline-changing because you’ve only shown that more intensive monitoring finds more AFib. Guideline-changing would be that finding that AFib and doing something about it impacts hard outcomes, and we don’t have that data yet,” said Dr. Passman, an electrophysiologist who is director of the Center for Arrhythmia Research and professor of medicine and preventive medicine at Northwestern University, Chicago.
The SEARCH-AF trial was funded by the Heart and Stroke Foundation of Canada, Bristol Myers Squibb, Pfizer, and Boehringer Ingelheim. Dr. Verma reported having received speaker’s fees and/or research support from those and other pharmaceutical companies. Dr. Freedman disclosed having no financial conflicts.
One in five patients at elevated stroke risk who underwent cardiac surgery with no history of atrial fibrillation preoperatively or at discharge developed postoperative AFib documented on a continuous cardiac rhythm monitoring device within the first 30 days after leaving the hospital in the randomized SEARCH-AF trial.
“Postoperative atrial fibrillation after cardiac surgery is not confined to the hospitalization period per se. We believe that these data should help inform on clinical practice guidelines on monitoring for postoperative atrial fibrillation in such patients,” said Subodh Verma, MD, PhD, reporting the results at the virtual American Heart Association scientific sessions.
“Guidelines provide little or no direction on optimal monitoring post cardiac surgery, particularly if patients are in sinus rhythm at discharge,” the surgeon noted.
SEARCH-AF was an open-label, multicenter study that included 336 patients at elevated stroke risk with an average CHA2DS2-VASc score of 4, no history of preoperative AFib, and none more than briefly with resolution during hospitalization. They were randomized to 30 days of postdischarge continuous cardiac rhythm monitoring with Medtronic’s SEEQ device, to Icentia’s CardioSTAT device, or to usual care, with Holter monitoring at the discretion of the treating physicians.
The primary result was a cumulative duration of AFib or atrial flutter of 6 minutes or longer during that 30-day period. This outcome occurred in 19.6% of the enhanced cardiac monitoring group and 1.7% of usual-care controls. Thus, there is an ongoing persistent occult risk of AFib that typically goes unrecognized. This 10-fold difference in the incidence of postoperative AFib translated into an absolute 17.9% between-group difference and a number-needed-to-treat of 6.
The secondary outcome of a cumulative atrial fib/flutter burden of 6 hours or more during 30 days occurred in 8.6% of the continuously monitored group and none of the controls. A cumulative AFib/flutter burden of 24 hours or greater occurred in 3.1% of the enhanced cardiac monitoring group and zero controls. These are AFib burdens that in other studies have been linked to increased risks of stroke and death, said Dr. Verma, professor of cardiovascular surgery at the University of Toronto.
“From a clinical standpoint, what this trial tells me is for my patients being discharged home tomorrow from the hospital, where they haven’t had AFib and I haven’t initiated anticoagulation, I have a low threshold to monitor these patients and to watch for periods of sustained unrecognized atrial fibrillation,” the surgeon added.
Experts: Results won’t change guidelines
Discussant Ben Freedman, MBBS, PhD, noted that the U.S. Preventive Services Task Force has stated that there are insufficient data available to recommend ECG screening for AFib to prevent stroke. Before the task force can be convinced to recommend it and for payers to cover it, a number of key questions need to be answered. And the SEARCH-AF trial doesn’t provide those answers, said Dr. Freedman, professor of cardiology and deputy director of the Heart Research Institute at the University of Sydney.
First off, it’ll be necessary to know if the risk posed by screen-detected AFib, including postoperative AFib, is similar to that of clinical AFib. Next, it must be shown that this screen-detected postoperative AFib is actionable; that is, that a screening strategy to detect postoperative AFib arising after discharge and then treat with oral anticoagulants will actually prevent more strokes than with usual care. There are large studies underway addressing that question, including HEARTLINE, STROKESTOP, and SAFERGUARD-AF, he observed.
In an interview, Rod S. Passman, MD, who gave a state-of-the-art talk on AFib detection at the meeting and wasn’t involved in SEARCH-AF, said he doesn’t consider the results practice-changing.
“It’s not guideline-changing because you’ve only shown that more intensive monitoring finds more AFib. Guideline-changing would be that finding that AFib and doing something about it impacts hard outcomes, and we don’t have that data yet,” said Dr. Passman, an electrophysiologist who is director of the Center for Arrhythmia Research and professor of medicine and preventive medicine at Northwestern University, Chicago.
The SEARCH-AF trial was funded by the Heart and Stroke Foundation of Canada, Bristol Myers Squibb, Pfizer, and Boehringer Ingelheim. Dr. Verma reported having received speaker’s fees and/or research support from those and other pharmaceutical companies. Dr. Freedman disclosed having no financial conflicts.
One in five patients at elevated stroke risk who underwent cardiac surgery with no history of atrial fibrillation preoperatively or at discharge developed postoperative AFib documented on a continuous cardiac rhythm monitoring device within the first 30 days after leaving the hospital in the randomized SEARCH-AF trial.
“Postoperative atrial fibrillation after cardiac surgery is not confined to the hospitalization period per se. We believe that these data should help inform on clinical practice guidelines on monitoring for postoperative atrial fibrillation in such patients,” said Subodh Verma, MD, PhD, reporting the results at the virtual American Heart Association scientific sessions.
“Guidelines provide little or no direction on optimal monitoring post cardiac surgery, particularly if patients are in sinus rhythm at discharge,” the surgeon noted.
SEARCH-AF was an open-label, multicenter study that included 336 patients at elevated stroke risk with an average CHA2DS2-VASc score of 4, no history of preoperative AFib, and none more than briefly with resolution during hospitalization. They were randomized to 30 days of postdischarge continuous cardiac rhythm monitoring with Medtronic’s SEEQ device, to Icentia’s CardioSTAT device, or to usual care, with Holter monitoring at the discretion of the treating physicians.
The primary result was a cumulative duration of AFib or atrial flutter of 6 minutes or longer during that 30-day period. This outcome occurred in 19.6% of the enhanced cardiac monitoring group and 1.7% of usual-care controls. Thus, there is an ongoing persistent occult risk of AFib that typically goes unrecognized. This 10-fold difference in the incidence of postoperative AFib translated into an absolute 17.9% between-group difference and a number-needed-to-treat of 6.
The secondary outcome of a cumulative atrial fib/flutter burden of 6 hours or more during 30 days occurred in 8.6% of the continuously monitored group and none of the controls. A cumulative AFib/flutter burden of 24 hours or greater occurred in 3.1% of the enhanced cardiac monitoring group and zero controls. These are AFib burdens that in other studies have been linked to increased risks of stroke and death, said Dr. Verma, professor of cardiovascular surgery at the University of Toronto.
“From a clinical standpoint, what this trial tells me is for my patients being discharged home tomorrow from the hospital, where they haven’t had AFib and I haven’t initiated anticoagulation, I have a low threshold to monitor these patients and to watch for periods of sustained unrecognized atrial fibrillation,” the surgeon added.
Experts: Results won’t change guidelines
Discussant Ben Freedman, MBBS, PhD, noted that the U.S. Preventive Services Task Force has stated that there are insufficient data available to recommend ECG screening for AFib to prevent stroke. Before the task force can be convinced to recommend it and for payers to cover it, a number of key questions need to be answered. And the SEARCH-AF trial doesn’t provide those answers, said Dr. Freedman, professor of cardiology and deputy director of the Heart Research Institute at the University of Sydney.
First off, it’ll be necessary to know if the risk posed by screen-detected AFib, including postoperative AFib, is similar to that of clinical AFib. Next, it must be shown that this screen-detected postoperative AFib is actionable; that is, that a screening strategy to detect postoperative AFib arising after discharge and then treat with oral anticoagulants will actually prevent more strokes than with usual care. There are large studies underway addressing that question, including HEARTLINE, STROKESTOP, and SAFERGUARD-AF, he observed.
In an interview, Rod S. Passman, MD, who gave a state-of-the-art talk on AFib detection at the meeting and wasn’t involved in SEARCH-AF, said he doesn’t consider the results practice-changing.
“It’s not guideline-changing because you’ve only shown that more intensive monitoring finds more AFib. Guideline-changing would be that finding that AFib and doing something about it impacts hard outcomes, and we don’t have that data yet,” said Dr. Passman, an electrophysiologist who is director of the Center for Arrhythmia Research and professor of medicine and preventive medicine at Northwestern University, Chicago.
The SEARCH-AF trial was funded by the Heart and Stroke Foundation of Canada, Bristol Myers Squibb, Pfizer, and Boehringer Ingelheim. Dr. Verma reported having received speaker’s fees and/or research support from those and other pharmaceutical companies. Dr. Freedman disclosed having no financial conflicts.
FROM AHA 2020
The Road to HCV Elimination with Joseph Lim, MD
What are the largest factors creating barriers to hepatitis C virus (HCV) elimination?
Dr. Lim: In 2020 there remain important barriers to access to treatment because of the high cost of drugs used to eradicate HCV. There are still opportunities for us to interact with major payors to ensure adequate access, both with private commercial payers, as well as with Medicaid. We know very well that there are existing barriers that impact a significant proportion of patients, but if you look at data from the private sector, it turns out that we are doing pretty well; At least 80% of payers are covering direct-acting antiviral (DAA) medications with minimal restriction.
However, with Medicaid it is quite the reverse story; In about two-thirds of states, there are at least one or more restrictions based on the stage of their fibrosis, sobriety requirements for alcohol and drug use, and specialty providers to prescribe the medication, among others. Based on data from the National Viral Hepatitis Roundtable, it is clear that there are still many states where if you have mild disease, or recently used drugs or alcohol, or are in a rural area where you do not have access to a gastroenterologist or infectious disease specialist, you cannot get treatment. That is still a major concern for access to care.
When we think about elimination, eradication, and extinction of human diseases, HCV represents one of the few for which we actually have the tools to cure the condition permanently with a simple regimen of 1 to 3 pills per day for 2 or 3 months, with a cure rate exceeding 95%. This is truly remarkable and provides us with a historic opportunity to eradicate HCV in the United States and worldwide.
When we can diagnose HCV and offer treatment, we have a very good success rate—but therein lies the challenge. The key rate limiting steps to achieving elimination are found in ongoing deficits in the HCV care cascade, including screening, diagnosis, linkage to care, and treatment. We believe that right now only about 50% of affected persons have been diagnosed, and therefore much work remains to be done in the screening/diagnosis step of the care cascade if we are to achieve meaningful progress towards HCV elimination.
In that spirit, there have been important advances in terms of policy and legislation to support broader population-based screening. The CDC and US Preventive Services Task Force initially recommended that all baby boomers (those born between 1945 and 1965) should be screened for HCV, in addition to those with established risk factors. These include individuals who have used drugs, either through a nose or through the vein, had a blood transfusion before 1992, tattoos or body piercings, accidental needlestick exposures, or high risk sexual contacts, However, data show that risk factor-based screening simply does not work. It is difficult for clinicians to routinely ask sensitive questions about historical risk factors.
Despite the remarkable success in development of curative therapies for HCV, the rate of new incident HCV infections has not been going down—It has actually been doubling to tripling over the last 5 years. We now have what we call a bi-modal distribution of HCV, which includes baby boomers and a second younger group, between age 18 and 34. The primary route of transmission in this younger cohort is injection drug use, which is largely tied to the opiate epidemic.
It is in this context that within the last year, 4 different organizations—the CDC, the United States Preventive Services Task Force (USPSTF), the American Association for the Study of Liver Diseases (AASLD), and the Infectious Diseases Society of America (IDSA)—have expanded their guidance documents to now recommend one-time HCV screening in all adults age 18 or older plus all pregnant women regardless of age. This guidance replaces the old guidelines focused on baby boomers and individuals with risk factors. This represents a fundamental and consequential shift in US strategy to improve population-based screening.
There is also a sense that a treatment as prevention strategy can be particularly impactful in reducing spread among high-risk populations, especially in persons who inject drugs (PWID). The concept is that if you can effectively remove HCV in high-risk populations by treating active users, this may prevent spread of HCV to others who would otherwise be exposed. Although HCV treatment in patients with active drug use has historically been viewed with skepticism, and in fact remains an exclusion factor by some payors, DAA therapy in PWID is strongly recommended by the AASLD/IDSA guidelines and is increasingly embraced in both specialty and non-specialty (eg, methadone clinics, community health centers, prison clinics) settings.
Could you please elaborate more on the updated CDC guidelines and the impact that those are having in practice?
Dr. Lim: Although the revised screening guidelines by CDC and other organizations represent a critical step to promote awareness by clinicians regarding the compelling evidence to support universal HCV screening of all American adults, the reality is that just because there is a recommendation for it, does not mean that it will always be followed. Clinicians in primary care and specialty practices alike are already burdened by guideline fatigue, and an ever-growing list of mandates of standard clinical practice such as colon cancer screening, mammography, cholesterol checks, etc., and now all of this in the context of COVID-19. This further complicates the task of implementing HCV screening recommendations in real-world clinical practice.
New data published this year show that the screening rates among baby boomers have increased from approximately 10% to 20% since the original recommendations in 2014. Although this represents an important step in the right direction, it is clear there is significant room for improvement. It remains to be seen what impact this transition from birth cohort screening to universal screening of all Americans age 18 and older will have on our ability to identify previously unidentified infected persons.
In 2016 the World Health Organization (WHO) Global Health Sector Strategy called for the elimination of HCV as a major health threat by 2030. At the current rate of transmission, and considering all the barriers you mentioned that still exist, do you think that this is still a realistic timeframe? Is there any other action that physicians specifically maintain to help reach the goal?
Dr. Lim: WHO's vision was to eliminate hepatitis C by 2030 as defined as the following: 1) diagnose 90% of infected persons, 2) offer treatment to 80% of infected persons, and 3) reduce HCV-associated mortality by 65%.
Unfortunately, the United States is highly unlikely to meet this goal by 2030. Based on recently published models, only 3 of 50 states may have a chance at meeting the elimination target by that deadline. But as a country, we already know that is just simply not going to happen—unless there are dramatic changes in governmental and multi-stakeholder commitment.
Globally, there are an estimated 12 countries that are projected to achieve elimination by 2030. Some of the most prominent examples include Egypt, The Republic of Georgia, Australia, Italy, and Japan. The United States is not in this grouping, and in fact our current models suggest that we may not even achieve this goal by 2050.
There is much work that needs to be done to address some of the systemic and institutional infrastructure issues that will support effective implementation of screening, diagnosis, and linkage of care. Drug access—although that remains an important issue—is actually not the driving factor in terms of our inability to meet our targets. Within the United States, the Department of Health and Human Services has taken the lead on developing a US-based strategy. Although there has been strong language to articulate what is required and the intentionality to work on HCV elimination, this has not yet been associated with adequate funding at the federal level. Without this funding, we are destined to make only modest progress towards elimination targets within the short and intermediate timeframe. Despite these challenges, organizations such as the AASLD, CDC, National Viral Hepatitis Roundtable, World Hepatitis Alliance, and the Coalition for Global Hepatitis Elimination remain vocal advocates to secure necessary resources and will continue to lead US efforts to implement effective strategies on the road to viral hepatitis elimination. These organizations cannot fulfill this mission alone—each of us as clinicians play a vital role in carrying out CDC and USPSTF recommendations in our individual clinical settings to ensure broad-based screening and diagnosis, timely linkage to care, and antiviral treatment.
What are the largest factors creating barriers to hepatitis C virus (HCV) elimination?
Dr. Lim: In 2020 there remain important barriers to access to treatment because of the high cost of drugs used to eradicate HCV. There are still opportunities for us to interact with major payors to ensure adequate access, both with private commercial payers, as well as with Medicaid. We know very well that there are existing barriers that impact a significant proportion of patients, but if you look at data from the private sector, it turns out that we are doing pretty well; At least 80% of payers are covering direct-acting antiviral (DAA) medications with minimal restriction.
However, with Medicaid it is quite the reverse story; In about two-thirds of states, there are at least one or more restrictions based on the stage of their fibrosis, sobriety requirements for alcohol and drug use, and specialty providers to prescribe the medication, among others. Based on data from the National Viral Hepatitis Roundtable, it is clear that there are still many states where if you have mild disease, or recently used drugs or alcohol, or are in a rural area where you do not have access to a gastroenterologist or infectious disease specialist, you cannot get treatment. That is still a major concern for access to care.
When we think about elimination, eradication, and extinction of human diseases, HCV represents one of the few for which we actually have the tools to cure the condition permanently with a simple regimen of 1 to 3 pills per day for 2 or 3 months, with a cure rate exceeding 95%. This is truly remarkable and provides us with a historic opportunity to eradicate HCV in the United States and worldwide.
When we can diagnose HCV and offer treatment, we have a very good success rate—but therein lies the challenge. The key rate limiting steps to achieving elimination are found in ongoing deficits in the HCV care cascade, including screening, diagnosis, linkage to care, and treatment. We believe that right now only about 50% of affected persons have been diagnosed, and therefore much work remains to be done in the screening/diagnosis step of the care cascade if we are to achieve meaningful progress towards HCV elimination.
In that spirit, there have been important advances in terms of policy and legislation to support broader population-based screening. The CDC and US Preventive Services Task Force initially recommended that all baby boomers (those born between 1945 and 1965) should be screened for HCV, in addition to those with established risk factors. These include individuals who have used drugs, either through a nose or through the vein, had a blood transfusion before 1992, tattoos or body piercings, accidental needlestick exposures, or high risk sexual contacts, However, data show that risk factor-based screening simply does not work. It is difficult for clinicians to routinely ask sensitive questions about historical risk factors.
Despite the remarkable success in development of curative therapies for HCV, the rate of new incident HCV infections has not been going down—It has actually been doubling to tripling over the last 5 years. We now have what we call a bi-modal distribution of HCV, which includes baby boomers and a second younger group, between age 18 and 34. The primary route of transmission in this younger cohort is injection drug use, which is largely tied to the opiate epidemic.
It is in this context that within the last year, 4 different organizations—the CDC, the United States Preventive Services Task Force (USPSTF), the American Association for the Study of Liver Diseases (AASLD), and the Infectious Diseases Society of America (IDSA)—have expanded their guidance documents to now recommend one-time HCV screening in all adults age 18 or older plus all pregnant women regardless of age. This guidance replaces the old guidelines focused on baby boomers and individuals with risk factors. This represents a fundamental and consequential shift in US strategy to improve population-based screening.
There is also a sense that a treatment as prevention strategy can be particularly impactful in reducing spread among high-risk populations, especially in persons who inject drugs (PWID). The concept is that if you can effectively remove HCV in high-risk populations by treating active users, this may prevent spread of HCV to others who would otherwise be exposed. Although HCV treatment in patients with active drug use has historically been viewed with skepticism, and in fact remains an exclusion factor by some payors, DAA therapy in PWID is strongly recommended by the AASLD/IDSA guidelines and is increasingly embraced in both specialty and non-specialty (eg, methadone clinics, community health centers, prison clinics) settings.
Could you please elaborate more on the updated CDC guidelines and the impact that those are having in practice?
Dr. Lim: Although the revised screening guidelines by CDC and other organizations represent a critical step to promote awareness by clinicians regarding the compelling evidence to support universal HCV screening of all American adults, the reality is that just because there is a recommendation for it, does not mean that it will always be followed. Clinicians in primary care and specialty practices alike are already burdened by guideline fatigue, and an ever-growing list of mandates of standard clinical practice such as colon cancer screening, mammography, cholesterol checks, etc., and now all of this in the context of COVID-19. This further complicates the task of implementing HCV screening recommendations in real-world clinical practice.
New data published this year show that the screening rates among baby boomers have increased from approximately 10% to 20% since the original recommendations in 2014. Although this represents an important step in the right direction, it is clear there is significant room for improvement. It remains to be seen what impact this transition from birth cohort screening to universal screening of all Americans age 18 and older will have on our ability to identify previously unidentified infected persons.
In 2016 the World Health Organization (WHO) Global Health Sector Strategy called for the elimination of HCV as a major health threat by 2030. At the current rate of transmission, and considering all the barriers you mentioned that still exist, do you think that this is still a realistic timeframe? Is there any other action that physicians specifically maintain to help reach the goal?
Dr. Lim: WHO's vision was to eliminate hepatitis C by 2030 as defined as the following: 1) diagnose 90% of infected persons, 2) offer treatment to 80% of infected persons, and 3) reduce HCV-associated mortality by 65%.
Unfortunately, the United States is highly unlikely to meet this goal by 2030. Based on recently published models, only 3 of 50 states may have a chance at meeting the elimination target by that deadline. But as a country, we already know that is just simply not going to happen—unless there are dramatic changes in governmental and multi-stakeholder commitment.
Globally, there are an estimated 12 countries that are projected to achieve elimination by 2030. Some of the most prominent examples include Egypt, The Republic of Georgia, Australia, Italy, and Japan. The United States is not in this grouping, and in fact our current models suggest that we may not even achieve this goal by 2050.
There is much work that needs to be done to address some of the systemic and institutional infrastructure issues that will support effective implementation of screening, diagnosis, and linkage of care. Drug access—although that remains an important issue—is actually not the driving factor in terms of our inability to meet our targets. Within the United States, the Department of Health and Human Services has taken the lead on developing a US-based strategy. Although there has been strong language to articulate what is required and the intentionality to work on HCV elimination, this has not yet been associated with adequate funding at the federal level. Without this funding, we are destined to make only modest progress towards elimination targets within the short and intermediate timeframe. Despite these challenges, organizations such as the AASLD, CDC, National Viral Hepatitis Roundtable, World Hepatitis Alliance, and the Coalition for Global Hepatitis Elimination remain vocal advocates to secure necessary resources and will continue to lead US efforts to implement effective strategies on the road to viral hepatitis elimination. These organizations cannot fulfill this mission alone—each of us as clinicians play a vital role in carrying out CDC and USPSTF recommendations in our individual clinical settings to ensure broad-based screening and diagnosis, timely linkage to care, and antiviral treatment.
What are the largest factors creating barriers to hepatitis C virus (HCV) elimination?
Dr. Lim: In 2020 there remain important barriers to access to treatment because of the high cost of drugs used to eradicate HCV. There are still opportunities for us to interact with major payors to ensure adequate access, both with private commercial payers, as well as with Medicaid. We know very well that there are existing barriers that impact a significant proportion of patients, but if you look at data from the private sector, it turns out that we are doing pretty well; At least 80% of payers are covering direct-acting antiviral (DAA) medications with minimal restriction.
However, with Medicaid it is quite the reverse story; In about two-thirds of states, there are at least one or more restrictions based on the stage of their fibrosis, sobriety requirements for alcohol and drug use, and specialty providers to prescribe the medication, among others. Based on data from the National Viral Hepatitis Roundtable, it is clear that there are still many states where if you have mild disease, or recently used drugs or alcohol, or are in a rural area where you do not have access to a gastroenterologist or infectious disease specialist, you cannot get treatment. That is still a major concern for access to care.
When we think about elimination, eradication, and extinction of human diseases, HCV represents one of the few for which we actually have the tools to cure the condition permanently with a simple regimen of 1 to 3 pills per day for 2 or 3 months, with a cure rate exceeding 95%. This is truly remarkable and provides us with a historic opportunity to eradicate HCV in the United States and worldwide.
When we can diagnose HCV and offer treatment, we have a very good success rate—but therein lies the challenge. The key rate limiting steps to achieving elimination are found in ongoing deficits in the HCV care cascade, including screening, diagnosis, linkage to care, and treatment. We believe that right now only about 50% of affected persons have been diagnosed, and therefore much work remains to be done in the screening/diagnosis step of the care cascade if we are to achieve meaningful progress towards HCV elimination.
In that spirit, there have been important advances in terms of policy and legislation to support broader population-based screening. The CDC and US Preventive Services Task Force initially recommended that all baby boomers (those born between 1945 and 1965) should be screened for HCV, in addition to those with established risk factors. These include individuals who have used drugs, either through a nose or through the vein, had a blood transfusion before 1992, tattoos or body piercings, accidental needlestick exposures, or high risk sexual contacts, However, data show that risk factor-based screening simply does not work. It is difficult for clinicians to routinely ask sensitive questions about historical risk factors.
Despite the remarkable success in development of curative therapies for HCV, the rate of new incident HCV infections has not been going down—It has actually been doubling to tripling over the last 5 years. We now have what we call a bi-modal distribution of HCV, which includes baby boomers and a second younger group, between age 18 and 34. The primary route of transmission in this younger cohort is injection drug use, which is largely tied to the opiate epidemic.
It is in this context that within the last year, 4 different organizations—the CDC, the United States Preventive Services Task Force (USPSTF), the American Association for the Study of Liver Diseases (AASLD), and the Infectious Diseases Society of America (IDSA)—have expanded their guidance documents to now recommend one-time HCV screening in all adults age 18 or older plus all pregnant women regardless of age. This guidance replaces the old guidelines focused on baby boomers and individuals with risk factors. This represents a fundamental and consequential shift in US strategy to improve population-based screening.
There is also a sense that a treatment as prevention strategy can be particularly impactful in reducing spread among high-risk populations, especially in persons who inject drugs (PWID). The concept is that if you can effectively remove HCV in high-risk populations by treating active users, this may prevent spread of HCV to others who would otherwise be exposed. Although HCV treatment in patients with active drug use has historically been viewed with skepticism, and in fact remains an exclusion factor by some payors, DAA therapy in PWID is strongly recommended by the AASLD/IDSA guidelines and is increasingly embraced in both specialty and non-specialty (eg, methadone clinics, community health centers, prison clinics) settings.
Could you please elaborate more on the updated CDC guidelines and the impact that those are having in practice?
Dr. Lim: Although the revised screening guidelines by CDC and other organizations represent a critical step to promote awareness by clinicians regarding the compelling evidence to support universal HCV screening of all American adults, the reality is that just because there is a recommendation for it, does not mean that it will always be followed. Clinicians in primary care and specialty practices alike are already burdened by guideline fatigue, and an ever-growing list of mandates of standard clinical practice such as colon cancer screening, mammography, cholesterol checks, etc., and now all of this in the context of COVID-19. This further complicates the task of implementing HCV screening recommendations in real-world clinical practice.
New data published this year show that the screening rates among baby boomers have increased from approximately 10% to 20% since the original recommendations in 2014. Although this represents an important step in the right direction, it is clear there is significant room for improvement. It remains to be seen what impact this transition from birth cohort screening to universal screening of all Americans age 18 and older will have on our ability to identify previously unidentified infected persons.
In 2016 the World Health Organization (WHO) Global Health Sector Strategy called for the elimination of HCV as a major health threat by 2030. At the current rate of transmission, and considering all the barriers you mentioned that still exist, do you think that this is still a realistic timeframe? Is there any other action that physicians specifically maintain to help reach the goal?
Dr. Lim: WHO's vision was to eliminate hepatitis C by 2030 as defined as the following: 1) diagnose 90% of infected persons, 2) offer treatment to 80% of infected persons, and 3) reduce HCV-associated mortality by 65%.
Unfortunately, the United States is highly unlikely to meet this goal by 2030. Based on recently published models, only 3 of 50 states may have a chance at meeting the elimination target by that deadline. But as a country, we already know that is just simply not going to happen—unless there are dramatic changes in governmental and multi-stakeholder commitment.
Globally, there are an estimated 12 countries that are projected to achieve elimination by 2030. Some of the most prominent examples include Egypt, The Republic of Georgia, Australia, Italy, and Japan. The United States is not in this grouping, and in fact our current models suggest that we may not even achieve this goal by 2050.
There is much work that needs to be done to address some of the systemic and institutional infrastructure issues that will support effective implementation of screening, diagnosis, and linkage of care. Drug access—although that remains an important issue—is actually not the driving factor in terms of our inability to meet our targets. Within the United States, the Department of Health and Human Services has taken the lead on developing a US-based strategy. Although there has been strong language to articulate what is required and the intentionality to work on HCV elimination, this has not yet been associated with adequate funding at the federal level. Without this funding, we are destined to make only modest progress towards elimination targets within the short and intermediate timeframe. Despite these challenges, organizations such as the AASLD, CDC, National Viral Hepatitis Roundtable, World Hepatitis Alliance, and the Coalition for Global Hepatitis Elimination remain vocal advocates to secure necessary resources and will continue to lead US efforts to implement effective strategies on the road to viral hepatitis elimination. These organizations cannot fulfill this mission alone—each of us as clinicians play a vital role in carrying out CDC and USPSTF recommendations in our individual clinical settings to ensure broad-based screening and diagnosis, timely linkage to care, and antiviral treatment.