User login
Bringing you the latest news, research and reviews, exclusive interviews, podcasts, quizzes, and more.
div[contains(@class, 'header__large-screen')]
div[contains(@class, 'read-next-article')]
div[contains(@class, 'main-prefix')]
div[contains(@class, 'nav-primary')]
nav[contains(@class, 'nav-primary')]
section[contains(@class, 'footer-nav-section-wrapper')]
footer[@id='footer']
section[contains(@class, 'nav-hidden')]
div[contains(@class, 'ce-card-content')]
nav[contains(@class, 'nav-ce-stack')]
div[contains(@class, 'view-medstat-quiz-listing-panes')]
div[contains(@class, 'pane-article-sidebar-latest-news')]
Full-dose anticoagulation reduces need for life support in COVID-19
Full-dose anticoagulation was superior to low, prophylactic doses in reducing the need for vital organ support such as ventilation in moderately ill patients hospitalized for COVID-19, according to a report released Jan. 22 by the National Institutes of Health (NIH).
“This is a major advance for patients hospitalized with COVID. Full dose of anticoagulation in these non-ICU patients improved outcomes and there’s a trend toward a reduction in mortality,” Judith Hochman, MD, director of the Cardiovascular Clinical Research Center at NYU Langone Medical Center, New York, said in an interview.
“We have treatments that are improving outcomes but not as many that reduce mortality, so we’re hopeful when the full dataset comes in that will be confirmed,” she said.
The observation of increased rates of blood clots and inflammation among COVID-19 patients, which can lead to complications such as lung failure, heart attack, and stroke, has given rise to various anticoagulant treatment protocols and a need for randomized data on routinely administering increased doses of anticoagulation to hospitalized patients.
Today’s top-line findings come from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – examining the safety and efficacy of full-dose anticoagulation to treat moderately ill or critically ill adults hospitalized with COVID-19 compared with a lower dose typically used to prevent blood clots in hospitalized patients.
In December 2020, all three trials paused enrollment of the critically ill subgroup after results showed that full-dose anticoagulation started in the intensive care unit (ICU) was not beneficial and may have been harmful in some patients.
Moderately ill patients with COVID-19, defined as those who did not require ICU care or organ support, made up 80% of participants at enrollment in the three trials, Dr. Hochman said.
Among more than 1,000 moderately ill patients reviewed as of the data cut with the data safety monitoring board, full doses of low molecular weight or unfractionated heparin were superior to low prophylactic doses for the primary endpoint of need for ventilation or other organ supportive interventions at 21 days after randomization.
This met the predefined threshold for 99% probability of superiority and recruitment was stopped, Dr. Hochman reported. “Obviously safety figured into this decision. The risk/benefit ratio was very clear.”
The results do not pertain to patients with a previous indication for anticoagulation, who were excluded from the trials.
Data from an additional 1,000 patients will be reviewed and the data published sometime in the next 2-3 months, she said.
With large numbers of COVID-19 patients requiring hospitalization, the outcomes could help reduce the overload on intensive care units around the world, the NIH noted.
The results also highlight the critical role of timing in the course of COVID-19.
“We believe that full anticoagulation is effective early in the disease course,” Dr. Hochman said. “Based on the results so far from these three platform trials, those that were very, very sick at the time of enrollment really didn’t benefit and we needed to have caught them at an earlier stage.
“It’s possible that the people in the ICU are just different and the minute they get sick they need the ICU; so we haven’t clearly demonstrated this time course and when to intervene, but that’s the implication of the findings.”
The question of even earlier treatment is being examined in the partner ACTIV-4B trial, which is enrolling patients with COVID-19 illness not requiring hospitalization and randomizing them to the direct oral anticoagulant apixaban or aspirin or placebo.
“It’s a very important trial and we really want to get the message out that patients should volunteer for it,” said Dr. Hochman, principal investigator of the ACTIV-4 trial.
In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.
The REMAP-CAP, ACTIV-4, and ATTACC study platforms span five continents in more than 300 hospitals and are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (United Kingdom), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).
A version of this article first appeared on Medscape.com.
Full-dose anticoagulation was superior to low, prophylactic doses in reducing the need for vital organ support such as ventilation in moderately ill patients hospitalized for COVID-19, according to a report released Jan. 22 by the National Institutes of Health (NIH).
“This is a major advance for patients hospitalized with COVID. Full dose of anticoagulation in these non-ICU patients improved outcomes and there’s a trend toward a reduction in mortality,” Judith Hochman, MD, director of the Cardiovascular Clinical Research Center at NYU Langone Medical Center, New York, said in an interview.
“We have treatments that are improving outcomes but not as many that reduce mortality, so we’re hopeful when the full dataset comes in that will be confirmed,” she said.
The observation of increased rates of blood clots and inflammation among COVID-19 patients, which can lead to complications such as lung failure, heart attack, and stroke, has given rise to various anticoagulant treatment protocols and a need for randomized data on routinely administering increased doses of anticoagulation to hospitalized patients.
Today’s top-line findings come from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – examining the safety and efficacy of full-dose anticoagulation to treat moderately ill or critically ill adults hospitalized with COVID-19 compared with a lower dose typically used to prevent blood clots in hospitalized patients.
In December 2020, all three trials paused enrollment of the critically ill subgroup after results showed that full-dose anticoagulation started in the intensive care unit (ICU) was not beneficial and may have been harmful in some patients.
Moderately ill patients with COVID-19, defined as those who did not require ICU care or organ support, made up 80% of participants at enrollment in the three trials, Dr. Hochman said.
Among more than 1,000 moderately ill patients reviewed as of the data cut with the data safety monitoring board, full doses of low molecular weight or unfractionated heparin were superior to low prophylactic doses for the primary endpoint of need for ventilation or other organ supportive interventions at 21 days after randomization.
This met the predefined threshold for 99% probability of superiority and recruitment was stopped, Dr. Hochman reported. “Obviously safety figured into this decision. The risk/benefit ratio was very clear.”
The results do not pertain to patients with a previous indication for anticoagulation, who were excluded from the trials.
Data from an additional 1,000 patients will be reviewed and the data published sometime in the next 2-3 months, she said.
With large numbers of COVID-19 patients requiring hospitalization, the outcomes could help reduce the overload on intensive care units around the world, the NIH noted.
The results also highlight the critical role of timing in the course of COVID-19.
“We believe that full anticoagulation is effective early in the disease course,” Dr. Hochman said. “Based on the results so far from these three platform trials, those that were very, very sick at the time of enrollment really didn’t benefit and we needed to have caught them at an earlier stage.
“It’s possible that the people in the ICU are just different and the minute they get sick they need the ICU; so we haven’t clearly demonstrated this time course and when to intervene, but that’s the implication of the findings.”
The question of even earlier treatment is being examined in the partner ACTIV-4B trial, which is enrolling patients with COVID-19 illness not requiring hospitalization and randomizing them to the direct oral anticoagulant apixaban or aspirin or placebo.
“It’s a very important trial and we really want to get the message out that patients should volunteer for it,” said Dr. Hochman, principal investigator of the ACTIV-4 trial.
In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.
The REMAP-CAP, ACTIV-4, and ATTACC study platforms span five continents in more than 300 hospitals and are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (United Kingdom), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).
A version of this article first appeared on Medscape.com.
Full-dose anticoagulation was superior to low, prophylactic doses in reducing the need for vital organ support such as ventilation in moderately ill patients hospitalized for COVID-19, according to a report released Jan. 22 by the National Institutes of Health (NIH).
“This is a major advance for patients hospitalized with COVID. Full dose of anticoagulation in these non-ICU patients improved outcomes and there’s a trend toward a reduction in mortality,” Judith Hochman, MD, director of the Cardiovascular Clinical Research Center at NYU Langone Medical Center, New York, said in an interview.
“We have treatments that are improving outcomes but not as many that reduce mortality, so we’re hopeful when the full dataset comes in that will be confirmed,” she said.
The observation of increased rates of blood clots and inflammation among COVID-19 patients, which can lead to complications such as lung failure, heart attack, and stroke, has given rise to various anticoagulant treatment protocols and a need for randomized data on routinely administering increased doses of anticoagulation to hospitalized patients.
Today’s top-line findings come from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – examining the safety and efficacy of full-dose anticoagulation to treat moderately ill or critically ill adults hospitalized with COVID-19 compared with a lower dose typically used to prevent blood clots in hospitalized patients.
In December 2020, all three trials paused enrollment of the critically ill subgroup after results showed that full-dose anticoagulation started in the intensive care unit (ICU) was not beneficial and may have been harmful in some patients.
Moderately ill patients with COVID-19, defined as those who did not require ICU care or organ support, made up 80% of participants at enrollment in the three trials, Dr. Hochman said.
Among more than 1,000 moderately ill patients reviewed as of the data cut with the data safety monitoring board, full doses of low molecular weight or unfractionated heparin were superior to low prophylactic doses for the primary endpoint of need for ventilation or other organ supportive interventions at 21 days after randomization.
This met the predefined threshold for 99% probability of superiority and recruitment was stopped, Dr. Hochman reported. “Obviously safety figured into this decision. The risk/benefit ratio was very clear.”
The results do not pertain to patients with a previous indication for anticoagulation, who were excluded from the trials.
Data from an additional 1,000 patients will be reviewed and the data published sometime in the next 2-3 months, she said.
With large numbers of COVID-19 patients requiring hospitalization, the outcomes could help reduce the overload on intensive care units around the world, the NIH noted.
The results also highlight the critical role of timing in the course of COVID-19.
“We believe that full anticoagulation is effective early in the disease course,” Dr. Hochman said. “Based on the results so far from these three platform trials, those that were very, very sick at the time of enrollment really didn’t benefit and we needed to have caught them at an earlier stage.
“It’s possible that the people in the ICU are just different and the minute they get sick they need the ICU; so we haven’t clearly demonstrated this time course and when to intervene, but that’s the implication of the findings.”
The question of even earlier treatment is being examined in the partner ACTIV-4B trial, which is enrolling patients with COVID-19 illness not requiring hospitalization and randomizing them to the direct oral anticoagulant apixaban or aspirin or placebo.
“It’s a very important trial and we really want to get the message out that patients should volunteer for it,” said Dr. Hochman, principal investigator of the ACTIV-4 trial.
In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.
The REMAP-CAP, ACTIV-4, and ATTACC study platforms span five continents in more than 300 hospitals and are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (United Kingdom), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).
A version of this article first appeared on Medscape.com.
COVID-19 drives physician burnout for some specialties
Physician burnout remains at a critical level, at 42% overall – the same percentage as last year – but COVID-19 has changed the specialties hit hardest, according to Medscape’s Death by 1,000 Cuts: Physician Burnout & Suicide Report.
Critical care physicians now top the list of those experiencing burnout, at 51%, up from 44% last year, followed by rheumatologists (50%, up from 46%) and infectious disease specialists (49%, up from 45%). Forty-nine percent of urologists reported burnout, but that was a reduction from 54% last year.
Last year, the specialties burdened most by burnout were urology, neurology, nephrology, endocrinology, and family medicine.
Women hit particularly hard
Women in medicine traditionally have experienced higher levels of burnout than men, and the pandemic seems to have widened that gap, with the divide now at 51% for women and 36% for men.
“Many women physicians are in families with children at home,” said Carol Bernstein, MD, psychiatrist at Montefiore Medical Center, New York. “It’s already known that women assume more responsibilities in the home than do men. The pressures have increased during COVID-19 – having to be their child’s teacher during home schooling, no child care, and the grandparents can’t babysit. In addition, all doctors and nurses are worried about bringing the virus home to their families.”
Data were collected from Aug. 30 through Nov. 5, 2020. More than 12,000 physicians from 29 specialties responded.
For many, (79%) burnout has been building over years, but for some (21%), it started with the pandemic. Factors cited include lack of adequate personal protective equipment, grief from losing patients, watching families suffer, long hours, and difficult working conditions.
More than 70% of those who responded feel that burnout has had at least a moderate impact on their lives.
“One-tenth consider it severe enough to consider leaving medicine,” survey authors wrote, “an unexpected outcome after having spent so many years in training to become a physician.”
Tragically, an estimated 300 physicians each year in the United States are consumed by the struggle and take their own lives.
One percent have attempted suicide
In this survey, 13% of physicians had thoughts of suicide, and 1% have attempted it; 81% said they had no thoughts of suicide; and 5% preferred not to answer.
By specialty, obstetricians/gynecologists were most likely to have thoughts of suicide (19%), followed by orthopedists (18%) and otolaryngologists and plastic surgeons (17%).
“I yell all the time, I am angry and frustrated all the time. I think about quitting all the time,” said an internist who admitted having suicidal thoughts. “No one in my organization cares about doing the right things for patients as much as I do.”
Yet, many with such thoughts tell no one. By age group, 32% of millennials, 40% of generation X physicians, and 41% of baby boomer physicians who had had thoughts of suicide said they had told no one about those thoughts.
Fear of being reported to the medical board, fear of colleagues finding out, and other factors perpetuate a cycle of burnout and depression, and most don’t seek help.
Top reasons physicians listed for not seeking help for burnout and depression include “symptoms are not severe enough” (52%); “I can deal with without help from a professional” (46%); and feeling “too busy” (40%).
Administrative tasks fuel burnout
The top driver of burnout continues to be “too many administrative tasks.” This year, 58% put it at the top. The next highest categories (named by 37%) were “spending too many hours at work” and “lack of respect from administrators/employers, colleagues or staff.” Others mentioned lack of control or insufficient compensation and government regulations.
Notably, only 8% said stress from treating COVID-19 patients was the top driver.
An internist said, “I’m working 6 days a week, nights, weekends, holidays!”
A general surgeon said, “Being forced to see four patients an hour when complicated patients and procedures are involved” was the biggest contributor to burnout.
One physician in the survey summarized it: “It’s all of these causes; it’s death by 1,000 cuts.”
Exercise tops coping list
Asked how they cope with stress and burnout, physicians put exercise at the top (48%). Next was talking with family and friends (43%), though 43% said they cope by isolating themselves.
Drinking alcohol and overeating junk food were up slightly in the past year: for alcohol, 26%, up from 24%; for junk food, 35%, up from 33%.
The action respondents said would help most to reduce burnout was “increased compensation to avoid financial stress,” chosen by 45%. Next, at 42%, was “more manageable work and schedule,” followed by greater respect from employers, colleagues, and staff (39%).
Asked whether their workplace offered programs to reduce stress and/or burnout, almost half (47%) of physicians said no; 35% said yes; and 18% didn’t know.
Participation in such programs has been low. Almost half (42%) of physicians in this survey said they would be unlikely to attend such a program. Thirty percent they would be likely to participate; 28% said they were neutral on the idea.
“Anti-stress/burnout programs focus on individual approaches to much larger problems,” Wendy K. Dean, MD, psychiatrist and president of Moral Injury of Healthcare, said in an interview. “The programs offer temporary symptomatic relief rather than lasting systemic change. Many physicians are frustrated by these approaches.”
A study last year by the Mayo Clinic found that “the most efficacious strategy to alleviate physician burnout will target organization-directed changes rather than the level of the individual.”
A version of this article first appeared on Medscape.com.
Physician burnout remains at a critical level, at 42% overall – the same percentage as last year – but COVID-19 has changed the specialties hit hardest, according to Medscape’s Death by 1,000 Cuts: Physician Burnout & Suicide Report.
Critical care physicians now top the list of those experiencing burnout, at 51%, up from 44% last year, followed by rheumatologists (50%, up from 46%) and infectious disease specialists (49%, up from 45%). Forty-nine percent of urologists reported burnout, but that was a reduction from 54% last year.
Last year, the specialties burdened most by burnout were urology, neurology, nephrology, endocrinology, and family medicine.
Women hit particularly hard
Women in medicine traditionally have experienced higher levels of burnout than men, and the pandemic seems to have widened that gap, with the divide now at 51% for women and 36% for men.
“Many women physicians are in families with children at home,” said Carol Bernstein, MD, psychiatrist at Montefiore Medical Center, New York. “It’s already known that women assume more responsibilities in the home than do men. The pressures have increased during COVID-19 – having to be their child’s teacher during home schooling, no child care, and the grandparents can’t babysit. In addition, all doctors and nurses are worried about bringing the virus home to their families.”
Data were collected from Aug. 30 through Nov. 5, 2020. More than 12,000 physicians from 29 specialties responded.
For many, (79%) burnout has been building over years, but for some (21%), it started with the pandemic. Factors cited include lack of adequate personal protective equipment, grief from losing patients, watching families suffer, long hours, and difficult working conditions.
More than 70% of those who responded feel that burnout has had at least a moderate impact on their lives.
“One-tenth consider it severe enough to consider leaving medicine,” survey authors wrote, “an unexpected outcome after having spent so many years in training to become a physician.”
Tragically, an estimated 300 physicians each year in the United States are consumed by the struggle and take their own lives.
One percent have attempted suicide
In this survey, 13% of physicians had thoughts of suicide, and 1% have attempted it; 81% said they had no thoughts of suicide; and 5% preferred not to answer.
By specialty, obstetricians/gynecologists were most likely to have thoughts of suicide (19%), followed by orthopedists (18%) and otolaryngologists and plastic surgeons (17%).
“I yell all the time, I am angry and frustrated all the time. I think about quitting all the time,” said an internist who admitted having suicidal thoughts. “No one in my organization cares about doing the right things for patients as much as I do.”
Yet, many with such thoughts tell no one. By age group, 32% of millennials, 40% of generation X physicians, and 41% of baby boomer physicians who had had thoughts of suicide said they had told no one about those thoughts.
Fear of being reported to the medical board, fear of colleagues finding out, and other factors perpetuate a cycle of burnout and depression, and most don’t seek help.
Top reasons physicians listed for not seeking help for burnout and depression include “symptoms are not severe enough” (52%); “I can deal with without help from a professional” (46%); and feeling “too busy” (40%).
Administrative tasks fuel burnout
The top driver of burnout continues to be “too many administrative tasks.” This year, 58% put it at the top. The next highest categories (named by 37%) were “spending too many hours at work” and “lack of respect from administrators/employers, colleagues or staff.” Others mentioned lack of control or insufficient compensation and government regulations.
Notably, only 8% said stress from treating COVID-19 patients was the top driver.
An internist said, “I’m working 6 days a week, nights, weekends, holidays!”
A general surgeon said, “Being forced to see four patients an hour when complicated patients and procedures are involved” was the biggest contributor to burnout.
One physician in the survey summarized it: “It’s all of these causes; it’s death by 1,000 cuts.”
Exercise tops coping list
Asked how they cope with stress and burnout, physicians put exercise at the top (48%). Next was talking with family and friends (43%), though 43% said they cope by isolating themselves.
Drinking alcohol and overeating junk food were up slightly in the past year: for alcohol, 26%, up from 24%; for junk food, 35%, up from 33%.
The action respondents said would help most to reduce burnout was “increased compensation to avoid financial stress,” chosen by 45%. Next, at 42%, was “more manageable work and schedule,” followed by greater respect from employers, colleagues, and staff (39%).
Asked whether their workplace offered programs to reduce stress and/or burnout, almost half (47%) of physicians said no; 35% said yes; and 18% didn’t know.
Participation in such programs has been low. Almost half (42%) of physicians in this survey said they would be unlikely to attend such a program. Thirty percent they would be likely to participate; 28% said they were neutral on the idea.
“Anti-stress/burnout programs focus on individual approaches to much larger problems,” Wendy K. Dean, MD, psychiatrist and president of Moral Injury of Healthcare, said in an interview. “The programs offer temporary symptomatic relief rather than lasting systemic change. Many physicians are frustrated by these approaches.”
A study last year by the Mayo Clinic found that “the most efficacious strategy to alleviate physician burnout will target organization-directed changes rather than the level of the individual.”
A version of this article first appeared on Medscape.com.
Physician burnout remains at a critical level, at 42% overall – the same percentage as last year – but COVID-19 has changed the specialties hit hardest, according to Medscape’s Death by 1,000 Cuts: Physician Burnout & Suicide Report.
Critical care physicians now top the list of those experiencing burnout, at 51%, up from 44% last year, followed by rheumatologists (50%, up from 46%) and infectious disease specialists (49%, up from 45%). Forty-nine percent of urologists reported burnout, but that was a reduction from 54% last year.
Last year, the specialties burdened most by burnout were urology, neurology, nephrology, endocrinology, and family medicine.
Women hit particularly hard
Women in medicine traditionally have experienced higher levels of burnout than men, and the pandemic seems to have widened that gap, with the divide now at 51% for women and 36% for men.
“Many women physicians are in families with children at home,” said Carol Bernstein, MD, psychiatrist at Montefiore Medical Center, New York. “It’s already known that women assume more responsibilities in the home than do men. The pressures have increased during COVID-19 – having to be their child’s teacher during home schooling, no child care, and the grandparents can’t babysit. In addition, all doctors and nurses are worried about bringing the virus home to their families.”
Data were collected from Aug. 30 through Nov. 5, 2020. More than 12,000 physicians from 29 specialties responded.
For many, (79%) burnout has been building over years, but for some (21%), it started with the pandemic. Factors cited include lack of adequate personal protective equipment, grief from losing patients, watching families suffer, long hours, and difficult working conditions.
More than 70% of those who responded feel that burnout has had at least a moderate impact on their lives.
“One-tenth consider it severe enough to consider leaving medicine,” survey authors wrote, “an unexpected outcome after having spent so many years in training to become a physician.”
Tragically, an estimated 300 physicians each year in the United States are consumed by the struggle and take their own lives.
One percent have attempted suicide
In this survey, 13% of physicians had thoughts of suicide, and 1% have attempted it; 81% said they had no thoughts of suicide; and 5% preferred not to answer.
By specialty, obstetricians/gynecologists were most likely to have thoughts of suicide (19%), followed by orthopedists (18%) and otolaryngologists and plastic surgeons (17%).
“I yell all the time, I am angry and frustrated all the time. I think about quitting all the time,” said an internist who admitted having suicidal thoughts. “No one in my organization cares about doing the right things for patients as much as I do.”
Yet, many with such thoughts tell no one. By age group, 32% of millennials, 40% of generation X physicians, and 41% of baby boomer physicians who had had thoughts of suicide said they had told no one about those thoughts.
Fear of being reported to the medical board, fear of colleagues finding out, and other factors perpetuate a cycle of burnout and depression, and most don’t seek help.
Top reasons physicians listed for not seeking help for burnout and depression include “symptoms are not severe enough” (52%); “I can deal with without help from a professional” (46%); and feeling “too busy” (40%).
Administrative tasks fuel burnout
The top driver of burnout continues to be “too many administrative tasks.” This year, 58% put it at the top. The next highest categories (named by 37%) were “spending too many hours at work” and “lack of respect from administrators/employers, colleagues or staff.” Others mentioned lack of control or insufficient compensation and government regulations.
Notably, only 8% said stress from treating COVID-19 patients was the top driver.
An internist said, “I’m working 6 days a week, nights, weekends, holidays!”
A general surgeon said, “Being forced to see four patients an hour when complicated patients and procedures are involved” was the biggest contributor to burnout.
One physician in the survey summarized it: “It’s all of these causes; it’s death by 1,000 cuts.”
Exercise tops coping list
Asked how they cope with stress and burnout, physicians put exercise at the top (48%). Next was talking with family and friends (43%), though 43% said they cope by isolating themselves.
Drinking alcohol and overeating junk food were up slightly in the past year: for alcohol, 26%, up from 24%; for junk food, 35%, up from 33%.
The action respondents said would help most to reduce burnout was “increased compensation to avoid financial stress,” chosen by 45%. Next, at 42%, was “more manageable work and schedule,” followed by greater respect from employers, colleagues, and staff (39%).
Asked whether their workplace offered programs to reduce stress and/or burnout, almost half (47%) of physicians said no; 35% said yes; and 18% didn’t know.
Participation in such programs has been low. Almost half (42%) of physicians in this survey said they would be unlikely to attend such a program. Thirty percent they would be likely to participate; 28% said they were neutral on the idea.
“Anti-stress/burnout programs focus on individual approaches to much larger problems,” Wendy K. Dean, MD, psychiatrist and president of Moral Injury of Healthcare, said in an interview. “The programs offer temporary symptomatic relief rather than lasting systemic change. Many physicians are frustrated by these approaches.”
A study last year by the Mayo Clinic found that “the most efficacious strategy to alleviate physician burnout will target organization-directed changes rather than the level of the individual.”
A version of this article first appeared on Medscape.com.
What we know and don’t know about virus variants and vaccines
About 20 states across the country have detected the more transmissible B.1.1.7 SARS-CoV-2 variant to date. Given the unknowns of the emerging situation, experts with the Infectious Diseases Society of America addressed vaccine effectiveness, how well equipped the United States is to track new mutations, and shared their impressions of President Joe Biden’s COVID-19 executive orders.
One of the major concerns remains the ability of COVID-19 vaccines to work on new strains. “All of our vaccines target the spike protein and try to elicit neutralizing antibodies that bind to that protein,” Mirella Salvatore, MD, assistant professor of medicine and population health sciences at Weill Cornell Medicine, New York, said during an IDSA press briefing on Thursday.
The B.1.1.7 mutation occurs in the “very important” spike protein, a component of the SARS-CoV-2 virus necessary for binding, which allows the virus to enter cells, added Dr. Salvatore, an IDSA fellow.
The evidence suggests that SARS-CoV-2 should be capable of producing one or two mutations per month. However, the B.1.1.7 variant surprised investigators in the United Kingdom when they first discovered the strain had 17 mutations, Dr. Salvatore said.
It’s still unknown why this particular strain is more transmissible, but Dr. Salvatore speculated that the mutation gives the virus an advantage and increases binding, allowing it to enter cells more easily. She added that the mutations might have arisen among immunocompromised people infected with SARS-CoV-2, but “that is just a hypothesis.”
On a positive note, Kathryn M. Edwards, MD, another IDSA fellow, explained at the briefing that the existing vaccines target more than one location on the virus’ spike protein. Therefore, “if there is a mutation that changes one structure of the spike protein, there will be other areas where the binding can occur.”
This polyclonal response “is why the vaccine can still be effective against this virus,” added Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program and professor of pediatrics at Vanderbilt University, Nashville, Tenn.
Dr. Salvatore emphasized that, although the new variant is more transmissible, it doesn’t appear to be more lethal. “This might affect overall mortality but not for the individual who gets the infection.”
Staying one step ahead
When asked for assurance that COVID-19 vaccines will work against emerging variants, Dr. Edwards said, “It may be we will have to change the vaccine so it is more responsive to new variants, but at this point that does not seem to be the case.”
Should the vaccines require an update, the messenger RNA vaccines have an advantage – researchers can rapidly revise them. “All you need to do is put all the little nucleotides together,” Dr. Edwards said.
“A number of us are looking at how this will work, and we look to influenza,” she added. Dr. Edwards drew an analogy to choosing – and sometimes updating – the influenza strains each year for the annual flu vaccine. With appropriate funding, the same system could be replicated to address any evolving changes to SARS-CoV-2.
On funding, Dr. Salvatore said more money would be required to optimize the surveillance system for emerging strains in the United States.
“We actually have this system – there is a wonderful network that sequences the influenza strains,” she said. “The structure exists, we just need the funding.”
“The CDC is getting the system tooled up to get more viruses to be sequenced,” Dr. Edwards said.
Both experts praised the CDC for its website with up-to-date surveillance information on emerging strains of SARS-CoV-2.
President Biden’s backing of science
A reporter asked each infectious disease expert to share their impression of President Biden’s newly signed COVID-19 executive orders.
“The biggest takeaway is the role of science and the lessons we’ve learned from masks, handwashing, and distancing,” Dr. Edwards said. “We need to heed the advice ... [especially] with a variant that is more contagious.
“It is encouraging that science will be listened to – that is the overall message,” she added.
Dr. Salvatore agreed, saying that the orders give “the feeling that we can now act by following science.”
“We have plenty of papers that show the effectiveness of masking,” for example, she said. Dr. Salvatore acknowledged that there are “a lot of contrasting ideas about masking” across the United States but stressed their importance.
“We should follow measures that we know work,” she said.
Both experts said more research is needed to stay ahead of this evolving scenario. “We still need a lot of basic science showing how this virus replicates in the cell,” Dr. Salvatore said. “We need to really characterize all these mutations and their functions.”
“We need to be concerned, do follow-up studies,” she added, “but we don’t need to panic.”
This article was based on an Infectious Diseases Society of America Media Briefing on Jan. 21, 2021. Dr. Salvatore disclosed that she is a site principal investigator on a study from Verily Life Sciences/Brin Foundation on Predictors of Severe COVID-19 Outcomes and principal investigator for an investigator-initiated study sponsored by Genentech on combination therapy in influenza. Dr. Edwards disclosed National Institutes of Health and Centers for Disease Control and Prevention grants; consulting for Bionet and IBM; and being a member of data safety and monitoring committees for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, and Merck.
A version of this article first appeared on Medscape.com.
About 20 states across the country have detected the more transmissible B.1.1.7 SARS-CoV-2 variant to date. Given the unknowns of the emerging situation, experts with the Infectious Diseases Society of America addressed vaccine effectiveness, how well equipped the United States is to track new mutations, and shared their impressions of President Joe Biden’s COVID-19 executive orders.
One of the major concerns remains the ability of COVID-19 vaccines to work on new strains. “All of our vaccines target the spike protein and try to elicit neutralizing antibodies that bind to that protein,” Mirella Salvatore, MD, assistant professor of medicine and population health sciences at Weill Cornell Medicine, New York, said during an IDSA press briefing on Thursday.
The B.1.1.7 mutation occurs in the “very important” spike protein, a component of the SARS-CoV-2 virus necessary for binding, which allows the virus to enter cells, added Dr. Salvatore, an IDSA fellow.
The evidence suggests that SARS-CoV-2 should be capable of producing one or two mutations per month. However, the B.1.1.7 variant surprised investigators in the United Kingdom when they first discovered the strain had 17 mutations, Dr. Salvatore said.
It’s still unknown why this particular strain is more transmissible, but Dr. Salvatore speculated that the mutation gives the virus an advantage and increases binding, allowing it to enter cells more easily. She added that the mutations might have arisen among immunocompromised people infected with SARS-CoV-2, but “that is just a hypothesis.”
On a positive note, Kathryn M. Edwards, MD, another IDSA fellow, explained at the briefing that the existing vaccines target more than one location on the virus’ spike protein. Therefore, “if there is a mutation that changes one structure of the spike protein, there will be other areas where the binding can occur.”
This polyclonal response “is why the vaccine can still be effective against this virus,” added Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program and professor of pediatrics at Vanderbilt University, Nashville, Tenn.
Dr. Salvatore emphasized that, although the new variant is more transmissible, it doesn’t appear to be more lethal. “This might affect overall mortality but not for the individual who gets the infection.”
Staying one step ahead
When asked for assurance that COVID-19 vaccines will work against emerging variants, Dr. Edwards said, “It may be we will have to change the vaccine so it is more responsive to new variants, but at this point that does not seem to be the case.”
Should the vaccines require an update, the messenger RNA vaccines have an advantage – researchers can rapidly revise them. “All you need to do is put all the little nucleotides together,” Dr. Edwards said.
“A number of us are looking at how this will work, and we look to influenza,” she added. Dr. Edwards drew an analogy to choosing – and sometimes updating – the influenza strains each year for the annual flu vaccine. With appropriate funding, the same system could be replicated to address any evolving changes to SARS-CoV-2.
On funding, Dr. Salvatore said more money would be required to optimize the surveillance system for emerging strains in the United States.
“We actually have this system – there is a wonderful network that sequences the influenza strains,” she said. “The structure exists, we just need the funding.”
“The CDC is getting the system tooled up to get more viruses to be sequenced,” Dr. Edwards said.
Both experts praised the CDC for its website with up-to-date surveillance information on emerging strains of SARS-CoV-2.
President Biden’s backing of science
A reporter asked each infectious disease expert to share their impression of President Biden’s newly signed COVID-19 executive orders.
“The biggest takeaway is the role of science and the lessons we’ve learned from masks, handwashing, and distancing,” Dr. Edwards said. “We need to heed the advice ... [especially] with a variant that is more contagious.
“It is encouraging that science will be listened to – that is the overall message,” she added.
Dr. Salvatore agreed, saying that the orders give “the feeling that we can now act by following science.”
“We have plenty of papers that show the effectiveness of masking,” for example, she said. Dr. Salvatore acknowledged that there are “a lot of contrasting ideas about masking” across the United States but stressed their importance.
“We should follow measures that we know work,” she said.
Both experts said more research is needed to stay ahead of this evolving scenario. “We still need a lot of basic science showing how this virus replicates in the cell,” Dr. Salvatore said. “We need to really characterize all these mutations and their functions.”
“We need to be concerned, do follow-up studies,” she added, “but we don’t need to panic.”
This article was based on an Infectious Diseases Society of America Media Briefing on Jan. 21, 2021. Dr. Salvatore disclosed that she is a site principal investigator on a study from Verily Life Sciences/Brin Foundation on Predictors of Severe COVID-19 Outcomes and principal investigator for an investigator-initiated study sponsored by Genentech on combination therapy in influenza. Dr. Edwards disclosed National Institutes of Health and Centers for Disease Control and Prevention grants; consulting for Bionet and IBM; and being a member of data safety and monitoring committees for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, and Merck.
A version of this article first appeared on Medscape.com.
About 20 states across the country have detected the more transmissible B.1.1.7 SARS-CoV-2 variant to date. Given the unknowns of the emerging situation, experts with the Infectious Diseases Society of America addressed vaccine effectiveness, how well equipped the United States is to track new mutations, and shared their impressions of President Joe Biden’s COVID-19 executive orders.
One of the major concerns remains the ability of COVID-19 vaccines to work on new strains. “All of our vaccines target the spike protein and try to elicit neutralizing antibodies that bind to that protein,” Mirella Salvatore, MD, assistant professor of medicine and population health sciences at Weill Cornell Medicine, New York, said during an IDSA press briefing on Thursday.
The B.1.1.7 mutation occurs in the “very important” spike protein, a component of the SARS-CoV-2 virus necessary for binding, which allows the virus to enter cells, added Dr. Salvatore, an IDSA fellow.
The evidence suggests that SARS-CoV-2 should be capable of producing one or two mutations per month. However, the B.1.1.7 variant surprised investigators in the United Kingdom when they first discovered the strain had 17 mutations, Dr. Salvatore said.
It’s still unknown why this particular strain is more transmissible, but Dr. Salvatore speculated that the mutation gives the virus an advantage and increases binding, allowing it to enter cells more easily. She added that the mutations might have arisen among immunocompromised people infected with SARS-CoV-2, but “that is just a hypothesis.”
On a positive note, Kathryn M. Edwards, MD, another IDSA fellow, explained at the briefing that the existing vaccines target more than one location on the virus’ spike protein. Therefore, “if there is a mutation that changes one structure of the spike protein, there will be other areas where the binding can occur.”
This polyclonal response “is why the vaccine can still be effective against this virus,” added Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program and professor of pediatrics at Vanderbilt University, Nashville, Tenn.
Dr. Salvatore emphasized that, although the new variant is more transmissible, it doesn’t appear to be more lethal. “This might affect overall mortality but not for the individual who gets the infection.”
Staying one step ahead
When asked for assurance that COVID-19 vaccines will work against emerging variants, Dr. Edwards said, “It may be we will have to change the vaccine so it is more responsive to new variants, but at this point that does not seem to be the case.”
Should the vaccines require an update, the messenger RNA vaccines have an advantage – researchers can rapidly revise them. “All you need to do is put all the little nucleotides together,” Dr. Edwards said.
“A number of us are looking at how this will work, and we look to influenza,” she added. Dr. Edwards drew an analogy to choosing – and sometimes updating – the influenza strains each year for the annual flu vaccine. With appropriate funding, the same system could be replicated to address any evolving changes to SARS-CoV-2.
On funding, Dr. Salvatore said more money would be required to optimize the surveillance system for emerging strains in the United States.
“We actually have this system – there is a wonderful network that sequences the influenza strains,” she said. “The structure exists, we just need the funding.”
“The CDC is getting the system tooled up to get more viruses to be sequenced,” Dr. Edwards said.
Both experts praised the CDC for its website with up-to-date surveillance information on emerging strains of SARS-CoV-2.
President Biden’s backing of science
A reporter asked each infectious disease expert to share their impression of President Biden’s newly signed COVID-19 executive orders.
“The biggest takeaway is the role of science and the lessons we’ve learned from masks, handwashing, and distancing,” Dr. Edwards said. “We need to heed the advice ... [especially] with a variant that is more contagious.
“It is encouraging that science will be listened to – that is the overall message,” she added.
Dr. Salvatore agreed, saying that the orders give “the feeling that we can now act by following science.”
“We have plenty of papers that show the effectiveness of masking,” for example, she said. Dr. Salvatore acknowledged that there are “a lot of contrasting ideas about masking” across the United States but stressed their importance.
“We should follow measures that we know work,” she said.
Both experts said more research is needed to stay ahead of this evolving scenario. “We still need a lot of basic science showing how this virus replicates in the cell,” Dr. Salvatore said. “We need to really characterize all these mutations and their functions.”
“We need to be concerned, do follow-up studies,” she added, “but we don’t need to panic.”
This article was based on an Infectious Diseases Society of America Media Briefing on Jan. 21, 2021. Dr. Salvatore disclosed that she is a site principal investigator on a study from Verily Life Sciences/Brin Foundation on Predictors of Severe COVID-19 Outcomes and principal investigator for an investigator-initiated study sponsored by Genentech on combination therapy in influenza. Dr. Edwards disclosed National Institutes of Health and Centers for Disease Control and Prevention grants; consulting for Bionet and IBM; and being a member of data safety and monitoring committees for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, and Merck.
A version of this article first appeared on Medscape.com.
Coronasomnia: Pervasive sleeplessness, self-medicating raise concerns of sleep experts
Among the many losses suffered by millions worldwide during the COVID-19 pandemic, the loss of sleep may be the most widespread, with potentially long-lasting, negative consequences on physical, mental, and emotional health, sleep researchers have found.
Results from multiple studies and surveys conducted during the pandemic show that a majority of subjects report clinically meaningful changes in sleep quality, sleep patterns, and sleep disturbances.
For example, a cross-sectional international survey conducted from late March through late April 2020 found that among more than 3,000 responders from 49 countries, 58% reported dissatisfaction with their sleep, and 40% reported a decrease in sleep quality during the pandemic, compared with pre-COVID-19 sleep, according to Uri Mandelkorn of the Natural Sleep Clinic in Jerusalem, and colleagues.
“In particular, this research raises the need to screen for worsening sleep patterns and use of sleeping aids in the more susceptible populations identified in this study, namely, women and people with insecure livelihoods or those subjected to strict quarantine. Health care providers should pay special attention to physical and psychological problems that this surge in sleep disturbances may cause,” they wrote. The report is in the Journal of Clinical Sleep Medicine.
Sleeping, more or less
A coauthor of that study, David Gozal, MD, FCCP, a pediatric pulmonologist and sleep medicine specialist at the University of Missouri in Columbia, said that the pandemic has had paradoxical effects on sleeps patterns for many.
“At the beginning, with the initial phases of lockdown for COVID, for most of the people whose jobs were not affected and who did not lose their jobs, [for whom] there was not the anxiety of being jobless and financially strapped, but who now were staying at home, there was actually a benefit. People started reporting getting more sleep and, more importantly, more vivid dreams and things of that nature,” he said in an interview.
“But as the lockdown progressed, we saw progressively and increasingly more people having difficulty falling asleep and staying asleep, using more medicines such as hypnotics to induce sleep, and we saw a 20% increase in the overall consumption of sleeping pills,” he said.
Similar results were seen in a cross-sectional survey of 843 adults in the United Kingdom, which showed that nearly 70% of participants reported a change in sleep patterns, only 45% reported having refreshing sleep, and 46% reported being sleepier during lockdown than before. Two-thirds of the respondents reported that the pandemic affected their mental health, and one-fourth reported increased alcohol consumption during lockdown. Those with suspected COVID-19 infections reported having more nightmares and abnormal sleep rhythms.
It is possible that the effects of COVID-19 infection on sleep may linger long after the infection itself has resolved, results of a cohort study from China suggest. As reported in The Lancet, among 1,655 patients discharged from the Jin Yin-tan hospital in Wuhan, 26% reported sleep disturbances 6 months after acute COVID-19 infection.
Self-medicating
Among 5,525 Canadians surveyed from April 3 through June 24, 2020, a large proportion reported the use of pharmacologic sleeps aids, said Tetyana Kendzerska, MD, PhD, assistant professor of medicine in the division of respirology at the University of Ottawa.
“At the time of the survey completion, 27% of participants reported taking sleeping aids (prescribed or [over] the counter); across the entire sample, 8% of respondents reported an increase in the frequency of sleeping medication use during the outbreak compared to before the outbreak,” she said in an interview.
Many people resort to self-medicating with over-the-counter preparations such as melatonin and pain-relief nighttime formulations containing diphenhydramine (Benadryl), a first-generation antihistamine with sedative properties, noted Kannan Ramar, MBBS, MD, a critical care, pulmonary, and sleep medicine specialist at the Mayo Clinic in Rochester, Minn., and current president of the American Academy of Sleep Medicine.
“When people are self-medicating for what they think is difficulty sleeping, the concern is that even if a diagnosis of insomnia has been established, there could be another, ongoing sleep disorder that may be undiagnosed, which might be causing the problem with insomnia,” he said in an interview.
“For example, obstructive sleep apnea might be causing people to wake up in the night or even contribute to difficulty falling asleep in the first place. So medicating for something without a known diagnosis may leave an underlying sleep disorder untreated, which won’t help the patient in either the short or the long term,” Dr. Ramar said.
Causes for concern
“For those people who have COVID, we have seen quite a few sleep issues develop. Those were not reported in the actual study, but in the clinic and subsequent studies published from other places,” Dr. Gozal said.
“People who suffered from COVID, and even people who supposedly did very well and were virtually asymptomatic or maybe had only a headache or fever but did not need to go to the hospital, many of those people reported either excessive sleepiness for a long period of time, and would sleep 2 or 3 hours more per night. Or the opposite was reported: There were those that after recovering reported that they couldn’t sleep – they were sleeping 4 or 5 hours when they normally sleep 7 or 8,” he said.
It’s also unclear from current evidence whether the reported uptick in sleep problems is related to stress or, in patients who have had COVID-19 infections, to physiologic causes.
Dr. Gozal said that insomnia in the time of COVID-19 could be attributed to a number of factors such as less daily exposure to natural light from people sheltering indoors, stress related to financial or health worries, depression, or other psychological factors.
It’s also, possible, however, that COVID-19-related physiological changes could contribute to sleep disorders, he said, pointing to a recent study in the Journal of Experimental Medicine showing that SARS-CoV-2, the virus that causes COVID-19, can bind to neurons and cause metabolic changes in both infected and neighboring cells.
“My guess is that some of it is related more to behavioral impacts – people develop depression, changes in mood, anxiety, and so on, and all of these can translate into difficulties with sleep,” he said.
“It could be that in some instances – not very commonly – the virus will affect areas that control sleep in our brain, and that therefore we may see too much or too little sleep, and how to differentiate between all of these is the area that clearly needs to be explored, particularly in light of the finding that the virus can bind to brain cells and can induce substantial issues in the brain cells.”
Compromised immunity
It has been well documented that in addition to being, as Shakespeare called it, “the balm of hurt minds,” sleep has an important role in supporting the immune system.
“Sleep and immunity go together,” Dr. Ramar said. “When people have adequate sleep, their immune system is boosted. We know that there are good data from hepatitis A and hepatitis B vaccinations, and recently on flu vaccination, that if people get sufficient duration of sleep before and after they receive the shot, their likelihood of building an immune response to that particular vaccination tends to go up.”
It’s reasonable to assume that the same would hold true for COVID-19 vaccinations, but this has yet to be shown, he added.
“We do know from the previous studies that persistent sleep problems can make people more susceptible to infection or impair recovery; not yet, I believe, from the COVID-19 infection perspective,” Dr. Kendzerska said. “In our study, we did find that, among other factors, having a chronic illness was associated with new sleep difficulties during the pandemic. We did not look separately if sleep difficulties were associated with the COVID-19 infection or symptoms, but this is a great question to address with longitudinal data we have.”
What to do?
All three sleep experts contacted for this article agreed that for patients with insomnia, mitigating stress through relaxation techniques or cognitive behavioral therapy is more beneficial than medication.
“Medications, even over-the-counter medications, all have side effects, and if one is taking a medication that has stimulants in place, such as pseudoephedrine in antihistamine combinations, that can potentially contribute to or exacerbate any underlying sleep disorders,” Dr. Ramar said.
Dr. Kendzerska recommended reserving medications such as melatonin, a chronobiotic therapy, for patients with sleep disorders related to circadian rhythm problems, including a sleep phase delay. Supplemental, short-term treatment with hypnotic agents such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata) should be used only as a last resort, she said.
Sleep medicine specialists recommend good sleep hygiene as the best means of obtaining restful sleep, including regular bed and wake times, limited exposure to stressful news (including COVID-19 stories), reduced consumption of alcohol and stimulants such as coffee or caffeine drinks, avoiding use of electronic devices in bed or near bedtime, and healthy lifestyle, including diet and exercise.
They also frown on self-medication with over-the-counter aids, because these products may not be addressing the underlying issue, as noted before.
“It is also foreseeable that there may be an increase in individuals who may require professional guidance to taper off from sleeping medications started or increased during the pandemic. While some of these sleep problems may be transient, it should be a high priority to ensure they do not evolve into chronic sleep disorders,” Dr. Kendzerska and colleagues wrote.
Research avenues
If there’s anything that causes specialists to lose sleep, it’s the lack of data or evidence to guide clinical care and research. Dr. Gozal emphasized that little is still known about the potential central nervous system effects of COVID-19, and said that should be an important focus for research into the still novel coronavirus.
“What happens post COVID and how might that affect subsequent recovery is a great question, and I don’t think we have good data there,” Dr. Ramar said. “What we do know is that patients develop the symptoms of fatigue, disrupted sleep, even ongoing fever, and unfortunately, this may persist for a long period of time even among patients who have otherwise recovered from COVID-19. We know that leaving that untreated from a sleep disorder perspective can exacerbate their daytime symptoms, and that’s where I would strongly recommend that they seek help with a sleep provider or if there are symptoms other than insomnia at least with a primary care provider.”
Among the many losses suffered by millions worldwide during the COVID-19 pandemic, the loss of sleep may be the most widespread, with potentially long-lasting, negative consequences on physical, mental, and emotional health, sleep researchers have found.
Results from multiple studies and surveys conducted during the pandemic show that a majority of subjects report clinically meaningful changes in sleep quality, sleep patterns, and sleep disturbances.
For example, a cross-sectional international survey conducted from late March through late April 2020 found that among more than 3,000 responders from 49 countries, 58% reported dissatisfaction with their sleep, and 40% reported a decrease in sleep quality during the pandemic, compared with pre-COVID-19 sleep, according to Uri Mandelkorn of the Natural Sleep Clinic in Jerusalem, and colleagues.
“In particular, this research raises the need to screen for worsening sleep patterns and use of sleeping aids in the more susceptible populations identified in this study, namely, women and people with insecure livelihoods or those subjected to strict quarantine. Health care providers should pay special attention to physical and psychological problems that this surge in sleep disturbances may cause,” they wrote. The report is in the Journal of Clinical Sleep Medicine.
Sleeping, more or less
A coauthor of that study, David Gozal, MD, FCCP, a pediatric pulmonologist and sleep medicine specialist at the University of Missouri in Columbia, said that the pandemic has had paradoxical effects on sleeps patterns for many.
“At the beginning, with the initial phases of lockdown for COVID, for most of the people whose jobs were not affected and who did not lose their jobs, [for whom] there was not the anxiety of being jobless and financially strapped, but who now were staying at home, there was actually a benefit. People started reporting getting more sleep and, more importantly, more vivid dreams and things of that nature,” he said in an interview.
“But as the lockdown progressed, we saw progressively and increasingly more people having difficulty falling asleep and staying asleep, using more medicines such as hypnotics to induce sleep, and we saw a 20% increase in the overall consumption of sleeping pills,” he said.
Similar results were seen in a cross-sectional survey of 843 adults in the United Kingdom, which showed that nearly 70% of participants reported a change in sleep patterns, only 45% reported having refreshing sleep, and 46% reported being sleepier during lockdown than before. Two-thirds of the respondents reported that the pandemic affected their mental health, and one-fourth reported increased alcohol consumption during lockdown. Those with suspected COVID-19 infections reported having more nightmares and abnormal sleep rhythms.
It is possible that the effects of COVID-19 infection on sleep may linger long after the infection itself has resolved, results of a cohort study from China suggest. As reported in The Lancet, among 1,655 patients discharged from the Jin Yin-tan hospital in Wuhan, 26% reported sleep disturbances 6 months after acute COVID-19 infection.
Self-medicating
Among 5,525 Canadians surveyed from April 3 through June 24, 2020, a large proportion reported the use of pharmacologic sleeps aids, said Tetyana Kendzerska, MD, PhD, assistant professor of medicine in the division of respirology at the University of Ottawa.
“At the time of the survey completion, 27% of participants reported taking sleeping aids (prescribed or [over] the counter); across the entire sample, 8% of respondents reported an increase in the frequency of sleeping medication use during the outbreak compared to before the outbreak,” she said in an interview.
Many people resort to self-medicating with over-the-counter preparations such as melatonin and pain-relief nighttime formulations containing diphenhydramine (Benadryl), a first-generation antihistamine with sedative properties, noted Kannan Ramar, MBBS, MD, a critical care, pulmonary, and sleep medicine specialist at the Mayo Clinic in Rochester, Minn., and current president of the American Academy of Sleep Medicine.
“When people are self-medicating for what they think is difficulty sleeping, the concern is that even if a diagnosis of insomnia has been established, there could be another, ongoing sleep disorder that may be undiagnosed, which might be causing the problem with insomnia,” he said in an interview.
“For example, obstructive sleep apnea might be causing people to wake up in the night or even contribute to difficulty falling asleep in the first place. So medicating for something without a known diagnosis may leave an underlying sleep disorder untreated, which won’t help the patient in either the short or the long term,” Dr. Ramar said.
Causes for concern
“For those people who have COVID, we have seen quite a few sleep issues develop. Those were not reported in the actual study, but in the clinic and subsequent studies published from other places,” Dr. Gozal said.
“People who suffered from COVID, and even people who supposedly did very well and were virtually asymptomatic or maybe had only a headache or fever but did not need to go to the hospital, many of those people reported either excessive sleepiness for a long period of time, and would sleep 2 or 3 hours more per night. Or the opposite was reported: There were those that after recovering reported that they couldn’t sleep – they were sleeping 4 or 5 hours when they normally sleep 7 or 8,” he said.
It’s also unclear from current evidence whether the reported uptick in sleep problems is related to stress or, in patients who have had COVID-19 infections, to physiologic causes.
Dr. Gozal said that insomnia in the time of COVID-19 could be attributed to a number of factors such as less daily exposure to natural light from people sheltering indoors, stress related to financial or health worries, depression, or other psychological factors.
It’s also, possible, however, that COVID-19-related physiological changes could contribute to sleep disorders, he said, pointing to a recent study in the Journal of Experimental Medicine showing that SARS-CoV-2, the virus that causes COVID-19, can bind to neurons and cause metabolic changes in both infected and neighboring cells.
“My guess is that some of it is related more to behavioral impacts – people develop depression, changes in mood, anxiety, and so on, and all of these can translate into difficulties with sleep,” he said.
“It could be that in some instances – not very commonly – the virus will affect areas that control sleep in our brain, and that therefore we may see too much or too little sleep, and how to differentiate between all of these is the area that clearly needs to be explored, particularly in light of the finding that the virus can bind to brain cells and can induce substantial issues in the brain cells.”
Compromised immunity
It has been well documented that in addition to being, as Shakespeare called it, “the balm of hurt minds,” sleep has an important role in supporting the immune system.
“Sleep and immunity go together,” Dr. Ramar said. “When people have adequate sleep, their immune system is boosted. We know that there are good data from hepatitis A and hepatitis B vaccinations, and recently on flu vaccination, that if people get sufficient duration of sleep before and after they receive the shot, their likelihood of building an immune response to that particular vaccination tends to go up.”
It’s reasonable to assume that the same would hold true for COVID-19 vaccinations, but this has yet to be shown, he added.
“We do know from the previous studies that persistent sleep problems can make people more susceptible to infection or impair recovery; not yet, I believe, from the COVID-19 infection perspective,” Dr. Kendzerska said. “In our study, we did find that, among other factors, having a chronic illness was associated with new sleep difficulties during the pandemic. We did not look separately if sleep difficulties were associated with the COVID-19 infection or symptoms, but this is a great question to address with longitudinal data we have.”
What to do?
All three sleep experts contacted for this article agreed that for patients with insomnia, mitigating stress through relaxation techniques or cognitive behavioral therapy is more beneficial than medication.
“Medications, even over-the-counter medications, all have side effects, and if one is taking a medication that has stimulants in place, such as pseudoephedrine in antihistamine combinations, that can potentially contribute to or exacerbate any underlying sleep disorders,” Dr. Ramar said.
Dr. Kendzerska recommended reserving medications such as melatonin, a chronobiotic therapy, for patients with sleep disorders related to circadian rhythm problems, including a sleep phase delay. Supplemental, short-term treatment with hypnotic agents such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata) should be used only as a last resort, she said.
Sleep medicine specialists recommend good sleep hygiene as the best means of obtaining restful sleep, including regular bed and wake times, limited exposure to stressful news (including COVID-19 stories), reduced consumption of alcohol and stimulants such as coffee or caffeine drinks, avoiding use of electronic devices in bed or near bedtime, and healthy lifestyle, including diet and exercise.
They also frown on self-medication with over-the-counter aids, because these products may not be addressing the underlying issue, as noted before.
“It is also foreseeable that there may be an increase in individuals who may require professional guidance to taper off from sleeping medications started or increased during the pandemic. While some of these sleep problems may be transient, it should be a high priority to ensure they do not evolve into chronic sleep disorders,” Dr. Kendzerska and colleagues wrote.
Research avenues
If there’s anything that causes specialists to lose sleep, it’s the lack of data or evidence to guide clinical care and research. Dr. Gozal emphasized that little is still known about the potential central nervous system effects of COVID-19, and said that should be an important focus for research into the still novel coronavirus.
“What happens post COVID and how might that affect subsequent recovery is a great question, and I don’t think we have good data there,” Dr. Ramar said. “What we do know is that patients develop the symptoms of fatigue, disrupted sleep, even ongoing fever, and unfortunately, this may persist for a long period of time even among patients who have otherwise recovered from COVID-19. We know that leaving that untreated from a sleep disorder perspective can exacerbate their daytime symptoms, and that’s where I would strongly recommend that they seek help with a sleep provider or if there are symptoms other than insomnia at least with a primary care provider.”
Among the many losses suffered by millions worldwide during the COVID-19 pandemic, the loss of sleep may be the most widespread, with potentially long-lasting, negative consequences on physical, mental, and emotional health, sleep researchers have found.
Results from multiple studies and surveys conducted during the pandemic show that a majority of subjects report clinically meaningful changes in sleep quality, sleep patterns, and sleep disturbances.
For example, a cross-sectional international survey conducted from late March through late April 2020 found that among more than 3,000 responders from 49 countries, 58% reported dissatisfaction with their sleep, and 40% reported a decrease in sleep quality during the pandemic, compared with pre-COVID-19 sleep, according to Uri Mandelkorn of the Natural Sleep Clinic in Jerusalem, and colleagues.
“In particular, this research raises the need to screen for worsening sleep patterns and use of sleeping aids in the more susceptible populations identified in this study, namely, women and people with insecure livelihoods or those subjected to strict quarantine. Health care providers should pay special attention to physical and psychological problems that this surge in sleep disturbances may cause,” they wrote. The report is in the Journal of Clinical Sleep Medicine.
Sleeping, more or less
A coauthor of that study, David Gozal, MD, FCCP, a pediatric pulmonologist and sleep medicine specialist at the University of Missouri in Columbia, said that the pandemic has had paradoxical effects on sleeps patterns for many.
“At the beginning, with the initial phases of lockdown for COVID, for most of the people whose jobs were not affected and who did not lose their jobs, [for whom] there was not the anxiety of being jobless and financially strapped, but who now were staying at home, there was actually a benefit. People started reporting getting more sleep and, more importantly, more vivid dreams and things of that nature,” he said in an interview.
“But as the lockdown progressed, we saw progressively and increasingly more people having difficulty falling asleep and staying asleep, using more medicines such as hypnotics to induce sleep, and we saw a 20% increase in the overall consumption of sleeping pills,” he said.
Similar results were seen in a cross-sectional survey of 843 adults in the United Kingdom, which showed that nearly 70% of participants reported a change in sleep patterns, only 45% reported having refreshing sleep, and 46% reported being sleepier during lockdown than before. Two-thirds of the respondents reported that the pandemic affected their mental health, and one-fourth reported increased alcohol consumption during lockdown. Those with suspected COVID-19 infections reported having more nightmares and abnormal sleep rhythms.
It is possible that the effects of COVID-19 infection on sleep may linger long after the infection itself has resolved, results of a cohort study from China suggest. As reported in The Lancet, among 1,655 patients discharged from the Jin Yin-tan hospital in Wuhan, 26% reported sleep disturbances 6 months after acute COVID-19 infection.
Self-medicating
Among 5,525 Canadians surveyed from April 3 through June 24, 2020, a large proportion reported the use of pharmacologic sleeps aids, said Tetyana Kendzerska, MD, PhD, assistant professor of medicine in the division of respirology at the University of Ottawa.
“At the time of the survey completion, 27% of participants reported taking sleeping aids (prescribed or [over] the counter); across the entire sample, 8% of respondents reported an increase in the frequency of sleeping medication use during the outbreak compared to before the outbreak,” she said in an interview.
Many people resort to self-medicating with over-the-counter preparations such as melatonin and pain-relief nighttime formulations containing diphenhydramine (Benadryl), a first-generation antihistamine with sedative properties, noted Kannan Ramar, MBBS, MD, a critical care, pulmonary, and sleep medicine specialist at the Mayo Clinic in Rochester, Minn., and current president of the American Academy of Sleep Medicine.
“When people are self-medicating for what they think is difficulty sleeping, the concern is that even if a diagnosis of insomnia has been established, there could be another, ongoing sleep disorder that may be undiagnosed, which might be causing the problem with insomnia,” he said in an interview.
“For example, obstructive sleep apnea might be causing people to wake up in the night or even contribute to difficulty falling asleep in the first place. So medicating for something without a known diagnosis may leave an underlying sleep disorder untreated, which won’t help the patient in either the short or the long term,” Dr. Ramar said.
Causes for concern
“For those people who have COVID, we have seen quite a few sleep issues develop. Those were not reported in the actual study, but in the clinic and subsequent studies published from other places,” Dr. Gozal said.
“People who suffered from COVID, and even people who supposedly did very well and were virtually asymptomatic or maybe had only a headache or fever but did not need to go to the hospital, many of those people reported either excessive sleepiness for a long period of time, and would sleep 2 or 3 hours more per night. Or the opposite was reported: There were those that after recovering reported that they couldn’t sleep – they were sleeping 4 or 5 hours when they normally sleep 7 or 8,” he said.
It’s also unclear from current evidence whether the reported uptick in sleep problems is related to stress or, in patients who have had COVID-19 infections, to physiologic causes.
Dr. Gozal said that insomnia in the time of COVID-19 could be attributed to a number of factors such as less daily exposure to natural light from people sheltering indoors, stress related to financial or health worries, depression, or other psychological factors.
It’s also, possible, however, that COVID-19-related physiological changes could contribute to sleep disorders, he said, pointing to a recent study in the Journal of Experimental Medicine showing that SARS-CoV-2, the virus that causes COVID-19, can bind to neurons and cause metabolic changes in both infected and neighboring cells.
“My guess is that some of it is related more to behavioral impacts – people develop depression, changes in mood, anxiety, and so on, and all of these can translate into difficulties with sleep,” he said.
“It could be that in some instances – not very commonly – the virus will affect areas that control sleep in our brain, and that therefore we may see too much or too little sleep, and how to differentiate between all of these is the area that clearly needs to be explored, particularly in light of the finding that the virus can bind to brain cells and can induce substantial issues in the brain cells.”
Compromised immunity
It has been well documented that in addition to being, as Shakespeare called it, “the balm of hurt minds,” sleep has an important role in supporting the immune system.
“Sleep and immunity go together,” Dr. Ramar said. “When people have adequate sleep, their immune system is boosted. We know that there are good data from hepatitis A and hepatitis B vaccinations, and recently on flu vaccination, that if people get sufficient duration of sleep before and after they receive the shot, their likelihood of building an immune response to that particular vaccination tends to go up.”
It’s reasonable to assume that the same would hold true for COVID-19 vaccinations, but this has yet to be shown, he added.
“We do know from the previous studies that persistent sleep problems can make people more susceptible to infection or impair recovery; not yet, I believe, from the COVID-19 infection perspective,” Dr. Kendzerska said. “In our study, we did find that, among other factors, having a chronic illness was associated with new sleep difficulties during the pandemic. We did not look separately if sleep difficulties were associated with the COVID-19 infection or symptoms, but this is a great question to address with longitudinal data we have.”
What to do?
All three sleep experts contacted for this article agreed that for patients with insomnia, mitigating stress through relaxation techniques or cognitive behavioral therapy is more beneficial than medication.
“Medications, even over-the-counter medications, all have side effects, and if one is taking a medication that has stimulants in place, such as pseudoephedrine in antihistamine combinations, that can potentially contribute to or exacerbate any underlying sleep disorders,” Dr. Ramar said.
Dr. Kendzerska recommended reserving medications such as melatonin, a chronobiotic therapy, for patients with sleep disorders related to circadian rhythm problems, including a sleep phase delay. Supplemental, short-term treatment with hypnotic agents such as zolpidem (Ambien), eszopiclone (Lunesta), or zaleplon (Sonata) should be used only as a last resort, she said.
Sleep medicine specialists recommend good sleep hygiene as the best means of obtaining restful sleep, including regular bed and wake times, limited exposure to stressful news (including COVID-19 stories), reduced consumption of alcohol and stimulants such as coffee or caffeine drinks, avoiding use of electronic devices in bed or near bedtime, and healthy lifestyle, including diet and exercise.
They also frown on self-medication with over-the-counter aids, because these products may not be addressing the underlying issue, as noted before.
“It is also foreseeable that there may be an increase in individuals who may require professional guidance to taper off from sleeping medications started or increased during the pandemic. While some of these sleep problems may be transient, it should be a high priority to ensure they do not evolve into chronic sleep disorders,” Dr. Kendzerska and colleagues wrote.
Research avenues
If there’s anything that causes specialists to lose sleep, it’s the lack of data or evidence to guide clinical care and research. Dr. Gozal emphasized that little is still known about the potential central nervous system effects of COVID-19, and said that should be an important focus for research into the still novel coronavirus.
“What happens post COVID and how might that affect subsequent recovery is a great question, and I don’t think we have good data there,” Dr. Ramar said. “What we do know is that patients develop the symptoms of fatigue, disrupted sleep, even ongoing fever, and unfortunately, this may persist for a long period of time even among patients who have otherwise recovered from COVID-19. We know that leaving that untreated from a sleep disorder perspective can exacerbate their daytime symptoms, and that’s where I would strongly recommend that they seek help with a sleep provider or if there are symptoms other than insomnia at least with a primary care provider.”
Monoclonal antibody combo treatment reduces viral load in mild to moderate COVID-19
A combination treatment of neutralizing monoclonal antibodies bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 at day 11 compared with placebo among nonhospitalized patients who had mild to moderate COVID-19, new data indicate.
However, bamlanivimab alone in three different single-infusion doses showed no significant reduction in viral load, compared with placebo, according to the phase 2/3 study by Robert L. Gottlieb, MD, PhD, of the Baylor University Medical Center and the Baylor Scott & White Research Institute, both in Dallas, and colleagues.
Findings from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study were published online Jan. 21 in JAMA. The results represent findings through Oct. 6, 2020.
BLAZE-1 was funded by Eli Lilly, which makes both of the antispike neutralizing antibodies. The trial was conducted at 49 U.S. centers and included 613 outpatients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms.
Patients were randomized to one of five groups (four treatment groups and a placebo control), and researchers analyzed between-group differences.
All four treatment arms suggest a trend toward reduction in viral load, which was the primary endpoint of the trial, but only the combination showed a statistically significant reduction.
The average age of patients was 44.7 years, 54.6% were female, 42.5% were Hispanic, and 67.1% had at least one risk factor for severe COVID-19 (aged ≥55 years, body mass index of at least 30, or relevant comorbidity such as hypertension).
Among secondary outcomes, there were no consistent differences between the monotherapy groups or the combination group versus placebo for the other measures of viral load or clinical symptom scores.
The proportion of patients who had COVID-19–related hospitalizations or ED visits was 5.8% (nine events) for placebo; 1.0% (one event) for the 700-mg group; 1.9% (two events) for 2,800 mg; 2.0% (two events) for 7,000 mg; and 0.9% (one event) for combination treatment.
“Combining these two neutralizing monoclonal antibodies in clinical use may enhance viral load reduction and decrease treatment-emergent resistant variants,” the authors concluded.
Safety profile comparison
As for adverse events, immediate hypersensitivity reactions were reported in nine patients (six bamlanivimab, two combination treatment, and one placebo). No deaths occurred during the study.
Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups; in 0.9% (1/112) of patients in the combination group; and in 0.6% (1/156) of patients in the placebo group.
The serious adverse event in the combination group was a urinary tract infection deemed unrelated to the study drug, the authors wrote.
The two most frequently reported side effects were nausea (3.0% for the 700-mg group; 3.7% for the 2,800-mg group; 5.0% for the 7,000-mg group; 3.6% for the combination group; and 3.8% for the placebo group) and diarrhea (1.0%, 1.9%, 5.9%, 0.9%, and 4.5%, respectively).
The authors included in the study’s limitations that the primary endpoint at day 11 may have been too late to best detect treatment effects.
“All patients, including those who received placebo, demonstrated substantial viral reduction by day 11,” they noted. “An earlier time point like day 3 or day 7 could possibly have been more appropriate to measure viral load.”
Currently, only remdesivir has been approved by the Food and Drug Administration for treating COVID-19, but convalescent plasma and neutralizing monoclonal antibodies have been granted emergency-use authorization.
In an accompanying editor’s note, Preeti N. Malani, MD, with the division of infectious diseases at the University of Michigan, Ann Arbor, and associate editor of JAMA, and Robert M. Golub, MD, deputy editor of JAMA, pointed out that these results differ from an earlier interim analysis of BLAZE-1 data.
A previous publication by Peter Chen, MD, with the department of medicine at Cedars Sinai Medical Center, Los Angeles, compared the three monotherapy groups (no combination group) with placebo, and in that study the 2,800-mg dose of bamlanivimab versus placebo achieved statistical significance for reduction in viral load from baseline at day 11, whereas the other two doses did not.
The editors explain that, in the study by Dr. Chen, “Follow-up for the placebo group was incomplete at the time of the database lock on Sept. 5, 2020. In the final analysis reported in the current article, the database was locked on Oct. 6, 2020, and the longer follow-up for the placebo group, which is now complete, resulted in changes in the primary outcome among that group.”
They concluded: “The comparison of the monotherapy groups against the final results for the placebo group led to changes in the effect sizes,” and the statistical significance of the 2,800-mg group was erased.
The editors pointed out that monoclonal antibodies are likely to benefit certain patients but definitive answers regarding which patients will benefit and under what circumstances will likely take more time than clinicians have to make decisions on treatment.
Meanwhile, as this news organization reported, the United States has spent $375 million on bamlanivimab and $450 million on Regeneron’s monoclonal antibody cocktail of casirivimab plus imdevimab, with the promise to spend billions more.
However, 80% of the 660,000 doses delivered by the two companies are still sitting on shelves, federal officials said in a press briefing last week, because of doubts about efficacy, lack of resources for infusion centers, and questions on reimbursement.
“While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit,” Dr. Malani and Dr. Golub wrote.
This trial was sponsored and funded by Eli Lilly. Dr. Gottlieb disclosed personal fees and nonfinancial support (medication for another trial) from Gilead Sciences and serving on an advisory board for Sentinel. Several coauthors have financial ties to Eli Lilly. Dr. Malani reported serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated. Dr. Golub disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A combination treatment of neutralizing monoclonal antibodies bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 at day 11 compared with placebo among nonhospitalized patients who had mild to moderate COVID-19, new data indicate.
However, bamlanivimab alone in three different single-infusion doses showed no significant reduction in viral load, compared with placebo, according to the phase 2/3 study by Robert L. Gottlieb, MD, PhD, of the Baylor University Medical Center and the Baylor Scott & White Research Institute, both in Dallas, and colleagues.
Findings from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study were published online Jan. 21 in JAMA. The results represent findings through Oct. 6, 2020.
BLAZE-1 was funded by Eli Lilly, which makes both of the antispike neutralizing antibodies. The trial was conducted at 49 U.S. centers and included 613 outpatients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms.
Patients were randomized to one of five groups (four treatment groups and a placebo control), and researchers analyzed between-group differences.
All four treatment arms suggest a trend toward reduction in viral load, which was the primary endpoint of the trial, but only the combination showed a statistically significant reduction.
The average age of patients was 44.7 years, 54.6% were female, 42.5% were Hispanic, and 67.1% had at least one risk factor for severe COVID-19 (aged ≥55 years, body mass index of at least 30, or relevant comorbidity such as hypertension).
Among secondary outcomes, there were no consistent differences between the monotherapy groups or the combination group versus placebo for the other measures of viral load or clinical symptom scores.
The proportion of patients who had COVID-19–related hospitalizations or ED visits was 5.8% (nine events) for placebo; 1.0% (one event) for the 700-mg group; 1.9% (two events) for 2,800 mg; 2.0% (two events) for 7,000 mg; and 0.9% (one event) for combination treatment.
“Combining these two neutralizing monoclonal antibodies in clinical use may enhance viral load reduction and decrease treatment-emergent resistant variants,” the authors concluded.
Safety profile comparison
As for adverse events, immediate hypersensitivity reactions were reported in nine patients (six bamlanivimab, two combination treatment, and one placebo). No deaths occurred during the study.
Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups; in 0.9% (1/112) of patients in the combination group; and in 0.6% (1/156) of patients in the placebo group.
The serious adverse event in the combination group was a urinary tract infection deemed unrelated to the study drug, the authors wrote.
The two most frequently reported side effects were nausea (3.0% for the 700-mg group; 3.7% for the 2,800-mg group; 5.0% for the 7,000-mg group; 3.6% for the combination group; and 3.8% for the placebo group) and diarrhea (1.0%, 1.9%, 5.9%, 0.9%, and 4.5%, respectively).
The authors included in the study’s limitations that the primary endpoint at day 11 may have been too late to best detect treatment effects.
“All patients, including those who received placebo, demonstrated substantial viral reduction by day 11,” they noted. “An earlier time point like day 3 or day 7 could possibly have been more appropriate to measure viral load.”
Currently, only remdesivir has been approved by the Food and Drug Administration for treating COVID-19, but convalescent plasma and neutralizing monoclonal antibodies have been granted emergency-use authorization.
In an accompanying editor’s note, Preeti N. Malani, MD, with the division of infectious diseases at the University of Michigan, Ann Arbor, and associate editor of JAMA, and Robert M. Golub, MD, deputy editor of JAMA, pointed out that these results differ from an earlier interim analysis of BLAZE-1 data.
A previous publication by Peter Chen, MD, with the department of medicine at Cedars Sinai Medical Center, Los Angeles, compared the three monotherapy groups (no combination group) with placebo, and in that study the 2,800-mg dose of bamlanivimab versus placebo achieved statistical significance for reduction in viral load from baseline at day 11, whereas the other two doses did not.
The editors explain that, in the study by Dr. Chen, “Follow-up for the placebo group was incomplete at the time of the database lock on Sept. 5, 2020. In the final analysis reported in the current article, the database was locked on Oct. 6, 2020, and the longer follow-up for the placebo group, which is now complete, resulted in changes in the primary outcome among that group.”
They concluded: “The comparison of the monotherapy groups against the final results for the placebo group led to changes in the effect sizes,” and the statistical significance of the 2,800-mg group was erased.
The editors pointed out that monoclonal antibodies are likely to benefit certain patients but definitive answers regarding which patients will benefit and under what circumstances will likely take more time than clinicians have to make decisions on treatment.
Meanwhile, as this news organization reported, the United States has spent $375 million on bamlanivimab and $450 million on Regeneron’s monoclonal antibody cocktail of casirivimab plus imdevimab, with the promise to spend billions more.
However, 80% of the 660,000 doses delivered by the two companies are still sitting on shelves, federal officials said in a press briefing last week, because of doubts about efficacy, lack of resources for infusion centers, and questions on reimbursement.
“While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit,” Dr. Malani and Dr. Golub wrote.
This trial was sponsored and funded by Eli Lilly. Dr. Gottlieb disclosed personal fees and nonfinancial support (medication for another trial) from Gilead Sciences and serving on an advisory board for Sentinel. Several coauthors have financial ties to Eli Lilly. Dr. Malani reported serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated. Dr. Golub disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A combination treatment of neutralizing monoclonal antibodies bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 at day 11 compared with placebo among nonhospitalized patients who had mild to moderate COVID-19, new data indicate.
However, bamlanivimab alone in three different single-infusion doses showed no significant reduction in viral load, compared with placebo, according to the phase 2/3 study by Robert L. Gottlieb, MD, PhD, of the Baylor University Medical Center and the Baylor Scott & White Research Institute, both in Dallas, and colleagues.
Findings from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study were published online Jan. 21 in JAMA. The results represent findings through Oct. 6, 2020.
BLAZE-1 was funded by Eli Lilly, which makes both of the antispike neutralizing antibodies. The trial was conducted at 49 U.S. centers and included 613 outpatients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms.
Patients were randomized to one of five groups (four treatment groups and a placebo control), and researchers analyzed between-group differences.
All four treatment arms suggest a trend toward reduction in viral load, which was the primary endpoint of the trial, but only the combination showed a statistically significant reduction.
The average age of patients was 44.7 years, 54.6% were female, 42.5% were Hispanic, and 67.1% had at least one risk factor for severe COVID-19 (aged ≥55 years, body mass index of at least 30, or relevant comorbidity such as hypertension).
Among secondary outcomes, there were no consistent differences between the monotherapy groups or the combination group versus placebo for the other measures of viral load or clinical symptom scores.
The proportion of patients who had COVID-19–related hospitalizations or ED visits was 5.8% (nine events) for placebo; 1.0% (one event) for the 700-mg group; 1.9% (two events) for 2,800 mg; 2.0% (two events) for 7,000 mg; and 0.9% (one event) for combination treatment.
“Combining these two neutralizing monoclonal antibodies in clinical use may enhance viral load reduction and decrease treatment-emergent resistant variants,” the authors concluded.
Safety profile comparison
As for adverse events, immediate hypersensitivity reactions were reported in nine patients (six bamlanivimab, two combination treatment, and one placebo). No deaths occurred during the study.
Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups; in 0.9% (1/112) of patients in the combination group; and in 0.6% (1/156) of patients in the placebo group.
The serious adverse event in the combination group was a urinary tract infection deemed unrelated to the study drug, the authors wrote.
The two most frequently reported side effects were nausea (3.0% for the 700-mg group; 3.7% for the 2,800-mg group; 5.0% for the 7,000-mg group; 3.6% for the combination group; and 3.8% for the placebo group) and diarrhea (1.0%, 1.9%, 5.9%, 0.9%, and 4.5%, respectively).
The authors included in the study’s limitations that the primary endpoint at day 11 may have been too late to best detect treatment effects.
“All patients, including those who received placebo, demonstrated substantial viral reduction by day 11,” they noted. “An earlier time point like day 3 or day 7 could possibly have been more appropriate to measure viral load.”
Currently, only remdesivir has been approved by the Food and Drug Administration for treating COVID-19, but convalescent plasma and neutralizing monoclonal antibodies have been granted emergency-use authorization.
In an accompanying editor’s note, Preeti N. Malani, MD, with the division of infectious diseases at the University of Michigan, Ann Arbor, and associate editor of JAMA, and Robert M. Golub, MD, deputy editor of JAMA, pointed out that these results differ from an earlier interim analysis of BLAZE-1 data.
A previous publication by Peter Chen, MD, with the department of medicine at Cedars Sinai Medical Center, Los Angeles, compared the three monotherapy groups (no combination group) with placebo, and in that study the 2,800-mg dose of bamlanivimab versus placebo achieved statistical significance for reduction in viral load from baseline at day 11, whereas the other two doses did not.
The editors explain that, in the study by Dr. Chen, “Follow-up for the placebo group was incomplete at the time of the database lock on Sept. 5, 2020. In the final analysis reported in the current article, the database was locked on Oct. 6, 2020, and the longer follow-up for the placebo group, which is now complete, resulted in changes in the primary outcome among that group.”
They concluded: “The comparison of the monotherapy groups against the final results for the placebo group led to changes in the effect sizes,” and the statistical significance of the 2,800-mg group was erased.
The editors pointed out that monoclonal antibodies are likely to benefit certain patients but definitive answers regarding which patients will benefit and under what circumstances will likely take more time than clinicians have to make decisions on treatment.
Meanwhile, as this news organization reported, the United States has spent $375 million on bamlanivimab and $450 million on Regeneron’s monoclonal antibody cocktail of casirivimab plus imdevimab, with the promise to spend billions more.
However, 80% of the 660,000 doses delivered by the two companies are still sitting on shelves, federal officials said in a press briefing last week, because of doubts about efficacy, lack of resources for infusion centers, and questions on reimbursement.
“While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit,” Dr. Malani and Dr. Golub wrote.
This trial was sponsored and funded by Eli Lilly. Dr. Gottlieb disclosed personal fees and nonfinancial support (medication for another trial) from Gilead Sciences and serving on an advisory board for Sentinel. Several coauthors have financial ties to Eli Lilly. Dr. Malani reported serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated. Dr. Golub disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Severe renal arteriosclerosis may indicate cardiovascular risk in lupus nephritis
Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.
Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.
In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.
To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.
Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.
Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.
The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.
The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).
Lack of statin use
The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.
The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.
Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.
In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.
To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.
Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.
Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.
The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.
The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).
Lack of statin use
The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.
The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.
Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.
In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.
To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.
Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.
Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.
The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.
The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).
Lack of statin use
The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.
The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM ARTHRITIS CARE & RESEARCH
Biggest challenges practices faced from COVID last year: MGMA
according to a December 2020 report from the Medical Group Management Association.
The report was assembled from the results of weekly Stat polls by MGMA, which consists of 15,000 group practices representing more than 350,000 physicians. During the course of the year, more than 4,800 practice leaders were surveyed, but the individual polls had far fewer respondents.
The 2020 data represents snapshots from different points in the developing public health crisis. Still, much of what practices experienced earlier in the pandemic continues to apply, and it’s likely to persist this year as long as the coronavirus spreads and its toll deepens.
One top-line conclusion of the report: the economic pain felt by practices has resulted in layoffs, furloughs, and/or reduced compensation for providers and staff.
In the May 19 weekly survey, 82% of respondents said some or all of their providers’ compensation had been affected by the crisis. About 62% said every provider had been affected. Provider compensation was cut in several ways, including reduced hours and salaries, reduced or eliminated bonuses, and lower allowances for continuing medical education.
About 61% of health care leaders said in the June 26 poll that their own compensation had decreased.
In the following week’s survey, one in three managers said their organization had reduced staff compensation. Nearly all of the respondents in this category predicted the salary reductions would be temporary.
As of March 17, early in the pandemic, 40% of health care leaders said they were experiencing staff shortages. An April 21 poll found that 53% of health care leaders were taking steps to address their providers’ and staffers’ mental health.
“The mental and emotional toll on everyone continues to be a concern, as public health authorities continue to report alarming numbers of new [COVID-19] cases, hospitalizations, and deaths,” MGMA commented.
Telehealth and remote monitoring
Nearly all of the health care leaders surveyed on March 31 reported that their practices had expanded telehealth access because of COVID-19. The percentage of patient visits handled remotely had dropped substantially by the fall, according to a Harvard University/Commonwealth Fund/Phreesia survey. Still, it remains significantly higher than it was before the pandemic.
“At the end of 2020, telemedicine continues to play a vital role in everyday practice operations and long-term planning,” the MGMA report said. One indication of this, the association said, is that health care leaders are recognizing new best practices in specialty telemedicine, such as pediatrics and ob.gyn.
According to an April 28 poll, the top three coding/billing challenges for telehealth and telephone visits amid COVID-19 were inconsistent payer rules, pay parity and accuracy, and documentation of virtual visits.
While the Centers for Medicare & Medicaid Services has loosened its regulations to allow reimbursement of telehealth in all locations and at the same level as in-person visits, most of those changes will not last beyond the public health crisis without new legislation.
More health care leaders are considering the use of remote patient monitoring, MGMA said, but only 21% of practices offered such services as of Sept. 15. The report drew a connection between these plans and the current challenge of deferred care.
In the July 21 poll, 87% of health care leaders reported that safety concerns were the top reason that patients deferred care amid COVID-19. The MGMA report quoted JaeLynn Williams, CEO of Air Methods, which provides helicopter ambulance services, as saying that many people are staying home even when they face life-threatening conditions such as chest pain, drug symptoms, inflamed appendix, and gallbladder pain.
Operational issues
Overall, MGMA said, practices that have taken a financial risk have done better during the pandemic than fee-for-service practices because their monthly capitation revenue has continued unabated. In contrast, “most groups’ struggles to sustain visits and procedures meant less revenue and lower compensation,” the report said.
In the August 18 survey, one in three health care leaders reported their practices were changing their operational metrics and how often they looked at those measures because of the pandemic. “Practice managers are asking for dashboard data in weeks instead of months to measure the drop in charges and forecast the resulting change in collections,” MGMA noted. “The type of data practice managers are asking for has also changed.”
Among the new metrics that practices are interested in, according to an MGMA article, are measures that track telehealth visits, the productivity of staff working at home, and the number of ancillary services and procedures that new patients might need based on historical data.
Nearly all health care leaders surveyed on Aug. 11 said the cost of obtaining personal protective equipment had increased during 2020. MGMA said it expects this situation to worsen if the pandemic lasts through the summer of 2021.
While everyone is talking about the botched launch of the COVID-19 vaccination campaign, there were also problems with flu vaccination in 2020. In the Sept. 25 poll, 34% of health care leaders reported their practices were experiencing delays in getting the flu vaccine.
Looking ahead
Looking further ahead, the report recommended that practices make plans to boost staff morale by restoring bonuses.
In addition, MGMA suggested that physician groups reassess their space needs. “The equation is simple – fewer nonclinical staff members at your facility means you should repurpose that office space or consider finding a better fit for your new real estate needs in 2021.”
Finally, MGMA noted that the practices expanding rather than contracting their business are those increasing their value-based revenues by taking on more risk. For those groups, “growing the patient panel can help [them] seek better rates in contract negotiations.”
A version of this article first appeared on Medscape.com.
according to a December 2020 report from the Medical Group Management Association.
The report was assembled from the results of weekly Stat polls by MGMA, which consists of 15,000 group practices representing more than 350,000 physicians. During the course of the year, more than 4,800 practice leaders were surveyed, but the individual polls had far fewer respondents.
The 2020 data represents snapshots from different points in the developing public health crisis. Still, much of what practices experienced earlier in the pandemic continues to apply, and it’s likely to persist this year as long as the coronavirus spreads and its toll deepens.
One top-line conclusion of the report: the economic pain felt by practices has resulted in layoffs, furloughs, and/or reduced compensation for providers and staff.
In the May 19 weekly survey, 82% of respondents said some or all of their providers’ compensation had been affected by the crisis. About 62% said every provider had been affected. Provider compensation was cut in several ways, including reduced hours and salaries, reduced or eliminated bonuses, and lower allowances for continuing medical education.
About 61% of health care leaders said in the June 26 poll that their own compensation had decreased.
In the following week’s survey, one in three managers said their organization had reduced staff compensation. Nearly all of the respondents in this category predicted the salary reductions would be temporary.
As of March 17, early in the pandemic, 40% of health care leaders said they were experiencing staff shortages. An April 21 poll found that 53% of health care leaders were taking steps to address their providers’ and staffers’ mental health.
“The mental and emotional toll on everyone continues to be a concern, as public health authorities continue to report alarming numbers of new [COVID-19] cases, hospitalizations, and deaths,” MGMA commented.
Telehealth and remote monitoring
Nearly all of the health care leaders surveyed on March 31 reported that their practices had expanded telehealth access because of COVID-19. The percentage of patient visits handled remotely had dropped substantially by the fall, according to a Harvard University/Commonwealth Fund/Phreesia survey. Still, it remains significantly higher than it was before the pandemic.
“At the end of 2020, telemedicine continues to play a vital role in everyday practice operations and long-term planning,” the MGMA report said. One indication of this, the association said, is that health care leaders are recognizing new best practices in specialty telemedicine, such as pediatrics and ob.gyn.
According to an April 28 poll, the top three coding/billing challenges for telehealth and telephone visits amid COVID-19 were inconsistent payer rules, pay parity and accuracy, and documentation of virtual visits.
While the Centers for Medicare & Medicaid Services has loosened its regulations to allow reimbursement of telehealth in all locations and at the same level as in-person visits, most of those changes will not last beyond the public health crisis without new legislation.
More health care leaders are considering the use of remote patient monitoring, MGMA said, but only 21% of practices offered such services as of Sept. 15. The report drew a connection between these plans and the current challenge of deferred care.
In the July 21 poll, 87% of health care leaders reported that safety concerns were the top reason that patients deferred care amid COVID-19. The MGMA report quoted JaeLynn Williams, CEO of Air Methods, which provides helicopter ambulance services, as saying that many people are staying home even when they face life-threatening conditions such as chest pain, drug symptoms, inflamed appendix, and gallbladder pain.
Operational issues
Overall, MGMA said, practices that have taken a financial risk have done better during the pandemic than fee-for-service practices because their monthly capitation revenue has continued unabated. In contrast, “most groups’ struggles to sustain visits and procedures meant less revenue and lower compensation,” the report said.
In the August 18 survey, one in three health care leaders reported their practices were changing their operational metrics and how often they looked at those measures because of the pandemic. “Practice managers are asking for dashboard data in weeks instead of months to measure the drop in charges and forecast the resulting change in collections,” MGMA noted. “The type of data practice managers are asking for has also changed.”
Among the new metrics that practices are interested in, according to an MGMA article, are measures that track telehealth visits, the productivity of staff working at home, and the number of ancillary services and procedures that new patients might need based on historical data.
Nearly all health care leaders surveyed on Aug. 11 said the cost of obtaining personal protective equipment had increased during 2020. MGMA said it expects this situation to worsen if the pandemic lasts through the summer of 2021.
While everyone is talking about the botched launch of the COVID-19 vaccination campaign, there were also problems with flu vaccination in 2020. In the Sept. 25 poll, 34% of health care leaders reported their practices were experiencing delays in getting the flu vaccine.
Looking ahead
Looking further ahead, the report recommended that practices make plans to boost staff morale by restoring bonuses.
In addition, MGMA suggested that physician groups reassess their space needs. “The equation is simple – fewer nonclinical staff members at your facility means you should repurpose that office space or consider finding a better fit for your new real estate needs in 2021.”
Finally, MGMA noted that the practices expanding rather than contracting their business are those increasing their value-based revenues by taking on more risk. For those groups, “growing the patient panel can help [them] seek better rates in contract negotiations.”
A version of this article first appeared on Medscape.com.
according to a December 2020 report from the Medical Group Management Association.
The report was assembled from the results of weekly Stat polls by MGMA, which consists of 15,000 group practices representing more than 350,000 physicians. During the course of the year, more than 4,800 practice leaders were surveyed, but the individual polls had far fewer respondents.
The 2020 data represents snapshots from different points in the developing public health crisis. Still, much of what practices experienced earlier in the pandemic continues to apply, and it’s likely to persist this year as long as the coronavirus spreads and its toll deepens.
One top-line conclusion of the report: the economic pain felt by practices has resulted in layoffs, furloughs, and/or reduced compensation for providers and staff.
In the May 19 weekly survey, 82% of respondents said some or all of their providers’ compensation had been affected by the crisis. About 62% said every provider had been affected. Provider compensation was cut in several ways, including reduced hours and salaries, reduced or eliminated bonuses, and lower allowances for continuing medical education.
About 61% of health care leaders said in the June 26 poll that their own compensation had decreased.
In the following week’s survey, one in three managers said their organization had reduced staff compensation. Nearly all of the respondents in this category predicted the salary reductions would be temporary.
As of March 17, early in the pandemic, 40% of health care leaders said they were experiencing staff shortages. An April 21 poll found that 53% of health care leaders were taking steps to address their providers’ and staffers’ mental health.
“The mental and emotional toll on everyone continues to be a concern, as public health authorities continue to report alarming numbers of new [COVID-19] cases, hospitalizations, and deaths,” MGMA commented.
Telehealth and remote monitoring
Nearly all of the health care leaders surveyed on March 31 reported that their practices had expanded telehealth access because of COVID-19. The percentage of patient visits handled remotely had dropped substantially by the fall, according to a Harvard University/Commonwealth Fund/Phreesia survey. Still, it remains significantly higher than it was before the pandemic.
“At the end of 2020, telemedicine continues to play a vital role in everyday practice operations and long-term planning,” the MGMA report said. One indication of this, the association said, is that health care leaders are recognizing new best practices in specialty telemedicine, such as pediatrics and ob.gyn.
According to an April 28 poll, the top three coding/billing challenges for telehealth and telephone visits amid COVID-19 were inconsistent payer rules, pay parity and accuracy, and documentation of virtual visits.
While the Centers for Medicare & Medicaid Services has loosened its regulations to allow reimbursement of telehealth in all locations and at the same level as in-person visits, most of those changes will not last beyond the public health crisis without new legislation.
More health care leaders are considering the use of remote patient monitoring, MGMA said, but only 21% of practices offered such services as of Sept. 15. The report drew a connection between these plans and the current challenge of deferred care.
In the July 21 poll, 87% of health care leaders reported that safety concerns were the top reason that patients deferred care amid COVID-19. The MGMA report quoted JaeLynn Williams, CEO of Air Methods, which provides helicopter ambulance services, as saying that many people are staying home even when they face life-threatening conditions such as chest pain, drug symptoms, inflamed appendix, and gallbladder pain.
Operational issues
Overall, MGMA said, practices that have taken a financial risk have done better during the pandemic than fee-for-service practices because their monthly capitation revenue has continued unabated. In contrast, “most groups’ struggles to sustain visits and procedures meant less revenue and lower compensation,” the report said.
In the August 18 survey, one in three health care leaders reported their practices were changing their operational metrics and how often they looked at those measures because of the pandemic. “Practice managers are asking for dashboard data in weeks instead of months to measure the drop in charges and forecast the resulting change in collections,” MGMA noted. “The type of data practice managers are asking for has also changed.”
Among the new metrics that practices are interested in, according to an MGMA article, are measures that track telehealth visits, the productivity of staff working at home, and the number of ancillary services and procedures that new patients might need based on historical data.
Nearly all health care leaders surveyed on Aug. 11 said the cost of obtaining personal protective equipment had increased during 2020. MGMA said it expects this situation to worsen if the pandemic lasts through the summer of 2021.
While everyone is talking about the botched launch of the COVID-19 vaccination campaign, there were also problems with flu vaccination in 2020. In the Sept. 25 poll, 34% of health care leaders reported their practices were experiencing delays in getting the flu vaccine.
Looking ahead
Looking further ahead, the report recommended that practices make plans to boost staff morale by restoring bonuses.
In addition, MGMA suggested that physician groups reassess their space needs. “The equation is simple – fewer nonclinical staff members at your facility means you should repurpose that office space or consider finding a better fit for your new real estate needs in 2021.”
Finally, MGMA noted that the practices expanding rather than contracting their business are those increasing their value-based revenues by taking on more risk. For those groups, “growing the patient panel can help [them] seek better rates in contract negotiations.”
A version of this article first appeared on Medscape.com.
ACEIs, ARBs safe to continue in COVID-19: Trial published
The BRACE-CORONA trial, the first randomized trial to address the question of whether patients with COVID-19 should continue to take ACE inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) – has now been published.
The study, which was conducted in patients hospitalized with COVID-19 who were taking ACEIs or ARBs before hospitalization, showed no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue versus those assigned to continue these medications.
There were, however, hints that continuing to take ACEIs or ARBs may be beneficial for patients with more severe COVID-19.
The study was first presented at last year’s European Society of Cardiology Congress and was reported by this news organization at that time. The study was published online in JAMA on Jan. 19, 2021.
“These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment,” the authors concluded.
Led by Renato D. Lopes, MD, Duke Clinical Research Institute, Durham, N.C., the researchers explained that there has been conflicting speculation about the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on the course of COVID-19.
On the one hand, observations from animal models suggest that ACEIs and ARBs up-regulate the expression of ACE2, a receptor involved in SARS-CoV-2 infection of host target cells. This led to suggestions that these medications may enhance viral binding and cell entry. Conversely, RAAS inhibitors could benefit patients with COVID-19 through effects on angiotensin II expression and subsequent increases in angiotensin 1-7 and 1-9, which have vasodilatory and anti-inflammatory effects that might attenuate lung injury.
The BRACE-CORONA trial included 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization. The median age of the patients was 55 years. Of these patients, 57.1% were considered to have mild cases at hospital admission, and 42.9% were considered to have moderate cases.
Results showed no significant difference in the number of days alive and out of the hospital for patients in the discontinuation group (mean, 21.9 days) in comparison with patients in the continuation group (mean, 22.9 days). The mean ratio was 0.95 (95% confidence interval, 0.90-1.01).
There also was no statistically significant difference in deaths (2.7% of the discontinuation group vs. 2.8% for the continuation group); cardiovascular death (0.6% vs. 0.3%), or COVID-19 progression (38.3% vs. 32.3%).
The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs. 7.7% in the continuation group), shock requiring vasopressors (8.4% vs. 7.1%), acute MI (7.5% vs. 4.6%), new or worsening heart failure (4.2% vs. 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs. 2.8%).
The authors note that hypertension is an important comorbidity in patients with COVID-19. Recent data suggest that immune dysfunction may contribute to poor outcomes among patients who have COVID-19 and hypertension.
It has been shown that, when use of long-term medications is discontinued during hospitalization, the use of those medications is often not resumed, owing to clinical inertia. Long-term outcomes worsen as a result, the authors reported. In the current study, all patients had hypertension, and more than 50% were obese; both of these comorbidities increase the risk for poor outcomes with COVID-19.
The investigators pointed out that a sensitivity analysis in which site was regarded as a random effect showed a statistically significant finding in favor of the group that continued ACEIs or ARBs. This finding was similar to that of the on-treatment analysis. There were also statistically significant interactions between treatment effect and some subgroups, such as patients with lower oxygen saturation and greater disease severity at hospital admission. For these patients, continuing ACEIs or ARBs may be beneficial.
“The primary analyses with the null results but wide 95% confidence intervals suggest that the study might have been underpowered to detect a statistically significant benefit of continuing ACEIs or ARBs,” they said.
Dr. Lopes has received grant support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi and consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Portola, and Sanofi.
A version of this article first appeared on Medscape.com.
The BRACE-CORONA trial, the first randomized trial to address the question of whether patients with COVID-19 should continue to take ACE inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) – has now been published.
The study, which was conducted in patients hospitalized with COVID-19 who were taking ACEIs or ARBs before hospitalization, showed no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue versus those assigned to continue these medications.
There were, however, hints that continuing to take ACEIs or ARBs may be beneficial for patients with more severe COVID-19.
The study was first presented at last year’s European Society of Cardiology Congress and was reported by this news organization at that time. The study was published online in JAMA on Jan. 19, 2021.
“These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment,” the authors concluded.
Led by Renato D. Lopes, MD, Duke Clinical Research Institute, Durham, N.C., the researchers explained that there has been conflicting speculation about the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on the course of COVID-19.
On the one hand, observations from animal models suggest that ACEIs and ARBs up-regulate the expression of ACE2, a receptor involved in SARS-CoV-2 infection of host target cells. This led to suggestions that these medications may enhance viral binding and cell entry. Conversely, RAAS inhibitors could benefit patients with COVID-19 through effects on angiotensin II expression and subsequent increases in angiotensin 1-7 and 1-9, which have vasodilatory and anti-inflammatory effects that might attenuate lung injury.
The BRACE-CORONA trial included 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization. The median age of the patients was 55 years. Of these patients, 57.1% were considered to have mild cases at hospital admission, and 42.9% were considered to have moderate cases.
Results showed no significant difference in the number of days alive and out of the hospital for patients in the discontinuation group (mean, 21.9 days) in comparison with patients in the continuation group (mean, 22.9 days). The mean ratio was 0.95 (95% confidence interval, 0.90-1.01).
There also was no statistically significant difference in deaths (2.7% of the discontinuation group vs. 2.8% for the continuation group); cardiovascular death (0.6% vs. 0.3%), or COVID-19 progression (38.3% vs. 32.3%).
The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs. 7.7% in the continuation group), shock requiring vasopressors (8.4% vs. 7.1%), acute MI (7.5% vs. 4.6%), new or worsening heart failure (4.2% vs. 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs. 2.8%).
The authors note that hypertension is an important comorbidity in patients with COVID-19. Recent data suggest that immune dysfunction may contribute to poor outcomes among patients who have COVID-19 and hypertension.
It has been shown that, when use of long-term medications is discontinued during hospitalization, the use of those medications is often not resumed, owing to clinical inertia. Long-term outcomes worsen as a result, the authors reported. In the current study, all patients had hypertension, and more than 50% were obese; both of these comorbidities increase the risk for poor outcomes with COVID-19.
The investigators pointed out that a sensitivity analysis in which site was regarded as a random effect showed a statistically significant finding in favor of the group that continued ACEIs or ARBs. This finding was similar to that of the on-treatment analysis. There were also statistically significant interactions between treatment effect and some subgroups, such as patients with lower oxygen saturation and greater disease severity at hospital admission. For these patients, continuing ACEIs or ARBs may be beneficial.
“The primary analyses with the null results but wide 95% confidence intervals suggest that the study might have been underpowered to detect a statistically significant benefit of continuing ACEIs or ARBs,” they said.
Dr. Lopes has received grant support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi and consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Portola, and Sanofi.
A version of this article first appeared on Medscape.com.
The BRACE-CORONA trial, the first randomized trial to address the question of whether patients with COVID-19 should continue to take ACE inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) – has now been published.
The study, which was conducted in patients hospitalized with COVID-19 who were taking ACEIs or ARBs before hospitalization, showed no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue versus those assigned to continue these medications.
There were, however, hints that continuing to take ACEIs or ARBs may be beneficial for patients with more severe COVID-19.
The study was first presented at last year’s European Society of Cardiology Congress and was reported by this news organization at that time. The study was published online in JAMA on Jan. 19, 2021.
“These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment,” the authors concluded.
Led by Renato D. Lopes, MD, Duke Clinical Research Institute, Durham, N.C., the researchers explained that there has been conflicting speculation about the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on the course of COVID-19.
On the one hand, observations from animal models suggest that ACEIs and ARBs up-regulate the expression of ACE2, a receptor involved in SARS-CoV-2 infection of host target cells. This led to suggestions that these medications may enhance viral binding and cell entry. Conversely, RAAS inhibitors could benefit patients with COVID-19 through effects on angiotensin II expression and subsequent increases in angiotensin 1-7 and 1-9, which have vasodilatory and anti-inflammatory effects that might attenuate lung injury.
The BRACE-CORONA trial included 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization. The median age of the patients was 55 years. Of these patients, 57.1% were considered to have mild cases at hospital admission, and 42.9% were considered to have moderate cases.
Results showed no significant difference in the number of days alive and out of the hospital for patients in the discontinuation group (mean, 21.9 days) in comparison with patients in the continuation group (mean, 22.9 days). The mean ratio was 0.95 (95% confidence interval, 0.90-1.01).
There also was no statistically significant difference in deaths (2.7% of the discontinuation group vs. 2.8% for the continuation group); cardiovascular death (0.6% vs. 0.3%), or COVID-19 progression (38.3% vs. 32.3%).
The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs. 7.7% in the continuation group), shock requiring vasopressors (8.4% vs. 7.1%), acute MI (7.5% vs. 4.6%), new or worsening heart failure (4.2% vs. 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs. 2.8%).
The authors note that hypertension is an important comorbidity in patients with COVID-19. Recent data suggest that immune dysfunction may contribute to poor outcomes among patients who have COVID-19 and hypertension.
It has been shown that, when use of long-term medications is discontinued during hospitalization, the use of those medications is often not resumed, owing to clinical inertia. Long-term outcomes worsen as a result, the authors reported. In the current study, all patients had hypertension, and more than 50% were obese; both of these comorbidities increase the risk for poor outcomes with COVID-19.
The investigators pointed out that a sensitivity analysis in which site was regarded as a random effect showed a statistically significant finding in favor of the group that continued ACEIs or ARBs. This finding was similar to that of the on-treatment analysis. There were also statistically significant interactions between treatment effect and some subgroups, such as patients with lower oxygen saturation and greater disease severity at hospital admission. For these patients, continuing ACEIs or ARBs may be beneficial.
“The primary analyses with the null results but wide 95% confidence intervals suggest that the study might have been underpowered to detect a statistically significant benefit of continuing ACEIs or ARBs,” they said.
Dr. Lopes has received grant support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi and consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Portola, and Sanofi.
A version of this article first appeared on Medscape.com.
Widespread liver disease missed in patients with T2D
Among these calls is a pending statement from the Endocrine Society, the American Association of Clinical Endocrinologists, the American Gastroenterology Association, and other groups on what the growing appreciation of highly prevalent liver disease in patients with type 2 diabetes (T2D) means for assessing and managing patients. Publication of the statement is expected by spring 2021, said Christos S. Mantzoros, MD, DSc, PhD, chief of endocrinology for the Veterans Affairs Boston Healthcare System and a representative from the Endocrine Society to the statement-writing panel.
This upcoming “Call to Action” from these groups argues for a “need to collaborate across disciplines, and work together on establishing clinical guidelines, and creating new diagnostics and therapeutics,” said Dr. Mantzoros in an interview.
“Over time, it is becoming clearer that management of NAFLD [nonalcoholic fatty liver disease]/NASH [nonalcoholic steatohepatitis] requires a multidisciplinary panel of doctors ranging from primary care practitioners, to endocrinologists, and hepatologists. Given that the nature of the disease crosses scientific discipline boundaries, and that the number of patients is so large (it is estimated that about one in four U.S. adults have NAFLD), not all patients can be treated at the limited number of hepatology centers.
“However, not all stakeholders have fully realized this fact, and no effort had been undertaken so far by any professional society to develop a coordinated approach and clinical care pathway for NAFLD/NASH. The ‘Call to Action’ meeting can be considered as a starting point for such an important effort,” said Dr. Mantzoros, who is also a professor of medicine at Harvard Medical School and director of the human nutrition unit at Beth Israel Deaconess Medical Center, both in Boston.
Dramatic prevalence rates in patients with T2D
Results from two independent epidemiology reports, published in December 2020, documented steatosis (the fatty liver of NAFLD) in 70%-74% of unselected U.S. patients with T2D, advanced liver fibrosis accompanying this disease in 6%-15%, and previously unrecognized cirrhosis in 3%-8%.
One of these reports analyzed 825 patients with T2D included in the National Health and Nutritional Examination Survey of 2017-2018 run by the Centers for Disease Control and Prevention. All these patients, selected to be representative of the overall U.S. adult population with T2D, underwent transient elastography to identify steatosis and fibrosis, the first U.S. National Health Survey to run this type of population-based survey. The results showed an overall steatosis prevalence of 74% with grade 3 steatosis in 58%, advanced liver fibrosis in 15%, and cirrhosis in 8%, reported the team of Italian researchers who analyzed the data .
The second study focused on a single-center series of 561 patients with T2D who also underwent screening by transient elastography during 2018-2020 and had no history of NAFLD or other liver disease, or alcohol abuse. The imaging results showed a NAFLD prevalence of 70%, with 54% of the entire group diagnosed with severe steatosis, severe fibrosis in 6%, and cirrhosis in 3%. Among the 54% of patients with severe steatosis, 30% also had severe liver fibrosis. About 70% of the 561 patients assessed came from either the family medicine or general internal medicine clinics of the University of Florida, Gainesville, with the remaining 30% enrolled from the center’s endocrinology/diabetes outpatient clinic.
Neither report documented a NASH prevalence, which cannot receive definitive diagnosis by imaging alone. “This is the first study of its kind in the U.S. to establish the magnitude of [liver] disease burden in random patients with T2D seeking regular outpatient care,” wrote the University of Florida research team, led by Kenneth Cusi, MD, professor and chief of the university’s division of endocrinology, diabetes, and metabolism. Their finding that patients with T2D and previously unknown to have NAFLD had a 15% prevalence of moderate or advanced liver fibrosis “should trigger a call to action by all clinicians taking care of patients with T2D. Patient and physician awareness of the hepatic and extrahepatic complications of NASH, and reversing current diagnosis and treatment inertia will be the only way to avert the looming epidemic of cirrhosis in patients with diabetes.”
“Endocrinologists don’t ‘see’ NAFLD and NASH” in their patients with T2D “ because they don’t think about it,” Dr. Mantzoros declared.
“Why is NASH underdiagnosed and undertreated? Because many physicians aren’t aware of it,” agreed Dr. Cusi during a talk in December 2020 at the 18th World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease (WCIRDC). “You never find what you don’t look for.”
“Endocrinologists should do the tests for NASH [in patients with T2D], but we’re all guilty of not doing it enough,” Tracey McLaughlin, MD, an endocrinologist and professor of medicine at Stanford (Calif.) University, commented during the WCIRDC.
These prevalence numbers demand that clinicians suspect liver disease “in any patient with diabetes, especially patients with obesity who are older and have components of metabolic syndrome,” said Dr. Mantzoros. “We need to screen, refer the most advanced cases, and treat the early- and mid-stage cases.”
How to find NASH
Both the American Diabetes Association and the European Association for the Study of Diabetes call for routine screening of patients with T2D, starting with a check of liver enzymes, such as ALT, but no clear consensus exists for the specifics of screening beyond that. Dr. Mantzoros, Dr. Cusi, and other experts agree that the scheme for assessing liver disease in patients with T2D starts with regular monitoring of elevations in liver enzymes including ALT. Next is noninvasive ultrasound assessment of the extent of liver fibrosis inferred from the organ’s stiffness using transient elastography. Another frequently cited initial screening tool is the Fibrosis-4 (FIB-4) score, which incorporates a patient’s age, platelet count, and levels of ALT and a second liver enzyme, AST.
“There is more consensus about FIB-4 and then elastography, but some people use tests other than FIB-4. Unfortunately there is no perfect diagnostic test today. A top priority is to define the best diagnostic test,” said Dr. Mantzoros, who is leading an effort to try to refine screening using artificial intelligence.
“FIB-4 is simple, easy, and well validated,” commented Dr. Cusi during the WCIRDC last December. “FIB-4 and elastography should get you pretty close” to identifying patients with T2D and significant liver disease.
But in a recent editorial, Dr. Cusi agreed on the need for “more reliable tests for the diagnosis of NASH and advanced fibrosis in patients with T2D. Significant work is being done in the field to validate novel and more sophisticated fibrosis biomarkers. Future studies will help us enter a new era of precision medicine where biomarkers will identify and target therapy to those with more active disease at risk for cirrhosis,” he wrote.
“The ultimate goal is to diagnose fibrosis at an early stage to prevent people from developing cirrhosis,” Dr. Cusi said in a recent written statement. “We’re trying to identify these problems before they’re unfixable. Once someone has cirrhosis, there isn’t a whole lot you can do.”
Pioglitazone remains the best-documented treatment
Perhaps some of the inertia in diagnosing NAFLD, NASH, and liver fibrosis in patients with T2D is dissatisfaction with current treatment options, although several proven options exist, notably weight loss and diet, and thiazolidinedione (TZD) pioglitazone. But weight loss and diet pose issues for patient compliance and durability of the intervention, and many clinicians consider pioglitazone flawed by its potential adverse effects.
“When we don’t have an established treatment for something, we tend to not measure it or go after it. That’s been true of liver disease” in patients with T2D, said Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif., during the WCIRDC.
Treatment with pioglitazone has resolved NASH in about a third of patients compared with placebo, prevented fibrosis progression, and cut cardiovascular disease events, noted Dr. Cusi during the WCIRDC.
“Pioglitazone is used in only 8% of patients with T2D, or less, but we need to use it more often because of its proven efficacy in patients with T2D and NASH” said Dr. Mantzoros. “The problem is that pioglitazone has side effects, including weight gain and fluid retention, that makes it less attractive unless one thinks about the diagnosis of NASH.”
Others highlight that the adverse effects of pioglitazone have been either misunderstood, or can be effectively minimized with careful dosing.
“The data with the TZDs are much stronger than the data from anything else. TZDs have gotten a bad name because they also work in the kidney and enhance fluid reabsorption. We use modest dosages of pioglitazone, 15 mg or 30 mg a day, to avoid excess fluid retention,” Ralph A. DeFronzo, MD, chief of the diabetes division and professor of medicine at the University of Texas Health Science Center, San Antonio, said during the WCIRDC. “The best drug for NASH is pioglitazone. No other drug beats it” based on current data, Dr. DeFronzo asserted.
Other strategies include the potential to pair pioglitazone with other interventions that can blunt a weight-gain effect. One intriguing combination would combine pioglitazone with a GLP-1 receptor agonist, a drug class that can produce significant weight loss. Results from a phase 2 study showed promise for semaglutide (Rybelsus) in treating patients with NASH.
Getting the name right
Another factor that may be keeping NAFLD and NASH from achieving a higher profile for patients with T2D are those names, which focus on what the diseases are not – nonalcoholic – rather than what they are.
A series of recent publications in both the endocrinology and hepatology literature have called for renaming these disorders either “metabolic (dysfunction)–associated fatty liver disease (MALFD)”, or “dysmetabolism-associated fatty liver disease (DALFD)”.
“The names NAFLD and NASH indicate absence of alcohol as a cause, but the disease is also characterized by the absence of other causes, such as autoimmune disorders or hepatitis. The names were coined when we did not know much about these diseases. We now know that it is dysmetabolism that causes these conditions, and so we need to adopt a new, more accurate name,” explained Dr. Mantzoros, who has published support for a name change.
While many agree, some have raised concerns as to whether a name change now is premature. A group of hepatologists recently published a rebuttal to an immediate name change , saying that, “although we are in agreement that metabolic fatty liver disease may more accurately and positively reflect the relevant risk factors better than the age-old term nonalcoholic fatty liver disease, the term still leaves a great deal of ambiguity. A name change will be appropriate when informed by a new understanding of the molecular basis of the disease entity, insights that fundamentally change risk stratification, or other important aspects of the disease. We may be on the cusp of this, but we are not there yet.”
Dr. Mantzoros agreed, but for somewhat different reasons.
“We need to be careful and deliberate, because there is a significant body of knowledge and a lot of data from clinical trials collected using the old definitions. We need to find an appropriate time frame for a [name] transition. We need to find a nice and robust way to productively bridge the old to the new,” he said. “We also need new diagnostic criteria, and new therapies. A new name and definition will facilitate progress.”
Dr. Mantzoros been a shareholder of and consultant to Coherus and Pangea, he has been a consultant to AstraZeneca, Eisai, Genfit, Intercept, Novo Nordisk, P.E.S., and Regeneron, and has received travel support from the Metabolic Institute of America and the California Walnut Commission. Dr. Cusi has been a consultant to and has received research funding from numerous drug companies. Dr. McLaughlin is a consultant to January AI. Dr. Handelsman has been a consultant to numerous drug companies. Dr. DeFronzo received research grants from AstraZeneca, Janssen, and Merck; he has been an adviser to AstraZeneca, Boehringer Ingelheim, Intarcia, Janssen, and Novo Nordisk; and he has been a speaker on behalf of AstraZeneca and Novo Nordisk.
Among these calls is a pending statement from the Endocrine Society, the American Association of Clinical Endocrinologists, the American Gastroenterology Association, and other groups on what the growing appreciation of highly prevalent liver disease in patients with type 2 diabetes (T2D) means for assessing and managing patients. Publication of the statement is expected by spring 2021, said Christos S. Mantzoros, MD, DSc, PhD, chief of endocrinology for the Veterans Affairs Boston Healthcare System and a representative from the Endocrine Society to the statement-writing panel.
This upcoming “Call to Action” from these groups argues for a “need to collaborate across disciplines, and work together on establishing clinical guidelines, and creating new diagnostics and therapeutics,” said Dr. Mantzoros in an interview.
“Over time, it is becoming clearer that management of NAFLD [nonalcoholic fatty liver disease]/NASH [nonalcoholic steatohepatitis] requires a multidisciplinary panel of doctors ranging from primary care practitioners, to endocrinologists, and hepatologists. Given that the nature of the disease crosses scientific discipline boundaries, and that the number of patients is so large (it is estimated that about one in four U.S. adults have NAFLD), not all patients can be treated at the limited number of hepatology centers.
“However, not all stakeholders have fully realized this fact, and no effort had been undertaken so far by any professional society to develop a coordinated approach and clinical care pathway for NAFLD/NASH. The ‘Call to Action’ meeting can be considered as a starting point for such an important effort,” said Dr. Mantzoros, who is also a professor of medicine at Harvard Medical School and director of the human nutrition unit at Beth Israel Deaconess Medical Center, both in Boston.
Dramatic prevalence rates in patients with T2D
Results from two independent epidemiology reports, published in December 2020, documented steatosis (the fatty liver of NAFLD) in 70%-74% of unselected U.S. patients with T2D, advanced liver fibrosis accompanying this disease in 6%-15%, and previously unrecognized cirrhosis in 3%-8%.
One of these reports analyzed 825 patients with T2D included in the National Health and Nutritional Examination Survey of 2017-2018 run by the Centers for Disease Control and Prevention. All these patients, selected to be representative of the overall U.S. adult population with T2D, underwent transient elastography to identify steatosis and fibrosis, the first U.S. National Health Survey to run this type of population-based survey. The results showed an overall steatosis prevalence of 74% with grade 3 steatosis in 58%, advanced liver fibrosis in 15%, and cirrhosis in 8%, reported the team of Italian researchers who analyzed the data .
The second study focused on a single-center series of 561 patients with T2D who also underwent screening by transient elastography during 2018-2020 and had no history of NAFLD or other liver disease, or alcohol abuse. The imaging results showed a NAFLD prevalence of 70%, with 54% of the entire group diagnosed with severe steatosis, severe fibrosis in 6%, and cirrhosis in 3%. Among the 54% of patients with severe steatosis, 30% also had severe liver fibrosis. About 70% of the 561 patients assessed came from either the family medicine or general internal medicine clinics of the University of Florida, Gainesville, with the remaining 30% enrolled from the center’s endocrinology/diabetes outpatient clinic.
Neither report documented a NASH prevalence, which cannot receive definitive diagnosis by imaging alone. “This is the first study of its kind in the U.S. to establish the magnitude of [liver] disease burden in random patients with T2D seeking regular outpatient care,” wrote the University of Florida research team, led by Kenneth Cusi, MD, professor and chief of the university’s division of endocrinology, diabetes, and metabolism. Their finding that patients with T2D and previously unknown to have NAFLD had a 15% prevalence of moderate or advanced liver fibrosis “should trigger a call to action by all clinicians taking care of patients with T2D. Patient and physician awareness of the hepatic and extrahepatic complications of NASH, and reversing current diagnosis and treatment inertia will be the only way to avert the looming epidemic of cirrhosis in patients with diabetes.”
“Endocrinologists don’t ‘see’ NAFLD and NASH” in their patients with T2D “ because they don’t think about it,” Dr. Mantzoros declared.
“Why is NASH underdiagnosed and undertreated? Because many physicians aren’t aware of it,” agreed Dr. Cusi during a talk in December 2020 at the 18th World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease (WCIRDC). “You never find what you don’t look for.”
“Endocrinologists should do the tests for NASH [in patients with T2D], but we’re all guilty of not doing it enough,” Tracey McLaughlin, MD, an endocrinologist and professor of medicine at Stanford (Calif.) University, commented during the WCIRDC.
These prevalence numbers demand that clinicians suspect liver disease “in any patient with diabetes, especially patients with obesity who are older and have components of metabolic syndrome,” said Dr. Mantzoros. “We need to screen, refer the most advanced cases, and treat the early- and mid-stage cases.”
How to find NASH
Both the American Diabetes Association and the European Association for the Study of Diabetes call for routine screening of patients with T2D, starting with a check of liver enzymes, such as ALT, but no clear consensus exists for the specifics of screening beyond that. Dr. Mantzoros, Dr. Cusi, and other experts agree that the scheme for assessing liver disease in patients with T2D starts with regular monitoring of elevations in liver enzymes including ALT. Next is noninvasive ultrasound assessment of the extent of liver fibrosis inferred from the organ’s stiffness using transient elastography. Another frequently cited initial screening tool is the Fibrosis-4 (FIB-4) score, which incorporates a patient’s age, platelet count, and levels of ALT and a second liver enzyme, AST.
“There is more consensus about FIB-4 and then elastography, but some people use tests other than FIB-4. Unfortunately there is no perfect diagnostic test today. A top priority is to define the best diagnostic test,” said Dr. Mantzoros, who is leading an effort to try to refine screening using artificial intelligence.
“FIB-4 is simple, easy, and well validated,” commented Dr. Cusi during the WCIRDC last December. “FIB-4 and elastography should get you pretty close” to identifying patients with T2D and significant liver disease.
But in a recent editorial, Dr. Cusi agreed on the need for “more reliable tests for the diagnosis of NASH and advanced fibrosis in patients with T2D. Significant work is being done in the field to validate novel and more sophisticated fibrosis biomarkers. Future studies will help us enter a new era of precision medicine where biomarkers will identify and target therapy to those with more active disease at risk for cirrhosis,” he wrote.
“The ultimate goal is to diagnose fibrosis at an early stage to prevent people from developing cirrhosis,” Dr. Cusi said in a recent written statement. “We’re trying to identify these problems before they’re unfixable. Once someone has cirrhosis, there isn’t a whole lot you can do.”
Pioglitazone remains the best-documented treatment
Perhaps some of the inertia in diagnosing NAFLD, NASH, and liver fibrosis in patients with T2D is dissatisfaction with current treatment options, although several proven options exist, notably weight loss and diet, and thiazolidinedione (TZD) pioglitazone. But weight loss and diet pose issues for patient compliance and durability of the intervention, and many clinicians consider pioglitazone flawed by its potential adverse effects.
“When we don’t have an established treatment for something, we tend to not measure it or go after it. That’s been true of liver disease” in patients with T2D, said Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif., during the WCIRDC.
Treatment with pioglitazone has resolved NASH in about a third of patients compared with placebo, prevented fibrosis progression, and cut cardiovascular disease events, noted Dr. Cusi during the WCIRDC.
“Pioglitazone is used in only 8% of patients with T2D, or less, but we need to use it more often because of its proven efficacy in patients with T2D and NASH” said Dr. Mantzoros. “The problem is that pioglitazone has side effects, including weight gain and fluid retention, that makes it less attractive unless one thinks about the diagnosis of NASH.”
Others highlight that the adverse effects of pioglitazone have been either misunderstood, or can be effectively minimized with careful dosing.
“The data with the TZDs are much stronger than the data from anything else. TZDs have gotten a bad name because they also work in the kidney and enhance fluid reabsorption. We use modest dosages of pioglitazone, 15 mg or 30 mg a day, to avoid excess fluid retention,” Ralph A. DeFronzo, MD, chief of the diabetes division and professor of medicine at the University of Texas Health Science Center, San Antonio, said during the WCIRDC. “The best drug for NASH is pioglitazone. No other drug beats it” based on current data, Dr. DeFronzo asserted.
Other strategies include the potential to pair pioglitazone with other interventions that can blunt a weight-gain effect. One intriguing combination would combine pioglitazone with a GLP-1 receptor agonist, a drug class that can produce significant weight loss. Results from a phase 2 study showed promise for semaglutide (Rybelsus) in treating patients with NASH.
Getting the name right
Another factor that may be keeping NAFLD and NASH from achieving a higher profile for patients with T2D are those names, which focus on what the diseases are not – nonalcoholic – rather than what they are.
A series of recent publications in both the endocrinology and hepatology literature have called for renaming these disorders either “metabolic (dysfunction)–associated fatty liver disease (MALFD)”, or “dysmetabolism-associated fatty liver disease (DALFD)”.
“The names NAFLD and NASH indicate absence of alcohol as a cause, but the disease is also characterized by the absence of other causes, such as autoimmune disorders or hepatitis. The names were coined when we did not know much about these diseases. We now know that it is dysmetabolism that causes these conditions, and so we need to adopt a new, more accurate name,” explained Dr. Mantzoros, who has published support for a name change.
While many agree, some have raised concerns as to whether a name change now is premature. A group of hepatologists recently published a rebuttal to an immediate name change , saying that, “although we are in agreement that metabolic fatty liver disease may more accurately and positively reflect the relevant risk factors better than the age-old term nonalcoholic fatty liver disease, the term still leaves a great deal of ambiguity. A name change will be appropriate when informed by a new understanding of the molecular basis of the disease entity, insights that fundamentally change risk stratification, or other important aspects of the disease. We may be on the cusp of this, but we are not there yet.”
Dr. Mantzoros agreed, but for somewhat different reasons.
“We need to be careful and deliberate, because there is a significant body of knowledge and a lot of data from clinical trials collected using the old definitions. We need to find an appropriate time frame for a [name] transition. We need to find a nice and robust way to productively bridge the old to the new,” he said. “We also need new diagnostic criteria, and new therapies. A new name and definition will facilitate progress.”
Dr. Mantzoros been a shareholder of and consultant to Coherus and Pangea, he has been a consultant to AstraZeneca, Eisai, Genfit, Intercept, Novo Nordisk, P.E.S., and Regeneron, and has received travel support from the Metabolic Institute of America and the California Walnut Commission. Dr. Cusi has been a consultant to and has received research funding from numerous drug companies. Dr. McLaughlin is a consultant to January AI. Dr. Handelsman has been a consultant to numerous drug companies. Dr. DeFronzo received research grants from AstraZeneca, Janssen, and Merck; he has been an adviser to AstraZeneca, Boehringer Ingelheim, Intarcia, Janssen, and Novo Nordisk; and he has been a speaker on behalf of AstraZeneca and Novo Nordisk.
Among these calls is a pending statement from the Endocrine Society, the American Association of Clinical Endocrinologists, the American Gastroenterology Association, and other groups on what the growing appreciation of highly prevalent liver disease in patients with type 2 diabetes (T2D) means for assessing and managing patients. Publication of the statement is expected by spring 2021, said Christos S. Mantzoros, MD, DSc, PhD, chief of endocrinology for the Veterans Affairs Boston Healthcare System and a representative from the Endocrine Society to the statement-writing panel.
This upcoming “Call to Action” from these groups argues for a “need to collaborate across disciplines, and work together on establishing clinical guidelines, and creating new diagnostics and therapeutics,” said Dr. Mantzoros in an interview.
“Over time, it is becoming clearer that management of NAFLD [nonalcoholic fatty liver disease]/NASH [nonalcoholic steatohepatitis] requires a multidisciplinary panel of doctors ranging from primary care practitioners, to endocrinologists, and hepatologists. Given that the nature of the disease crosses scientific discipline boundaries, and that the number of patients is so large (it is estimated that about one in four U.S. adults have NAFLD), not all patients can be treated at the limited number of hepatology centers.
“However, not all stakeholders have fully realized this fact, and no effort had been undertaken so far by any professional society to develop a coordinated approach and clinical care pathway for NAFLD/NASH. The ‘Call to Action’ meeting can be considered as a starting point for such an important effort,” said Dr. Mantzoros, who is also a professor of medicine at Harvard Medical School and director of the human nutrition unit at Beth Israel Deaconess Medical Center, both in Boston.
Dramatic prevalence rates in patients with T2D
Results from two independent epidemiology reports, published in December 2020, documented steatosis (the fatty liver of NAFLD) in 70%-74% of unselected U.S. patients with T2D, advanced liver fibrosis accompanying this disease in 6%-15%, and previously unrecognized cirrhosis in 3%-8%.
One of these reports analyzed 825 patients with T2D included in the National Health and Nutritional Examination Survey of 2017-2018 run by the Centers for Disease Control and Prevention. All these patients, selected to be representative of the overall U.S. adult population with T2D, underwent transient elastography to identify steatosis and fibrosis, the first U.S. National Health Survey to run this type of population-based survey. The results showed an overall steatosis prevalence of 74% with grade 3 steatosis in 58%, advanced liver fibrosis in 15%, and cirrhosis in 8%, reported the team of Italian researchers who analyzed the data .
The second study focused on a single-center series of 561 patients with T2D who also underwent screening by transient elastography during 2018-2020 and had no history of NAFLD or other liver disease, or alcohol abuse. The imaging results showed a NAFLD prevalence of 70%, with 54% of the entire group diagnosed with severe steatosis, severe fibrosis in 6%, and cirrhosis in 3%. Among the 54% of patients with severe steatosis, 30% also had severe liver fibrosis. About 70% of the 561 patients assessed came from either the family medicine or general internal medicine clinics of the University of Florida, Gainesville, with the remaining 30% enrolled from the center’s endocrinology/diabetes outpatient clinic.
Neither report documented a NASH prevalence, which cannot receive definitive diagnosis by imaging alone. “This is the first study of its kind in the U.S. to establish the magnitude of [liver] disease burden in random patients with T2D seeking regular outpatient care,” wrote the University of Florida research team, led by Kenneth Cusi, MD, professor and chief of the university’s division of endocrinology, diabetes, and metabolism. Their finding that patients with T2D and previously unknown to have NAFLD had a 15% prevalence of moderate or advanced liver fibrosis “should trigger a call to action by all clinicians taking care of patients with T2D. Patient and physician awareness of the hepatic and extrahepatic complications of NASH, and reversing current diagnosis and treatment inertia will be the only way to avert the looming epidemic of cirrhosis in patients with diabetes.”
“Endocrinologists don’t ‘see’ NAFLD and NASH” in their patients with T2D “ because they don’t think about it,” Dr. Mantzoros declared.
“Why is NASH underdiagnosed and undertreated? Because many physicians aren’t aware of it,” agreed Dr. Cusi during a talk in December 2020 at the 18th World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease (WCIRDC). “You never find what you don’t look for.”
“Endocrinologists should do the tests for NASH [in patients with T2D], but we’re all guilty of not doing it enough,” Tracey McLaughlin, MD, an endocrinologist and professor of medicine at Stanford (Calif.) University, commented during the WCIRDC.
These prevalence numbers demand that clinicians suspect liver disease “in any patient with diabetes, especially patients with obesity who are older and have components of metabolic syndrome,” said Dr. Mantzoros. “We need to screen, refer the most advanced cases, and treat the early- and mid-stage cases.”
How to find NASH
Both the American Diabetes Association and the European Association for the Study of Diabetes call for routine screening of patients with T2D, starting with a check of liver enzymes, such as ALT, but no clear consensus exists for the specifics of screening beyond that. Dr. Mantzoros, Dr. Cusi, and other experts agree that the scheme for assessing liver disease in patients with T2D starts with regular monitoring of elevations in liver enzymes including ALT. Next is noninvasive ultrasound assessment of the extent of liver fibrosis inferred from the organ’s stiffness using transient elastography. Another frequently cited initial screening tool is the Fibrosis-4 (FIB-4) score, which incorporates a patient’s age, platelet count, and levels of ALT and a second liver enzyme, AST.
“There is more consensus about FIB-4 and then elastography, but some people use tests other than FIB-4. Unfortunately there is no perfect diagnostic test today. A top priority is to define the best diagnostic test,” said Dr. Mantzoros, who is leading an effort to try to refine screening using artificial intelligence.
“FIB-4 is simple, easy, and well validated,” commented Dr. Cusi during the WCIRDC last December. “FIB-4 and elastography should get you pretty close” to identifying patients with T2D and significant liver disease.
But in a recent editorial, Dr. Cusi agreed on the need for “more reliable tests for the diagnosis of NASH and advanced fibrosis in patients with T2D. Significant work is being done in the field to validate novel and more sophisticated fibrosis biomarkers. Future studies will help us enter a new era of precision medicine where biomarkers will identify and target therapy to those with more active disease at risk for cirrhosis,” he wrote.
“The ultimate goal is to diagnose fibrosis at an early stage to prevent people from developing cirrhosis,” Dr. Cusi said in a recent written statement. “We’re trying to identify these problems before they’re unfixable. Once someone has cirrhosis, there isn’t a whole lot you can do.”
Pioglitazone remains the best-documented treatment
Perhaps some of the inertia in diagnosing NAFLD, NASH, and liver fibrosis in patients with T2D is dissatisfaction with current treatment options, although several proven options exist, notably weight loss and diet, and thiazolidinedione (TZD) pioglitazone. But weight loss and diet pose issues for patient compliance and durability of the intervention, and many clinicians consider pioglitazone flawed by its potential adverse effects.
“When we don’t have an established treatment for something, we tend to not measure it or go after it. That’s been true of liver disease” in patients with T2D, said Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif., during the WCIRDC.
Treatment with pioglitazone has resolved NASH in about a third of patients compared with placebo, prevented fibrosis progression, and cut cardiovascular disease events, noted Dr. Cusi during the WCIRDC.
“Pioglitazone is used in only 8% of patients with T2D, or less, but we need to use it more often because of its proven efficacy in patients with T2D and NASH” said Dr. Mantzoros. “The problem is that pioglitazone has side effects, including weight gain and fluid retention, that makes it less attractive unless one thinks about the diagnosis of NASH.”
Others highlight that the adverse effects of pioglitazone have been either misunderstood, or can be effectively minimized with careful dosing.
“The data with the TZDs are much stronger than the data from anything else. TZDs have gotten a bad name because they also work in the kidney and enhance fluid reabsorption. We use modest dosages of pioglitazone, 15 mg or 30 mg a day, to avoid excess fluid retention,” Ralph A. DeFronzo, MD, chief of the diabetes division and professor of medicine at the University of Texas Health Science Center, San Antonio, said during the WCIRDC. “The best drug for NASH is pioglitazone. No other drug beats it” based on current data, Dr. DeFronzo asserted.
Other strategies include the potential to pair pioglitazone with other interventions that can blunt a weight-gain effect. One intriguing combination would combine pioglitazone with a GLP-1 receptor agonist, a drug class that can produce significant weight loss. Results from a phase 2 study showed promise for semaglutide (Rybelsus) in treating patients with NASH.
Getting the name right
Another factor that may be keeping NAFLD and NASH from achieving a higher profile for patients with T2D are those names, which focus on what the diseases are not – nonalcoholic – rather than what they are.
A series of recent publications in both the endocrinology and hepatology literature have called for renaming these disorders either “metabolic (dysfunction)–associated fatty liver disease (MALFD)”, or “dysmetabolism-associated fatty liver disease (DALFD)”.
“The names NAFLD and NASH indicate absence of alcohol as a cause, but the disease is also characterized by the absence of other causes, such as autoimmune disorders or hepatitis. The names were coined when we did not know much about these diseases. We now know that it is dysmetabolism that causes these conditions, and so we need to adopt a new, more accurate name,” explained Dr. Mantzoros, who has published support for a name change.
While many agree, some have raised concerns as to whether a name change now is premature. A group of hepatologists recently published a rebuttal to an immediate name change , saying that, “although we are in agreement that metabolic fatty liver disease may more accurately and positively reflect the relevant risk factors better than the age-old term nonalcoholic fatty liver disease, the term still leaves a great deal of ambiguity. A name change will be appropriate when informed by a new understanding of the molecular basis of the disease entity, insights that fundamentally change risk stratification, or other important aspects of the disease. We may be on the cusp of this, but we are not there yet.”
Dr. Mantzoros agreed, but for somewhat different reasons.
“We need to be careful and deliberate, because there is a significant body of knowledge and a lot of data from clinical trials collected using the old definitions. We need to find an appropriate time frame for a [name] transition. We need to find a nice and robust way to productively bridge the old to the new,” he said. “We also need new diagnostic criteria, and new therapies. A new name and definition will facilitate progress.”
Dr. Mantzoros been a shareholder of and consultant to Coherus and Pangea, he has been a consultant to AstraZeneca, Eisai, Genfit, Intercept, Novo Nordisk, P.E.S., and Regeneron, and has received travel support from the Metabolic Institute of America and the California Walnut Commission. Dr. Cusi has been a consultant to and has received research funding from numerous drug companies. Dr. McLaughlin is a consultant to January AI. Dr. Handelsman has been a consultant to numerous drug companies. Dr. DeFronzo received research grants from AstraZeneca, Janssen, and Merck; he has been an adviser to AstraZeneca, Boehringer Ingelheim, Intarcia, Janssen, and Novo Nordisk; and he has been a speaker on behalf of AstraZeneca and Novo Nordisk.
President Biden signs 10 new orders to help fight COVID-19
“For the past year, we couldn’t rely on the federal government to act with the urgency and focus and coordination we needed, and we have seen the tragic cost of that failure,” Mr. Biden said in remarks from the White House, unveiling his 198-page National Strategy for the COVID-19 Response and Pandemic Preparedness.
He said as many as 500,000 Americans will have died by February. “It’s going to take months for us to turn things around,” he said.
“Our national strategy is comprehensive – it’s based on science, not politics; it’s based on truth, not denial,” Mr. Biden said. He also promised to restore public trust, in part by having scientists and public health experts speak to the public. “That’s why you’ll be hearing a lot more from Dr. Fauci again, not from the president,” he said, adding that the experts will be “free from political interference.”
While the president’s executive orders can help accomplish some of the plan’s proposals, the majority will require new funding from Congress and will be included in the $1.9 trillion American Rescue package that Mr. Biden hopes legislators will approve.
Ten new orders
The 10 new pandemic-related orders Biden signed on Jan. 21 follow two he signed on his first day in office.
One establishes a COVID-19 Response Office responsible for coordinating the pandemic response across all federal departments and agencies and also reestablishes the White House Directorate on Global Health Security and Biodefense, which was disabled by the Trump administration.
The other order requires masks and physical distancing in all federal buildings, on all federal lands, and by federal employees and contractors.
Among the new orders will be directives that:
- Require individuals to also wear masks in airports and planes, and when using other modes of public transportation including trains, boats, and intercity buses, and also require international travelers to produce proof of a recent negative COVID-19 test prior to entry and to quarantine after entry.
- Federal agencies use all powers, including the Defense Production Act, to accelerate manufacturing and delivery of supplies such as N95 masks, gowns, gloves, swabs, reagents, pipette tips, rapid test kits, and nitrocellulose material for rapid antigen tests, and all equipment and material needed to accelerate manufacture, delivery, and administration of COVID-19 vaccine.
- Create a Pandemic Testing Board to expand supply and access, to promote more surge capacity, and to ensure equitable access to tests.
- Facilitate discovery, development, and trials of potential COVID-19 treatments, as well as expand access to programs that can meet the long-term health needs of those recovering from the disease.
- Facilitate more and better data sharing that will allow businesses, schools, hospitals, and individuals to make real-time decisions based on spread in their community.
- Direct the Education and Health & Human Services departments to provide schools and child-care operations guidance on how to reopen and operate safely.
- Direct the Occupational Safety and Health Administration (OSHA) to immediately release clear guidance for employers to help keep workers safe and to enforce health and safety requirements.
The plan also sets goals for vaccination – including 100 million shots in the administration’s first 100 days. President Biden had already previewed his goals for vaccination, including setting up mass vaccination sites and mobile vaccination sites. During his remarks, Mr. Biden said that he had already directed the Federal Emergency Management Agency (FEMA) to begin setting up the vaccination centers.
The administration is also going to look into improving reimbursement for giving vaccines. As a start, the HHS will ask the Centers for Medicare & Medicaid Services to consider if a higher rate “may more accurately compensate providers,” according to the Biden plan.
“But the brutal truth is it will take months before we can get the majority of Americans vaccinated,” said Mr. Biden.
As part of the goal of ensuring an equitable pandemic response, the president will sign an order that establishes a COVID-19 Health Equity Task Force. The task force is charged with providing recommendations for allocating resources and funding in communities with inequities in COVID-19 outcomes by race, ethnicity, geography, disability, and other considerations.
Finally, the administration has committed to being more transparent and sharing more information. The national plan calls for the federal government to conduct regular, expert-led, science-based public briefings and to release regular reports on the pandemic. The administration said it will launch massive science-based public information campaigns – in multiple languages – to educate Americans on masks, testing, and vaccines, and also work to counter misinformation and disinformation.
The American Academy of Family Physicians (AAFP) applauded Mr. Biden’s initiative. “If enacted, this bold legislative agenda will provide much-needed support to American families struggling during the pandemic – especially communities of color and those hardest hit by the virus,” Ada D. Stewart, MD, AAFP president, said in a statement.
Dr. Stewart also noted that family physicians “are uniquely positioned in their communities to educate patients, prioritize access, and coordinate administration of the COVID-19 vaccines,” and urged the administration to ensure that family physicians and staff be vaccinated as soon as possible, to help them “more safely provide care to their communities.”
A version of this article first appeared on Medscape.com.
“For the past year, we couldn’t rely on the federal government to act with the urgency and focus and coordination we needed, and we have seen the tragic cost of that failure,” Mr. Biden said in remarks from the White House, unveiling his 198-page National Strategy for the COVID-19 Response and Pandemic Preparedness.
He said as many as 500,000 Americans will have died by February. “It’s going to take months for us to turn things around,” he said.
“Our national strategy is comprehensive – it’s based on science, not politics; it’s based on truth, not denial,” Mr. Biden said. He also promised to restore public trust, in part by having scientists and public health experts speak to the public. “That’s why you’ll be hearing a lot more from Dr. Fauci again, not from the president,” he said, adding that the experts will be “free from political interference.”
While the president’s executive orders can help accomplish some of the plan’s proposals, the majority will require new funding from Congress and will be included in the $1.9 trillion American Rescue package that Mr. Biden hopes legislators will approve.
Ten new orders
The 10 new pandemic-related orders Biden signed on Jan. 21 follow two he signed on his first day in office.
One establishes a COVID-19 Response Office responsible for coordinating the pandemic response across all federal departments and agencies and also reestablishes the White House Directorate on Global Health Security and Biodefense, which was disabled by the Trump administration.
The other order requires masks and physical distancing in all federal buildings, on all federal lands, and by federal employees and contractors.
Among the new orders will be directives that:
- Require individuals to also wear masks in airports and planes, and when using other modes of public transportation including trains, boats, and intercity buses, and also require international travelers to produce proof of a recent negative COVID-19 test prior to entry and to quarantine after entry.
- Federal agencies use all powers, including the Defense Production Act, to accelerate manufacturing and delivery of supplies such as N95 masks, gowns, gloves, swabs, reagents, pipette tips, rapid test kits, and nitrocellulose material for rapid antigen tests, and all equipment and material needed to accelerate manufacture, delivery, and administration of COVID-19 vaccine.
- Create a Pandemic Testing Board to expand supply and access, to promote more surge capacity, and to ensure equitable access to tests.
- Facilitate discovery, development, and trials of potential COVID-19 treatments, as well as expand access to programs that can meet the long-term health needs of those recovering from the disease.
- Facilitate more and better data sharing that will allow businesses, schools, hospitals, and individuals to make real-time decisions based on spread in their community.
- Direct the Education and Health & Human Services departments to provide schools and child-care operations guidance on how to reopen and operate safely.
- Direct the Occupational Safety and Health Administration (OSHA) to immediately release clear guidance for employers to help keep workers safe and to enforce health and safety requirements.
The plan also sets goals for vaccination – including 100 million shots in the administration’s first 100 days. President Biden had already previewed his goals for vaccination, including setting up mass vaccination sites and mobile vaccination sites. During his remarks, Mr. Biden said that he had already directed the Federal Emergency Management Agency (FEMA) to begin setting up the vaccination centers.
The administration is also going to look into improving reimbursement for giving vaccines. As a start, the HHS will ask the Centers for Medicare & Medicaid Services to consider if a higher rate “may more accurately compensate providers,” according to the Biden plan.
“But the brutal truth is it will take months before we can get the majority of Americans vaccinated,” said Mr. Biden.
As part of the goal of ensuring an equitable pandemic response, the president will sign an order that establishes a COVID-19 Health Equity Task Force. The task force is charged with providing recommendations for allocating resources and funding in communities with inequities in COVID-19 outcomes by race, ethnicity, geography, disability, and other considerations.
Finally, the administration has committed to being more transparent and sharing more information. The national plan calls for the federal government to conduct regular, expert-led, science-based public briefings and to release regular reports on the pandemic. The administration said it will launch massive science-based public information campaigns – in multiple languages – to educate Americans on masks, testing, and vaccines, and also work to counter misinformation and disinformation.
The American Academy of Family Physicians (AAFP) applauded Mr. Biden’s initiative. “If enacted, this bold legislative agenda will provide much-needed support to American families struggling during the pandemic – especially communities of color and those hardest hit by the virus,” Ada D. Stewart, MD, AAFP president, said in a statement.
Dr. Stewart also noted that family physicians “are uniquely positioned in their communities to educate patients, prioritize access, and coordinate administration of the COVID-19 vaccines,” and urged the administration to ensure that family physicians and staff be vaccinated as soon as possible, to help them “more safely provide care to their communities.”
A version of this article first appeared on Medscape.com.
“For the past year, we couldn’t rely on the federal government to act with the urgency and focus and coordination we needed, and we have seen the tragic cost of that failure,” Mr. Biden said in remarks from the White House, unveiling his 198-page National Strategy for the COVID-19 Response and Pandemic Preparedness.
He said as many as 500,000 Americans will have died by February. “It’s going to take months for us to turn things around,” he said.
“Our national strategy is comprehensive – it’s based on science, not politics; it’s based on truth, not denial,” Mr. Biden said. He also promised to restore public trust, in part by having scientists and public health experts speak to the public. “That’s why you’ll be hearing a lot more from Dr. Fauci again, not from the president,” he said, adding that the experts will be “free from political interference.”
While the president’s executive orders can help accomplish some of the plan’s proposals, the majority will require new funding from Congress and will be included in the $1.9 trillion American Rescue package that Mr. Biden hopes legislators will approve.
Ten new orders
The 10 new pandemic-related orders Biden signed on Jan. 21 follow two he signed on his first day in office.
One establishes a COVID-19 Response Office responsible for coordinating the pandemic response across all federal departments and agencies and also reestablishes the White House Directorate on Global Health Security and Biodefense, which was disabled by the Trump administration.
The other order requires masks and physical distancing in all federal buildings, on all federal lands, and by federal employees and contractors.
Among the new orders will be directives that:
- Require individuals to also wear masks in airports and planes, and when using other modes of public transportation including trains, boats, and intercity buses, and also require international travelers to produce proof of a recent negative COVID-19 test prior to entry and to quarantine after entry.
- Federal agencies use all powers, including the Defense Production Act, to accelerate manufacturing and delivery of supplies such as N95 masks, gowns, gloves, swabs, reagents, pipette tips, rapid test kits, and nitrocellulose material for rapid antigen tests, and all equipment and material needed to accelerate manufacture, delivery, and administration of COVID-19 vaccine.
- Create a Pandemic Testing Board to expand supply and access, to promote more surge capacity, and to ensure equitable access to tests.
- Facilitate discovery, development, and trials of potential COVID-19 treatments, as well as expand access to programs that can meet the long-term health needs of those recovering from the disease.
- Facilitate more and better data sharing that will allow businesses, schools, hospitals, and individuals to make real-time decisions based on spread in their community.
- Direct the Education and Health & Human Services departments to provide schools and child-care operations guidance on how to reopen and operate safely.
- Direct the Occupational Safety and Health Administration (OSHA) to immediately release clear guidance for employers to help keep workers safe and to enforce health and safety requirements.
The plan also sets goals for vaccination – including 100 million shots in the administration’s first 100 days. President Biden had already previewed his goals for vaccination, including setting up mass vaccination sites and mobile vaccination sites. During his remarks, Mr. Biden said that he had already directed the Federal Emergency Management Agency (FEMA) to begin setting up the vaccination centers.
The administration is also going to look into improving reimbursement for giving vaccines. As a start, the HHS will ask the Centers for Medicare & Medicaid Services to consider if a higher rate “may more accurately compensate providers,” according to the Biden plan.
“But the brutal truth is it will take months before we can get the majority of Americans vaccinated,” said Mr. Biden.
As part of the goal of ensuring an equitable pandemic response, the president will sign an order that establishes a COVID-19 Health Equity Task Force. The task force is charged with providing recommendations for allocating resources and funding in communities with inequities in COVID-19 outcomes by race, ethnicity, geography, disability, and other considerations.
Finally, the administration has committed to being more transparent and sharing more information. The national plan calls for the federal government to conduct regular, expert-led, science-based public briefings and to release regular reports on the pandemic. The administration said it will launch massive science-based public information campaigns – in multiple languages – to educate Americans on masks, testing, and vaccines, and also work to counter misinformation and disinformation.
The American Academy of Family Physicians (AAFP) applauded Mr. Biden’s initiative. “If enacted, this bold legislative agenda will provide much-needed support to American families struggling during the pandemic – especially communities of color and those hardest hit by the virus,” Ada D. Stewart, MD, AAFP president, said in a statement.
Dr. Stewart also noted that family physicians “are uniquely positioned in their communities to educate patients, prioritize access, and coordinate administration of the COVID-19 vaccines,” and urged the administration to ensure that family physicians and staff be vaccinated as soon as possible, to help them “more safely provide care to their communities.”
A version of this article first appeared on Medscape.com.