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Five-day course of oral antiviral appears to stop SARS-CoV-2 in its tracks
A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.
That led Carlos del Rio, MD, distinguished professor of medicine at Emory University, Atlanta, to suggest a future in which a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe disease, similar to Tamiflu for influenza.
“I think it’s critically important,” he said of the data. Emory University was involved in the trial of molnupiravir but Dr. del Rio was not part of that team. “This drug offers the first antiviral oral drug that then could be used in an outpatient setting.”
Still, Dr. del Rio said it’s too soon to call this particular drug the breakthrough clinicians need to keep people out of the ICU. “It has the potential to be practice changing; it’s not practice changing at the moment.”
Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the Conference on Retroviruses and Opportunistic Infections, agreed. While the data are promising, “We will need to see if people get better from actual illness” to assess the real value of the drug in clinical care.
“That’s a phase 3 objective we’ll need to prove,” she said in an interview.
Phase 2/3 efficacy and safety studies of the drug are now underway in hospitalized and nonhospitalized patients.
In a brief prerecorded presentation of the data, Dr. Painter laid out what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing viral error catastrophe (Proc Natl Acad Sci U S A. 2002 Oct 15;99[21]:13374-6) – essentially overloading the virus with replication and mutation until the virus burns itself out and can’t produce replicable copies.
In this phase 2a, randomized, double-blind, controlled trial, researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection by day 4. Participants were randomly assigned to three different groups: 200 mg of molnupiravir, 400 mg, or 800 mg. The 200-mg arm was matched 1:1 with a placebo-controlled group, and the other two groups had three participants in the active group for every one control.
Participants took the pills twice daily for 5 days, and then were followed for a total of 28 days to monitor for complications or adverse events. At days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for polymerase chain reaction tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus that’s present is actually capable of infecting others.
Notably, the pills do not have to be refrigerated at any point in the process, alleviating the cold-chain challenges that have plagued vaccines.
“There’s an urgent need for an easily produced, transported, stored, and administered antiviral drug against SARS-CoV-2,” Dr. Painter said.
Of the 202 people recruited, 182 had swabs that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.
By day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients receiving any dose of molnupiravir. But by day 5, none of the participants receiving the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable virus.
Halfway through the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200-mg group had detectable virus in the nasopharynx, compared with 21% in the 400-mg group and just 12.5% in the 800-mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200-mg and the 400-mg arms, it was only statistically significant in the 800-mg arm.
In contrast, by the end of the 5 days in the placebo groups, infectious virus varied from 18.2% in the 200-mg placebo group to 30% in the 800-mg group. This points out the variability of the disease course of SARS-CoV-2.
“You just don’t know” which infections will lead to serious disease, Dr. Painter said in an interview. “And don’t you wish we did?”
Seven participants discontinued treatment, though only four experienced adverse events. Three of those discontinued the trial because of adverse events. The study is still blinded, so it’s unclear what those events were, but Dr. Painter said that they were not thought to be related to the study drug.
The bottom line, said Dr. Painter, was that people treated with molnupiravir had starkly different outcomes in lab measures during the study.
“An average of 10 days after symptom onset, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there wasn’t just virus in the nasopharynx, but it was capable of replicating, Dr. Painter said. “In contrast, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients.”
A version of this article first appeared on Medscape.com.
A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.
That led Carlos del Rio, MD, distinguished professor of medicine at Emory University, Atlanta, to suggest a future in which a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe disease, similar to Tamiflu for influenza.
“I think it’s critically important,” he said of the data. Emory University was involved in the trial of molnupiravir but Dr. del Rio was not part of that team. “This drug offers the first antiviral oral drug that then could be used in an outpatient setting.”
Still, Dr. del Rio said it’s too soon to call this particular drug the breakthrough clinicians need to keep people out of the ICU. “It has the potential to be practice changing; it’s not practice changing at the moment.”
Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the Conference on Retroviruses and Opportunistic Infections, agreed. While the data are promising, “We will need to see if people get better from actual illness” to assess the real value of the drug in clinical care.
“That’s a phase 3 objective we’ll need to prove,” she said in an interview.
Phase 2/3 efficacy and safety studies of the drug are now underway in hospitalized and nonhospitalized patients.
In a brief prerecorded presentation of the data, Dr. Painter laid out what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing viral error catastrophe (Proc Natl Acad Sci U S A. 2002 Oct 15;99[21]:13374-6) – essentially overloading the virus with replication and mutation until the virus burns itself out and can’t produce replicable copies.
In this phase 2a, randomized, double-blind, controlled trial, researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection by day 4. Participants were randomly assigned to three different groups: 200 mg of molnupiravir, 400 mg, or 800 mg. The 200-mg arm was matched 1:1 with a placebo-controlled group, and the other two groups had three participants in the active group for every one control.
Participants took the pills twice daily for 5 days, and then were followed for a total of 28 days to monitor for complications or adverse events. At days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for polymerase chain reaction tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus that’s present is actually capable of infecting others.
Notably, the pills do not have to be refrigerated at any point in the process, alleviating the cold-chain challenges that have plagued vaccines.
“There’s an urgent need for an easily produced, transported, stored, and administered antiviral drug against SARS-CoV-2,” Dr. Painter said.
Of the 202 people recruited, 182 had swabs that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.
By day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients receiving any dose of molnupiravir. But by day 5, none of the participants receiving the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable virus.
Halfway through the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200-mg group had detectable virus in the nasopharynx, compared with 21% in the 400-mg group and just 12.5% in the 800-mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200-mg and the 400-mg arms, it was only statistically significant in the 800-mg arm.
In contrast, by the end of the 5 days in the placebo groups, infectious virus varied from 18.2% in the 200-mg placebo group to 30% in the 800-mg group. This points out the variability of the disease course of SARS-CoV-2.
“You just don’t know” which infections will lead to serious disease, Dr. Painter said in an interview. “And don’t you wish we did?”
Seven participants discontinued treatment, though only four experienced adverse events. Three of those discontinued the trial because of adverse events. The study is still blinded, so it’s unclear what those events were, but Dr. Painter said that they were not thought to be related to the study drug.
The bottom line, said Dr. Painter, was that people treated with molnupiravir had starkly different outcomes in lab measures during the study.
“An average of 10 days after symptom onset, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there wasn’t just virus in the nasopharynx, but it was capable of replicating, Dr. Painter said. “In contrast, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients.”
A version of this article first appeared on Medscape.com.
A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.
That led Carlos del Rio, MD, distinguished professor of medicine at Emory University, Atlanta, to suggest a future in which a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe disease, similar to Tamiflu for influenza.
“I think it’s critically important,” he said of the data. Emory University was involved in the trial of molnupiravir but Dr. del Rio was not part of that team. “This drug offers the first antiviral oral drug that then could be used in an outpatient setting.”
Still, Dr. del Rio said it’s too soon to call this particular drug the breakthrough clinicians need to keep people out of the ICU. “It has the potential to be practice changing; it’s not practice changing at the moment.”
Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the Conference on Retroviruses and Opportunistic Infections, agreed. While the data are promising, “We will need to see if people get better from actual illness” to assess the real value of the drug in clinical care.
“That’s a phase 3 objective we’ll need to prove,” she said in an interview.
Phase 2/3 efficacy and safety studies of the drug are now underway in hospitalized and nonhospitalized patients.
In a brief prerecorded presentation of the data, Dr. Painter laid out what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing viral error catastrophe (Proc Natl Acad Sci U S A. 2002 Oct 15;99[21]:13374-6) – essentially overloading the virus with replication and mutation until the virus burns itself out and can’t produce replicable copies.
In this phase 2a, randomized, double-blind, controlled trial, researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection by day 4. Participants were randomly assigned to three different groups: 200 mg of molnupiravir, 400 mg, or 800 mg. The 200-mg arm was matched 1:1 with a placebo-controlled group, and the other two groups had three participants in the active group for every one control.
Participants took the pills twice daily for 5 days, and then were followed for a total of 28 days to monitor for complications or adverse events. At days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for polymerase chain reaction tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus that’s present is actually capable of infecting others.
Notably, the pills do not have to be refrigerated at any point in the process, alleviating the cold-chain challenges that have plagued vaccines.
“There’s an urgent need for an easily produced, transported, stored, and administered antiviral drug against SARS-CoV-2,” Dr. Painter said.
Of the 202 people recruited, 182 had swabs that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.
By day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients receiving any dose of molnupiravir. But by day 5, none of the participants receiving the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable virus.
Halfway through the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200-mg group had detectable virus in the nasopharynx, compared with 21% in the 400-mg group and just 12.5% in the 800-mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200-mg and the 400-mg arms, it was only statistically significant in the 800-mg arm.
In contrast, by the end of the 5 days in the placebo groups, infectious virus varied from 18.2% in the 200-mg placebo group to 30% in the 800-mg group. This points out the variability of the disease course of SARS-CoV-2.
“You just don’t know” which infections will lead to serious disease, Dr. Painter said in an interview. “And don’t you wish we did?”
Seven participants discontinued treatment, though only four experienced adverse events. Three of those discontinued the trial because of adverse events. The study is still blinded, so it’s unclear what those events were, but Dr. Painter said that they were not thought to be related to the study drug.
The bottom line, said Dr. Painter, was that people treated with molnupiravir had starkly different outcomes in lab measures during the study.
“An average of 10 days after symptom onset, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there wasn’t just virus in the nasopharynx, but it was capable of replicating, Dr. Painter said. “In contrast, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients.”
A version of this article first appeared on Medscape.com.
CDC: Vaccinated people can gather indoors without masks
People who are fully vaccinated against COVID-19 can safely gather unmasked and inside with nonvulnerable people who are not yet immunized, according to long-awaited guidance released by the CDC.
“Today’s action represents an important first step. It is not our final destination,” CDC Director Rochelle Walensky, MD, said March 8 at a White House briefing. “As more people get vaccinated, levels of COVID-19 infection decline in communities, and as our understanding of COVID immunity improves, we look forward to updating these recommendations to the public.”
According to the new guidance, people who are at least 2 weeks out from their last dose can:
- Visit with other fully vaccinated people indoors without wearing masks or physical distancing.
- Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
- Avoid quarantine and testing following exposure to someone if they remain asymptomatic.
However, there are still restrictions that will remain until further data are collected. Those who are fully vaccinated must still:
- Wear masks and physically distance in public settings and around people at high risk for severe disease.
- Wear masks and physically distance when visiting unvaccinated people from more than one household.
- Avoid medium- and large-sized gatherings.
- Avoid travel.
People considered at high risk for severe disease include older adults and those with cancer, chronic kidney disease, COPD, Down syndrome, heart disease, heart failure, a weakened immune system, obesity, sickle cell disease, and type 2 diabetes. The category also includes pregnant women and smokers.
“In public spaces, fully vaccinated people should continue to follow guidance to protect themselves and others, including wearing a well-fitted mask, physical distancing (at least 6 feet), avoiding crowds, avoiding poorly ventilated spaces, covering coughs and sneezes, washing hands often, and following any applicable workplace or school guidance,” the guidance says. “Fully vaccinated people should still watch for symptoms of COVID-19, especially following an exposure to someone with suspected or confirmed COVID-19.”
Respecting travel restrictions is still crucial, Dr. Walensky said, given past surges and variants that have emerged after periods of increased travel.
"We would like to give the opportunity for vaccinated grandparents to visit children and grandchildren who are healthy and local,” Dr. Walensky said.
But, she said, “It’s important to realize as we’re working through this that over 90% of the population is not yet vaccinated.”
For now, there are not enough data on transmission rates from those who are vaccinated to the rest of the public. However, Anthony Fauci, MD, said at a briefing last month that preliminary data are “pointing in a very favorable direction.”
Studies from Spain and Israel published last month showed the amount of viral load – or the amount of the COVID-19 virus in someone’s body – is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have the vaccine. Lower viral load means much lower chances of passing the virus to someone else, Dr. Fauci said.
“The science of COVID-19 is complex,” Dr. Walensky said, “and our understanding of it continues to evolve.”
A version of this article first appeared on WebMD.com.
People who are fully vaccinated against COVID-19 can safely gather unmasked and inside with nonvulnerable people who are not yet immunized, according to long-awaited guidance released by the CDC.
“Today’s action represents an important first step. It is not our final destination,” CDC Director Rochelle Walensky, MD, said March 8 at a White House briefing. “As more people get vaccinated, levels of COVID-19 infection decline in communities, and as our understanding of COVID immunity improves, we look forward to updating these recommendations to the public.”
According to the new guidance, people who are at least 2 weeks out from their last dose can:
- Visit with other fully vaccinated people indoors without wearing masks or physical distancing.
- Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
- Avoid quarantine and testing following exposure to someone if they remain asymptomatic.
However, there are still restrictions that will remain until further data are collected. Those who are fully vaccinated must still:
- Wear masks and physically distance in public settings and around people at high risk for severe disease.
- Wear masks and physically distance when visiting unvaccinated people from more than one household.
- Avoid medium- and large-sized gatherings.
- Avoid travel.
People considered at high risk for severe disease include older adults and those with cancer, chronic kidney disease, COPD, Down syndrome, heart disease, heart failure, a weakened immune system, obesity, sickle cell disease, and type 2 diabetes. The category also includes pregnant women and smokers.
“In public spaces, fully vaccinated people should continue to follow guidance to protect themselves and others, including wearing a well-fitted mask, physical distancing (at least 6 feet), avoiding crowds, avoiding poorly ventilated spaces, covering coughs and sneezes, washing hands often, and following any applicable workplace or school guidance,” the guidance says. “Fully vaccinated people should still watch for symptoms of COVID-19, especially following an exposure to someone with suspected or confirmed COVID-19.”
Respecting travel restrictions is still crucial, Dr. Walensky said, given past surges and variants that have emerged after periods of increased travel.
"We would like to give the opportunity for vaccinated grandparents to visit children and grandchildren who are healthy and local,” Dr. Walensky said.
But, she said, “It’s important to realize as we’re working through this that over 90% of the population is not yet vaccinated.”
For now, there are not enough data on transmission rates from those who are vaccinated to the rest of the public. However, Anthony Fauci, MD, said at a briefing last month that preliminary data are “pointing in a very favorable direction.”
Studies from Spain and Israel published last month showed the amount of viral load – or the amount of the COVID-19 virus in someone’s body – is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have the vaccine. Lower viral load means much lower chances of passing the virus to someone else, Dr. Fauci said.
“The science of COVID-19 is complex,” Dr. Walensky said, “and our understanding of it continues to evolve.”
A version of this article first appeared on WebMD.com.
People who are fully vaccinated against COVID-19 can safely gather unmasked and inside with nonvulnerable people who are not yet immunized, according to long-awaited guidance released by the CDC.
“Today’s action represents an important first step. It is not our final destination,” CDC Director Rochelle Walensky, MD, said March 8 at a White House briefing. “As more people get vaccinated, levels of COVID-19 infection decline in communities, and as our understanding of COVID immunity improves, we look forward to updating these recommendations to the public.”
According to the new guidance, people who are at least 2 weeks out from their last dose can:
- Visit with other fully vaccinated people indoors without wearing masks or physical distancing.
- Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
- Avoid quarantine and testing following exposure to someone if they remain asymptomatic.
However, there are still restrictions that will remain until further data are collected. Those who are fully vaccinated must still:
- Wear masks and physically distance in public settings and around people at high risk for severe disease.
- Wear masks and physically distance when visiting unvaccinated people from more than one household.
- Avoid medium- and large-sized gatherings.
- Avoid travel.
People considered at high risk for severe disease include older adults and those with cancer, chronic kidney disease, COPD, Down syndrome, heart disease, heart failure, a weakened immune system, obesity, sickle cell disease, and type 2 diabetes. The category also includes pregnant women and smokers.
“In public spaces, fully vaccinated people should continue to follow guidance to protect themselves and others, including wearing a well-fitted mask, physical distancing (at least 6 feet), avoiding crowds, avoiding poorly ventilated spaces, covering coughs and sneezes, washing hands often, and following any applicable workplace or school guidance,” the guidance says. “Fully vaccinated people should still watch for symptoms of COVID-19, especially following an exposure to someone with suspected or confirmed COVID-19.”
Respecting travel restrictions is still crucial, Dr. Walensky said, given past surges and variants that have emerged after periods of increased travel.
"We would like to give the opportunity for vaccinated grandparents to visit children and grandchildren who are healthy and local,” Dr. Walensky said.
But, she said, “It’s important to realize as we’re working through this that over 90% of the population is not yet vaccinated.”
For now, there are not enough data on transmission rates from those who are vaccinated to the rest of the public. However, Anthony Fauci, MD, said at a briefing last month that preliminary data are “pointing in a very favorable direction.”
Studies from Spain and Israel published last month showed the amount of viral load – or the amount of the COVID-19 virus in someone’s body – is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have the vaccine. Lower viral load means much lower chances of passing the virus to someone else, Dr. Fauci said.
“The science of COVID-19 is complex,” Dr. Walensky said, “and our understanding of it continues to evolve.”
A version of this article first appeared on WebMD.com.
RECOVERY trial of COVID-19 treatments stops colchicine arm
On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.
“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.
“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.
“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).
The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.
As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.
The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).
Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.
Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.
Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”
A version of this article first appeared on Medscape.com.
On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.
“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.
“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.
“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).
The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.
As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.
The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).
Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.
Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.
Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”
A version of this article first appeared on Medscape.com.
On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.
“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.
“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.
“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).
The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.
As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.
The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).
Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.
Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.
Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”
A version of this article first appeared on Medscape.com.
MIS-C follow-up proves challenging across pediatric hospitals
The discovery of any novel disease or condition means a steep learning curve as physicians must develop protocols for diagnosis, management, and follow-up on the fly in the midst of admitting and treating patients. Medical society task forces and committees often release interim guidance during the learning process, but each institution ultimately has to determine what works for them based on their resources, clinical experience, and patient population.
But when the novel condition demands the involvement of multiple different specialties, the challenge of management grows even more complex – as does follow-up after patients are discharged. Such has been the story with multisystem inflammatory syndrome in children (MIS-C), a complication of COVID-19 that shares some features with Kawasaki disease.
The similarities to Kawasaki provided physicians a place to start in developing appropriate treatment regimens and involved a similar interdisciplinary team from, at the least, cardiology and rheumatology, plus infectious disease since MIS-C results from COVID-19.
“It literally has it in the name – multisystem essentially hints that there are multiple specialties involved, multiple hands in the pot trying to manage the kids, and so each specialty has their own kind of unique role in the patient’s care even on the outpatient side,” said Samina S. Bhumbra, MD, an infectious disease pediatrician at Riley Hospital for Children and assistant professor of clinical pediatrics at Indiana University in Indianapolis. “This isn’t a disease that falls under one specialty.”
By July, the American College of Rheumatology had issued interim clinical guidance for management that most children’s hospitals have followed or slightly adapted. But ACR guidelines could not address how each institution should handle outpatient follow-up visits, especially since those visits required, again, at least cardiology and rheumatology if not infectious disease or other specialties as well.
“When their kids are admitted to the hospital, to be told at discharge you have to be followed up by all these specialists is a lot to handle,” Dr. Bhumbra said. But just as it’s difficult for parents to deal with the need to see several different doctors after discharge, it can be difficult at some institutions for physicians to design a follow-up schedule that can accommodate families, especially families who live far from the hospital in the first place.
“Some of our follow-up is disjointed because all of our clinics had never been on the same day just because of staff availability,” Dr. Bhumbra said. “But it can be a 2- to 3-hour drive for some of our patients, depending on how far they’re coming.”
Many of them can’t make that drive more than once in the same month, much less the same week.
“If you have multiple visits, it makes it more likely that they’re not showing up,” said Ryan M. Serrano, MD, a pediatric cardiologist at Riley and assistant professor of pediatrics at Indiana University. Riley used telehealth when possible, especially if families could get labs done near home. But pediatric echocardiograms require technicians who have experience with children, so families need to come to the hospital.
Children’s hospitals have therefore had to adapt scheduling strategies or develop pediatric specialty clinics to coordinate across the multiple departments and accommodate a complex follow-up regimen that is still evolving as physicians learn more about MIS-C.
Determining a follow-up regimen
Even before determining how to coordinate appointments, hospitals had to decide what follow-up itself should be.
“How long do we follow these patients and how often do we follow them?” said Melissa S. Oliver, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University.
“We’re seeing that a lot of our patients rapidly respond when they get appropriate therapy, but we don’t know about long-term outcomes yet. We’re all still learning.”
At Children’s Hospital of Philadelphia, infectious disease follows up 4-6 weeks post discharge. The cardiology division came up with a follow-up plan that has evolved over time, said Matthew Elias, MD, an attending cardiologist at CHOP’s Cardiac Center and clinical assistant professor of pediatrics at the University of Pennsylvania, Philadelphia.
Patients get an EKG and echocardiogram at 2 weeks and, if their condition is stable, 6 weeks after discharge. After that, it depends on the patient’s clinical situation. Patients with moderately diminished left ventricular systolic function are recommended to get an MRI scan 3 months after discharge and, if old enough, exercise stress tests. Otherwise, they are seen at 6 months, but that appointment is optional for those whose prior echos have consistently been normal.
Other institutions, including Riley, are following a similar schedule of 2-week, 6-week, and 6-month postdischarge follow-ups, and most plan to do a 1-year follow-up as well, although that 1-year mark hasn’t arrived yet for most. Most do rheumatology labs at the 2-week appointment and use that to determine steroids management and whether labs are needed at the 6-week appointment. If labs have normalized, they aren’t done at 6 months. Small variations in follow-up management exist across institutions, but all are remaining open to changes. Riley, for example, is considering MRI screening for ongoing cardiac inflammation at 6 months to a year for all patients, Dr. Serrano said.
The dedicated clinic model
The two challenges Riley needed to address were the lack of a clear consensus on what MIS-C follow-up should look like and the need for continuity of care, Dr. Serrano said.
Regular discussion in departmental meetings at Riley “progressed from how do we take care of them and what treatments do we give them to how do we follow them and manage them in outpatient,” Dr. Oliver said. In the inpatient setting, they had an interdisciplinary team, but how could they maintain that for outpatients without overwhelming the families?
“I think the main challenge is for the families to identify who is leading the care for them,” said Martha M. Rodriguez, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University. That sometimes led to families picking which follow-up appointments they would attend and which they would skip if they could not make them all – and sometimes they skipped the more important ones. “They would go to the appointment with me and then miss the cardiology appointments and the echocardiogram, which was more important to follow any abnormalities in the heart,” Dr. Rodriguez said.
After trying to coordinate separate follow-up appointments for months, Riley ultimately decided to form a dedicated clinic for MIS-C follow-up – a “one-stop shop” single appointment at each follow-up, Dr. Bhumbra said, that covers labs, EKG, echocardiogram, and any other necessary tests.
“Our goal with the clinic is to make life easier for the families and to be able to coordinate the appointments,” Dr. Rodriguez said. “They will be able to see the three of us, and it would be easier for us to communicate with each other about their plan.”
The clinic began Feb. 11 and occurs twice a month. Though it’s just begun, Dr. Oliver said the first clinic went well, and it’s helping them figure out the role each specialty needs to play in follow-up care.
“For us with rheumatology, after lab values have returned to normal and they’re off steroids, sometimes we think there isn’t much more we can contribute to,” she said. And then there are the patients who didn’t see any rheumatologists while inpatients.
“That’s what we’re trying to figure out as well,” Dr. Oliver said. “Should we be seeing every single kid regardless of whether we were involved in their inpatient [stay] or only seeing the ones we’ve seen?” She expects the coming months will help them work that out.
Texas Children’s Hospital in Houston also uses a dedicated clinic, but they set it up before the first MIS-C patient came through the doors, said Sara Kristen Sexson Tejtel, MD, a pediatric cardiologist at Texas Children’s. The hospital already has other types of multidisciplinary clinics, and they anticipated the challenge of getting families to come to too many appointments in a short period of time.
“Getting someone to come back once is hard enough,” Dr. Sexson Tejtel said. “Getting them to come back twice is impossible.”
Infectious disease is less involved at Texas Children’s, so it’s primarily Dr. Sexson Tejtel and her rheumatologist colleague who see the patients. They hold the clinic once a week, twice if needed.
“It does make the appointment a little longer, but I think the patients appreciate that everything can be addressed with that one visit,” Dr. Sexson Tejtel said. “Being in the hospital as long as some of these kids are is so hard, so making any of that easy as possible is so helpful.” A single appointment also allows the doctors to work together on what labs are needed so that children don’t need multiple labs drawn.
At the appointment, she and the rheumatologist enter the patient’s room and take the patient’s history together.
“It’s nice because it makes the family not to have to repeat things and tell the same story over and over,” she said. “Sometimes I ask questions that then the rheumatologist jumps off of, and then sometimes he’ll ask questions, and I’ll think, ‘Ooh, I’ll ask more questions about that.’ ”
In fact, this team approach at all clinics has made her a more thoughtful, well-rounded physician, she said.
“I have learned so much going to all of my multidisciplinary clinics, and I think I’m able to better care for my patients because I’m not just thinking about it from a cardiac perspective,” she said. “It takes some work, but it’s not hard and I think it is beneficial both for the patient and for the physician. This team approach is definitely where we’re trying to live right now.”
Separate but coordinated appointments
A dedicated clinic isn’t the answer for all institutions, however. At Children’s Hospital of Philadelphia, the size of the networks and all its satellites made a one-stop shop impractical.
“We talked about a consolidated clinic early on, when MIS-C was first emerging and all our groups were collaborating and coming up with our inpatient and outpatient care pathways,” said Sanjeev K. Swami, MD, an infectious disease pediatrician at CHOP and associate professor of clinical pediatrics at the University of Pennsylvania. But timing varies on when each specialist wants to see the families return, and existing clinic schedules and locations varied too much.
So CHOP coordinates appointments individually for each patient, depending on where the patient lives and sometimes stacking them on the same day when possible. Sometimes infectious disease or rheumatology use telehealth, and CHOP, like the other hospitals, prioritizes cardiology, especially for the patients who had cardiac abnormalities in the hospital, Dr. Swami said.
“All three of our groups try to be as flexible as possible. We’ve had a really good collaboration between our groups,” he said, and spreading out follow-up allows specialists to ask about concerns raised at previous appointments, ensuring stronger continuity of care.
“We can make sure things are getting followed up on,” Dr. Swami said. “I think that has been beneficial to make sure things aren’t falling through the cracks.”
CHOP cardiologist Dr. Elias said that ongoing communication, among providers and with families, has been absolutely crucial.
“Everyone’s been talking so frequently about our MIS-C patients while inpatient that by the time they’re an outpatient, it seems to work smoothly, where families are hearing similar items but with a different flair, one from infectious, one from rheumatology, and one from cardiology,” he said.
Children’s Mercy in Kansas City, Mo., also has multiple satellite clinics and follows a model similar to that of CHOP. They discussed having a dedicated multidisciplinary team for each MIS-C patient, but even the logistics of that were difficult, said Emily J. Fox, MD, a rheumatologist and assistant professor of pediatrics at the University of Missouri-Kansas City.
Instead, Children’s Mercy tries to coordinate follow-up appointments to be on the same day and often use telehealth for the rheumatology appointments. Families that live closer to the hospital’s location in Joplin, Mo., go in for their cardiology appointment there, and then Dr. Fox conducts a telehealth appointment with the help of nurses in Joplin.
“We really do try hard, especially since these kids are in the hospital for a long time, to make the coordination as easy as possible,” Dr. Fox said. “This was all was very new, especially in the beginning, but I think at least our group is getting a little bit more comfortable in managing these patients.”
Looking ahead
The biggest question that still looms is what happens to these children, if anything, down the line.
“What was unique about this was this was a new disease we were all learning about together with no baseline,” Dr. Swami said. “None of us had ever seen this condition before.”
So far, the prognosis for the vast majority of children is good. “Most of these kids survive, most of them are doing well, and they almost all recover,” Dr. Serrano said. Labs tend to normalize by 6 weeks post discharge, if not much earlier, and not much cardiac involvement is showing up at later follow-ups. But not even a year has passed, so there’s plenty to learn. “We don’t know if there’s long-term risk. I would not be surprised if 20 years down the road we’re finding out things about this that we had no idea” about, Dr. Serrano said. “Everybody wants answers, and nobody has any, and the answers we have may end up being wrong. That’s how it goes when you’re dealing with something you’ve never seen.”
Research underway will ideally begin providing those answers soon. CHOP is a participating site in an NIH-NHLBI–sponsored study, called COVID MUSIC, that is tracking long-term outcomes for MIS-C at 30 centers across the United States and Canada for 5 years.
“That will really definitely be helpful in answering some of the questions about long-term outcomes,” Dr. Elias said. “We hope this is going to be a transient issue and that patients won’t have any long-term manifestations, but we don’t know that yet.”
Meanwhile, one benefit that has come out of the pandemic is strong collaboration, Dr. Bhumbra said.
“The biggest thing we’re all eagerly waiting and hoping for is standard guidelines on how best to follow-up on these kids, but I know that’s a ways away,” Dr. Bhumbra said. So for now, each institution is doing what it can to develop protocols that they feel best serve the patients’ needs, such as Riley’s new dedicated MIS-C clinic. “It takes a village to take care of these kids, and MIS-C has proven that having a clinic with all three specialties at one clinic is going to be great for the families.”
Dr. Fox serves on a committee for Pfizer unrelated to MIS-C. No other doctors interviewed for this story had relevant conflicts of interest to disclose.
The discovery of any novel disease or condition means a steep learning curve as physicians must develop protocols for diagnosis, management, and follow-up on the fly in the midst of admitting and treating patients. Medical society task forces and committees often release interim guidance during the learning process, but each institution ultimately has to determine what works for them based on their resources, clinical experience, and patient population.
But when the novel condition demands the involvement of multiple different specialties, the challenge of management grows even more complex – as does follow-up after patients are discharged. Such has been the story with multisystem inflammatory syndrome in children (MIS-C), a complication of COVID-19 that shares some features with Kawasaki disease.
The similarities to Kawasaki provided physicians a place to start in developing appropriate treatment regimens and involved a similar interdisciplinary team from, at the least, cardiology and rheumatology, plus infectious disease since MIS-C results from COVID-19.
“It literally has it in the name – multisystem essentially hints that there are multiple specialties involved, multiple hands in the pot trying to manage the kids, and so each specialty has their own kind of unique role in the patient’s care even on the outpatient side,” said Samina S. Bhumbra, MD, an infectious disease pediatrician at Riley Hospital for Children and assistant professor of clinical pediatrics at Indiana University in Indianapolis. “This isn’t a disease that falls under one specialty.”
By July, the American College of Rheumatology had issued interim clinical guidance for management that most children’s hospitals have followed or slightly adapted. But ACR guidelines could not address how each institution should handle outpatient follow-up visits, especially since those visits required, again, at least cardiology and rheumatology if not infectious disease or other specialties as well.
“When their kids are admitted to the hospital, to be told at discharge you have to be followed up by all these specialists is a lot to handle,” Dr. Bhumbra said. But just as it’s difficult for parents to deal with the need to see several different doctors after discharge, it can be difficult at some institutions for physicians to design a follow-up schedule that can accommodate families, especially families who live far from the hospital in the first place.
“Some of our follow-up is disjointed because all of our clinics had never been on the same day just because of staff availability,” Dr. Bhumbra said. “But it can be a 2- to 3-hour drive for some of our patients, depending on how far they’re coming.”
Many of them can’t make that drive more than once in the same month, much less the same week.
“If you have multiple visits, it makes it more likely that they’re not showing up,” said Ryan M. Serrano, MD, a pediatric cardiologist at Riley and assistant professor of pediatrics at Indiana University. Riley used telehealth when possible, especially if families could get labs done near home. But pediatric echocardiograms require technicians who have experience with children, so families need to come to the hospital.
Children’s hospitals have therefore had to adapt scheduling strategies or develop pediatric specialty clinics to coordinate across the multiple departments and accommodate a complex follow-up regimen that is still evolving as physicians learn more about MIS-C.
Determining a follow-up regimen
Even before determining how to coordinate appointments, hospitals had to decide what follow-up itself should be.
“How long do we follow these patients and how often do we follow them?” said Melissa S. Oliver, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University.
“We’re seeing that a lot of our patients rapidly respond when they get appropriate therapy, but we don’t know about long-term outcomes yet. We’re all still learning.”
At Children’s Hospital of Philadelphia, infectious disease follows up 4-6 weeks post discharge. The cardiology division came up with a follow-up plan that has evolved over time, said Matthew Elias, MD, an attending cardiologist at CHOP’s Cardiac Center and clinical assistant professor of pediatrics at the University of Pennsylvania, Philadelphia.
Patients get an EKG and echocardiogram at 2 weeks and, if their condition is stable, 6 weeks after discharge. After that, it depends on the patient’s clinical situation. Patients with moderately diminished left ventricular systolic function are recommended to get an MRI scan 3 months after discharge and, if old enough, exercise stress tests. Otherwise, they are seen at 6 months, but that appointment is optional for those whose prior echos have consistently been normal.
Other institutions, including Riley, are following a similar schedule of 2-week, 6-week, and 6-month postdischarge follow-ups, and most plan to do a 1-year follow-up as well, although that 1-year mark hasn’t arrived yet for most. Most do rheumatology labs at the 2-week appointment and use that to determine steroids management and whether labs are needed at the 6-week appointment. If labs have normalized, they aren’t done at 6 months. Small variations in follow-up management exist across institutions, but all are remaining open to changes. Riley, for example, is considering MRI screening for ongoing cardiac inflammation at 6 months to a year for all patients, Dr. Serrano said.
The dedicated clinic model
The two challenges Riley needed to address were the lack of a clear consensus on what MIS-C follow-up should look like and the need for continuity of care, Dr. Serrano said.
Regular discussion in departmental meetings at Riley “progressed from how do we take care of them and what treatments do we give them to how do we follow them and manage them in outpatient,” Dr. Oliver said. In the inpatient setting, they had an interdisciplinary team, but how could they maintain that for outpatients without overwhelming the families?
“I think the main challenge is for the families to identify who is leading the care for them,” said Martha M. Rodriguez, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University. That sometimes led to families picking which follow-up appointments they would attend and which they would skip if they could not make them all – and sometimes they skipped the more important ones. “They would go to the appointment with me and then miss the cardiology appointments and the echocardiogram, which was more important to follow any abnormalities in the heart,” Dr. Rodriguez said.
After trying to coordinate separate follow-up appointments for months, Riley ultimately decided to form a dedicated clinic for MIS-C follow-up – a “one-stop shop” single appointment at each follow-up, Dr. Bhumbra said, that covers labs, EKG, echocardiogram, and any other necessary tests.
“Our goal with the clinic is to make life easier for the families and to be able to coordinate the appointments,” Dr. Rodriguez said. “They will be able to see the three of us, and it would be easier for us to communicate with each other about their plan.”
The clinic began Feb. 11 and occurs twice a month. Though it’s just begun, Dr. Oliver said the first clinic went well, and it’s helping them figure out the role each specialty needs to play in follow-up care.
“For us with rheumatology, after lab values have returned to normal and they’re off steroids, sometimes we think there isn’t much more we can contribute to,” she said. And then there are the patients who didn’t see any rheumatologists while inpatients.
“That’s what we’re trying to figure out as well,” Dr. Oliver said. “Should we be seeing every single kid regardless of whether we were involved in their inpatient [stay] or only seeing the ones we’ve seen?” She expects the coming months will help them work that out.
Texas Children’s Hospital in Houston also uses a dedicated clinic, but they set it up before the first MIS-C patient came through the doors, said Sara Kristen Sexson Tejtel, MD, a pediatric cardiologist at Texas Children’s. The hospital already has other types of multidisciplinary clinics, and they anticipated the challenge of getting families to come to too many appointments in a short period of time.
“Getting someone to come back once is hard enough,” Dr. Sexson Tejtel said. “Getting them to come back twice is impossible.”
Infectious disease is less involved at Texas Children’s, so it’s primarily Dr. Sexson Tejtel and her rheumatologist colleague who see the patients. They hold the clinic once a week, twice if needed.
“It does make the appointment a little longer, but I think the patients appreciate that everything can be addressed with that one visit,” Dr. Sexson Tejtel said. “Being in the hospital as long as some of these kids are is so hard, so making any of that easy as possible is so helpful.” A single appointment also allows the doctors to work together on what labs are needed so that children don’t need multiple labs drawn.
At the appointment, she and the rheumatologist enter the patient’s room and take the patient’s history together.
“It’s nice because it makes the family not to have to repeat things and tell the same story over and over,” she said. “Sometimes I ask questions that then the rheumatologist jumps off of, and then sometimes he’ll ask questions, and I’ll think, ‘Ooh, I’ll ask more questions about that.’ ”
In fact, this team approach at all clinics has made her a more thoughtful, well-rounded physician, she said.
“I have learned so much going to all of my multidisciplinary clinics, and I think I’m able to better care for my patients because I’m not just thinking about it from a cardiac perspective,” she said. “It takes some work, but it’s not hard and I think it is beneficial both for the patient and for the physician. This team approach is definitely where we’re trying to live right now.”
Separate but coordinated appointments
A dedicated clinic isn’t the answer for all institutions, however. At Children’s Hospital of Philadelphia, the size of the networks and all its satellites made a one-stop shop impractical.
“We talked about a consolidated clinic early on, when MIS-C was first emerging and all our groups were collaborating and coming up with our inpatient and outpatient care pathways,” said Sanjeev K. Swami, MD, an infectious disease pediatrician at CHOP and associate professor of clinical pediatrics at the University of Pennsylvania. But timing varies on when each specialist wants to see the families return, and existing clinic schedules and locations varied too much.
So CHOP coordinates appointments individually for each patient, depending on where the patient lives and sometimes stacking them on the same day when possible. Sometimes infectious disease or rheumatology use telehealth, and CHOP, like the other hospitals, prioritizes cardiology, especially for the patients who had cardiac abnormalities in the hospital, Dr. Swami said.
“All three of our groups try to be as flexible as possible. We’ve had a really good collaboration between our groups,” he said, and spreading out follow-up allows specialists to ask about concerns raised at previous appointments, ensuring stronger continuity of care.
“We can make sure things are getting followed up on,” Dr. Swami said. “I think that has been beneficial to make sure things aren’t falling through the cracks.”
CHOP cardiologist Dr. Elias said that ongoing communication, among providers and with families, has been absolutely crucial.
“Everyone’s been talking so frequently about our MIS-C patients while inpatient that by the time they’re an outpatient, it seems to work smoothly, where families are hearing similar items but with a different flair, one from infectious, one from rheumatology, and one from cardiology,” he said.
Children’s Mercy in Kansas City, Mo., also has multiple satellite clinics and follows a model similar to that of CHOP. They discussed having a dedicated multidisciplinary team for each MIS-C patient, but even the logistics of that were difficult, said Emily J. Fox, MD, a rheumatologist and assistant professor of pediatrics at the University of Missouri-Kansas City.
Instead, Children’s Mercy tries to coordinate follow-up appointments to be on the same day and often use telehealth for the rheumatology appointments. Families that live closer to the hospital’s location in Joplin, Mo., go in for their cardiology appointment there, and then Dr. Fox conducts a telehealth appointment with the help of nurses in Joplin.
“We really do try hard, especially since these kids are in the hospital for a long time, to make the coordination as easy as possible,” Dr. Fox said. “This was all was very new, especially in the beginning, but I think at least our group is getting a little bit more comfortable in managing these patients.”
Looking ahead
The biggest question that still looms is what happens to these children, if anything, down the line.
“What was unique about this was this was a new disease we were all learning about together with no baseline,” Dr. Swami said. “None of us had ever seen this condition before.”
So far, the prognosis for the vast majority of children is good. “Most of these kids survive, most of them are doing well, and they almost all recover,” Dr. Serrano said. Labs tend to normalize by 6 weeks post discharge, if not much earlier, and not much cardiac involvement is showing up at later follow-ups. But not even a year has passed, so there’s plenty to learn. “We don’t know if there’s long-term risk. I would not be surprised if 20 years down the road we’re finding out things about this that we had no idea” about, Dr. Serrano said. “Everybody wants answers, and nobody has any, and the answers we have may end up being wrong. That’s how it goes when you’re dealing with something you’ve never seen.”
Research underway will ideally begin providing those answers soon. CHOP is a participating site in an NIH-NHLBI–sponsored study, called COVID MUSIC, that is tracking long-term outcomes for MIS-C at 30 centers across the United States and Canada for 5 years.
“That will really definitely be helpful in answering some of the questions about long-term outcomes,” Dr. Elias said. “We hope this is going to be a transient issue and that patients won’t have any long-term manifestations, but we don’t know that yet.”
Meanwhile, one benefit that has come out of the pandemic is strong collaboration, Dr. Bhumbra said.
“The biggest thing we’re all eagerly waiting and hoping for is standard guidelines on how best to follow-up on these kids, but I know that’s a ways away,” Dr. Bhumbra said. So for now, each institution is doing what it can to develop protocols that they feel best serve the patients’ needs, such as Riley’s new dedicated MIS-C clinic. “It takes a village to take care of these kids, and MIS-C has proven that having a clinic with all three specialties at one clinic is going to be great for the families.”
Dr. Fox serves on a committee for Pfizer unrelated to MIS-C. No other doctors interviewed for this story had relevant conflicts of interest to disclose.
The discovery of any novel disease or condition means a steep learning curve as physicians must develop protocols for diagnosis, management, and follow-up on the fly in the midst of admitting and treating patients. Medical society task forces and committees often release interim guidance during the learning process, but each institution ultimately has to determine what works for them based on their resources, clinical experience, and patient population.
But when the novel condition demands the involvement of multiple different specialties, the challenge of management grows even more complex – as does follow-up after patients are discharged. Such has been the story with multisystem inflammatory syndrome in children (MIS-C), a complication of COVID-19 that shares some features with Kawasaki disease.
The similarities to Kawasaki provided physicians a place to start in developing appropriate treatment regimens and involved a similar interdisciplinary team from, at the least, cardiology and rheumatology, plus infectious disease since MIS-C results from COVID-19.
“It literally has it in the name – multisystem essentially hints that there are multiple specialties involved, multiple hands in the pot trying to manage the kids, and so each specialty has their own kind of unique role in the patient’s care even on the outpatient side,” said Samina S. Bhumbra, MD, an infectious disease pediatrician at Riley Hospital for Children and assistant professor of clinical pediatrics at Indiana University in Indianapolis. “This isn’t a disease that falls under one specialty.”
By July, the American College of Rheumatology had issued interim clinical guidance for management that most children’s hospitals have followed or slightly adapted. But ACR guidelines could not address how each institution should handle outpatient follow-up visits, especially since those visits required, again, at least cardiology and rheumatology if not infectious disease or other specialties as well.
“When their kids are admitted to the hospital, to be told at discharge you have to be followed up by all these specialists is a lot to handle,” Dr. Bhumbra said. But just as it’s difficult for parents to deal with the need to see several different doctors after discharge, it can be difficult at some institutions for physicians to design a follow-up schedule that can accommodate families, especially families who live far from the hospital in the first place.
“Some of our follow-up is disjointed because all of our clinics had never been on the same day just because of staff availability,” Dr. Bhumbra said. “But it can be a 2- to 3-hour drive for some of our patients, depending on how far they’re coming.”
Many of them can’t make that drive more than once in the same month, much less the same week.
“If you have multiple visits, it makes it more likely that they’re not showing up,” said Ryan M. Serrano, MD, a pediatric cardiologist at Riley and assistant professor of pediatrics at Indiana University. Riley used telehealth when possible, especially if families could get labs done near home. But pediatric echocardiograms require technicians who have experience with children, so families need to come to the hospital.
Children’s hospitals have therefore had to adapt scheduling strategies or develop pediatric specialty clinics to coordinate across the multiple departments and accommodate a complex follow-up regimen that is still evolving as physicians learn more about MIS-C.
Determining a follow-up regimen
Even before determining how to coordinate appointments, hospitals had to decide what follow-up itself should be.
“How long do we follow these patients and how often do we follow them?” said Melissa S. Oliver, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University.
“We’re seeing that a lot of our patients rapidly respond when they get appropriate therapy, but we don’t know about long-term outcomes yet. We’re all still learning.”
At Children’s Hospital of Philadelphia, infectious disease follows up 4-6 weeks post discharge. The cardiology division came up with a follow-up plan that has evolved over time, said Matthew Elias, MD, an attending cardiologist at CHOP’s Cardiac Center and clinical assistant professor of pediatrics at the University of Pennsylvania, Philadelphia.
Patients get an EKG and echocardiogram at 2 weeks and, if their condition is stable, 6 weeks after discharge. After that, it depends on the patient’s clinical situation. Patients with moderately diminished left ventricular systolic function are recommended to get an MRI scan 3 months after discharge and, if old enough, exercise stress tests. Otherwise, they are seen at 6 months, but that appointment is optional for those whose prior echos have consistently been normal.
Other institutions, including Riley, are following a similar schedule of 2-week, 6-week, and 6-month postdischarge follow-ups, and most plan to do a 1-year follow-up as well, although that 1-year mark hasn’t arrived yet for most. Most do rheumatology labs at the 2-week appointment and use that to determine steroids management and whether labs are needed at the 6-week appointment. If labs have normalized, they aren’t done at 6 months. Small variations in follow-up management exist across institutions, but all are remaining open to changes. Riley, for example, is considering MRI screening for ongoing cardiac inflammation at 6 months to a year for all patients, Dr. Serrano said.
The dedicated clinic model
The two challenges Riley needed to address were the lack of a clear consensus on what MIS-C follow-up should look like and the need for continuity of care, Dr. Serrano said.
Regular discussion in departmental meetings at Riley “progressed from how do we take care of them and what treatments do we give them to how do we follow them and manage them in outpatient,” Dr. Oliver said. In the inpatient setting, they had an interdisciplinary team, but how could they maintain that for outpatients without overwhelming the families?
“I think the main challenge is for the families to identify who is leading the care for them,” said Martha M. Rodriguez, MD, a rheumatologist at Riley and assistant professor of clinical pediatrics at Indiana University. That sometimes led to families picking which follow-up appointments they would attend and which they would skip if they could not make them all – and sometimes they skipped the more important ones. “They would go to the appointment with me and then miss the cardiology appointments and the echocardiogram, which was more important to follow any abnormalities in the heart,” Dr. Rodriguez said.
After trying to coordinate separate follow-up appointments for months, Riley ultimately decided to form a dedicated clinic for MIS-C follow-up – a “one-stop shop” single appointment at each follow-up, Dr. Bhumbra said, that covers labs, EKG, echocardiogram, and any other necessary tests.
“Our goal with the clinic is to make life easier for the families and to be able to coordinate the appointments,” Dr. Rodriguez said. “They will be able to see the three of us, and it would be easier for us to communicate with each other about their plan.”
The clinic began Feb. 11 and occurs twice a month. Though it’s just begun, Dr. Oliver said the first clinic went well, and it’s helping them figure out the role each specialty needs to play in follow-up care.
“For us with rheumatology, after lab values have returned to normal and they’re off steroids, sometimes we think there isn’t much more we can contribute to,” she said. And then there are the patients who didn’t see any rheumatologists while inpatients.
“That’s what we’re trying to figure out as well,” Dr. Oliver said. “Should we be seeing every single kid regardless of whether we were involved in their inpatient [stay] or only seeing the ones we’ve seen?” She expects the coming months will help them work that out.
Texas Children’s Hospital in Houston also uses a dedicated clinic, but they set it up before the first MIS-C patient came through the doors, said Sara Kristen Sexson Tejtel, MD, a pediatric cardiologist at Texas Children’s. The hospital already has other types of multidisciplinary clinics, and they anticipated the challenge of getting families to come to too many appointments in a short period of time.
“Getting someone to come back once is hard enough,” Dr. Sexson Tejtel said. “Getting them to come back twice is impossible.”
Infectious disease is less involved at Texas Children’s, so it’s primarily Dr. Sexson Tejtel and her rheumatologist colleague who see the patients. They hold the clinic once a week, twice if needed.
“It does make the appointment a little longer, but I think the patients appreciate that everything can be addressed with that one visit,” Dr. Sexson Tejtel said. “Being in the hospital as long as some of these kids are is so hard, so making any of that easy as possible is so helpful.” A single appointment also allows the doctors to work together on what labs are needed so that children don’t need multiple labs drawn.
At the appointment, she and the rheumatologist enter the patient’s room and take the patient’s history together.
“It’s nice because it makes the family not to have to repeat things and tell the same story over and over,” she said. “Sometimes I ask questions that then the rheumatologist jumps off of, and then sometimes he’ll ask questions, and I’ll think, ‘Ooh, I’ll ask more questions about that.’ ”
In fact, this team approach at all clinics has made her a more thoughtful, well-rounded physician, she said.
“I have learned so much going to all of my multidisciplinary clinics, and I think I’m able to better care for my patients because I’m not just thinking about it from a cardiac perspective,” she said. “It takes some work, but it’s not hard and I think it is beneficial both for the patient and for the physician. This team approach is definitely where we’re trying to live right now.”
Separate but coordinated appointments
A dedicated clinic isn’t the answer for all institutions, however. At Children’s Hospital of Philadelphia, the size of the networks and all its satellites made a one-stop shop impractical.
“We talked about a consolidated clinic early on, when MIS-C was first emerging and all our groups were collaborating and coming up with our inpatient and outpatient care pathways,” said Sanjeev K. Swami, MD, an infectious disease pediatrician at CHOP and associate professor of clinical pediatrics at the University of Pennsylvania. But timing varies on when each specialist wants to see the families return, and existing clinic schedules and locations varied too much.
So CHOP coordinates appointments individually for each patient, depending on where the patient lives and sometimes stacking them on the same day when possible. Sometimes infectious disease or rheumatology use telehealth, and CHOP, like the other hospitals, prioritizes cardiology, especially for the patients who had cardiac abnormalities in the hospital, Dr. Swami said.
“All three of our groups try to be as flexible as possible. We’ve had a really good collaboration between our groups,” he said, and spreading out follow-up allows specialists to ask about concerns raised at previous appointments, ensuring stronger continuity of care.
“We can make sure things are getting followed up on,” Dr. Swami said. “I think that has been beneficial to make sure things aren’t falling through the cracks.”
CHOP cardiologist Dr. Elias said that ongoing communication, among providers and with families, has been absolutely crucial.
“Everyone’s been talking so frequently about our MIS-C patients while inpatient that by the time they’re an outpatient, it seems to work smoothly, where families are hearing similar items but with a different flair, one from infectious, one from rheumatology, and one from cardiology,” he said.
Children’s Mercy in Kansas City, Mo., also has multiple satellite clinics and follows a model similar to that of CHOP. They discussed having a dedicated multidisciplinary team for each MIS-C patient, but even the logistics of that were difficult, said Emily J. Fox, MD, a rheumatologist and assistant professor of pediatrics at the University of Missouri-Kansas City.
Instead, Children’s Mercy tries to coordinate follow-up appointments to be on the same day and often use telehealth for the rheumatology appointments. Families that live closer to the hospital’s location in Joplin, Mo., go in for their cardiology appointment there, and then Dr. Fox conducts a telehealth appointment with the help of nurses in Joplin.
“We really do try hard, especially since these kids are in the hospital for a long time, to make the coordination as easy as possible,” Dr. Fox said. “This was all was very new, especially in the beginning, but I think at least our group is getting a little bit more comfortable in managing these patients.”
Looking ahead
The biggest question that still looms is what happens to these children, if anything, down the line.
“What was unique about this was this was a new disease we were all learning about together with no baseline,” Dr. Swami said. “None of us had ever seen this condition before.”
So far, the prognosis for the vast majority of children is good. “Most of these kids survive, most of them are doing well, and they almost all recover,” Dr. Serrano said. Labs tend to normalize by 6 weeks post discharge, if not much earlier, and not much cardiac involvement is showing up at later follow-ups. But not even a year has passed, so there’s plenty to learn. “We don’t know if there’s long-term risk. I would not be surprised if 20 years down the road we’re finding out things about this that we had no idea” about, Dr. Serrano said. “Everybody wants answers, and nobody has any, and the answers we have may end up being wrong. That’s how it goes when you’re dealing with something you’ve never seen.”
Research underway will ideally begin providing those answers soon. CHOP is a participating site in an NIH-NHLBI–sponsored study, called COVID MUSIC, that is tracking long-term outcomes for MIS-C at 30 centers across the United States and Canada for 5 years.
“That will really definitely be helpful in answering some of the questions about long-term outcomes,” Dr. Elias said. “We hope this is going to be a transient issue and that patients won’t have any long-term manifestations, but we don’t know that yet.”
Meanwhile, one benefit that has come out of the pandemic is strong collaboration, Dr. Bhumbra said.
“The biggest thing we’re all eagerly waiting and hoping for is standard guidelines on how best to follow-up on these kids, but I know that’s a ways away,” Dr. Bhumbra said. So for now, each institution is doing what it can to develop protocols that they feel best serve the patients’ needs, such as Riley’s new dedicated MIS-C clinic. “It takes a village to take care of these kids, and MIS-C has proven that having a clinic with all three specialties at one clinic is going to be great for the families.”
Dr. Fox serves on a committee for Pfizer unrelated to MIS-C. No other doctors interviewed for this story had relevant conflicts of interest to disclose.
Dining restrictions, mask mandates tied to less illness, death, CDC reaffirms
The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.
Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.
On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.
The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.
The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.
They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted.
The differences were statistically significant, with P values of .02, <.01, and .04, respectively.
COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.
Both these differences were statistically significant (P < .01).
This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
Masks make a difference
The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.
Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.
These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.
The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.
The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.
CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.
“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”
Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.
These are not the first CDC data to show that mask mandates make a difference.
In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.
Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”
The researchers have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.
Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.
On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.
The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.
The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.
They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted.
The differences were statistically significant, with P values of .02, <.01, and .04, respectively.
COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.
Both these differences were statistically significant (P < .01).
This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
Masks make a difference
The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.
Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.
These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.
The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.
The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.
CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.
“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”
Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.
These are not the first CDC data to show that mask mandates make a difference.
In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.
Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”
The researchers have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.
Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.
On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.
The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.
The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.
They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted.
The differences were statistically significant, with P values of .02, <.01, and .04, respectively.
COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.
Both these differences were statistically significant (P < .01).
This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
Masks make a difference
The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.
Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.
These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.
The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.
The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.
CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.
“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”
Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.
These are not the first CDC data to show that mask mandates make a difference.
In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.
Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”
The researchers have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BMI, age, and sex affect COVID-19 vaccine antibody response
The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.
The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.
The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.
“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.
“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.
“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
Results contrast with Pfizer trials of vaccine
The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.
Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.
“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.
Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.
However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.
“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
Findings reported in British newspapers
The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.
The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”
Most make the point that there were only 26 people with obesity among the 248 persons in the study.
“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.
“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.
Antibody responses differ by BMI, age, and sex
In the Italian study, the participants – 158 women and 90 men – were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.
After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.
Titers of SARS-CoV-2–binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) and those aged 47-56 years (239.8 AU/mL; P = .005), those aged 37 years and younger versus those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37-47 years versus those older than 56 years (330.9 vs. 182.4 AU/mL; P = .01).
Antibody response was significantly greater for women than for men (338.5 vs. 212.6 AU/mL; P = .001).
Humoral responses were greater in persons of normal-weight BMI (18.5-24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL), compared with persons with preobesity, defined as BMI of 25-29.9 (222.4 AU/mL), and those with obesity (BMI ≥30; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).
“Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems,” the researchers noted.
Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).
“We strongly believe that our results are extremely encouraging and useful for the scientific community,” Dr. Pellini and colleagues concluded.
The authors disclosed no relevant financial relationships. Dr. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.
This article was updated on 3/8/21.
A version of this article first appeared on Medscape.com.
The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.
The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.
The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.
“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.
“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.
“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
Results contrast with Pfizer trials of vaccine
The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.
Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.
“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.
Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.
However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.
“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
Findings reported in British newspapers
The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.
The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”
Most make the point that there were only 26 people with obesity among the 248 persons in the study.
“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.
“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.
Antibody responses differ by BMI, age, and sex
In the Italian study, the participants – 158 women and 90 men – were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.
After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.
Titers of SARS-CoV-2–binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) and those aged 47-56 years (239.8 AU/mL; P = .005), those aged 37 years and younger versus those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37-47 years versus those older than 56 years (330.9 vs. 182.4 AU/mL; P = .01).
Antibody response was significantly greater for women than for men (338.5 vs. 212.6 AU/mL; P = .001).
Humoral responses were greater in persons of normal-weight BMI (18.5-24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL), compared with persons with preobesity, defined as BMI of 25-29.9 (222.4 AU/mL), and those with obesity (BMI ≥30; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).
“Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems,” the researchers noted.
Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).
“We strongly believe that our results are extremely encouraging and useful for the scientific community,” Dr. Pellini and colleagues concluded.
The authors disclosed no relevant financial relationships. Dr. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.
This article was updated on 3/8/21.
A version of this article first appeared on Medscape.com.
The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.
The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.
The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.
“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.
“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.
“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
Results contrast with Pfizer trials of vaccine
The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.
Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.
“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.
Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.
However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.
“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
Findings reported in British newspapers
The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.
The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”
Most make the point that there were only 26 people with obesity among the 248 persons in the study.
“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.
“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.
Antibody responses differ by BMI, age, and sex
In the Italian study, the participants – 158 women and 90 men – were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.
After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.
Titers of SARS-CoV-2–binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) and those aged 47-56 years (239.8 AU/mL; P = .005), those aged 37 years and younger versus those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37-47 years versus those older than 56 years (330.9 vs. 182.4 AU/mL; P = .01).
Antibody response was significantly greater for women than for men (338.5 vs. 212.6 AU/mL; P = .001).
Humoral responses were greater in persons of normal-weight BMI (18.5-24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL), compared with persons with preobesity, defined as BMI of 25-29.9 (222.4 AU/mL), and those with obesity (BMI ≥30; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).
“Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems,” the researchers noted.
Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).
“We strongly believe that our results are extremely encouraging and useful for the scientific community,” Dr. Pellini and colleagues concluded.
The authors disclosed no relevant financial relationships. Dr. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.
This article was updated on 3/8/21.
A version of this article first appeared on Medscape.com.
JAMA podcast on racism in medicine faces backlash
Published on Feb. 23, the episode is hosted on JAMA’s learning platform for doctors and is available for continuing medical education credits.
“No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast,” JAMA wrote in a Twitter post to promote the episode. That tweet has since been deleted.
The episode features host Ed Livingston, MD, deputy editor for clinical reviews and education at JAMA, and guest Mitchell Katz, MD, president and CEO for NYC Health + Hospitals and deputy editor for JAMA Internal Medicine. Dr. Livingston approaches the episode as “structural racism for skeptics,” and Dr. Katz tries to explain how structural racism deepens health disparities and what health systems can do about it.
“Many physicians are skeptical of structural racism, the idea that economic, educational, and other societal systems preferentially disadvantage Black Americans and other communities of color,” the episode description says.
In the podcast, Dr. Livingston and Dr. Katz speak about health care disparities and racial inequality. Dr. Livingston, who says he “didn’t understand the concept” going into the episode, suggests that racism was made illegal in the 1960s and that the discussion of “structural racism” should shift away from the term “racism” and focus on socioeconomic status instead.
“What you’re talking about isn’t so much racism ... it isn’t their race, it isn’t their color, it’s their socioeconomic status,” Dr. Livingston says. “Is that a fair statement?”
But Dr. Katz says that “acknowledging structural racism can be helpful to us. Structural racism refers to a system in which policies or practices or how we look at people perpetuates racial inequality.”
Dr. Katz points to the creation of a hospital in San Francisco in the 1880s to treat patients of Chinese ethnicity separately. Outside of health care, he talks about environmental racism between neighborhoods with inequalities in hospitals, schools, and social services.
“All of those things have an impact on that minority person,” Dr. Katz says. “The big thing we can all do is move away from trying to interrogate each other’s opinions and move to a place where we are looking at the policies of our institutions and making sure that they promote equality.”
Dr. Livingston concludes the episode by reemphasizing that “racism” should be taken out of the conversation and it should instead focus on the “structural” aspect of socioeconomics.
“Minorities ... aren’t [in those neighborhoods] because they’re not allowed to buy houses or they can’t get a job because they’re Black or Hispanic. That would be illegal,” Dr. Livingston says. “But disproportionality does exist.”
Efforts to reach Dr. Livingston were unsuccessful. Dr. Katz distanced himself from Dr. Livingston in a statement released on March 4.
“Systemic and interpersonal racism both still exist in our country — they must be rooted out. I do not share the JAMA host’s belief of doing away with the word ‘racism’ will help us be more successful in ending inequities that exists across racial and ethnic lines,” Dr. Katz said. “Further, I believe that we will only produce an equitable society when social and political structures do not continue to produce and perpetuate disparate results based on social race and ethnicity.”
Dr. Katz reiterated that both interpersonal and structural racism continue to exist in the United States, “and it is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it.”
He also recommended JAMA use this controversy “as a learning opportunity for continued dialogue and create another podcast series as an open conversation that invites diverse experts in the field to have an open discussion about structural racism in healthcare.”
The podcast and JAMA’s tweet promoting it were widely criticized on Twitter. In interviews with WebMD, many doctors expressed disbelief that such a respected journal would lend its name to this podcast episode.
B. Bobby Chiong, MD, a radiologist in New York, said although JAMA’s effort to engage with its audience about racism is laudable, it missed the mark.
“I think the backlash comes from how they tried to make a podcast about the subject and somehow made themselves an example of unconscious bias and unfamiliarity with just how embedded in our system is structural racism,” he said.
Perhaps the podcast’s worst offense was its failure to address the painful history of racial bias in this country that still permeates the medical community, says Tamara Saint-Surin, MD, assistant professor at the University of North Carolina at Chapel Hill.
“For physicians in leadership to have the belief that structural racism does not exist in medicine, they don’t really appreciate what affects their patients and what their patients were dealing with,” Dr. Saint-Surin said in an interview. “It was a very harmful podcast and goes to show we still have so much work to do.”
Along with a flawed premise, she says, the podcast was not nearly long enough to address such a nuanced issue. And Dr. Livingston focused on interpersonal racism rather than structural racism, she said, failing to address widespread problems such as higher rates of asthma among Black populations living in areas with poor air quality.
The number of Black doctors remains low and the lack of representation adds to an environment already rife with racism, according to many medical professionals.
Shirlene Obuobi, MD, an internal medicine doctor in Chicago, said JAMA failed to live up to its own standards by publishing material that lacked research and expertise.
“I can’t submit a clinical trial to JAMA without them combing through methods with a fine-tooth comb,” Dr. Obuobi said. “They didn’t uphold the standards they normally apply to anyone else.”
Both the editor of JAMA and the head of the American Medical Association issued statements criticizing the episode and the tweet that promoted it.
JAMA Editor-in-Chief Howard Bauchner, MD, said, “The language of the tweet, and some portions of the podcast, do not reflect my commitment as editorial leader of JAMA and JAMA Network to call out and discuss the adverse effects of injustice, inequity, and racism in society and medicine as JAMA has done for many years.” He said JAMA will schedule a future podcast to address the concerns raised about the recent episode.
AMA CEO James L. Madara, MD, said, “The AMA’s House of Delegates passed policy stating that racism is structural, systemic, cultural, and interpersonal, and we are deeply disturbed – and angered – by a recent JAMA podcast that questioned the existence of structural racism and the affiliated tweet that promoted the podcast and stated ‘no physician is racist, so how can there be structural racism in health care?’ ”
He continued: “JAMA has editorial independence from AMA, but this tweet and podcast are inconsistent with the policies and views of AMA, and I’m concerned about and acknowledge the harms they have caused. Structural racism in health care and our society exists, and it is incumbent on all of us to fix it.”
This article was updated 3/5/21.
A version of this article first appeared on WebMD.com.
Published on Feb. 23, the episode is hosted on JAMA’s learning platform for doctors and is available for continuing medical education credits.
“No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast,” JAMA wrote in a Twitter post to promote the episode. That tweet has since been deleted.
The episode features host Ed Livingston, MD, deputy editor for clinical reviews and education at JAMA, and guest Mitchell Katz, MD, president and CEO for NYC Health + Hospitals and deputy editor for JAMA Internal Medicine. Dr. Livingston approaches the episode as “structural racism for skeptics,” and Dr. Katz tries to explain how structural racism deepens health disparities and what health systems can do about it.
“Many physicians are skeptical of structural racism, the idea that economic, educational, and other societal systems preferentially disadvantage Black Americans and other communities of color,” the episode description says.
In the podcast, Dr. Livingston and Dr. Katz speak about health care disparities and racial inequality. Dr. Livingston, who says he “didn’t understand the concept” going into the episode, suggests that racism was made illegal in the 1960s and that the discussion of “structural racism” should shift away from the term “racism” and focus on socioeconomic status instead.
“What you’re talking about isn’t so much racism ... it isn’t their race, it isn’t their color, it’s their socioeconomic status,” Dr. Livingston says. “Is that a fair statement?”
But Dr. Katz says that “acknowledging structural racism can be helpful to us. Structural racism refers to a system in which policies or practices or how we look at people perpetuates racial inequality.”
Dr. Katz points to the creation of a hospital in San Francisco in the 1880s to treat patients of Chinese ethnicity separately. Outside of health care, he talks about environmental racism between neighborhoods with inequalities in hospitals, schools, and social services.
“All of those things have an impact on that minority person,” Dr. Katz says. “The big thing we can all do is move away from trying to interrogate each other’s opinions and move to a place where we are looking at the policies of our institutions and making sure that they promote equality.”
Dr. Livingston concludes the episode by reemphasizing that “racism” should be taken out of the conversation and it should instead focus on the “structural” aspect of socioeconomics.
“Minorities ... aren’t [in those neighborhoods] because they’re not allowed to buy houses or they can’t get a job because they’re Black or Hispanic. That would be illegal,” Dr. Livingston says. “But disproportionality does exist.”
Efforts to reach Dr. Livingston were unsuccessful. Dr. Katz distanced himself from Dr. Livingston in a statement released on March 4.
“Systemic and interpersonal racism both still exist in our country — they must be rooted out. I do not share the JAMA host’s belief of doing away with the word ‘racism’ will help us be more successful in ending inequities that exists across racial and ethnic lines,” Dr. Katz said. “Further, I believe that we will only produce an equitable society when social and political structures do not continue to produce and perpetuate disparate results based on social race and ethnicity.”
Dr. Katz reiterated that both interpersonal and structural racism continue to exist in the United States, “and it is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it.”
He also recommended JAMA use this controversy “as a learning opportunity for continued dialogue and create another podcast series as an open conversation that invites diverse experts in the field to have an open discussion about structural racism in healthcare.”
The podcast and JAMA’s tweet promoting it were widely criticized on Twitter. In interviews with WebMD, many doctors expressed disbelief that such a respected journal would lend its name to this podcast episode.
B. Bobby Chiong, MD, a radiologist in New York, said although JAMA’s effort to engage with its audience about racism is laudable, it missed the mark.
“I think the backlash comes from how they tried to make a podcast about the subject and somehow made themselves an example of unconscious bias and unfamiliarity with just how embedded in our system is structural racism,” he said.
Perhaps the podcast’s worst offense was its failure to address the painful history of racial bias in this country that still permeates the medical community, says Tamara Saint-Surin, MD, assistant professor at the University of North Carolina at Chapel Hill.
“For physicians in leadership to have the belief that structural racism does not exist in medicine, they don’t really appreciate what affects their patients and what their patients were dealing with,” Dr. Saint-Surin said in an interview. “It was a very harmful podcast and goes to show we still have so much work to do.”
Along with a flawed premise, she says, the podcast was not nearly long enough to address such a nuanced issue. And Dr. Livingston focused on interpersonal racism rather than structural racism, she said, failing to address widespread problems such as higher rates of asthma among Black populations living in areas with poor air quality.
The number of Black doctors remains low and the lack of representation adds to an environment already rife with racism, according to many medical professionals.
Shirlene Obuobi, MD, an internal medicine doctor in Chicago, said JAMA failed to live up to its own standards by publishing material that lacked research and expertise.
“I can’t submit a clinical trial to JAMA without them combing through methods with a fine-tooth comb,” Dr. Obuobi said. “They didn’t uphold the standards they normally apply to anyone else.”
Both the editor of JAMA and the head of the American Medical Association issued statements criticizing the episode and the tweet that promoted it.
JAMA Editor-in-Chief Howard Bauchner, MD, said, “The language of the tweet, and some portions of the podcast, do not reflect my commitment as editorial leader of JAMA and JAMA Network to call out and discuss the adverse effects of injustice, inequity, and racism in society and medicine as JAMA has done for many years.” He said JAMA will schedule a future podcast to address the concerns raised about the recent episode.
AMA CEO James L. Madara, MD, said, “The AMA’s House of Delegates passed policy stating that racism is structural, systemic, cultural, and interpersonal, and we are deeply disturbed – and angered – by a recent JAMA podcast that questioned the existence of structural racism and the affiliated tweet that promoted the podcast and stated ‘no physician is racist, so how can there be structural racism in health care?’ ”
He continued: “JAMA has editorial independence from AMA, but this tweet and podcast are inconsistent with the policies and views of AMA, and I’m concerned about and acknowledge the harms they have caused. Structural racism in health care and our society exists, and it is incumbent on all of us to fix it.”
This article was updated 3/5/21.
A version of this article first appeared on WebMD.com.
Published on Feb. 23, the episode is hosted on JAMA’s learning platform for doctors and is available for continuing medical education credits.
“No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast,” JAMA wrote in a Twitter post to promote the episode. That tweet has since been deleted.
The episode features host Ed Livingston, MD, deputy editor for clinical reviews and education at JAMA, and guest Mitchell Katz, MD, president and CEO for NYC Health + Hospitals and deputy editor for JAMA Internal Medicine. Dr. Livingston approaches the episode as “structural racism for skeptics,” and Dr. Katz tries to explain how structural racism deepens health disparities and what health systems can do about it.
“Many physicians are skeptical of structural racism, the idea that economic, educational, and other societal systems preferentially disadvantage Black Americans and other communities of color,” the episode description says.
In the podcast, Dr. Livingston and Dr. Katz speak about health care disparities and racial inequality. Dr. Livingston, who says he “didn’t understand the concept” going into the episode, suggests that racism was made illegal in the 1960s and that the discussion of “structural racism” should shift away from the term “racism” and focus on socioeconomic status instead.
“What you’re talking about isn’t so much racism ... it isn’t their race, it isn’t their color, it’s their socioeconomic status,” Dr. Livingston says. “Is that a fair statement?”
But Dr. Katz says that “acknowledging structural racism can be helpful to us. Structural racism refers to a system in which policies or practices or how we look at people perpetuates racial inequality.”
Dr. Katz points to the creation of a hospital in San Francisco in the 1880s to treat patients of Chinese ethnicity separately. Outside of health care, he talks about environmental racism between neighborhoods with inequalities in hospitals, schools, and social services.
“All of those things have an impact on that minority person,” Dr. Katz says. “The big thing we can all do is move away from trying to interrogate each other’s opinions and move to a place where we are looking at the policies of our institutions and making sure that they promote equality.”
Dr. Livingston concludes the episode by reemphasizing that “racism” should be taken out of the conversation and it should instead focus on the “structural” aspect of socioeconomics.
“Minorities ... aren’t [in those neighborhoods] because they’re not allowed to buy houses or they can’t get a job because they’re Black or Hispanic. That would be illegal,” Dr. Livingston says. “But disproportionality does exist.”
Efforts to reach Dr. Livingston were unsuccessful. Dr. Katz distanced himself from Dr. Livingston in a statement released on March 4.
“Systemic and interpersonal racism both still exist in our country — they must be rooted out. I do not share the JAMA host’s belief of doing away with the word ‘racism’ will help us be more successful in ending inequities that exists across racial and ethnic lines,” Dr. Katz said. “Further, I believe that we will only produce an equitable society when social and political structures do not continue to produce and perpetuate disparate results based on social race and ethnicity.”
Dr. Katz reiterated that both interpersonal and structural racism continue to exist in the United States, “and it is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it.”
He also recommended JAMA use this controversy “as a learning opportunity for continued dialogue and create another podcast series as an open conversation that invites diverse experts in the field to have an open discussion about structural racism in healthcare.”
The podcast and JAMA’s tweet promoting it were widely criticized on Twitter. In interviews with WebMD, many doctors expressed disbelief that such a respected journal would lend its name to this podcast episode.
B. Bobby Chiong, MD, a radiologist in New York, said although JAMA’s effort to engage with its audience about racism is laudable, it missed the mark.
“I think the backlash comes from how they tried to make a podcast about the subject and somehow made themselves an example of unconscious bias and unfamiliarity with just how embedded in our system is structural racism,” he said.
Perhaps the podcast’s worst offense was its failure to address the painful history of racial bias in this country that still permeates the medical community, says Tamara Saint-Surin, MD, assistant professor at the University of North Carolina at Chapel Hill.
“For physicians in leadership to have the belief that structural racism does not exist in medicine, they don’t really appreciate what affects their patients and what their patients were dealing with,” Dr. Saint-Surin said in an interview. “It was a very harmful podcast and goes to show we still have so much work to do.”
Along with a flawed premise, she says, the podcast was not nearly long enough to address such a nuanced issue. And Dr. Livingston focused on interpersonal racism rather than structural racism, she said, failing to address widespread problems such as higher rates of asthma among Black populations living in areas with poor air quality.
The number of Black doctors remains low and the lack of representation adds to an environment already rife with racism, according to many medical professionals.
Shirlene Obuobi, MD, an internal medicine doctor in Chicago, said JAMA failed to live up to its own standards by publishing material that lacked research and expertise.
“I can’t submit a clinical trial to JAMA without them combing through methods with a fine-tooth comb,” Dr. Obuobi said. “They didn’t uphold the standards they normally apply to anyone else.”
Both the editor of JAMA and the head of the American Medical Association issued statements criticizing the episode and the tweet that promoted it.
JAMA Editor-in-Chief Howard Bauchner, MD, said, “The language of the tweet, and some portions of the podcast, do not reflect my commitment as editorial leader of JAMA and JAMA Network to call out and discuss the adverse effects of injustice, inequity, and racism in society and medicine as JAMA has done for many years.” He said JAMA will schedule a future podcast to address the concerns raised about the recent episode.
AMA CEO James L. Madara, MD, said, “The AMA’s House of Delegates passed policy stating that racism is structural, systemic, cultural, and interpersonal, and we are deeply disturbed – and angered – by a recent JAMA podcast that questioned the existence of structural racism and the affiliated tweet that promoted the podcast and stated ‘no physician is racist, so how can there be structural racism in health care?’ ”
He continued: “JAMA has editorial independence from AMA, but this tweet and podcast are inconsistent with the policies and views of AMA, and I’m concerned about and acknowledge the harms they have caused. Structural racism in health care and our society exists, and it is incumbent on all of us to fix it.”
This article was updated 3/5/21.
A version of this article first appeared on WebMD.com.
Docs become dog groomers and warehouse workers after COVID-19 work loss
One of the biggest conundrums of the COVID-19 pandemic has been the simultaneous panic-hiring of medical professionals in hot spots and significant downsizing of staff across the country. From huge hospital systems to private practices, the stoppage of breast reductions and knee replacements, not to mention the drops in motor vehicle accidents and bar fights, have quieted operating rooms and emergency departments and put doctors’ jobs on the chopping block. A widely cited survey suggests that 21% of doctors have had a work reduction due to COVID-19.
For many American doctors, this is their first extended period of unemployment. Unlike engineers or those with MBAs who might see their fortunes rise and fall with the whims of recessions and boom times, physicians are not exactly accustomed to being laid off. However, doctors were already smarting for years due to falling salaries and decreased autonomy, punctuated by endless clicks on electronic medical records software.
Stephanie Eschenbach Morgan, MD, a breast radiologist in North Carolina, trained for 10 years after college before earning a true physician’s salary.
“Being furloughed was awful. Initially, it was only going to be 2 weeks, and then it turned into 2 months with no pay,” she reflected.
Dr. Eschenbach Morgan and her surgeon husband, who lost a full quarter’s salary, had to ask for grace periods on their credit card and mortgage payments because they had paid a large tax bill right before the pandemic began. “We couldn’t get any stimulus help, so that added insult to injury,” she said.
With her time spent waiting in a holding pattern, Dr. Eschenbach Morgan homeschooled her two young children and started putting a home gym together. She went on a home organizing spree, started a garden, and, perhaps most impressively, caught up with 5 years of photo albums.
A bonus she noted: “I didn’t set an alarm for 2 months.”
Shella Farooki, MD, a radiologist in California, was also focused on homeschooling, itself a demanding job, and veered toward retirement. When one of her work contracts furloughed her (“at one point, I made $30K a month for [their business]”), she started saving money at home, teaching the kids, and applied for a Paycheck Protection Program loan. Her husband, a hospitalist, had had his shifts cut. Dr. Farooki tried a radiology artificial intelligence firm but backed out when she was asked to read 9,200 studies for them for $2,000 per month.
Now, she thinks about leaving medicine “every day.”
Some doctors are questioning whether they should be in medicine in the first place. Family medicine physician Jonathan Polak, MD, faced with his own pink slip, turned to pink T-shirts instead. His girlfriend manages an outlet of the teen fashion retailer Justice. Dr. Polak, who finished his residency just 2 years ago, didn’t hesitate to take a $10-an-hour gig as a stock doc, once even finding himself delivering a shelving unit from the shuttering store to a physician fleeing the city for rural New Hampshire to “escape.”
There’s no escape for him – yet. Saddled with “astronomical” student loans, he had considered grocery store work as well. Dr. Polak knows he can’t work part time or go into teaching long term, as he might like.
Even so, he’s doing everything he can to not be in patient care for the long haul – it’s just not what he thought it would be.
“The culture of medicine, bureaucracy, endless paperwork and charting, and threat of litigation sucks a lot of the joy out of it to the point that I don’t see myself doing it forever when imagining myself 5-10 years into it.”
Still, he recently took an 18-month hospital contract that will force him to move to Florida, but he’s also been turning himself into a veritable Renaissance man; composing music, training for an ultramarathon, studying the latest medical findings, roadtripping, and launching a podcast about dog grooming with a master groomer. “We found parallels between medicine and dog grooming,” he says, somewhat convincingly.
Also working the ruff life is Jen Tserng, MD, a former forensic pathologist who landed on news websites in recent years for becoming a professional dogwalker and housesitter without a permanent home. Dr. Tserng knows doctors were restless and unhappy before COVID-19, their thoughts wandering where the grass might be greener.
As her profile grew, she found her inbox gathering messages from disaffected medical minions: students with a fear of failing or staring down residency application season and employed doctors sick of the constant grind. As she recounted those de facto life coach conversations (“What do you really enjoy?” “Do you really like dogs?”) by phone from New York, she said matter-of-factly, “They don’t call because of COVID. They call because they hate their lives.”
Michelle Mudge-Riley, MD, a physician in Texas, has been seeing this shift for some time as well. She recently held a virtual version of her Physicians Helping Physicians conference, where doctors hear from their peers working successfully in fields like pharmaceuticals and real estate investing.
When COVID-19 hit, Dr. Mudge-Riley quickly pivoted to a virtual platform, where the MDs and DOs huddled in breakout rooms having honest chats about their fears and tentative hopes about their new careers.
“There has been increased interest in nonclinical exploration into full- and part-time careers, as well as side hustles, since COVID began,” she said. “Many physicians have had their hours or pay cut, and some have been laid off. Others are furloughed. Some just want out of an environment where they don’t feel safe.”
An ear, nose, and throat surgeon, Maansi Doshi, MD, from central California, didn’t feel safe – so she left. She had returned from India sick with a mystery virus right as the pandemic began (she said her COVID-19 tests were all negative) and was waiting to get well enough to go back to her private practice job. However, she said she clashed with Trump-supporting colleagues she feared might not be taking the pandemic seriously enough.
Finally getting over a relapse of her mystery virus, Dr. Doshi emailed her resignation in May. Her husband, family practice doctor Mark Mangiapane, MD, gave his job notice weeks later in solidarity because he worked in the same building. Together, they have embraced gardening, a Peloton splurge, and learning business skills to open private practices – solo primary care for him; ENT with a focus on her favorite surgery, rhinoplasty, for her.
Dr. Mangiapane had considered editing medical brochures and also tried to apply for a job as a county public health officer in rural California, but he received his own shock when he learned the county intended to open schools in the midst of the pandemic despite advisement to the contrary by the former health officer.
He retreated from job listings altogether after hearing his would-be peers were getting death threats – targeting their children.
Both doctors felt COVID-19 pushed them beyond their comfort zones. “If COVID hadn’t happened, I would be working. ... Be ‘owned.’ In a weird way, COVID made me more independent and take a risk with my career.”
Obstetrician Kwandaa Roberts, MD, certainly did; she took a budding interest in decorating dollhouses straight to Instagram and national news fame, and she is now a TV-show expert on “Sell This House.”
Like Dr. Doshi and Dr. Mangiapane, Dr. Polak wants to be more in control of his future – even if selling T-shirts at a mall means a certain loss of status along the way.
“Aside from my passion to learn and to have that connection with people, I went into medicine ... because of the job security I thought existed,” he said. “I would say that my getting furloughed has changed my view of the United States in a dramatic way. I do not feel as confident in the U.S. economy and general way of life as I did a year ago. And I am taking a number of steps to put myself in a more fluid, adaptable position in case another crisis like this occurs or if the current state of things worsens.”
A version of this article first appeared on Medscape.com.
One of the biggest conundrums of the COVID-19 pandemic has been the simultaneous panic-hiring of medical professionals in hot spots and significant downsizing of staff across the country. From huge hospital systems to private practices, the stoppage of breast reductions and knee replacements, not to mention the drops in motor vehicle accidents and bar fights, have quieted operating rooms and emergency departments and put doctors’ jobs on the chopping block. A widely cited survey suggests that 21% of doctors have had a work reduction due to COVID-19.
For many American doctors, this is their first extended period of unemployment. Unlike engineers or those with MBAs who might see their fortunes rise and fall with the whims of recessions and boom times, physicians are not exactly accustomed to being laid off. However, doctors were already smarting for years due to falling salaries and decreased autonomy, punctuated by endless clicks on electronic medical records software.
Stephanie Eschenbach Morgan, MD, a breast radiologist in North Carolina, trained for 10 years after college before earning a true physician’s salary.
“Being furloughed was awful. Initially, it was only going to be 2 weeks, and then it turned into 2 months with no pay,” she reflected.
Dr. Eschenbach Morgan and her surgeon husband, who lost a full quarter’s salary, had to ask for grace periods on their credit card and mortgage payments because they had paid a large tax bill right before the pandemic began. “We couldn’t get any stimulus help, so that added insult to injury,” she said.
With her time spent waiting in a holding pattern, Dr. Eschenbach Morgan homeschooled her two young children and started putting a home gym together. She went on a home organizing spree, started a garden, and, perhaps most impressively, caught up with 5 years of photo albums.
A bonus she noted: “I didn’t set an alarm for 2 months.”
Shella Farooki, MD, a radiologist in California, was also focused on homeschooling, itself a demanding job, and veered toward retirement. When one of her work contracts furloughed her (“at one point, I made $30K a month for [their business]”), she started saving money at home, teaching the kids, and applied for a Paycheck Protection Program loan. Her husband, a hospitalist, had had his shifts cut. Dr. Farooki tried a radiology artificial intelligence firm but backed out when she was asked to read 9,200 studies for them for $2,000 per month.
Now, she thinks about leaving medicine “every day.”
Some doctors are questioning whether they should be in medicine in the first place. Family medicine physician Jonathan Polak, MD, faced with his own pink slip, turned to pink T-shirts instead. His girlfriend manages an outlet of the teen fashion retailer Justice. Dr. Polak, who finished his residency just 2 years ago, didn’t hesitate to take a $10-an-hour gig as a stock doc, once even finding himself delivering a shelving unit from the shuttering store to a physician fleeing the city for rural New Hampshire to “escape.”
There’s no escape for him – yet. Saddled with “astronomical” student loans, he had considered grocery store work as well. Dr. Polak knows he can’t work part time or go into teaching long term, as he might like.
Even so, he’s doing everything he can to not be in patient care for the long haul – it’s just not what he thought it would be.
“The culture of medicine, bureaucracy, endless paperwork and charting, and threat of litigation sucks a lot of the joy out of it to the point that I don’t see myself doing it forever when imagining myself 5-10 years into it.”
Still, he recently took an 18-month hospital contract that will force him to move to Florida, but he’s also been turning himself into a veritable Renaissance man; composing music, training for an ultramarathon, studying the latest medical findings, roadtripping, and launching a podcast about dog grooming with a master groomer. “We found parallels between medicine and dog grooming,” he says, somewhat convincingly.
Also working the ruff life is Jen Tserng, MD, a former forensic pathologist who landed on news websites in recent years for becoming a professional dogwalker and housesitter without a permanent home. Dr. Tserng knows doctors were restless and unhappy before COVID-19, their thoughts wandering where the grass might be greener.
As her profile grew, she found her inbox gathering messages from disaffected medical minions: students with a fear of failing or staring down residency application season and employed doctors sick of the constant grind. As she recounted those de facto life coach conversations (“What do you really enjoy?” “Do you really like dogs?”) by phone from New York, she said matter-of-factly, “They don’t call because of COVID. They call because they hate their lives.”
Michelle Mudge-Riley, MD, a physician in Texas, has been seeing this shift for some time as well. She recently held a virtual version of her Physicians Helping Physicians conference, where doctors hear from their peers working successfully in fields like pharmaceuticals and real estate investing.
When COVID-19 hit, Dr. Mudge-Riley quickly pivoted to a virtual platform, where the MDs and DOs huddled in breakout rooms having honest chats about their fears and tentative hopes about their new careers.
“There has been increased interest in nonclinical exploration into full- and part-time careers, as well as side hustles, since COVID began,” she said. “Many physicians have had their hours or pay cut, and some have been laid off. Others are furloughed. Some just want out of an environment where they don’t feel safe.”
An ear, nose, and throat surgeon, Maansi Doshi, MD, from central California, didn’t feel safe – so she left. She had returned from India sick with a mystery virus right as the pandemic began (she said her COVID-19 tests were all negative) and was waiting to get well enough to go back to her private practice job. However, she said she clashed with Trump-supporting colleagues she feared might not be taking the pandemic seriously enough.
Finally getting over a relapse of her mystery virus, Dr. Doshi emailed her resignation in May. Her husband, family practice doctor Mark Mangiapane, MD, gave his job notice weeks later in solidarity because he worked in the same building. Together, they have embraced gardening, a Peloton splurge, and learning business skills to open private practices – solo primary care for him; ENT with a focus on her favorite surgery, rhinoplasty, for her.
Dr. Mangiapane had considered editing medical brochures and also tried to apply for a job as a county public health officer in rural California, but he received his own shock when he learned the county intended to open schools in the midst of the pandemic despite advisement to the contrary by the former health officer.
He retreated from job listings altogether after hearing his would-be peers were getting death threats – targeting their children.
Both doctors felt COVID-19 pushed them beyond their comfort zones. “If COVID hadn’t happened, I would be working. ... Be ‘owned.’ In a weird way, COVID made me more independent and take a risk with my career.”
Obstetrician Kwandaa Roberts, MD, certainly did; she took a budding interest in decorating dollhouses straight to Instagram and national news fame, and she is now a TV-show expert on “Sell This House.”
Like Dr. Doshi and Dr. Mangiapane, Dr. Polak wants to be more in control of his future – even if selling T-shirts at a mall means a certain loss of status along the way.
“Aside from my passion to learn and to have that connection with people, I went into medicine ... because of the job security I thought existed,” he said. “I would say that my getting furloughed has changed my view of the United States in a dramatic way. I do not feel as confident in the U.S. economy and general way of life as I did a year ago. And I am taking a number of steps to put myself in a more fluid, adaptable position in case another crisis like this occurs or if the current state of things worsens.”
A version of this article first appeared on Medscape.com.
One of the biggest conundrums of the COVID-19 pandemic has been the simultaneous panic-hiring of medical professionals in hot spots and significant downsizing of staff across the country. From huge hospital systems to private practices, the stoppage of breast reductions and knee replacements, not to mention the drops in motor vehicle accidents and bar fights, have quieted operating rooms and emergency departments and put doctors’ jobs on the chopping block. A widely cited survey suggests that 21% of doctors have had a work reduction due to COVID-19.
For many American doctors, this is their first extended period of unemployment. Unlike engineers or those with MBAs who might see their fortunes rise and fall with the whims of recessions and boom times, physicians are not exactly accustomed to being laid off. However, doctors were already smarting for years due to falling salaries and decreased autonomy, punctuated by endless clicks on electronic medical records software.
Stephanie Eschenbach Morgan, MD, a breast radiologist in North Carolina, trained for 10 years after college before earning a true physician’s salary.
“Being furloughed was awful. Initially, it was only going to be 2 weeks, and then it turned into 2 months with no pay,” she reflected.
Dr. Eschenbach Morgan and her surgeon husband, who lost a full quarter’s salary, had to ask for grace periods on their credit card and mortgage payments because they had paid a large tax bill right before the pandemic began. “We couldn’t get any stimulus help, so that added insult to injury,” she said.
With her time spent waiting in a holding pattern, Dr. Eschenbach Morgan homeschooled her two young children and started putting a home gym together. She went on a home organizing spree, started a garden, and, perhaps most impressively, caught up with 5 years of photo albums.
A bonus she noted: “I didn’t set an alarm for 2 months.”
Shella Farooki, MD, a radiologist in California, was also focused on homeschooling, itself a demanding job, and veered toward retirement. When one of her work contracts furloughed her (“at one point, I made $30K a month for [their business]”), she started saving money at home, teaching the kids, and applied for a Paycheck Protection Program loan. Her husband, a hospitalist, had had his shifts cut. Dr. Farooki tried a radiology artificial intelligence firm but backed out when she was asked to read 9,200 studies for them for $2,000 per month.
Now, she thinks about leaving medicine “every day.”
Some doctors are questioning whether they should be in medicine in the first place. Family medicine physician Jonathan Polak, MD, faced with his own pink slip, turned to pink T-shirts instead. His girlfriend manages an outlet of the teen fashion retailer Justice. Dr. Polak, who finished his residency just 2 years ago, didn’t hesitate to take a $10-an-hour gig as a stock doc, once even finding himself delivering a shelving unit from the shuttering store to a physician fleeing the city for rural New Hampshire to “escape.”
There’s no escape for him – yet. Saddled with “astronomical” student loans, he had considered grocery store work as well. Dr. Polak knows he can’t work part time or go into teaching long term, as he might like.
Even so, he’s doing everything he can to not be in patient care for the long haul – it’s just not what he thought it would be.
“The culture of medicine, bureaucracy, endless paperwork and charting, and threat of litigation sucks a lot of the joy out of it to the point that I don’t see myself doing it forever when imagining myself 5-10 years into it.”
Still, he recently took an 18-month hospital contract that will force him to move to Florida, but he’s also been turning himself into a veritable Renaissance man; composing music, training for an ultramarathon, studying the latest medical findings, roadtripping, and launching a podcast about dog grooming with a master groomer. “We found parallels between medicine and dog grooming,” he says, somewhat convincingly.
Also working the ruff life is Jen Tserng, MD, a former forensic pathologist who landed on news websites in recent years for becoming a professional dogwalker and housesitter without a permanent home. Dr. Tserng knows doctors were restless and unhappy before COVID-19, their thoughts wandering where the grass might be greener.
As her profile grew, she found her inbox gathering messages from disaffected medical minions: students with a fear of failing or staring down residency application season and employed doctors sick of the constant grind. As she recounted those de facto life coach conversations (“What do you really enjoy?” “Do you really like dogs?”) by phone from New York, she said matter-of-factly, “They don’t call because of COVID. They call because they hate their lives.”
Michelle Mudge-Riley, MD, a physician in Texas, has been seeing this shift for some time as well. She recently held a virtual version of her Physicians Helping Physicians conference, where doctors hear from their peers working successfully in fields like pharmaceuticals and real estate investing.
When COVID-19 hit, Dr. Mudge-Riley quickly pivoted to a virtual platform, where the MDs and DOs huddled in breakout rooms having honest chats about their fears and tentative hopes about their new careers.
“There has been increased interest in nonclinical exploration into full- and part-time careers, as well as side hustles, since COVID began,” she said. “Many physicians have had their hours or pay cut, and some have been laid off. Others are furloughed. Some just want out of an environment where they don’t feel safe.”
An ear, nose, and throat surgeon, Maansi Doshi, MD, from central California, didn’t feel safe – so she left. She had returned from India sick with a mystery virus right as the pandemic began (she said her COVID-19 tests were all negative) and was waiting to get well enough to go back to her private practice job. However, she said she clashed with Trump-supporting colleagues she feared might not be taking the pandemic seriously enough.
Finally getting over a relapse of her mystery virus, Dr. Doshi emailed her resignation in May. Her husband, family practice doctor Mark Mangiapane, MD, gave his job notice weeks later in solidarity because he worked in the same building. Together, they have embraced gardening, a Peloton splurge, and learning business skills to open private practices – solo primary care for him; ENT with a focus on her favorite surgery, rhinoplasty, for her.
Dr. Mangiapane had considered editing medical brochures and also tried to apply for a job as a county public health officer in rural California, but he received his own shock when he learned the county intended to open schools in the midst of the pandemic despite advisement to the contrary by the former health officer.
He retreated from job listings altogether after hearing his would-be peers were getting death threats – targeting their children.
Both doctors felt COVID-19 pushed them beyond their comfort zones. “If COVID hadn’t happened, I would be working. ... Be ‘owned.’ In a weird way, COVID made me more independent and take a risk with my career.”
Obstetrician Kwandaa Roberts, MD, certainly did; she took a budding interest in decorating dollhouses straight to Instagram and national news fame, and she is now a TV-show expert on “Sell This House.”
Like Dr. Doshi and Dr. Mangiapane, Dr. Polak wants to be more in control of his future – even if selling T-shirts at a mall means a certain loss of status along the way.
“Aside from my passion to learn and to have that connection with people, I went into medicine ... because of the job security I thought existed,” he said. “I would say that my getting furloughed has changed my view of the United States in a dramatic way. I do not feel as confident in the U.S. economy and general way of life as I did a year ago. And I am taking a number of steps to put myself in a more fluid, adaptable position in case another crisis like this occurs or if the current state of things worsens.”
A version of this article first appeared on Medscape.com.
Rural women receive antibiotics for longer than necessary for UTIs
Women living in rural areas were significantly more likely than were those in urban areas to receive inappropriate antibiotic prescriptions for urinary tract infections, based on data from an observational cohort study of more than 600,000 women.
Uncomplicated urinary tract infections (UTIs) are common among otherwise healthy women in the United States, and certain antibiotics are recommended as first-line therapy, wrote Abbye W. Clark, MD, of Washington University, St. Louis, and colleagues.
“However, the majority of antibiotic prescriptions for uncomplicated UTI are suboptimal because they are written for nonrecommended agents and durations,” they said.
Addressing rural health disparities has become a focus in the United States, and previous studies of respiratory tract infections have shown differences in antibiotic prescribing based on geographic region; “however, no large-scale studies have evaluated rural-urban differences in inappropriate outpatient prescribing for UTI,” they added.
In a study published in Infection Control & Hospital Epidemiology, the researchers identified 670,450 women aged 18-44 years who received oral antibiotics for uncomplicated UTIs between 2010 to 2015, using a commercial insurance database to determine diagnosis and antibiotic prescription information. Women were defined as urban if they lived in a metropolitan statistical area of at least 50,000 inhabitants (86.2%); all other women were defined as rural (13.8%). The median age was 30 years for both groups.
Overall, 46.7% of the women received prescriptions for inappropriate antibiotics, and 76.1% received antibiotics for inappropriate durations.
Antibiotics and durations were defined as appropriate or inappropriate based on current clinical guidelines. “We classified first-line agents (nitrofurantoin, TMP-SMX, fosfomycin) as appropriate and non–first-line agents (fluoroquinolones, beta-lactams) as inappropriate,” the researchers said.
The regimens classified as appropriate duration were “nitrofurantoin 5-day regimen, TMP-SMX (including TMP monotherapy) 3-day regimen, fosfomycin 1-day regimen, fluoroquinolones 3-day regimen, and beta-lactams 3- to 7-day regimen. All other regimens were classified as inappropriate duration,” they noted.
More rural women receive long-duration antibiotics
In a multivariate analysis, similar percentages of antibiotics for rural and urban women consisted of inappropriate agents (45.9% vs. 46.9%) including use of fluoroquinolones (41.0% vs. 41.7%) and beta-lactams (4.8% vs. 5.0%).
However, across all antibiotics, women in rural areas were more likely than were women in urban areas to receive prescriptions for inappropriately long durations (83.9% vs. 75.9%, adjusted risk ratio 1.10).
The percentage of women who received inappropriate antibiotic agents was not significantly different based on geographic region of the country.
From 2011 to 2015, the quarterly proportion of women overall who received inappropriate agents and antibiotics for inappropriate durations decreased slightly (48.5% to 43.7% and 78.3% to 73.4%, respectively), the researchers noted.
The study findings were limited by several factors including the potentially lenient definition of antibiotic duration, a study population that disproportionately oversampled from the South and undersampled from the West, use of ZIP codes to determine rural vs. urban status, lack of data on race and income, and lack of access to urine culture results, the researchers noted.
However, “our study identified rural-urban differences in antibiotic prescribing, including an actionable disparity in the duration of antibiotics that disproportionately affects women who live in rural locations,” they said.
“Given the large quantity of inappropriate prescriptions annually in the U.S., as well as the negative patient- and society-level consequences of unnecessary exposure to antibiotics, antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing, particularly in rural settings,” they concluded.
Data support need for education and stewardship
“This manuscript provides valuable information to all women’s health providers regarding the importance of antibiotic stewardship,” David M. Jaspan, DO, and Natasha Abdullah, MD, Einstein Medical Center, Philadelphia, said in an interview. Whether urban or rural, over 45% of the patients received inappropriate non–first-line treatment and 76% of the prescriptions were for an inappropriate duration (98.8% for longer than recommended), they emphasized.
“The potential negative impact of antibiotic resistance, coupled with the potential for increased side effects, should prompt providers to ensure that when treating uncomplicated UTIs in women, that the choice of treatment and the duration of treatment is tailored to the patient’s needs,” the Dr. Jaspan and Dr. Abdullah said.
To improve antibiotic prescribing, especially at the local and regional level, “We encourage providers to familiarize themselves with local information as it pertains to known resistance when prescribing empiric treatment regimens for uncomplicated UTIs,” they said.
The study was supported by the National Center for Advancing Translational Sciences at the National Institutes of Health. Lead author Dr. Clark, as well as Dr. Jaspan and Dr. Abdullah, had no financial conflicts to disclose.
Women living in rural areas were significantly more likely than were those in urban areas to receive inappropriate antibiotic prescriptions for urinary tract infections, based on data from an observational cohort study of more than 600,000 women.
Uncomplicated urinary tract infections (UTIs) are common among otherwise healthy women in the United States, and certain antibiotics are recommended as first-line therapy, wrote Abbye W. Clark, MD, of Washington University, St. Louis, and colleagues.
“However, the majority of antibiotic prescriptions for uncomplicated UTI are suboptimal because they are written for nonrecommended agents and durations,” they said.
Addressing rural health disparities has become a focus in the United States, and previous studies of respiratory tract infections have shown differences in antibiotic prescribing based on geographic region; “however, no large-scale studies have evaluated rural-urban differences in inappropriate outpatient prescribing for UTI,” they added.
In a study published in Infection Control & Hospital Epidemiology, the researchers identified 670,450 women aged 18-44 years who received oral antibiotics for uncomplicated UTIs between 2010 to 2015, using a commercial insurance database to determine diagnosis and antibiotic prescription information. Women were defined as urban if they lived in a metropolitan statistical area of at least 50,000 inhabitants (86.2%); all other women were defined as rural (13.8%). The median age was 30 years for both groups.
Overall, 46.7% of the women received prescriptions for inappropriate antibiotics, and 76.1% received antibiotics for inappropriate durations.
Antibiotics and durations were defined as appropriate or inappropriate based on current clinical guidelines. “We classified first-line agents (nitrofurantoin, TMP-SMX, fosfomycin) as appropriate and non–first-line agents (fluoroquinolones, beta-lactams) as inappropriate,” the researchers said.
The regimens classified as appropriate duration were “nitrofurantoin 5-day regimen, TMP-SMX (including TMP monotherapy) 3-day regimen, fosfomycin 1-day regimen, fluoroquinolones 3-day regimen, and beta-lactams 3- to 7-day regimen. All other regimens were classified as inappropriate duration,” they noted.
More rural women receive long-duration antibiotics
In a multivariate analysis, similar percentages of antibiotics for rural and urban women consisted of inappropriate agents (45.9% vs. 46.9%) including use of fluoroquinolones (41.0% vs. 41.7%) and beta-lactams (4.8% vs. 5.0%).
However, across all antibiotics, women in rural areas were more likely than were women in urban areas to receive prescriptions for inappropriately long durations (83.9% vs. 75.9%, adjusted risk ratio 1.10).
The percentage of women who received inappropriate antibiotic agents was not significantly different based on geographic region of the country.
From 2011 to 2015, the quarterly proportion of women overall who received inappropriate agents and antibiotics for inappropriate durations decreased slightly (48.5% to 43.7% and 78.3% to 73.4%, respectively), the researchers noted.
The study findings were limited by several factors including the potentially lenient definition of antibiotic duration, a study population that disproportionately oversampled from the South and undersampled from the West, use of ZIP codes to determine rural vs. urban status, lack of data on race and income, and lack of access to urine culture results, the researchers noted.
However, “our study identified rural-urban differences in antibiotic prescribing, including an actionable disparity in the duration of antibiotics that disproportionately affects women who live in rural locations,” they said.
“Given the large quantity of inappropriate prescriptions annually in the U.S., as well as the negative patient- and society-level consequences of unnecessary exposure to antibiotics, antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing, particularly in rural settings,” they concluded.
Data support need for education and stewardship
“This manuscript provides valuable information to all women’s health providers regarding the importance of antibiotic stewardship,” David M. Jaspan, DO, and Natasha Abdullah, MD, Einstein Medical Center, Philadelphia, said in an interview. Whether urban or rural, over 45% of the patients received inappropriate non–first-line treatment and 76% of the prescriptions were for an inappropriate duration (98.8% for longer than recommended), they emphasized.
“The potential negative impact of antibiotic resistance, coupled with the potential for increased side effects, should prompt providers to ensure that when treating uncomplicated UTIs in women, that the choice of treatment and the duration of treatment is tailored to the patient’s needs,” the Dr. Jaspan and Dr. Abdullah said.
To improve antibiotic prescribing, especially at the local and regional level, “We encourage providers to familiarize themselves with local information as it pertains to known resistance when prescribing empiric treatment regimens for uncomplicated UTIs,” they said.
The study was supported by the National Center for Advancing Translational Sciences at the National Institutes of Health. Lead author Dr. Clark, as well as Dr. Jaspan and Dr. Abdullah, had no financial conflicts to disclose.
Women living in rural areas were significantly more likely than were those in urban areas to receive inappropriate antibiotic prescriptions for urinary tract infections, based on data from an observational cohort study of more than 600,000 women.
Uncomplicated urinary tract infections (UTIs) are common among otherwise healthy women in the United States, and certain antibiotics are recommended as first-line therapy, wrote Abbye W. Clark, MD, of Washington University, St. Louis, and colleagues.
“However, the majority of antibiotic prescriptions for uncomplicated UTI are suboptimal because they are written for nonrecommended agents and durations,” they said.
Addressing rural health disparities has become a focus in the United States, and previous studies of respiratory tract infections have shown differences in antibiotic prescribing based on geographic region; “however, no large-scale studies have evaluated rural-urban differences in inappropriate outpatient prescribing for UTI,” they added.
In a study published in Infection Control & Hospital Epidemiology, the researchers identified 670,450 women aged 18-44 years who received oral antibiotics for uncomplicated UTIs between 2010 to 2015, using a commercial insurance database to determine diagnosis and antibiotic prescription information. Women were defined as urban if they lived in a metropolitan statistical area of at least 50,000 inhabitants (86.2%); all other women were defined as rural (13.8%). The median age was 30 years for both groups.
Overall, 46.7% of the women received prescriptions for inappropriate antibiotics, and 76.1% received antibiotics for inappropriate durations.
Antibiotics and durations were defined as appropriate or inappropriate based on current clinical guidelines. “We classified first-line agents (nitrofurantoin, TMP-SMX, fosfomycin) as appropriate and non–first-line agents (fluoroquinolones, beta-lactams) as inappropriate,” the researchers said.
The regimens classified as appropriate duration were “nitrofurantoin 5-day regimen, TMP-SMX (including TMP monotherapy) 3-day regimen, fosfomycin 1-day regimen, fluoroquinolones 3-day regimen, and beta-lactams 3- to 7-day regimen. All other regimens were classified as inappropriate duration,” they noted.
More rural women receive long-duration antibiotics
In a multivariate analysis, similar percentages of antibiotics for rural and urban women consisted of inappropriate agents (45.9% vs. 46.9%) including use of fluoroquinolones (41.0% vs. 41.7%) and beta-lactams (4.8% vs. 5.0%).
However, across all antibiotics, women in rural areas were more likely than were women in urban areas to receive prescriptions for inappropriately long durations (83.9% vs. 75.9%, adjusted risk ratio 1.10).
The percentage of women who received inappropriate antibiotic agents was not significantly different based on geographic region of the country.
From 2011 to 2015, the quarterly proportion of women overall who received inappropriate agents and antibiotics for inappropriate durations decreased slightly (48.5% to 43.7% and 78.3% to 73.4%, respectively), the researchers noted.
The study findings were limited by several factors including the potentially lenient definition of antibiotic duration, a study population that disproportionately oversampled from the South and undersampled from the West, use of ZIP codes to determine rural vs. urban status, lack of data on race and income, and lack of access to urine culture results, the researchers noted.
However, “our study identified rural-urban differences in antibiotic prescribing, including an actionable disparity in the duration of antibiotics that disproportionately affects women who live in rural locations,” they said.
“Given the large quantity of inappropriate prescriptions annually in the U.S., as well as the negative patient- and society-level consequences of unnecessary exposure to antibiotics, antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing, particularly in rural settings,” they concluded.
Data support need for education and stewardship
“This manuscript provides valuable information to all women’s health providers regarding the importance of antibiotic stewardship,” David M. Jaspan, DO, and Natasha Abdullah, MD, Einstein Medical Center, Philadelphia, said in an interview. Whether urban or rural, over 45% of the patients received inappropriate non–first-line treatment and 76% of the prescriptions were for an inappropriate duration (98.8% for longer than recommended), they emphasized.
“The potential negative impact of antibiotic resistance, coupled with the potential for increased side effects, should prompt providers to ensure that when treating uncomplicated UTIs in women, that the choice of treatment and the duration of treatment is tailored to the patient’s needs,” the Dr. Jaspan and Dr. Abdullah said.
To improve antibiotic prescribing, especially at the local and regional level, “We encourage providers to familiarize themselves with local information as it pertains to known resistance when prescribing empiric treatment regimens for uncomplicated UTIs,” they said.
The study was supported by the National Center for Advancing Translational Sciences at the National Institutes of Health. Lead author Dr. Clark, as well as Dr. Jaspan and Dr. Abdullah, had no financial conflicts to disclose.
FROM INFECTION CONTROL & HOSPITAL EPIDEMIOLOGY
Maribavir seen as superior to other antivirals for CMV clearance post transplant
Maribavir, an investigational antiviral agent with a novel mechanism of action, was superior to other antiviral strategies at clearing cytomegalovirus (CMV) viremia and controlling symptoms in hematopoietic cell or solid-organ transplant recipients, results of a phase 3 clinical trial showed.
CMV viremia clearance at study week 8 was seen in 55.7% of all patients randomized to receive maribavir, compared with 23.9% for patients assigned to receive investigator-assigned therapy (IAT), Francisco Marty, MD, from the Dana-Farber Cancer Institute in Boston reported at the Transplant & Cellular Therapies Meetings.
“Maribavir’s benefit was driven by lower incidence of treatment-limiting toxicities, compared with IAT,” he said a late-breaking abstract session during the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
“Available anti-CMV antivirals are limited by development of resistance and toxicities, particularly myelosuppression with the use of valganciclovir and nephrotoxicity with the use of foscarnet and cidofovir. Alternative treatment options are required to address this unmet medical need,” he said.
Maribavir inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.
Details of trial
In the phase 3 SHP620-30e trial (NCT02931539), Dr. Marty and colleagues enrolled patients with relapsed or refractory CMV infections after hematopoietic cell transplant (HCT) or solid-organ transplant (SOT) and after stratification by transplant type and screening CMV DNA level randomly assigned them on a 2:1 basis to receive either maribavir 400 mg twice daily (235 patients) or IAT (117 patients), consisting of either ganciclovir/valganciclovir, foscarnet, cidofovir, or combined foscarnet and val/ganciclovir.
The primary endpoint of viremia clearance at 8 weeks was defined as plasma CMV DNA less than 137 IU/mL in two consecutive tests at a central laboratory at least 5 days apart beginning at the end of week 8.
The trial met its primary endpoint, with a viremia clearance rate of 55.7% with maribavir versus 23.9% with IAT.
The viremia clearance rates were similar in each of the transplant groups: 55.9% versus 20.8%, respectively, in patients who underwent HCT, and 55.6% versus 26.1% in patients who underwent SOT (P < .001).
Clearance rates among patients with CMV DNA below 9,100 IU/mL at baseline were 62.1% with maribavir versus 24.7% with IAT. Among patients with baseline CMV DNA of 9100 IU/mL or above, the respective rates were 43.9% versus 21.9%.
CMV viremia clearance continued from week 8 to week 16 in 18.7% of patients assigned to maribavir and to 10.3% of patients randomized to IAT (P < .013).
The median time to first CMV viremia clearance as 22 days with maribavir versus 27 days with IAT (P = .039).
All-cause mortality was similar between the groups, at 11.5% versus 11.1%, respectively.
The incidences of serious and severe treatment-emergent adverse events (TEAE) were 38.5% and 32.1%, respectively, in the maribavir group, and 37.1% and 37.9% in the IAT group.
Any TEAE leading to study drug discontinuation was less common with maribavir, occurring in 13.2% of patients, compared with 31.9% of patients on IAT. Serious TEAEs leading to drug discontinuation occurred in 8.5% versus 14.7%, respectively.
Serious TEAEs leading to death occurred in 6.8% of patients on maribavir versus 5.2% of those on IAT.
Role of letermovir
In the question-and-answer session following the presentation, comoderator Monalisa Ghosh, MD, from the University of Michigan, Ann Arbor, asked whether any patients in the study were currently on letermovir (Prevymis) prophylaxis, and whether any patients had previously been treated with letermovir but had CMV reactivation and were then treated on study.
Dr. Marty noted that the trial was designed before letermovir was approved for CMV prophylaxis in adults who have undergone an allogeneic HCT.
“Nobody was on letermovir at the beginning of the trial,” he replied, but noted that some patients who were enrolled and had infections that were refractory or resistant to valganciclovir, foscarnet, or a combination of the two received letermovir as secondary prophylaxis.
“I haven’t got the data to tell you how often [letermovir] was used; I think part of the lack of mortality benefit [with maribavir] may be due to the fact that people jumped into secondary prophylaxis with letermovir to minimize the toxicities that we saw,” he said.
Although maribavir has not as of this writing received Food and Drug Administration approval, the drug may be available to some patients through a compassionate-use program from Takeda, Dr. Marty noted.
The study was funded by Shire ViroPharma. Dr. Marty disclosed research funding from Shire and from others. Dr. Ghosh had no relevant disclosures.
Maribavir, an investigational antiviral agent with a novel mechanism of action, was superior to other antiviral strategies at clearing cytomegalovirus (CMV) viremia and controlling symptoms in hematopoietic cell or solid-organ transplant recipients, results of a phase 3 clinical trial showed.
CMV viremia clearance at study week 8 was seen in 55.7% of all patients randomized to receive maribavir, compared with 23.9% for patients assigned to receive investigator-assigned therapy (IAT), Francisco Marty, MD, from the Dana-Farber Cancer Institute in Boston reported at the Transplant & Cellular Therapies Meetings.
“Maribavir’s benefit was driven by lower incidence of treatment-limiting toxicities, compared with IAT,” he said a late-breaking abstract session during the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
“Available anti-CMV antivirals are limited by development of resistance and toxicities, particularly myelosuppression with the use of valganciclovir and nephrotoxicity with the use of foscarnet and cidofovir. Alternative treatment options are required to address this unmet medical need,” he said.
Maribavir inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.
Details of trial
In the phase 3 SHP620-30e trial (NCT02931539), Dr. Marty and colleagues enrolled patients with relapsed or refractory CMV infections after hematopoietic cell transplant (HCT) or solid-organ transplant (SOT) and after stratification by transplant type and screening CMV DNA level randomly assigned them on a 2:1 basis to receive either maribavir 400 mg twice daily (235 patients) or IAT (117 patients), consisting of either ganciclovir/valganciclovir, foscarnet, cidofovir, or combined foscarnet and val/ganciclovir.
The primary endpoint of viremia clearance at 8 weeks was defined as plasma CMV DNA less than 137 IU/mL in two consecutive tests at a central laboratory at least 5 days apart beginning at the end of week 8.
The trial met its primary endpoint, with a viremia clearance rate of 55.7% with maribavir versus 23.9% with IAT.
The viremia clearance rates were similar in each of the transplant groups: 55.9% versus 20.8%, respectively, in patients who underwent HCT, and 55.6% versus 26.1% in patients who underwent SOT (P < .001).
Clearance rates among patients with CMV DNA below 9,100 IU/mL at baseline were 62.1% with maribavir versus 24.7% with IAT. Among patients with baseline CMV DNA of 9100 IU/mL or above, the respective rates were 43.9% versus 21.9%.
CMV viremia clearance continued from week 8 to week 16 in 18.7% of patients assigned to maribavir and to 10.3% of patients randomized to IAT (P < .013).
The median time to first CMV viremia clearance as 22 days with maribavir versus 27 days with IAT (P = .039).
All-cause mortality was similar between the groups, at 11.5% versus 11.1%, respectively.
The incidences of serious and severe treatment-emergent adverse events (TEAE) were 38.5% and 32.1%, respectively, in the maribavir group, and 37.1% and 37.9% in the IAT group.
Any TEAE leading to study drug discontinuation was less common with maribavir, occurring in 13.2% of patients, compared with 31.9% of patients on IAT. Serious TEAEs leading to drug discontinuation occurred in 8.5% versus 14.7%, respectively.
Serious TEAEs leading to death occurred in 6.8% of patients on maribavir versus 5.2% of those on IAT.
Role of letermovir
In the question-and-answer session following the presentation, comoderator Monalisa Ghosh, MD, from the University of Michigan, Ann Arbor, asked whether any patients in the study were currently on letermovir (Prevymis) prophylaxis, and whether any patients had previously been treated with letermovir but had CMV reactivation and were then treated on study.
Dr. Marty noted that the trial was designed before letermovir was approved for CMV prophylaxis in adults who have undergone an allogeneic HCT.
“Nobody was on letermovir at the beginning of the trial,” he replied, but noted that some patients who were enrolled and had infections that were refractory or resistant to valganciclovir, foscarnet, or a combination of the two received letermovir as secondary prophylaxis.
“I haven’t got the data to tell you how often [letermovir] was used; I think part of the lack of mortality benefit [with maribavir] may be due to the fact that people jumped into secondary prophylaxis with letermovir to minimize the toxicities that we saw,” he said.
Although maribavir has not as of this writing received Food and Drug Administration approval, the drug may be available to some patients through a compassionate-use program from Takeda, Dr. Marty noted.
The study was funded by Shire ViroPharma. Dr. Marty disclosed research funding from Shire and from others. Dr. Ghosh had no relevant disclosures.
Maribavir, an investigational antiviral agent with a novel mechanism of action, was superior to other antiviral strategies at clearing cytomegalovirus (CMV) viremia and controlling symptoms in hematopoietic cell or solid-organ transplant recipients, results of a phase 3 clinical trial showed.
CMV viremia clearance at study week 8 was seen in 55.7% of all patients randomized to receive maribavir, compared with 23.9% for patients assigned to receive investigator-assigned therapy (IAT), Francisco Marty, MD, from the Dana-Farber Cancer Institute in Boston reported at the Transplant & Cellular Therapies Meetings.
“Maribavir’s benefit was driven by lower incidence of treatment-limiting toxicities, compared with IAT,” he said a late-breaking abstract session during the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
“Available anti-CMV antivirals are limited by development of resistance and toxicities, particularly myelosuppression with the use of valganciclovir and nephrotoxicity with the use of foscarnet and cidofovir. Alternative treatment options are required to address this unmet medical need,” he said.
Maribavir inhibits the CMV UL97 protein kinase and is thought to affect several critical processes in CMV replication, including viral DNA synthesis, viral gene expression, encapsidation, and egress of mature capsids from the nucleus.
Details of trial
In the phase 3 SHP620-30e trial (NCT02931539), Dr. Marty and colleagues enrolled patients with relapsed or refractory CMV infections after hematopoietic cell transplant (HCT) or solid-organ transplant (SOT) and after stratification by transplant type and screening CMV DNA level randomly assigned them on a 2:1 basis to receive either maribavir 400 mg twice daily (235 patients) or IAT (117 patients), consisting of either ganciclovir/valganciclovir, foscarnet, cidofovir, or combined foscarnet and val/ganciclovir.
The primary endpoint of viremia clearance at 8 weeks was defined as plasma CMV DNA less than 137 IU/mL in two consecutive tests at a central laboratory at least 5 days apart beginning at the end of week 8.
The trial met its primary endpoint, with a viremia clearance rate of 55.7% with maribavir versus 23.9% with IAT.
The viremia clearance rates were similar in each of the transplant groups: 55.9% versus 20.8%, respectively, in patients who underwent HCT, and 55.6% versus 26.1% in patients who underwent SOT (P < .001).
Clearance rates among patients with CMV DNA below 9,100 IU/mL at baseline were 62.1% with maribavir versus 24.7% with IAT. Among patients with baseline CMV DNA of 9100 IU/mL or above, the respective rates were 43.9% versus 21.9%.
CMV viremia clearance continued from week 8 to week 16 in 18.7% of patients assigned to maribavir and to 10.3% of patients randomized to IAT (P < .013).
The median time to first CMV viremia clearance as 22 days with maribavir versus 27 days with IAT (P = .039).
All-cause mortality was similar between the groups, at 11.5% versus 11.1%, respectively.
The incidences of serious and severe treatment-emergent adverse events (TEAE) were 38.5% and 32.1%, respectively, in the maribavir group, and 37.1% and 37.9% in the IAT group.
Any TEAE leading to study drug discontinuation was less common with maribavir, occurring in 13.2% of patients, compared with 31.9% of patients on IAT. Serious TEAEs leading to drug discontinuation occurred in 8.5% versus 14.7%, respectively.
Serious TEAEs leading to death occurred in 6.8% of patients on maribavir versus 5.2% of those on IAT.
Role of letermovir
In the question-and-answer session following the presentation, comoderator Monalisa Ghosh, MD, from the University of Michigan, Ann Arbor, asked whether any patients in the study were currently on letermovir (Prevymis) prophylaxis, and whether any patients had previously been treated with letermovir but had CMV reactivation and were then treated on study.
Dr. Marty noted that the trial was designed before letermovir was approved for CMV prophylaxis in adults who have undergone an allogeneic HCT.
“Nobody was on letermovir at the beginning of the trial,” he replied, but noted that some patients who were enrolled and had infections that were refractory or resistant to valganciclovir, foscarnet, or a combination of the two received letermovir as secondary prophylaxis.
“I haven’t got the data to tell you how often [letermovir] was used; I think part of the lack of mortality benefit [with maribavir] may be due to the fact that people jumped into secondary prophylaxis with letermovir to minimize the toxicities that we saw,” he said.
Although maribavir has not as of this writing received Food and Drug Administration approval, the drug may be available to some patients through a compassionate-use program from Takeda, Dr. Marty noted.
The study was funded by Shire ViroPharma. Dr. Marty disclosed research funding from Shire and from others. Dr. Ghosh had no relevant disclosures.
FROM TCT 2021