Hematology News

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

Delirium should be included on checklists of the presenting signs and symptoms of COVID-19, particularly in elderly adults, according to a multicenter study of seniors visiting emergency departments.

Overall, 28% of the 817 older adults who presented to the emergency department and were diagnosed with COVID-19 had delirium, according to a study published online November 19 in JAMA Network Open. Moreover, 16% of these patients had delirium that was not accompanied by typical symptoms or signs of SARS-CoV-2 infection.

Among patients with delirium, there was a greater probability of admission to the intensive care unit compared with patients who presented without delirium (adjusted relative risk [aRR], 1.67; 95% CI, 1.30 – 2.15), as well as a greater probability of death (aRR, 1.24; 95% CI, 1.00 – 1.55).

“These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation,” write Maura Kennedy, MD, MPH, and colleagues.

“I was absolutely seeing cases of delirium where there were no other symptoms of COVID-19, but we didn’t have lot of data on the frequency of this,” explained Kennedy, an emergency department physician at Massachusetts General Hospital and an assistant professor of emergency medicine at Harvard Medical School, Boston.

“And the rate was somewhat surprising compared with that seen in non-COVID studies of delirium, but then our study population was more at risk, coming from long-term care facilities and having prior stroke or dementia,” she said. The most common form of delirium was hypoactive sleepiness and nonresponsiveness, although hyperactivity and agitation were also seen.

Kennedy thinks the addition of delirium as a common presenting symptom to diagnostic checklists would prevent some cases from being missed and allow earlier identification and management of COVID-19 patients at high risk for poor outcomes. “We certainly don’t want to send them back undiagnosed to a long-term care facility or promote transmission within the hospital,” she told Medscape Medical News.

That step has already been implemented in some US centers. “Delirium is something we’ve been looking at since the early summer,” said geriatrician Angela Catic, MD, an assistant professor at Baylor College of Medicine’s Huffington Center on Aging and the Michael E. DeBakey VA Medical Center, Houston, Texas.

“If we see delirium, we’re looking for COVID-19,” said Catic, who was not involved in the study.

In Catic’s experience, it is “not at all atypical” to see patients whose only symptom of COVID-19 is delirium. As with other infections and diseases, “the aging brain is incredibly vulnerable,” she said.

According to William W. Hung, MD, MPH, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York City, delirium is “generally a common sign of something seriously wrong” in older adults. “In the case of COVID-19, low oxygenation caused by the infection may play a role,” he told Medscape Medical News. Although he agreed that delirium should be included in the differential diagnosis of COVID-19, how frequently it is the only symptom at presentation would need to be determined in a considerably larger population, he said.

Joining the company of those observing this COVID-19 manifestation is Christopher R. Carpenter, MD, a professor of emergency medicine at Washington University in St. Louis, St. Louis, Missouri. He was not a participant in the current study.

“I have absolutely seen and documented delirium as the presenting complaint in older adult patients who were ultimately diagnosed with SARS-CoV-2, and since March, I contemplate SARS-CoV-2 each time I identify delirium,” Carpenter told Medscape Medical News. “Honestly, I ― and most of my colleagues ― are considering SARS-CoV-2 for a range of symptoms and complaints these days, because of the odd presentations we’ve all encountered.”
 

Study details

For the study, Kennedy and colleagues enrolled consecutive adults aged 65 years and older who were diagnosed with active COVID-19 and who presented to emergency departments at seven centers in Massachusetts, Maine, Connecticut, Michigan, and North Carolina on or after March 13, 2020. Active infection with SARS-CoV-2 was determined on the basis of results of nasal swab polymerase chain reaction tests (99% of cases) or the appearance and distribution of ground-glass opacities on chest radiography or CT (1%).

Of the 817 patients enrolled, 386 (47%) were men, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean age of patients was 77.7 years (standard deviation, 8.2). Their age placed them at risk for chronic comorbidities and cognitive problems; indeed, 15% had at least four chronic conditions, and 30% had existing cognitive impairment.

The authors note that among the 226 patients (28%) who had delirium at presentation, 60 (27%) had experienced delirium for a duration of 2 to 7 days.

Additionally, of the 226 patients who exhibited delirium as a primary symptom, 84 (37%) showed no typical COVID-19 symptoms or signs, such as cough, fever, or shortness of breath.

The presence of delirium did not correlate with any of the typical COVID-19 symptoms in particular; Kennedy noted that only 56% of patients in the cohort had a fever at presentation.

Delirium at presentation was significantly associated with a median hospital stay of more than 8 days (aRR, 1.14; 95% CI, .97 – 1.35) and a greater risk for discharge to a rehabilitation facility (aRR, 1.55; 95% CI, 1.07 – 2.26). Factors associated with delirium included age older than 75 years, residence in a nursing home or assisted-living facility, previous use of psychoactive medications, vision impairment, hearing impairment, stroke, and Parkinson’s disease.

Kennedy noted that the rate of delirium observed in this study is much higher than that generally reported in emergency department studies conducted before the COVID-19 pandemic. In those studies, the delirium rate ranged from 7% to 20%. The associated risk factors, however, are comparable.

“Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations with COVID-19, with previously reported rates of 22% to 33% among hospitalized patients,” Kennedy and associates write.

In Carpenter’s opinion, the development of incident delirium while receiving care in the emergency department, as opposed to delirium at the time of presentation, has been exacerbated by the no-visitor policies mandated by the pandemic, which have prevented visits even from personal caregivers of patients with moderate to severe dementia. “Although healthcare systems need to be cognizant of the risk of spread to uninfected caregivers, there’s a risk-benefit balance that must be found, because having one caregiver at the bedside can prevent delirium in cognitively impaired patients,” said Carpenter, who was not involved in the current study.

Among the barriers to improving the situation, Carpenter cited the lack of routine delirium screening and the absence of high-quality evidence to support emergency department interventions to mitigate delirium.

“Layer those challenges on top of COVID-19’s rapidly evolving diagnostic landscape, frequent atypical presentations, and asymptomatic carriers across all age groups and the negative impact of delirium is magnified,” Carpenter said.

Once elderly patients are hospitalized, Kennedy recommends the nonpharmacologic guidelines of the Hospital Elder Life Program for reducing delirium risk. Recommendations include the providing of adequate sleep, hydration, and nutrition, as well as function restoration, precipitant avoidance, and reorientation.

The study was supported in part by the National Institute on Aging and the Massachusetts Medical School. The authors, Carpenter, Hung, and Catic have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Delirium should be included on checklists of the presenting signs and symptoms of COVID-19, particularly in elderly adults, according to a multicenter study of seniors visiting emergency departments.

Overall, 28% of the 817 older adults who presented to the emergency department and were diagnosed with COVID-19 had delirium, according to a study published online November 19 in JAMA Network Open. Moreover, 16% of these patients had delirium that was not accompanied by typical symptoms or signs of SARS-CoV-2 infection.

Among patients with delirium, there was a greater probability of admission to the intensive care unit compared with patients who presented without delirium (adjusted relative risk [aRR], 1.67; 95% CI, 1.30 – 2.15), as well as a greater probability of death (aRR, 1.24; 95% CI, 1.00 – 1.55).

“These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation,” write Maura Kennedy, MD, MPH, and colleagues.

“I was absolutely seeing cases of delirium where there were no other symptoms of COVID-19, but we didn’t have lot of data on the frequency of this,” explained Kennedy, an emergency department physician at Massachusetts General Hospital and an assistant professor of emergency medicine at Harvard Medical School, Boston.

“And the rate was somewhat surprising compared with that seen in non-COVID studies of delirium, but then our study population was more at risk, coming from long-term care facilities and having prior stroke or dementia,” she said. The most common form of delirium was hypoactive sleepiness and nonresponsiveness, although hyperactivity and agitation were also seen.

Kennedy thinks the addition of delirium as a common presenting symptom to diagnostic checklists would prevent some cases from being missed and allow earlier identification and management of COVID-19 patients at high risk for poor outcomes. “We certainly don’t want to send them back undiagnosed to a long-term care facility or promote transmission within the hospital,” she told Medscape Medical News.

That step has already been implemented in some US centers. “Delirium is something we’ve been looking at since the early summer,” said geriatrician Angela Catic, MD, an assistant professor at Baylor College of Medicine’s Huffington Center on Aging and the Michael E. DeBakey VA Medical Center, Houston, Texas.

“If we see delirium, we’re looking for COVID-19,” said Catic, who was not involved in the study.

In Catic’s experience, it is “not at all atypical” to see patients whose only symptom of COVID-19 is delirium. As with other infections and diseases, “the aging brain is incredibly vulnerable,” she said.

According to William W. Hung, MD, MPH, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York City, delirium is “generally a common sign of something seriously wrong” in older adults. “In the case of COVID-19, low oxygenation caused by the infection may play a role,” he told Medscape Medical News. Although he agreed that delirium should be included in the differential diagnosis of COVID-19, how frequently it is the only symptom at presentation would need to be determined in a considerably larger population, he said.

Joining the company of those observing this COVID-19 manifestation is Christopher R. Carpenter, MD, a professor of emergency medicine at Washington University in St. Louis, St. Louis, Missouri. He was not a participant in the current study.

“I have absolutely seen and documented delirium as the presenting complaint in older adult patients who were ultimately diagnosed with SARS-CoV-2, and since March, I contemplate SARS-CoV-2 each time I identify delirium,” Carpenter told Medscape Medical News. “Honestly, I ― and most of my colleagues ― are considering SARS-CoV-2 for a range of symptoms and complaints these days, because of the odd presentations we’ve all encountered.”
 

Study details

For the study, Kennedy and colleagues enrolled consecutive adults aged 65 years and older who were diagnosed with active COVID-19 and who presented to emergency departments at seven centers in Massachusetts, Maine, Connecticut, Michigan, and North Carolina on or after March 13, 2020. Active infection with SARS-CoV-2 was determined on the basis of results of nasal swab polymerase chain reaction tests (99% of cases) or the appearance and distribution of ground-glass opacities on chest radiography or CT (1%).

Of the 817 patients enrolled, 386 (47%) were men, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean age of patients was 77.7 years (standard deviation, 8.2). Their age placed them at risk for chronic comorbidities and cognitive problems; indeed, 15% had at least four chronic conditions, and 30% had existing cognitive impairment.

The authors note that among the 226 patients (28%) who had delirium at presentation, 60 (27%) had experienced delirium for a duration of 2 to 7 days.

Additionally, of the 226 patients who exhibited delirium as a primary symptom, 84 (37%) showed no typical COVID-19 symptoms or signs, such as cough, fever, or shortness of breath.

The presence of delirium did not correlate with any of the typical COVID-19 symptoms in particular; Kennedy noted that only 56% of patients in the cohort had a fever at presentation.

Delirium at presentation was significantly associated with a median hospital stay of more than 8 days (aRR, 1.14; 95% CI, .97 – 1.35) and a greater risk for discharge to a rehabilitation facility (aRR, 1.55; 95% CI, 1.07 – 2.26). Factors associated with delirium included age older than 75 years, residence in a nursing home or assisted-living facility, previous use of psychoactive medications, vision impairment, hearing impairment, stroke, and Parkinson’s disease.

Kennedy noted that the rate of delirium observed in this study is much higher than that generally reported in emergency department studies conducted before the COVID-19 pandemic. In those studies, the delirium rate ranged from 7% to 20%. The associated risk factors, however, are comparable.

“Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations with COVID-19, with previously reported rates of 22% to 33% among hospitalized patients,” Kennedy and associates write.

In Carpenter’s opinion, the development of incident delirium while receiving care in the emergency department, as opposed to delirium at the time of presentation, has been exacerbated by the no-visitor policies mandated by the pandemic, which have prevented visits even from personal caregivers of patients with moderate to severe dementia. “Although healthcare systems need to be cognizant of the risk of spread to uninfected caregivers, there’s a risk-benefit balance that must be found, because having one caregiver at the bedside can prevent delirium in cognitively impaired patients,” said Carpenter, who was not involved in the current study.

Among the barriers to improving the situation, Carpenter cited the lack of routine delirium screening and the absence of high-quality evidence to support emergency department interventions to mitigate delirium.

“Layer those challenges on top of COVID-19’s rapidly evolving diagnostic landscape, frequent atypical presentations, and asymptomatic carriers across all age groups and the negative impact of delirium is magnified,” Carpenter said.

Once elderly patients are hospitalized, Kennedy recommends the nonpharmacologic guidelines of the Hospital Elder Life Program for reducing delirium risk. Recommendations include the providing of adequate sleep, hydration, and nutrition, as well as function restoration, precipitant avoidance, and reorientation.

The study was supported in part by the National Institute on Aging and the Massachusetts Medical School. The authors, Carpenter, Hung, and Catic have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Delirium should be included on checklists of the presenting signs and symptoms of COVID-19, particularly in elderly adults, according to a multicenter study of seniors visiting emergency departments.

Overall, 28% of the 817 older adults who presented to the emergency department and were diagnosed with COVID-19 had delirium, according to a study published online November 19 in JAMA Network Open. Moreover, 16% of these patients had delirium that was not accompanied by typical symptoms or signs of SARS-CoV-2 infection.

Among patients with delirium, there was a greater probability of admission to the intensive care unit compared with patients who presented without delirium (adjusted relative risk [aRR], 1.67; 95% CI, 1.30 – 2.15), as well as a greater probability of death (aRR, 1.24; 95% CI, 1.00 – 1.55).

“These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation,” write Maura Kennedy, MD, MPH, and colleagues.

“I was absolutely seeing cases of delirium where there were no other symptoms of COVID-19, but we didn’t have lot of data on the frequency of this,” explained Kennedy, an emergency department physician at Massachusetts General Hospital and an assistant professor of emergency medicine at Harvard Medical School, Boston.

“And the rate was somewhat surprising compared with that seen in non-COVID studies of delirium, but then our study population was more at risk, coming from long-term care facilities and having prior stroke or dementia,” she said. The most common form of delirium was hypoactive sleepiness and nonresponsiveness, although hyperactivity and agitation were also seen.

Kennedy thinks the addition of delirium as a common presenting symptom to diagnostic checklists would prevent some cases from being missed and allow earlier identification and management of COVID-19 patients at high risk for poor outcomes. “We certainly don’t want to send them back undiagnosed to a long-term care facility or promote transmission within the hospital,” she told Medscape Medical News.

That step has already been implemented in some US centers. “Delirium is something we’ve been looking at since the early summer,” said geriatrician Angela Catic, MD, an assistant professor at Baylor College of Medicine’s Huffington Center on Aging and the Michael E. DeBakey VA Medical Center, Houston, Texas.

“If we see delirium, we’re looking for COVID-19,” said Catic, who was not involved in the study.

In Catic’s experience, it is “not at all atypical” to see patients whose only symptom of COVID-19 is delirium. As with other infections and diseases, “the aging brain is incredibly vulnerable,” she said.

According to William W. Hung, MD, MPH, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York City, delirium is “generally a common sign of something seriously wrong” in older adults. “In the case of COVID-19, low oxygenation caused by the infection may play a role,” he told Medscape Medical News. Although he agreed that delirium should be included in the differential diagnosis of COVID-19, how frequently it is the only symptom at presentation would need to be determined in a considerably larger population, he said.

Joining the company of those observing this COVID-19 manifestation is Christopher R. Carpenter, MD, a professor of emergency medicine at Washington University in St. Louis, St. Louis, Missouri. He was not a participant in the current study.

“I have absolutely seen and documented delirium as the presenting complaint in older adult patients who were ultimately diagnosed with SARS-CoV-2, and since March, I contemplate SARS-CoV-2 each time I identify delirium,” Carpenter told Medscape Medical News. “Honestly, I ― and most of my colleagues ― are considering SARS-CoV-2 for a range of symptoms and complaints these days, because of the odd presentations we’ve all encountered.”
 

Study details

For the study, Kennedy and colleagues enrolled consecutive adults aged 65 years and older who were diagnosed with active COVID-19 and who presented to emergency departments at seven centers in Massachusetts, Maine, Connecticut, Michigan, and North Carolina on or after March 13, 2020. Active infection with SARS-CoV-2 was determined on the basis of results of nasal swab polymerase chain reaction tests (99% of cases) or the appearance and distribution of ground-glass opacities on chest radiography or CT (1%).

Of the 817 patients enrolled, 386 (47%) were men, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean age of patients was 77.7 years (standard deviation, 8.2). Their age placed them at risk for chronic comorbidities and cognitive problems; indeed, 15% had at least four chronic conditions, and 30% had existing cognitive impairment.

The authors note that among the 226 patients (28%) who had delirium at presentation, 60 (27%) had experienced delirium for a duration of 2 to 7 days.

Additionally, of the 226 patients who exhibited delirium as a primary symptom, 84 (37%) showed no typical COVID-19 symptoms or signs, such as cough, fever, or shortness of breath.

The presence of delirium did not correlate with any of the typical COVID-19 symptoms in particular; Kennedy noted that only 56% of patients in the cohort had a fever at presentation.

Delirium at presentation was significantly associated with a median hospital stay of more than 8 days (aRR, 1.14; 95% CI, .97 – 1.35) and a greater risk for discharge to a rehabilitation facility (aRR, 1.55; 95% CI, 1.07 – 2.26). Factors associated with delirium included age older than 75 years, residence in a nursing home or assisted-living facility, previous use of psychoactive medications, vision impairment, hearing impairment, stroke, and Parkinson’s disease.

Kennedy noted that the rate of delirium observed in this study is much higher than that generally reported in emergency department studies conducted before the COVID-19 pandemic. In those studies, the delirium rate ranged from 7% to 20%. The associated risk factors, however, are comparable.

“Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations with COVID-19, with previously reported rates of 22% to 33% among hospitalized patients,” Kennedy and associates write.

In Carpenter’s opinion, the development of incident delirium while receiving care in the emergency department, as opposed to delirium at the time of presentation, has been exacerbated by the no-visitor policies mandated by the pandemic, which have prevented visits even from personal caregivers of patients with moderate to severe dementia. “Although healthcare systems need to be cognizant of the risk of spread to uninfected caregivers, there’s a risk-benefit balance that must be found, because having one caregiver at the bedside can prevent delirium in cognitively impaired patients,” said Carpenter, who was not involved in the current study.

Among the barriers to improving the situation, Carpenter cited the lack of routine delirium screening and the absence of high-quality evidence to support emergency department interventions to mitigate delirium.

“Layer those challenges on top of COVID-19’s rapidly evolving diagnostic landscape, frequent atypical presentations, and asymptomatic carriers across all age groups and the negative impact of delirium is magnified,” Carpenter said.

Once elderly patients are hospitalized, Kennedy recommends the nonpharmacologic guidelines of the Hospital Elder Life Program for reducing delirium risk. Recommendations include the providing of adequate sleep, hydration, and nutrition, as well as function restoration, precipitant avoidance, and reorientation.

The study was supported in part by the National Institute on Aging and the Massachusetts Medical School. The authors, Carpenter, Hung, and Catic have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The COVID-19 pandemic has decimated the bottom lines of many private practices, prompting physician-owners to seriously contemplate selling.

Physician-owners have had to sell at lower prices, reflecting lower cash flow under COVID-19. But sales prices may rebound following news on Nov. 9 that a COVID-19 vaccine candidate produced by Pfizer and its German partner, BioNTech, may be ready for initial distribution before the end of the year.

“There are a lot of ifs still, but if things go according to expectations, we may see an increase in the value of practices,” said Mark O. Dietrich, a CPA in Framingham, Mass., who deals mostly with valuations of physician practices.

“Practice valuations have been lower because many patients have kept away and cash flow has been reduced,” Mr. Dietrich said. “But once patients feel safe, that barrier would be removed, and cash flow, which sales prices are generally based on, could rise. However, this may take a while. One major hurdle would be getting people to take the vaccine.”
 

Many doctors have been contemplating closing

The nation is currently undergoing a significant spike in COVID-19 hospitalizations, which could prompt another COVID-19–related downturn in practice volume, as occurred earlier in the year. That downturn forced many private practitioners to contemplate selling their practices.

In a survey released this summer by McKinsey & Company, 53% of independent physicians reported that they were worried about their practices surviving. Although many physicians have now reopened their offices, patient volume is reduced, and physicians are earning far less than before.

“In many cases, physicians who had been considering retirement in the next few years have moved their planning up and want to sell as soon as possible,” said John D. Fanburg, an attorney at Brach Eichler, a law firm in Roseland, N.J., who specializes in medical practice sales and mergers.

“For physicians over age 65, it’s not just worries about finances; it’s also worries about the health risks of staying open,” Mr. Fanburg added.

Mid-career physicians are also selling their practices. Many of them become employees of the hospital, large practice, or private-equity firm that bought the practice – receiving a level of compensation set by the sales agreement.
 

Will your practice be hard to sell?

With so many physicians ready to sell, are there enough potential buyers to acquire them all? Probably not, said Mr. Dietrich.

“Many hospitals may not need new practices right now,” he said. “In the depths of the pandemic, they furloughed many of their existing doctors and may not have brought all of them back yet.”

In fact, because of the pandemic, some buyers have delayed sales that were already in progress, said Monica H. Kaden, director of business valuations at Sobel Valuations, based in Livingston, N.J.

“Buyers are not only worried about their own cash flow but also about the possibility of lower revenues of the selling practices due to COVID-19,” she said, citing a very large multispecialty group that has put its purchase of a another large multispecialty group on hold.
 

Practice values have (temporarily) fallen

Many potential buyers are still looking, though. One thing that drives them is the possibility of discounted sales because of COVID-19. “The sense I get is that a lot of hospitals see this as an opportunity to pick up practices on the cheap,” Mr. Dietrich said.

COVID-19 has been reducing practice values somewhat, said Reed Tinsley, a CPA in Houston who performs medical practice valuations and runs a practice brokerage firm. “Practice revenues and net income are lower under COVID-19, so prices are lower.”

Ms. Kadan advised physicians to hold off selling if they can afford to wait. “It’s always best to sell when the practice volume looks the best, because then the practice is worth more. But there are doctors who can’t wait because revenues are really falling and they are running out of money. They may have no choice but to sell.”

Even in the best of times, not all practices can be sold, said Sean Tinsley, a broker and licensed financial adviser at Tinsley Medical Practice Brokers in Austin, Tex., which he runs with his father, Reed Tinsley.

“We turn down about as many deals to sell practices as we accept,” he said. “Brokers have to be very selective because we don’t get paid until the practice gets sold. Generally, we won’t take practices in rural areas or practices that still only have a fraction of their pre–COVID-19 volume.”
 

How long will it take to sell your practice?

Some practices find a buyer within weeks, but in other cases, it can take as long as a year, he said. Once the buyer is located, preparing the paperwork for the sale can take 45-60 days.

Doctors can sell their practices on their own, but a broker can help them find potential buyers and select the right price. Business brokers generally receive a greater percentage of the sales price than residential brokers. They have greater command of business and finance, and the sale is more complex than a residential sale.

The broker may also help with selling the building where the practice is located, which is usually a separate sale, said Bruce E. Wood, an attorney at CCB Law in Syracuse, N.Y., who deals with practice sales. “A hospital buying your practice may not want to buy the building, so it has to be sold separately. You can always sell the space to a different buyer.”
 

What’s the right price for your practice?

For small practices, brokers often set a price by establishing a multiple, such as two times net earnings, Sean Tinsley said. In many cases, practices haven’t retained net earnings, so the broker uses gross annual revenue and sets the price at 50%-55% of that figure.

An alternative that is widely used in the business world and for many large practices is to base the price on earnings before interest, taxes, depreciation, and amortization (EBITDA). To determine a price, the EBITDA is then multiplied by a particular multiple, which depends on the perceived value of the practice.

Higher multiples go to practices that have a qualified management team, have documented financial policies and procedures, or have had significant past growth. Generally, the multiple of EBITDA at smaller practices is 1 or 2; larger practices have a multiple of 5-7 times EBITDA, Sean Tinsley said.

COVID-19 has had the effect of reducing the multiple somewhat. “As market forces shift from a seller’s market to a buyer’s market, multiples will likely remain below pre–COVID-19 levels for the remainder of 2020 and the first half of 2021,” one report stated.

Certified valuators like Reed Tinsley have more complex ways to establish the value of a practice, but as a broker, Sean Tinsley tends to use the multiples approach. He asserted that the prices derived from this method are on the mark. “Almost all the time we sell at the asking price.”
 

Using valuations to set the price

A more complex and expensive way to set a price for a practice is to order a valuation of the practice. The valuator issues a report that runs dozens of pages and costs thousands of dollars.

Mr. Fanburg said that very few physicians selling practices order valuation reports, owing to the cost and complexity. As a result, “they don’t have a clear idea what their practices are worth.”

A comprehensive report is called a conclusion of value. The amount it finds – expressed as a range – is called “fair market value.” The report can be used in the courts for legal disputes as well as for deriving a sales price.

Practices that don’t want to pay for a conclusion of value can ask a valuator to assemble a less extensive report, called an opinion of calculated value. Also known as a calculation engagement or engagement letter, it still costs several thousand dollars.

This report has limited validity and can’t be used in the courts, according to Jarrod Barraza, a certified valuator in the Nashville, Tenn., office of Horne, a health care business valuator. “When I issue an engagement letter, I am not talking as an appraiser but as a valuation consultant, and I don’t call the result fair market value; it’s only estimating,” he said.

For all of the precision of formal reports, however, valuations of a practice can vary widely, according to Reed Tinsley. “Two valuations using the same methodology can differ by $300,000.”

Also, the valuation can be well above a reasonable asking price, said Sean Tinsley. “The market dictates the price. A traditional valuation almost invariably quotes a higher return than the market is willing to pay.”
 

Buyers’ valuations

Physicians who decide not to get a valuation still have to deal with valuations ordered by buyers. Hospitals and large practices often order valuations of the practices they want to buy, and private-equity firms use methods much like a valuation for the practices they are interested in.

Buyers rarely share the valuation report with the seller, so the seller has to accept the buyer’s price without being able to review the thought process behind it, Mr. Fanburg said. “Relying on the buyer to tell you what you’re worth means you may sell your practice well below its true value.”

When the buyer orders a valuation, the valuator interviews managers of the practice and asks for a great deal of information, says G. Don Barbo, managing director at VMG Health, a health care valuation firm based in Dallas.

Mr. Barbo said these documents include financial statements for the practice, usually going back 3-5 years; productivity reports for doctors and other providers; accounts receivables; reports of fixed assets; a roster of employees; employment agreements and management services agreements; reports on payer mix; facility leases and equipment lease agreements; budgets and projections; and tax returns.

Mr. Dietrich said valuators hone in on the practice’s current procedural terminology codes. “If the practice is coding too high, this would artificially increase the profit and purported value of the practice. For example, coding at 99214 rather than 99213 for an established patient means that the practice is being paid 45% more for each visit.” The valuator then reduces the value of the practice on the basis of the extent of the improper up-coding.

Mr. Barbo said some sellers don’t want all the scrutiny of the buyer’s valuation and just sell the practice’s tangible assets – furnishings, fixtures, and equipment – which do not require a great deal of documentation but yield a much lower price.
 

A primer on valuations

As a valuator, “my job is to project into the future,” Mr. Barraza said. “I am trying to see how the practice will fare going forward.”

Mr. Dietrich agreed, with one caveat: “As Yogi Berra said: ‘It’s difficult to make predictions, especially about the future.’ ”

The formal valuation assesses the practice in three ways: measuring income, assets, and what other practices sell for, called the market approach.

With the income approach, the most used measurement for practices, one tries to determine future income, which is what buyers are most interested in, Mr. Dietrich said. The income equals revenue (total collections) minus operating expenses and overhead.

“You are then left with all the money the physician is paid,” he said. “The issue is, how much is attributed to the physician’s own labor and how much to his or her ownership of the practice? This second category helps determine the value of the practice.”

The market approach is often used as a way to double-check the accuracy of the income approach. The appraiser looks for the prices of similar practices that have already been sold and then adjusts the price on the basis of differences with the practice up for sale.

The asset approach may be used when the practice has no positive cash flow. It establishes a price for tangible assets, which are often much lower in value than the values that the other approaches come up with. The asset approach can be a lower-priced alternative for practices that can’t be measured under the income or market approach.

“Equipment appraisers can do an inventory of your equipment,” Mr. Wood said. “Generally, equipment that is more than 3 years old, such as computers, is not that valuable, but an ultrasound machine probably has some resale value.”
 

Will the buyer pay for goodwill?

Many practice owners hope they can get money for the “goodwill” of their practice when they sell. Goodwill basically represents the reputation of the practice, which is difficult to pinpoint, and Mr. Wood said buyers often don’t want to pay for it.

“The goodwill is a wild card,” Mr. Wood said. “It can range from zero to crazy numbers. There is a Goodwill Registry – a list of the goodwill in other practice sales – that you can consult.”

One simple way to calculate the goodwill, he said, is to take the value of the practice based on examining income and remove the value of tangible assets. What is left is considered the goodwill.

Another form of intangible asset that is sometimes lumped together with goodwill is the value of the practice’s trained staff. “Some buyers agree to pay for the staff in place, because they plan to use that staff,” Ms. Kadan said. In one large deal she was involved with, the buyer agreed to pay something for the selling practice’s staff of 180 people.

Another item that buyers also do not typically pay for is the practice’s accounts receivable. They may also not pay for any liabilities the practice holds, such as the facility lease, equipment lease, and maintenance contracts, Mr. Barbo said. “The buyer then often stipulates that all liabilities are left to the practice, or stipulates any specific liabilities that it may assume.”
 

Selling to other doctors

Doctors can sell practices or shares in practices to other doctors. A retiring physician, for example, can sell his or her share to the other partners. A valuator may be brought in to establish the value of the doctor’s equity interest in the practice.

“Generally, practice buyouts aren’t lucrative for selling physician,” Mr. Wood said. “There are exceptions, of course, such as specialty practices in some cases.”

A practice can also be sold to a new doctor or to a previously employed physician who wants to be an owner. These physicians usually need to get a bank loan to buy the practice.

The bank assesses the finances of the selling practice to determine whether the buying physician will earn enough money to pay back the loan. “Banks don’t want lend more than the gross annual revenue of the practice, and some banks will only lend at 65% of gross annual revenue,” Sean Tinsley said.

COVID-19 has seriously affected banks’ lending decisions. Banks stopped lending to practice buyers at the beginning of the pandemic, and when they started lending again, they were more cautious, Sean Tinsley said. “Generally, banks want to see the practice at 85%-90% of pre–COVID-19 numbers before they make a loan.”

He added that, if a buyer can’t get a bank loan, the selling doctor may decide to finance the sale. The buyer agrees to a payment schedule to pay off the full price over several years.
 

Selling to or merging with other practices

The usual buyer is another practice, Reed Tinsley said. “You can sell to a group, but prices are low because, with COVID-19, buyers don’t want to incur a lot of money up front. Or you can merge with the practice, which means the selling doctor usually doesn’t get any money, but he does get a share in the larger practice. In that case, the partnership is the object of value, and it can be cashed out when the physician leaves the practice.”

Mergers can get very complicated. Mr. Fanburg said he has been working with seven groups that are merging into one. “The merger was scheduled to go live last January, but it was slowed down over negotiations about new managed care contracts and putting together a management structure, plus the groups were a little wary of each other. Now the deal is scheduled to go live next January.”

One advantage to selling to a larger entity, such as a big group practice or a hospital, is that the selling physician benefits from the higher reimbursement rates that large providers usually command. “If the buyer has more favorable reimbursement rates with insurers, it could pay the selling doctor much more than he is making now,” Mr. Barraza said.
 

Hospitals as buyers

Because of COVID-19, currently many hospitals don’t have money to buy more practices. However, this is most likely a temporary situation.

Hospitals typically offer less money than other buyers, according to Sean Tinsley. “We have never sold to a hospital, because hospitals generally don’t pay for goodwill. They pay for the practice assets and offer a dollar amount for each chart.”

Hospitals have to be careful not to pay physicians more than the usual amount for their practices, because the extra amount could be seen as a kickback for referrals, which would violate the federal Stark law and Anti-Kickback Statute. Not-for-profit hospitals also have to comply with regulations at the Internal Revenue Service.

Hospitals usually require that the selling physician continue to work in the practice after it is sold. The selling physician’s presence helps ensure that the practice’s output will not decline after sale. Although the sales price may be low, the hospital may make up for it by paying a higher compensation, Sean Tinsley said.
 

Selling to private-equity firms

Private-equity purchases are financed by investors who essentially want to “flip” practices – that is, they want to make them more profitable and then sell them to someone else. The private-equity firm starts by buying a “platform” practice, which forms the core of the venture. It then buys smaller practices that will be managed by the platform practice.

The number of private-equity deals increased continually through 2019, then plummeted in March because of COVID-19, but by the summer, activity began to rise again.

Physicians are very intrigued about selling to private-equity firms because they are known to pay the most for practices. But private-equity buyers focus on a fairly narrow group of specialties.

Generally, Sean Tinsley said, private-equity firms only look for pain, dermatology, and ophthalmology practices, but they have been starting to branch out to specialties such as gastroenterology. In 2018, there were only two private-equity deals for gastroenterology practices, but in 2019, there were 16, according to one assessment.

Private-equity firms buy very few of the practices they initially review, according to Mr. Fanburg. “Private equity negotiates with dozens or even hundreds of physician practices at a time, with only 1%-5% of those practices actually being acquired.”

The private-equity firm’s upfront payment to selling physicians is quite high, but then the physicians become employees of the new group and earn much less in compensation than they earned on this own.

“In order for the venture to get any value out of the acquisition, the doctors have to make less going forward than they did historically,” Mr. Dietrich said. That freed-up money boosts the value of the venture.

When the platform practice is sold – usually after 5 years or so – “chances are the management team will be replaced,” Mr. Fanburg said. “There could be new policies and objectives, which could mean a bumpy ride for physicians.”
 

Do you really want to sell?

“When a group of physicians comes to me asking for help selling their practice, my first question is, Why are you doing this?” Mr. Fanburg said. “You need a better reason for selling than just the money.

“Once you make the leap, there is a certain amount of autonomy you lose,” he continued. “The sale gives you an economic boost, but it may not be enough for the long haul. If you stay on with the buyer, your compensation is often lower. That makes sense if you’re retiring, but not if you’re a younger physician with many years of practice in the years ahead.

“When physicians say they see no other way out except to sell,” Mr. Fanburg said, “I tell them that their buyer will see a path to future growth for your practice. If you think reimbursements are getting worse, why are the buyers pressing ahead?”

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

The COVID-19 pandemic has decimated the bottom lines of many private practices, prompting physician-owners to seriously contemplate selling.

Physician-owners have had to sell at lower prices, reflecting lower cash flow under COVID-19. But sales prices may rebound following news on Nov. 9 that a COVID-19 vaccine candidate produced by Pfizer and its German partner, BioNTech, may be ready for initial distribution before the end of the year.

“There are a lot of ifs still, but if things go according to expectations, we may see an increase in the value of practices,” said Mark O. Dietrich, a CPA in Framingham, Mass., who deals mostly with valuations of physician practices.

“Practice valuations have been lower because many patients have kept away and cash flow has been reduced,” Mr. Dietrich said. “But once patients feel safe, that barrier would be removed, and cash flow, which sales prices are generally based on, could rise. However, this may take a while. One major hurdle would be getting people to take the vaccine.”
 

Many doctors have been contemplating closing

The nation is currently undergoing a significant spike in COVID-19 hospitalizations, which could prompt another COVID-19–related downturn in practice volume, as occurred earlier in the year. That downturn forced many private practitioners to contemplate selling their practices.

In a survey released this summer by McKinsey & Company, 53% of independent physicians reported that they were worried about their practices surviving. Although many physicians have now reopened their offices, patient volume is reduced, and physicians are earning far less than before.

“In many cases, physicians who had been considering retirement in the next few years have moved their planning up and want to sell as soon as possible,” said John D. Fanburg, an attorney at Brach Eichler, a law firm in Roseland, N.J., who specializes in medical practice sales and mergers.

“For physicians over age 65, it’s not just worries about finances; it’s also worries about the health risks of staying open,” Mr. Fanburg added.

Mid-career physicians are also selling their practices. Many of them become employees of the hospital, large practice, or private-equity firm that bought the practice – receiving a level of compensation set by the sales agreement.
 

Will your practice be hard to sell?

With so many physicians ready to sell, are there enough potential buyers to acquire them all? Probably not, said Mr. Dietrich.

“Many hospitals may not need new practices right now,” he said. “In the depths of the pandemic, they furloughed many of their existing doctors and may not have brought all of them back yet.”

In fact, because of the pandemic, some buyers have delayed sales that were already in progress, said Monica H. Kaden, director of business valuations at Sobel Valuations, based in Livingston, N.J.

“Buyers are not only worried about their own cash flow but also about the possibility of lower revenues of the selling practices due to COVID-19,” she said, citing a very large multispecialty group that has put its purchase of a another large multispecialty group on hold.
 

Practice values have (temporarily) fallen

Many potential buyers are still looking, though. One thing that drives them is the possibility of discounted sales because of COVID-19. “The sense I get is that a lot of hospitals see this as an opportunity to pick up practices on the cheap,” Mr. Dietrich said.

COVID-19 has been reducing practice values somewhat, said Reed Tinsley, a CPA in Houston who performs medical practice valuations and runs a practice brokerage firm. “Practice revenues and net income are lower under COVID-19, so prices are lower.”

Ms. Kadan advised physicians to hold off selling if they can afford to wait. “It’s always best to sell when the practice volume looks the best, because then the practice is worth more. But there are doctors who can’t wait because revenues are really falling and they are running out of money. They may have no choice but to sell.”

Even in the best of times, not all practices can be sold, said Sean Tinsley, a broker and licensed financial adviser at Tinsley Medical Practice Brokers in Austin, Tex., which he runs with his father, Reed Tinsley.

“We turn down about as many deals to sell practices as we accept,” he said. “Brokers have to be very selective because we don’t get paid until the practice gets sold. Generally, we won’t take practices in rural areas or practices that still only have a fraction of their pre–COVID-19 volume.”
 

How long will it take to sell your practice?

Some practices find a buyer within weeks, but in other cases, it can take as long as a year, he said. Once the buyer is located, preparing the paperwork for the sale can take 45-60 days.

Doctors can sell their practices on their own, but a broker can help them find potential buyers and select the right price. Business brokers generally receive a greater percentage of the sales price than residential brokers. They have greater command of business and finance, and the sale is more complex than a residential sale.

The broker may also help with selling the building where the practice is located, which is usually a separate sale, said Bruce E. Wood, an attorney at CCB Law in Syracuse, N.Y., who deals with practice sales. “A hospital buying your practice may not want to buy the building, so it has to be sold separately. You can always sell the space to a different buyer.”
 

What’s the right price for your practice?

For small practices, brokers often set a price by establishing a multiple, such as two times net earnings, Sean Tinsley said. In many cases, practices haven’t retained net earnings, so the broker uses gross annual revenue and sets the price at 50%-55% of that figure.

An alternative that is widely used in the business world and for many large practices is to base the price on earnings before interest, taxes, depreciation, and amortization (EBITDA). To determine a price, the EBITDA is then multiplied by a particular multiple, which depends on the perceived value of the practice.

Higher multiples go to practices that have a qualified management team, have documented financial policies and procedures, or have had significant past growth. Generally, the multiple of EBITDA at smaller practices is 1 or 2; larger practices have a multiple of 5-7 times EBITDA, Sean Tinsley said.

COVID-19 has had the effect of reducing the multiple somewhat. “As market forces shift from a seller’s market to a buyer’s market, multiples will likely remain below pre–COVID-19 levels for the remainder of 2020 and the first half of 2021,” one report stated.

Certified valuators like Reed Tinsley have more complex ways to establish the value of a practice, but as a broker, Sean Tinsley tends to use the multiples approach. He asserted that the prices derived from this method are on the mark. “Almost all the time we sell at the asking price.”
 

Using valuations to set the price

A more complex and expensive way to set a price for a practice is to order a valuation of the practice. The valuator issues a report that runs dozens of pages and costs thousands of dollars.

Mr. Fanburg said that very few physicians selling practices order valuation reports, owing to the cost and complexity. As a result, “they don’t have a clear idea what their practices are worth.”

A comprehensive report is called a conclusion of value. The amount it finds – expressed as a range – is called “fair market value.” The report can be used in the courts for legal disputes as well as for deriving a sales price.

Practices that don’t want to pay for a conclusion of value can ask a valuator to assemble a less extensive report, called an opinion of calculated value. Also known as a calculation engagement or engagement letter, it still costs several thousand dollars.

This report has limited validity and can’t be used in the courts, according to Jarrod Barraza, a certified valuator in the Nashville, Tenn., office of Horne, a health care business valuator. “When I issue an engagement letter, I am not talking as an appraiser but as a valuation consultant, and I don’t call the result fair market value; it’s only estimating,” he said.

For all of the precision of formal reports, however, valuations of a practice can vary widely, according to Reed Tinsley. “Two valuations using the same methodology can differ by $300,000.”

Also, the valuation can be well above a reasonable asking price, said Sean Tinsley. “The market dictates the price. A traditional valuation almost invariably quotes a higher return than the market is willing to pay.”
 

Buyers’ valuations

Physicians who decide not to get a valuation still have to deal with valuations ordered by buyers. Hospitals and large practices often order valuations of the practices they want to buy, and private-equity firms use methods much like a valuation for the practices they are interested in.

Buyers rarely share the valuation report with the seller, so the seller has to accept the buyer’s price without being able to review the thought process behind it, Mr. Fanburg said. “Relying on the buyer to tell you what you’re worth means you may sell your practice well below its true value.”

When the buyer orders a valuation, the valuator interviews managers of the practice and asks for a great deal of information, says G. Don Barbo, managing director at VMG Health, a health care valuation firm based in Dallas.

Mr. Barbo said these documents include financial statements for the practice, usually going back 3-5 years; productivity reports for doctors and other providers; accounts receivables; reports of fixed assets; a roster of employees; employment agreements and management services agreements; reports on payer mix; facility leases and equipment lease agreements; budgets and projections; and tax returns.

Mr. Dietrich said valuators hone in on the practice’s current procedural terminology codes. “If the practice is coding too high, this would artificially increase the profit and purported value of the practice. For example, coding at 99214 rather than 99213 for an established patient means that the practice is being paid 45% more for each visit.” The valuator then reduces the value of the practice on the basis of the extent of the improper up-coding.

Mr. Barbo said some sellers don’t want all the scrutiny of the buyer’s valuation and just sell the practice’s tangible assets – furnishings, fixtures, and equipment – which do not require a great deal of documentation but yield a much lower price.
 

A primer on valuations

As a valuator, “my job is to project into the future,” Mr. Barraza said. “I am trying to see how the practice will fare going forward.”

Mr. Dietrich agreed, with one caveat: “As Yogi Berra said: ‘It’s difficult to make predictions, especially about the future.’ ”

The formal valuation assesses the practice in three ways: measuring income, assets, and what other practices sell for, called the market approach.

With the income approach, the most used measurement for practices, one tries to determine future income, which is what buyers are most interested in, Mr. Dietrich said. The income equals revenue (total collections) minus operating expenses and overhead.

“You are then left with all the money the physician is paid,” he said. “The issue is, how much is attributed to the physician’s own labor and how much to his or her ownership of the practice? This second category helps determine the value of the practice.”

The market approach is often used as a way to double-check the accuracy of the income approach. The appraiser looks for the prices of similar practices that have already been sold and then adjusts the price on the basis of differences with the practice up for sale.

The asset approach may be used when the practice has no positive cash flow. It establishes a price for tangible assets, which are often much lower in value than the values that the other approaches come up with. The asset approach can be a lower-priced alternative for practices that can’t be measured under the income or market approach.

“Equipment appraisers can do an inventory of your equipment,” Mr. Wood said. “Generally, equipment that is more than 3 years old, such as computers, is not that valuable, but an ultrasound machine probably has some resale value.”
 

Will the buyer pay for goodwill?

Many practice owners hope they can get money for the “goodwill” of their practice when they sell. Goodwill basically represents the reputation of the practice, which is difficult to pinpoint, and Mr. Wood said buyers often don’t want to pay for it.

“The goodwill is a wild card,” Mr. Wood said. “It can range from zero to crazy numbers. There is a Goodwill Registry – a list of the goodwill in other practice sales – that you can consult.”

One simple way to calculate the goodwill, he said, is to take the value of the practice based on examining income and remove the value of tangible assets. What is left is considered the goodwill.

Another form of intangible asset that is sometimes lumped together with goodwill is the value of the practice’s trained staff. “Some buyers agree to pay for the staff in place, because they plan to use that staff,” Ms. Kadan said. In one large deal she was involved with, the buyer agreed to pay something for the selling practice’s staff of 180 people.

Another item that buyers also do not typically pay for is the practice’s accounts receivable. They may also not pay for any liabilities the practice holds, such as the facility lease, equipment lease, and maintenance contracts, Mr. Barbo said. “The buyer then often stipulates that all liabilities are left to the practice, or stipulates any specific liabilities that it may assume.”
 

Selling to other doctors

Doctors can sell practices or shares in practices to other doctors. A retiring physician, for example, can sell his or her share to the other partners. A valuator may be brought in to establish the value of the doctor’s equity interest in the practice.

“Generally, practice buyouts aren’t lucrative for selling physician,” Mr. Wood said. “There are exceptions, of course, such as specialty practices in some cases.”

A practice can also be sold to a new doctor or to a previously employed physician who wants to be an owner. These physicians usually need to get a bank loan to buy the practice.

The bank assesses the finances of the selling practice to determine whether the buying physician will earn enough money to pay back the loan. “Banks don’t want lend more than the gross annual revenue of the practice, and some banks will only lend at 65% of gross annual revenue,” Sean Tinsley said.

COVID-19 has seriously affected banks’ lending decisions. Banks stopped lending to practice buyers at the beginning of the pandemic, and when they started lending again, they were more cautious, Sean Tinsley said. “Generally, banks want to see the practice at 85%-90% of pre–COVID-19 numbers before they make a loan.”

He added that, if a buyer can’t get a bank loan, the selling doctor may decide to finance the sale. The buyer agrees to a payment schedule to pay off the full price over several years.
 

Selling to or merging with other practices

The usual buyer is another practice, Reed Tinsley said. “You can sell to a group, but prices are low because, with COVID-19, buyers don’t want to incur a lot of money up front. Or you can merge with the practice, which means the selling doctor usually doesn’t get any money, but he does get a share in the larger practice. In that case, the partnership is the object of value, and it can be cashed out when the physician leaves the practice.”

Mergers can get very complicated. Mr. Fanburg said he has been working with seven groups that are merging into one. “The merger was scheduled to go live last January, but it was slowed down over negotiations about new managed care contracts and putting together a management structure, plus the groups were a little wary of each other. Now the deal is scheduled to go live next January.”

One advantage to selling to a larger entity, such as a big group practice or a hospital, is that the selling physician benefits from the higher reimbursement rates that large providers usually command. “If the buyer has more favorable reimbursement rates with insurers, it could pay the selling doctor much more than he is making now,” Mr. Barraza said.
 

Hospitals as buyers

Because of COVID-19, currently many hospitals don’t have money to buy more practices. However, this is most likely a temporary situation.

Hospitals typically offer less money than other buyers, according to Sean Tinsley. “We have never sold to a hospital, because hospitals generally don’t pay for goodwill. They pay for the practice assets and offer a dollar amount for each chart.”

Hospitals have to be careful not to pay physicians more than the usual amount for their practices, because the extra amount could be seen as a kickback for referrals, which would violate the federal Stark law and Anti-Kickback Statute. Not-for-profit hospitals also have to comply with regulations at the Internal Revenue Service.

Hospitals usually require that the selling physician continue to work in the practice after it is sold. The selling physician’s presence helps ensure that the practice’s output will not decline after sale. Although the sales price may be low, the hospital may make up for it by paying a higher compensation, Sean Tinsley said.
 

Selling to private-equity firms

Private-equity purchases are financed by investors who essentially want to “flip” practices – that is, they want to make them more profitable and then sell them to someone else. The private-equity firm starts by buying a “platform” practice, which forms the core of the venture. It then buys smaller practices that will be managed by the platform practice.

The number of private-equity deals increased continually through 2019, then plummeted in March because of COVID-19, but by the summer, activity began to rise again.

Physicians are very intrigued about selling to private-equity firms because they are known to pay the most for practices. But private-equity buyers focus on a fairly narrow group of specialties.

Generally, Sean Tinsley said, private-equity firms only look for pain, dermatology, and ophthalmology practices, but they have been starting to branch out to specialties such as gastroenterology. In 2018, there were only two private-equity deals for gastroenterology practices, but in 2019, there were 16, according to one assessment.

Private-equity firms buy very few of the practices they initially review, according to Mr. Fanburg. “Private equity negotiates with dozens or even hundreds of physician practices at a time, with only 1%-5% of those practices actually being acquired.”

The private-equity firm’s upfront payment to selling physicians is quite high, but then the physicians become employees of the new group and earn much less in compensation than they earned on this own.

“In order for the venture to get any value out of the acquisition, the doctors have to make less going forward than they did historically,” Mr. Dietrich said. That freed-up money boosts the value of the venture.

When the platform practice is sold – usually after 5 years or so – “chances are the management team will be replaced,” Mr. Fanburg said. “There could be new policies and objectives, which could mean a bumpy ride for physicians.”
 

Do you really want to sell?

“When a group of physicians comes to me asking for help selling their practice, my first question is, Why are you doing this?” Mr. Fanburg said. “You need a better reason for selling than just the money.

“Once you make the leap, there is a certain amount of autonomy you lose,” he continued. “The sale gives you an economic boost, but it may not be enough for the long haul. If you stay on with the buyer, your compensation is often lower. That makes sense if you’re retiring, but not if you’re a younger physician with many years of practice in the years ahead.

“When physicians say they see no other way out except to sell,” Mr. Fanburg said, “I tell them that their buyer will see a path to future growth for your practice. If you think reimbursements are getting worse, why are the buyers pressing ahead?”

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

The COVID-19 pandemic has decimated the bottom lines of many private practices, prompting physician-owners to seriously contemplate selling.

Physician-owners have had to sell at lower prices, reflecting lower cash flow under COVID-19. But sales prices may rebound following news on Nov. 9 that a COVID-19 vaccine candidate produced by Pfizer and its German partner, BioNTech, may be ready for initial distribution before the end of the year.

“There are a lot of ifs still, but if things go according to expectations, we may see an increase in the value of practices,” said Mark O. Dietrich, a CPA in Framingham, Mass., who deals mostly with valuations of physician practices.

“Practice valuations have been lower because many patients have kept away and cash flow has been reduced,” Mr. Dietrich said. “But once patients feel safe, that barrier would be removed, and cash flow, which sales prices are generally based on, could rise. However, this may take a while. One major hurdle would be getting people to take the vaccine.”
 

Many doctors have been contemplating closing

The nation is currently undergoing a significant spike in COVID-19 hospitalizations, which could prompt another COVID-19–related downturn in practice volume, as occurred earlier in the year. That downturn forced many private practitioners to contemplate selling their practices.

In a survey released this summer by McKinsey & Company, 53% of independent physicians reported that they were worried about their practices surviving. Although many physicians have now reopened their offices, patient volume is reduced, and physicians are earning far less than before.

“In many cases, physicians who had been considering retirement in the next few years have moved their planning up and want to sell as soon as possible,” said John D. Fanburg, an attorney at Brach Eichler, a law firm in Roseland, N.J., who specializes in medical practice sales and mergers.

“For physicians over age 65, it’s not just worries about finances; it’s also worries about the health risks of staying open,” Mr. Fanburg added.

Mid-career physicians are also selling their practices. Many of them become employees of the hospital, large practice, or private-equity firm that bought the practice – receiving a level of compensation set by the sales agreement.
 

Will your practice be hard to sell?

With so many physicians ready to sell, are there enough potential buyers to acquire them all? Probably not, said Mr. Dietrich.

“Many hospitals may not need new practices right now,” he said. “In the depths of the pandemic, they furloughed many of their existing doctors and may not have brought all of them back yet.”

In fact, because of the pandemic, some buyers have delayed sales that were already in progress, said Monica H. Kaden, director of business valuations at Sobel Valuations, based in Livingston, N.J.

“Buyers are not only worried about their own cash flow but also about the possibility of lower revenues of the selling practices due to COVID-19,” she said, citing a very large multispecialty group that has put its purchase of a another large multispecialty group on hold.
 

Practice values have (temporarily) fallen

Many potential buyers are still looking, though. One thing that drives them is the possibility of discounted sales because of COVID-19. “The sense I get is that a lot of hospitals see this as an opportunity to pick up practices on the cheap,” Mr. Dietrich said.

COVID-19 has been reducing practice values somewhat, said Reed Tinsley, a CPA in Houston who performs medical practice valuations and runs a practice brokerage firm. “Practice revenues and net income are lower under COVID-19, so prices are lower.”

Ms. Kadan advised physicians to hold off selling if they can afford to wait. “It’s always best to sell when the practice volume looks the best, because then the practice is worth more. But there are doctors who can’t wait because revenues are really falling and they are running out of money. They may have no choice but to sell.”

Even in the best of times, not all practices can be sold, said Sean Tinsley, a broker and licensed financial adviser at Tinsley Medical Practice Brokers in Austin, Tex., which he runs with his father, Reed Tinsley.

“We turn down about as many deals to sell practices as we accept,” he said. “Brokers have to be very selective because we don’t get paid until the practice gets sold. Generally, we won’t take practices in rural areas or practices that still only have a fraction of their pre–COVID-19 volume.”
 

How long will it take to sell your practice?

Some practices find a buyer within weeks, but in other cases, it can take as long as a year, he said. Once the buyer is located, preparing the paperwork for the sale can take 45-60 days.

Doctors can sell their practices on their own, but a broker can help them find potential buyers and select the right price. Business brokers generally receive a greater percentage of the sales price than residential brokers. They have greater command of business and finance, and the sale is more complex than a residential sale.

The broker may also help with selling the building where the practice is located, which is usually a separate sale, said Bruce E. Wood, an attorney at CCB Law in Syracuse, N.Y., who deals with practice sales. “A hospital buying your practice may not want to buy the building, so it has to be sold separately. You can always sell the space to a different buyer.”
 

What’s the right price for your practice?

For small practices, brokers often set a price by establishing a multiple, such as two times net earnings, Sean Tinsley said. In many cases, practices haven’t retained net earnings, so the broker uses gross annual revenue and sets the price at 50%-55% of that figure.

An alternative that is widely used in the business world and for many large practices is to base the price on earnings before interest, taxes, depreciation, and amortization (EBITDA). To determine a price, the EBITDA is then multiplied by a particular multiple, which depends on the perceived value of the practice.

Higher multiples go to practices that have a qualified management team, have documented financial policies and procedures, or have had significant past growth. Generally, the multiple of EBITDA at smaller practices is 1 or 2; larger practices have a multiple of 5-7 times EBITDA, Sean Tinsley said.

COVID-19 has had the effect of reducing the multiple somewhat. “As market forces shift from a seller’s market to a buyer’s market, multiples will likely remain below pre–COVID-19 levels for the remainder of 2020 and the first half of 2021,” one report stated.

Certified valuators like Reed Tinsley have more complex ways to establish the value of a practice, but as a broker, Sean Tinsley tends to use the multiples approach. He asserted that the prices derived from this method are on the mark. “Almost all the time we sell at the asking price.”
 

Using valuations to set the price

A more complex and expensive way to set a price for a practice is to order a valuation of the practice. The valuator issues a report that runs dozens of pages and costs thousands of dollars.

Mr. Fanburg said that very few physicians selling practices order valuation reports, owing to the cost and complexity. As a result, “they don’t have a clear idea what their practices are worth.”

A comprehensive report is called a conclusion of value. The amount it finds – expressed as a range – is called “fair market value.” The report can be used in the courts for legal disputes as well as for deriving a sales price.

Practices that don’t want to pay for a conclusion of value can ask a valuator to assemble a less extensive report, called an opinion of calculated value. Also known as a calculation engagement or engagement letter, it still costs several thousand dollars.

This report has limited validity and can’t be used in the courts, according to Jarrod Barraza, a certified valuator in the Nashville, Tenn., office of Horne, a health care business valuator. “When I issue an engagement letter, I am not talking as an appraiser but as a valuation consultant, and I don’t call the result fair market value; it’s only estimating,” he said.

For all of the precision of formal reports, however, valuations of a practice can vary widely, according to Reed Tinsley. “Two valuations using the same methodology can differ by $300,000.”

Also, the valuation can be well above a reasonable asking price, said Sean Tinsley. “The market dictates the price. A traditional valuation almost invariably quotes a higher return than the market is willing to pay.”
 

Buyers’ valuations

Physicians who decide not to get a valuation still have to deal with valuations ordered by buyers. Hospitals and large practices often order valuations of the practices they want to buy, and private-equity firms use methods much like a valuation for the practices they are interested in.

Buyers rarely share the valuation report with the seller, so the seller has to accept the buyer’s price without being able to review the thought process behind it, Mr. Fanburg said. “Relying on the buyer to tell you what you’re worth means you may sell your practice well below its true value.”

When the buyer orders a valuation, the valuator interviews managers of the practice and asks for a great deal of information, says G. Don Barbo, managing director at VMG Health, a health care valuation firm based in Dallas.

Mr. Barbo said these documents include financial statements for the practice, usually going back 3-5 years; productivity reports for doctors and other providers; accounts receivables; reports of fixed assets; a roster of employees; employment agreements and management services agreements; reports on payer mix; facility leases and equipment lease agreements; budgets and projections; and tax returns.

Mr. Dietrich said valuators hone in on the practice’s current procedural terminology codes. “If the practice is coding too high, this would artificially increase the profit and purported value of the practice. For example, coding at 99214 rather than 99213 for an established patient means that the practice is being paid 45% more for each visit.” The valuator then reduces the value of the practice on the basis of the extent of the improper up-coding.

Mr. Barbo said some sellers don’t want all the scrutiny of the buyer’s valuation and just sell the practice’s tangible assets – furnishings, fixtures, and equipment – which do not require a great deal of documentation but yield a much lower price.
 

A primer on valuations

As a valuator, “my job is to project into the future,” Mr. Barraza said. “I am trying to see how the practice will fare going forward.”

Mr. Dietrich agreed, with one caveat: “As Yogi Berra said: ‘It’s difficult to make predictions, especially about the future.’ ”

The formal valuation assesses the practice in three ways: measuring income, assets, and what other practices sell for, called the market approach.

With the income approach, the most used measurement for practices, one tries to determine future income, which is what buyers are most interested in, Mr. Dietrich said. The income equals revenue (total collections) minus operating expenses and overhead.

“You are then left with all the money the physician is paid,” he said. “The issue is, how much is attributed to the physician’s own labor and how much to his or her ownership of the practice? This second category helps determine the value of the practice.”

The market approach is often used as a way to double-check the accuracy of the income approach. The appraiser looks for the prices of similar practices that have already been sold and then adjusts the price on the basis of differences with the practice up for sale.

The asset approach may be used when the practice has no positive cash flow. It establishes a price for tangible assets, which are often much lower in value than the values that the other approaches come up with. The asset approach can be a lower-priced alternative for practices that can’t be measured under the income or market approach.

“Equipment appraisers can do an inventory of your equipment,” Mr. Wood said. “Generally, equipment that is more than 3 years old, such as computers, is not that valuable, but an ultrasound machine probably has some resale value.”
 

Will the buyer pay for goodwill?

Many practice owners hope they can get money for the “goodwill” of their practice when they sell. Goodwill basically represents the reputation of the practice, which is difficult to pinpoint, and Mr. Wood said buyers often don’t want to pay for it.

“The goodwill is a wild card,” Mr. Wood said. “It can range from zero to crazy numbers. There is a Goodwill Registry – a list of the goodwill in other practice sales – that you can consult.”

One simple way to calculate the goodwill, he said, is to take the value of the practice based on examining income and remove the value of tangible assets. What is left is considered the goodwill.

Another form of intangible asset that is sometimes lumped together with goodwill is the value of the practice’s trained staff. “Some buyers agree to pay for the staff in place, because they plan to use that staff,” Ms. Kadan said. In one large deal she was involved with, the buyer agreed to pay something for the selling practice’s staff of 180 people.

Another item that buyers also do not typically pay for is the practice’s accounts receivable. They may also not pay for any liabilities the practice holds, such as the facility lease, equipment lease, and maintenance contracts, Mr. Barbo said. “The buyer then often stipulates that all liabilities are left to the practice, or stipulates any specific liabilities that it may assume.”
 

Selling to other doctors

Doctors can sell practices or shares in practices to other doctors. A retiring physician, for example, can sell his or her share to the other partners. A valuator may be brought in to establish the value of the doctor’s equity interest in the practice.

“Generally, practice buyouts aren’t lucrative for selling physician,” Mr. Wood said. “There are exceptions, of course, such as specialty practices in some cases.”

A practice can also be sold to a new doctor or to a previously employed physician who wants to be an owner. These physicians usually need to get a bank loan to buy the practice.

The bank assesses the finances of the selling practice to determine whether the buying physician will earn enough money to pay back the loan. “Banks don’t want lend more than the gross annual revenue of the practice, and some banks will only lend at 65% of gross annual revenue,” Sean Tinsley said.

COVID-19 has seriously affected banks’ lending decisions. Banks stopped lending to practice buyers at the beginning of the pandemic, and when they started lending again, they were more cautious, Sean Tinsley said. “Generally, banks want to see the practice at 85%-90% of pre–COVID-19 numbers before they make a loan.”

He added that, if a buyer can’t get a bank loan, the selling doctor may decide to finance the sale. The buyer agrees to a payment schedule to pay off the full price over several years.
 

Selling to or merging with other practices

The usual buyer is another practice, Reed Tinsley said. “You can sell to a group, but prices are low because, with COVID-19, buyers don’t want to incur a lot of money up front. Or you can merge with the practice, which means the selling doctor usually doesn’t get any money, but he does get a share in the larger practice. In that case, the partnership is the object of value, and it can be cashed out when the physician leaves the practice.”

Mergers can get very complicated. Mr. Fanburg said he has been working with seven groups that are merging into one. “The merger was scheduled to go live last January, but it was slowed down over negotiations about new managed care contracts and putting together a management structure, plus the groups were a little wary of each other. Now the deal is scheduled to go live next January.”

One advantage to selling to a larger entity, such as a big group practice or a hospital, is that the selling physician benefits from the higher reimbursement rates that large providers usually command. “If the buyer has more favorable reimbursement rates with insurers, it could pay the selling doctor much more than he is making now,” Mr. Barraza said.
 

Hospitals as buyers

Because of COVID-19, currently many hospitals don’t have money to buy more practices. However, this is most likely a temporary situation.

Hospitals typically offer less money than other buyers, according to Sean Tinsley. “We have never sold to a hospital, because hospitals generally don’t pay for goodwill. They pay for the practice assets and offer a dollar amount for each chart.”

Hospitals have to be careful not to pay physicians more than the usual amount for their practices, because the extra amount could be seen as a kickback for referrals, which would violate the federal Stark law and Anti-Kickback Statute. Not-for-profit hospitals also have to comply with regulations at the Internal Revenue Service.

Hospitals usually require that the selling physician continue to work in the practice after it is sold. The selling physician’s presence helps ensure that the practice’s output will not decline after sale. Although the sales price may be low, the hospital may make up for it by paying a higher compensation, Sean Tinsley said.
 

Selling to private-equity firms

Private-equity purchases are financed by investors who essentially want to “flip” practices – that is, they want to make them more profitable and then sell them to someone else. The private-equity firm starts by buying a “platform” practice, which forms the core of the venture. It then buys smaller practices that will be managed by the platform practice.

The number of private-equity deals increased continually through 2019, then plummeted in March because of COVID-19, but by the summer, activity began to rise again.

Physicians are very intrigued about selling to private-equity firms because they are known to pay the most for practices. But private-equity buyers focus on a fairly narrow group of specialties.

Generally, Sean Tinsley said, private-equity firms only look for pain, dermatology, and ophthalmology practices, but they have been starting to branch out to specialties such as gastroenterology. In 2018, there were only two private-equity deals for gastroenterology practices, but in 2019, there were 16, according to one assessment.

Private-equity firms buy very few of the practices they initially review, according to Mr. Fanburg. “Private equity negotiates with dozens or even hundreds of physician practices at a time, with only 1%-5% of those practices actually being acquired.”

The private-equity firm’s upfront payment to selling physicians is quite high, but then the physicians become employees of the new group and earn much less in compensation than they earned on this own.

“In order for the venture to get any value out of the acquisition, the doctors have to make less going forward than they did historically,” Mr. Dietrich said. That freed-up money boosts the value of the venture.

When the platform practice is sold – usually after 5 years or so – “chances are the management team will be replaced,” Mr. Fanburg said. “There could be new policies and objectives, which could mean a bumpy ride for physicians.”
 

Do you really want to sell?

“When a group of physicians comes to me asking for help selling their practice, my first question is, Why are you doing this?” Mr. Fanburg said. “You need a better reason for selling than just the money.

“Once you make the leap, there is a certain amount of autonomy you lose,” he continued. “The sale gives you an economic boost, but it may not be enough for the long haul. If you stay on with the buyer, your compensation is often lower. That makes sense if you’re retiring, but not if you’re a younger physician with many years of practice in the years ahead.

“When physicians say they see no other way out except to sell,” Mr. Fanburg said, “I tell them that their buyer will see a path to future growth for your practice. If you think reimbursements are getting worse, why are the buyers pressing ahead?”

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

Pfizer and its German partner BioNTech have filed an application with the US Food and Drug Administration (FDA) for an emergency use authorization of its vaccine against COVID-19, the disease caused by SARS-CoV-2, according to a company news release.

It is the latest step in what has been an extraordinarily fast-paced development and testing process, with the companies having reported interim results of phase 3 trials on November 9 and final results this past Wednesday, as reported by Medscape Medical News. The vaccine, BNT162b2, which uses a messenger RNA-based platform, was ultimately found to have 95% efficacy and more than 94% efficacy in individuals over age 65.  

“The process of the speed did not compromise at all safety, nor did it compromise scientific integrity,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at a White House press briefing yesterday.

“We need to put to rest any concept that this was rushed in an inappropriate way,” he said. “This is really solid.”

Pfizer and BioNTech said they believe they have met the FDA’s safety data requirements for emergency use authorization (EUA). The agency in October outlined its expectations for safety and efficacy to secure an EUA.

“Filing in the US represents a critical milestone in our journey to deliver a COVID-19 vaccine to the world, and we now have a more complete picture of both the efficacy and safety profile of our vaccine, giving us confidence in its potential,” said Albert Bourla, MD, Pfizer’s chairman and CEO, in its release.

The FDA is expected to hold a meeting of its Vaccines and Related Biological Products Advisory Committee sometime in December to review the safety and efficacy data in the companies’ application. The committee will review:

• Efficacy data from a total 170 confirmed cases of COVID-19 in the phase 3 study.
• Safety data from a randomly assigned subset of 8000 participants 18 years and older.
• Data on 19,000 enrollees who have been followed for a median of 2 months after the second and final dose.
• Data on the manufacturing processes.

According to Pfizer, the companies plan to submit the efficacy and safety data to a peer-reviewed journal once they have completed their analysis.
 

Vaccine logistics

The companies — which funded their own trials — signed an agreement with the US government’s Operation Warp Speed program in July to provide 100 million doses of its vaccine following FDA authorization or approval in exchange for $1.95 billion. The US government has the option to acquire up to 500 million more doses.

Pfizer and BioNTech said they will be able to supply 50 million doses globally in 2020 and up to 1.3 billion doses by the end of 2021. The vaccine must be given in two doses, spaced 21 days apart. Pfizer expects to be ready to distribute the vaccine within hours after FDA authorization.

The US government is still on track to deliver the Pfizer vaccine within 24 hours of an FDA authorization, said Operation Warp Speed’s Chief Operating Officer Gen. Gustave F. Perna at yesterday’s White House briefing.

Vice President Mike Pence emphasized that point at the briefing: “The moment that the FDA concludes that that vaccine is safe and effective, we have a system in place to begin within 24 hours shipping that vaccine to hospitals, healthcare facilities and, 24 hours after that, literally injecting that vaccine into Americans,” he said.

The vaccine will be pushed out through 64 jurisdictions already part of the Centers for Disease Control and Prevention’s vaccines for children distribution program, and will likely be divided up according to population, said Perna.

Pfizer’s vaccine must be shipped and stored at –70°C (–94°F), which has presented logistical and storage issues. The company is testing out delivery methods, including a pilot delivery program in New Mexico, Rhode Island, Tennessee, and Texas that will be active after an FDA authorization. States, hospitals, and pharmacy chains are also buying special freezers.

The National Academies of Sciences, Engineering, and Medicine issued recommendations in October that healthcare workers, first responders, older Americans living in congregate settings (eg, nursing homes), and people with underlying health conditions be the first to receive a coronavirus vaccine. The CDC’s Advisory Committee on Immunization Practices will also be issuing recommendations as soon as the FDA authorizes a vaccine.

Pfizer and BioNTech are also seeking approval for the vaccine with several regulatory agencies around the world, including the European Medicines Agency and the Medicines & Healthcare Products Regulatory Agency (MHRA) in the United Kingdom.

This article first appeared on Medscape.com.

Pfizer and its German partner BioNTech have filed an application with the US Food and Drug Administration (FDA) for an emergency use authorization of its vaccine against COVID-19, the disease caused by SARS-CoV-2, according to a company news release.

It is the latest step in what has been an extraordinarily fast-paced development and testing process, with the companies having reported interim results of phase 3 trials on November 9 and final results this past Wednesday, as reported by Medscape Medical News. The vaccine, BNT162b2, which uses a messenger RNA-based platform, was ultimately found to have 95% efficacy and more than 94% efficacy in individuals over age 65.  

“The process of the speed did not compromise at all safety, nor did it compromise scientific integrity,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at a White House press briefing yesterday.

“We need to put to rest any concept that this was rushed in an inappropriate way,” he said. “This is really solid.”

Pfizer and BioNTech said they believe they have met the FDA’s safety data requirements for emergency use authorization (EUA). The agency in October outlined its expectations for safety and efficacy to secure an EUA.

“Filing in the US represents a critical milestone in our journey to deliver a COVID-19 vaccine to the world, and we now have a more complete picture of both the efficacy and safety profile of our vaccine, giving us confidence in its potential,” said Albert Bourla, MD, Pfizer’s chairman and CEO, in its release.

The FDA is expected to hold a meeting of its Vaccines and Related Biological Products Advisory Committee sometime in December to review the safety and efficacy data in the companies’ application. The committee will review:

• Efficacy data from a total 170 confirmed cases of COVID-19 in the phase 3 study.
• Safety data from a randomly assigned subset of 8000 participants 18 years and older.
• Data on 19,000 enrollees who have been followed for a median of 2 months after the second and final dose.
• Data on the manufacturing processes.

According to Pfizer, the companies plan to submit the efficacy and safety data to a peer-reviewed journal once they have completed their analysis.
 

Vaccine logistics

The companies — which funded their own trials — signed an agreement with the US government’s Operation Warp Speed program in July to provide 100 million doses of its vaccine following FDA authorization or approval in exchange for $1.95 billion. The US government has the option to acquire up to 500 million more doses.

Pfizer and BioNTech said they will be able to supply 50 million doses globally in 2020 and up to 1.3 billion doses by the end of 2021. The vaccine must be given in two doses, spaced 21 days apart. Pfizer expects to be ready to distribute the vaccine within hours after FDA authorization.

The US government is still on track to deliver the Pfizer vaccine within 24 hours of an FDA authorization, said Operation Warp Speed’s Chief Operating Officer Gen. Gustave F. Perna at yesterday’s White House briefing.

Vice President Mike Pence emphasized that point at the briefing: “The moment that the FDA concludes that that vaccine is safe and effective, we have a system in place to begin within 24 hours shipping that vaccine to hospitals, healthcare facilities and, 24 hours after that, literally injecting that vaccine into Americans,” he said.

The vaccine will be pushed out through 64 jurisdictions already part of the Centers for Disease Control and Prevention’s vaccines for children distribution program, and will likely be divided up according to population, said Perna.

Pfizer’s vaccine must be shipped and stored at –70°C (–94°F), which has presented logistical and storage issues. The company is testing out delivery methods, including a pilot delivery program in New Mexico, Rhode Island, Tennessee, and Texas that will be active after an FDA authorization. States, hospitals, and pharmacy chains are also buying special freezers.

The National Academies of Sciences, Engineering, and Medicine issued recommendations in October that healthcare workers, first responders, older Americans living in congregate settings (eg, nursing homes), and people with underlying health conditions be the first to receive a coronavirus vaccine. The CDC’s Advisory Committee on Immunization Practices will also be issuing recommendations as soon as the FDA authorizes a vaccine.

Pfizer and BioNTech are also seeking approval for the vaccine with several regulatory agencies around the world, including the European Medicines Agency and the Medicines & Healthcare Products Regulatory Agency (MHRA) in the United Kingdom.

This article first appeared on Medscape.com.

Pfizer and its German partner BioNTech have filed an application with the US Food and Drug Administration (FDA) for an emergency use authorization of its vaccine against COVID-19, the disease caused by SARS-CoV-2, according to a company news release.

It is the latest step in what has been an extraordinarily fast-paced development and testing process, with the companies having reported interim results of phase 3 trials on November 9 and final results this past Wednesday, as reported by Medscape Medical News. The vaccine, BNT162b2, which uses a messenger RNA-based platform, was ultimately found to have 95% efficacy and more than 94% efficacy in individuals over age 65.  

“The process of the speed did not compromise at all safety, nor did it compromise scientific integrity,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at a White House press briefing yesterday.

“We need to put to rest any concept that this was rushed in an inappropriate way,” he said. “This is really solid.”

Pfizer and BioNTech said they believe they have met the FDA’s safety data requirements for emergency use authorization (EUA). The agency in October outlined its expectations for safety and efficacy to secure an EUA.

“Filing in the US represents a critical milestone in our journey to deliver a COVID-19 vaccine to the world, and we now have a more complete picture of both the efficacy and safety profile of our vaccine, giving us confidence in its potential,” said Albert Bourla, MD, Pfizer’s chairman and CEO, in its release.

The FDA is expected to hold a meeting of its Vaccines and Related Biological Products Advisory Committee sometime in December to review the safety and efficacy data in the companies’ application. The committee will review:

• Efficacy data from a total 170 confirmed cases of COVID-19 in the phase 3 study.
• Safety data from a randomly assigned subset of 8000 participants 18 years and older.
• Data on 19,000 enrollees who have been followed for a median of 2 months after the second and final dose.
• Data on the manufacturing processes.

According to Pfizer, the companies plan to submit the efficacy and safety data to a peer-reviewed journal once they have completed their analysis.
 

Vaccine logistics

The companies — which funded their own trials — signed an agreement with the US government’s Operation Warp Speed program in July to provide 100 million doses of its vaccine following FDA authorization or approval in exchange for $1.95 billion. The US government has the option to acquire up to 500 million more doses.

Pfizer and BioNTech said they will be able to supply 50 million doses globally in 2020 and up to 1.3 billion doses by the end of 2021. The vaccine must be given in two doses, spaced 21 days apart. Pfizer expects to be ready to distribute the vaccine within hours after FDA authorization.

The US government is still on track to deliver the Pfizer vaccine within 24 hours of an FDA authorization, said Operation Warp Speed’s Chief Operating Officer Gen. Gustave F. Perna at yesterday’s White House briefing.

Vice President Mike Pence emphasized that point at the briefing: “The moment that the FDA concludes that that vaccine is safe and effective, we have a system in place to begin within 24 hours shipping that vaccine to hospitals, healthcare facilities and, 24 hours after that, literally injecting that vaccine into Americans,” he said.

The vaccine will be pushed out through 64 jurisdictions already part of the Centers for Disease Control and Prevention’s vaccines for children distribution program, and will likely be divided up according to population, said Perna.

Pfizer’s vaccine must be shipped and stored at –70°C (–94°F), which has presented logistical and storage issues. The company is testing out delivery methods, including a pilot delivery program in New Mexico, Rhode Island, Tennessee, and Texas that will be active after an FDA authorization. States, hospitals, and pharmacy chains are also buying special freezers.

The National Academies of Sciences, Engineering, and Medicine issued recommendations in October that healthcare workers, first responders, older Americans living in congregate settings (eg, nursing homes), and people with underlying health conditions be the first to receive a coronavirus vaccine. The CDC’s Advisory Committee on Immunization Practices will also be issuing recommendations as soon as the FDA authorizes a vaccine.

Pfizer and BioNTech are also seeking approval for the vaccine with several regulatory agencies around the world, including the European Medicines Agency and the Medicines & Healthcare Products Regulatory Agency (MHRA) in the United Kingdom.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

Patients with hemophilia A or von Willebrand disease undergoing anterior cruciate ligament (ACL) reconstruction had rates of postoperative complications and ACL reinjuries that were not significantly different from those control patients. However, the cost of health care utilization was significantly greater for the hemophilia A and von Willebrand disease patients, according to a large retrospective database study published online in The Knee.

All patients who underwent an ACL reconstruction from 2010 to 2014 in a large commercial database were assessed. Patients with hemophilia A, hemophilia B, and von Willebrand disease were identified. Patient demographics, cost of surgery, blood product use, concomitant injuries, repeat ACL injury, complications, and various operative variables were collected.

A total of 33 patients with hemophilia A, 3 with hemophilia B patients, 63 with von Willebrand disease and 103,478 control patients who had ACL reconstruction were compared, according to Connor Zale, MD, and colleagues at Penn State Hershey (Pa.) Medical Center.
 

Similar outcomes, higher costs

Complications – including length of hospital stay, postoperative hemorrhage within 14 days after surgery, infection rates within 90 days of surgery, lysis of adhesions or manipulation under anesthesia within 90 days of surgery, concomitant injuries to the knee, additional ACL injury within 1 year of surgery, deep-vein thrombosis, and pulmonary embolism – were not statistically different between the hemophilia/von Willebrand cohorts and the control group, according to the researchers.

However, surgery and postoperative care were costlier in the hemophilia A and von Willebrand cohorts. Total health care utilization within 30 days of ACL reconstruction was significantly more expensive for patients with hemophilia A ($25,982) and those with von Willebrand disease ($16,445), compared with those among controls ($12,887). In addition, the total health care utilization costs within 90 days of ACL reconstruction were significantly higher for patients with hemophilia A ($30,310) and those with von Willebrand disease ($20,355), compared with those among controls ($14,564), with all P values less than .001.

None of the patients with hemophilia A or those with von Willebrand received blood products perioperatively, had a known major hemarthrosis, or were readmitted within 30 or 90 days, the authors noted, adding that this finding differs from previous studies. The authors speculated that, since no blood products were administered and there was no significant difference in postoperative hemorrhage, the patients with hemophilia A were preoperatively optimized for an acceptable prothrombin time and international normalized ratio and/or were more effectively managed postoperatively.

“Many surgeons may be fearful of performing an ACL reconstruction on those with hemophilia A, hemophilia B, and von Willebrand disease due to concerns over risk of a major hemarthrosis and other complications postoperatively. This study observed that hemophilia A and von Willebrand disease patients who underwent an ACL reconstruction had rates of postoperative complications that were not statistically different than those who underwent ACL reconstructions and did not have a known hypocoagulable condition,” the researchers concluded.

The authors reported that they had no potential conflicts of interest to disclose.

[email protected]

SOURCE: Zale C et al. Knee. 2020;27(6):1729-34.

Patients with hemophilia A or von Willebrand disease undergoing anterior cruciate ligament (ACL) reconstruction had rates of postoperative complications and ACL reinjuries that were not significantly different from those control patients. However, the cost of health care utilization was significantly greater for the hemophilia A and von Willebrand disease patients, according to a large retrospective database study published online in The Knee.

All patients who underwent an ACL reconstruction from 2010 to 2014 in a large commercial database were assessed. Patients with hemophilia A, hemophilia B, and von Willebrand disease were identified. Patient demographics, cost of surgery, blood product use, concomitant injuries, repeat ACL injury, complications, and various operative variables were collected.

A total of 33 patients with hemophilia A, 3 with hemophilia B patients, 63 with von Willebrand disease and 103,478 control patients who had ACL reconstruction were compared, according to Connor Zale, MD, and colleagues at Penn State Hershey (Pa.) Medical Center.
 

Similar outcomes, higher costs

Complications – including length of hospital stay, postoperative hemorrhage within 14 days after surgery, infection rates within 90 days of surgery, lysis of adhesions or manipulation under anesthesia within 90 days of surgery, concomitant injuries to the knee, additional ACL injury within 1 year of surgery, deep-vein thrombosis, and pulmonary embolism – were not statistically different between the hemophilia/von Willebrand cohorts and the control group, according to the researchers.

However, surgery and postoperative care were costlier in the hemophilia A and von Willebrand cohorts. Total health care utilization within 30 days of ACL reconstruction was significantly more expensive for patients with hemophilia A ($25,982) and those with von Willebrand disease ($16,445), compared with those among controls ($12,887). In addition, the total health care utilization costs within 90 days of ACL reconstruction were significantly higher for patients with hemophilia A ($30,310) and those with von Willebrand disease ($20,355), compared with those among controls ($14,564), with all P values less than .001.

None of the patients with hemophilia A or those with von Willebrand received blood products perioperatively, had a known major hemarthrosis, or were readmitted within 30 or 90 days, the authors noted, adding that this finding differs from previous studies. The authors speculated that, since no blood products were administered and there was no significant difference in postoperative hemorrhage, the patients with hemophilia A were preoperatively optimized for an acceptable prothrombin time and international normalized ratio and/or were more effectively managed postoperatively.

“Many surgeons may be fearful of performing an ACL reconstruction on those with hemophilia A, hemophilia B, and von Willebrand disease due to concerns over risk of a major hemarthrosis and other complications postoperatively. This study observed that hemophilia A and von Willebrand disease patients who underwent an ACL reconstruction had rates of postoperative complications that were not statistically different than those who underwent ACL reconstructions and did not have a known hypocoagulable condition,” the researchers concluded.

The authors reported that they had no potential conflicts of interest to disclose.

[email protected]

SOURCE: Zale C et al. Knee. 2020;27(6):1729-34.

Patients with hemophilia A or von Willebrand disease undergoing anterior cruciate ligament (ACL) reconstruction had rates of postoperative complications and ACL reinjuries that were not significantly different from those control patients. However, the cost of health care utilization was significantly greater for the hemophilia A and von Willebrand disease patients, according to a large retrospective database study published online in The Knee.

All patients who underwent an ACL reconstruction from 2010 to 2014 in a large commercial database were assessed. Patients with hemophilia A, hemophilia B, and von Willebrand disease were identified. Patient demographics, cost of surgery, blood product use, concomitant injuries, repeat ACL injury, complications, and various operative variables were collected.

A total of 33 patients with hemophilia A, 3 with hemophilia B patients, 63 with von Willebrand disease and 103,478 control patients who had ACL reconstruction were compared, according to Connor Zale, MD, and colleagues at Penn State Hershey (Pa.) Medical Center.
 

Similar outcomes, higher costs

Complications – including length of hospital stay, postoperative hemorrhage within 14 days after surgery, infection rates within 90 days of surgery, lysis of adhesions or manipulation under anesthesia within 90 days of surgery, concomitant injuries to the knee, additional ACL injury within 1 year of surgery, deep-vein thrombosis, and pulmonary embolism – were not statistically different between the hemophilia/von Willebrand cohorts and the control group, according to the researchers.

However, surgery and postoperative care were costlier in the hemophilia A and von Willebrand cohorts. Total health care utilization within 30 days of ACL reconstruction was significantly more expensive for patients with hemophilia A ($25,982) and those with von Willebrand disease ($16,445), compared with those among controls ($12,887). In addition, the total health care utilization costs within 90 days of ACL reconstruction were significantly higher for patients with hemophilia A ($30,310) and those with von Willebrand disease ($20,355), compared with those among controls ($14,564), with all P values less than .001.

None of the patients with hemophilia A or those with von Willebrand received blood products perioperatively, had a known major hemarthrosis, or were readmitted within 30 or 90 days, the authors noted, adding that this finding differs from previous studies. The authors speculated that, since no blood products were administered and there was no significant difference in postoperative hemorrhage, the patients with hemophilia A were preoperatively optimized for an acceptable prothrombin time and international normalized ratio and/or were more effectively managed postoperatively.

“Many surgeons may be fearful of performing an ACL reconstruction on those with hemophilia A, hemophilia B, and von Willebrand disease due to concerns over risk of a major hemarthrosis and other complications postoperatively. This study observed that hemophilia A and von Willebrand disease patients who underwent an ACL reconstruction had rates of postoperative complications that were not statistically different than those who underwent ACL reconstructions and did not have a known hypocoagulable condition,” the researchers concluded.

The authors reported that they had no potential conflicts of interest to disclose.

[email protected]

SOURCE: Zale C et al. Knee. 2020;27(6):1729-34.

The FDA issued an emergency use authorization Tuesday for the first self-testing COVID-19 kit to use at home, which provides results in about 30 minutes.

The Lucira COVID-19 All-In-One Test-Kit is a single-use test that has a nasal swab to collect samples for people ages 14 and older. It’s available only by prescription, which can be given by a doctor who suspects a patient may have contracted the coronavirus.

“While COVID-19 diagnostic tests have been authorized for at-home collection, this is the first that can be fully self-administered and provide results at home,” FDA Commissioner Stephen Hahn, MD, said in the statement.

The test kit can also be used in doctor’s offices, hospitals, urgent care centers, and emergency rooms for all ages, but samples must be collected by a health care professional if the patient is under age 14.

After using the nasal swab, the test works by swirling the sample in a vial and then placing it in the provided test unit, according to the FDA. Within 30 minutes, the results appear on the unit’s light-up display. People who receive a positive result should self-isolate and seek care from their doctor. Those who test negative but have COVID-like symptoms should follow up with their doctor, since a negative result doesn’t necessarily mean they don’t have the coronavirus.

Testing is still a key part of controlling the spread of the coronavirus, Reuters reports. The United States surpassed 11 million infections Sunday, only 8 days after passing 10 million cases.

With the at-home testing kit, public health officials still need to track and monitor results. As part of the emergency use authorization, the FDA requires doctors who prescribe the tests to report all results to public health authorities based on local, state, and federal requirements. Lucira Health, the test maker, also created box labeling and instructions to help doctors to report results.

“Now, more Americans who may have COVID-19 will be able to take immediate action, based on their results, to protect themselves and those around them,” Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, said in the statement.

This article first appeared on WebMD.com.

The FDA issued an emergency use authorization Tuesday for the first self-testing COVID-19 kit to use at home, which provides results in about 30 minutes.

The Lucira COVID-19 All-In-One Test-Kit is a single-use test that has a nasal swab to collect samples for people ages 14 and older. It’s available only by prescription, which can be given by a doctor who suspects a patient may have contracted the coronavirus.

“While COVID-19 diagnostic tests have been authorized for at-home collection, this is the first that can be fully self-administered and provide results at home,” FDA Commissioner Stephen Hahn, MD, said in the statement.

The test kit can also be used in doctor’s offices, hospitals, urgent care centers, and emergency rooms for all ages, but samples must be collected by a health care professional if the patient is under age 14.

After using the nasal swab, the test works by swirling the sample in a vial and then placing it in the provided test unit, according to the FDA. Within 30 minutes, the results appear on the unit’s light-up display. People who receive a positive result should self-isolate and seek care from their doctor. Those who test negative but have COVID-like symptoms should follow up with their doctor, since a negative result doesn’t necessarily mean they don’t have the coronavirus.

Testing is still a key part of controlling the spread of the coronavirus, Reuters reports. The United States surpassed 11 million infections Sunday, only 8 days after passing 10 million cases.

With the at-home testing kit, public health officials still need to track and monitor results. As part of the emergency use authorization, the FDA requires doctors who prescribe the tests to report all results to public health authorities based on local, state, and federal requirements. Lucira Health, the test maker, also created box labeling and instructions to help doctors to report results.

“Now, more Americans who may have COVID-19 will be able to take immediate action, based on their results, to protect themselves and those around them,” Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, said in the statement.

This article first appeared on WebMD.com.

The FDA issued an emergency use authorization Tuesday for the first self-testing COVID-19 kit to use at home, which provides results in about 30 minutes.

The Lucira COVID-19 All-In-One Test-Kit is a single-use test that has a nasal swab to collect samples for people ages 14 and older. It’s available only by prescription, which can be given by a doctor who suspects a patient may have contracted the coronavirus.

“While COVID-19 diagnostic tests have been authorized for at-home collection, this is the first that can be fully self-administered and provide results at home,” FDA Commissioner Stephen Hahn, MD, said in the statement.

The test kit can also be used in doctor’s offices, hospitals, urgent care centers, and emergency rooms for all ages, but samples must be collected by a health care professional if the patient is under age 14.

After using the nasal swab, the test works by swirling the sample in a vial and then placing it in the provided test unit, according to the FDA. Within 30 minutes, the results appear on the unit’s light-up display. People who receive a positive result should self-isolate and seek care from their doctor. Those who test negative but have COVID-like symptoms should follow up with their doctor, since a negative result doesn’t necessarily mean they don’t have the coronavirus.

Testing is still a key part of controlling the spread of the coronavirus, Reuters reports. The United States surpassed 11 million infections Sunday, only 8 days after passing 10 million cases.

With the at-home testing kit, public health officials still need to track and monitor results. As part of the emergency use authorization, the FDA requires doctors who prescribe the tests to report all results to public health authorities based on local, state, and federal requirements. Lucira Health, the test maker, also created box labeling and instructions to help doctors to report results.

“Now, more Americans who may have COVID-19 will be able to take immediate action, based on their results, to protect themselves and those around them,” Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, said in the statement.

This article first appeared on WebMD.com.

Researchers are testing whether a probiotic called Lactobacillus rhamnosus GG can prevent COVID-19 in household contacts of COVID patients.

On the Nov. 12 episode of the Blood & Cancer podcast, Anthony D. Sung, MD, of Duke University, Durham, N.C., joined host David H. Henry, MD, of Penn Medicine in Philadelphia, to discuss the trial of LGG as well as other research. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Here we are in COVID. We’re recording this the first week in November. Sadly, cases are spiking in the country. And I understand you’ve got some information that you might share about how manipulating ... the microbiome that we all exist with inside our gut might somehow play into doing better or worse with COVID.

Anthony Sung, MD: Absolutely. So, as associate director of the Duke Microbiome Center, I was approached by one of my colleagues, Paul Wischmeyer, who is a professor of anesthesiology and critical care medicine at Duke. Paul had previously done some very nice murine studies with the probiotic Lactobacillus rhamnosus GG, or LGG.

He showed, in a murine model of pseudomonas pneumonia, that giving LGG to mice would help modulate their microbiome and, in turn, their immune system, leading to decreased inflammation, decreased TNF-alpha, IL [interleukin]-2, and IL-6, [and] increased Treg cells [Clin Nutr. 2017;36[6]:1549-57]. This also helped prevent lung injury, and it actually significantly improved survival in mice receiving LGG [Shock. 2013;40[6]:496-503].

In addition, there has been a randomized clinical trial of LGG showing that its administration would help prevent ventilator-associated pneumonia, or VAP [Am J Respir Crit Care Med. 2010 Oct 15;182[8]:1058-64].

And a few years ago, there was another RCT [randomized, controlled trial], published in Nature, showing that another Lactobacillus product significantly decreased the combined endpoint of sepsis and mortality, primarily by reducing lower respiratory tract infection [Nature. 2017 Aug 24;548[7668]:407-12].
 

Dr. Henry: And how is that working? What is the bacillus doing to help us?

Dr. Sung: We think it’s through modulating the immune system. As mentioned in Paul’s studies, we saw significantly decreased amounts of TNF-alpha, IL-2, and IL-6, which are the same cytokines that have been implicated in COVID-19 and associated with increased lung injury in patients during this pandemic.

And we believe that by giving individuals this probiotic, LGG, we may help modulate the immune system, decrease lung injury and symptoms, and maybe even prevent COVID-19.

So with support from the Duke Microbiome Center, as well as private donations and philanthropy, we are conducting a randomized clinical trial of LGG to prevent COVID-19 in household contacts who’ve been exposed to the disease. In other words, if someone in the house gets COVID-19, we want to try to prophylax everybody else living in that house and prevent them from coming down with the same infection.
 

Dr. Henry: And this is an oral administration?

Dr. Sung: Correct. This is an oral pill, two pills once a day.

Dr. Henry: And it’s an ongoing study, of course, in COVID right now?

Dr. Sung: Correct. So we have an IND [investigational new drug application] from the FDA [Food and Drug Administration], and we are actively recruiting subjects both at Duke University, but also due to the unique study design, we can enroll patients anywhere across the country. Because of the importance of social distancing, everything is done remotely.

So a household contact can hear about us, either through your podcast or one of our Facebook ads or through other media. They can reach out to our study website, which is https://sites.duke.edu/protectehc, or reach out to us at our study email, [email protected].

And we can go ahead and screen them for eligibility in our trial. And if they are eligible and they consent to participate, we will mail them a package basically overnight, FedEx, containing either LGG or placebo, as well as kits so that they can self-collect their stool and nasal swabs so we can test it for SARS-CoV-2 by PCR [polymerase chain reaction] and look at the microbiome.

Dr. Sung and Dr. Henry have no relevant disclosures. Funding for the trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

Researchers are testing whether a probiotic called Lactobacillus rhamnosus GG can prevent COVID-19 in household contacts of COVID patients.

On the Nov. 12 episode of the Blood & Cancer podcast, Anthony D. Sung, MD, of Duke University, Durham, N.C., joined host David H. Henry, MD, of Penn Medicine in Philadelphia, to discuss the trial of LGG as well as other research. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Here we are in COVID. We’re recording this the first week in November. Sadly, cases are spiking in the country. And I understand you’ve got some information that you might share about how manipulating ... the microbiome that we all exist with inside our gut might somehow play into doing better or worse with COVID.

Anthony Sung, MD: Absolutely. So, as associate director of the Duke Microbiome Center, I was approached by one of my colleagues, Paul Wischmeyer, who is a professor of anesthesiology and critical care medicine at Duke. Paul had previously done some very nice murine studies with the probiotic Lactobacillus rhamnosus GG, or LGG.

He showed, in a murine model of pseudomonas pneumonia, that giving LGG to mice would help modulate their microbiome and, in turn, their immune system, leading to decreased inflammation, decreased TNF-alpha, IL [interleukin]-2, and IL-6, [and] increased Treg cells [Clin Nutr. 2017;36[6]:1549-57]. This also helped prevent lung injury, and it actually significantly improved survival in mice receiving LGG [Shock. 2013;40[6]:496-503].

In addition, there has been a randomized clinical trial of LGG showing that its administration would help prevent ventilator-associated pneumonia, or VAP [Am J Respir Crit Care Med. 2010 Oct 15;182[8]:1058-64].

And a few years ago, there was another RCT [randomized, controlled trial], published in Nature, showing that another Lactobacillus product significantly decreased the combined endpoint of sepsis and mortality, primarily by reducing lower respiratory tract infection [Nature. 2017 Aug 24;548[7668]:407-12].
 

Dr. Henry: And how is that working? What is the bacillus doing to help us?

Dr. Sung: We think it’s through modulating the immune system. As mentioned in Paul’s studies, we saw significantly decreased amounts of TNF-alpha, IL-2, and IL-6, which are the same cytokines that have been implicated in COVID-19 and associated with increased lung injury in patients during this pandemic.

And we believe that by giving individuals this probiotic, LGG, we may help modulate the immune system, decrease lung injury and symptoms, and maybe even prevent COVID-19.

So with support from the Duke Microbiome Center, as well as private donations and philanthropy, we are conducting a randomized clinical trial of LGG to prevent COVID-19 in household contacts who’ve been exposed to the disease. In other words, if someone in the house gets COVID-19, we want to try to prophylax everybody else living in that house and prevent them from coming down with the same infection.
 

Dr. Henry: And this is an oral administration?

Dr. Sung: Correct. This is an oral pill, two pills once a day.

Dr. Henry: And it’s an ongoing study, of course, in COVID right now?

Dr. Sung: Correct. So we have an IND [investigational new drug application] from the FDA [Food and Drug Administration], and we are actively recruiting subjects both at Duke University, but also due to the unique study design, we can enroll patients anywhere across the country. Because of the importance of social distancing, everything is done remotely.

So a household contact can hear about us, either through your podcast or one of our Facebook ads or through other media. They can reach out to our study website, which is https://sites.duke.edu/protectehc, or reach out to us at our study email, [email protected].

And we can go ahead and screen them for eligibility in our trial. And if they are eligible and they consent to participate, we will mail them a package basically overnight, FedEx, containing either LGG or placebo, as well as kits so that they can self-collect their stool and nasal swabs so we can test it for SARS-CoV-2 by PCR [polymerase chain reaction] and look at the microbiome.

Dr. Sung and Dr. Henry have no relevant disclosures. Funding for the trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

Researchers are testing whether a probiotic called Lactobacillus rhamnosus GG can prevent COVID-19 in household contacts of COVID patients.

On the Nov. 12 episode of the Blood & Cancer podcast, Anthony D. Sung, MD, of Duke University, Durham, N.C., joined host David H. Henry, MD, of Penn Medicine in Philadelphia, to discuss the trial of LGG as well as other research. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Here we are in COVID. We’re recording this the first week in November. Sadly, cases are spiking in the country. And I understand you’ve got some information that you might share about how manipulating ... the microbiome that we all exist with inside our gut might somehow play into doing better or worse with COVID.

Anthony Sung, MD: Absolutely. So, as associate director of the Duke Microbiome Center, I was approached by one of my colleagues, Paul Wischmeyer, who is a professor of anesthesiology and critical care medicine at Duke. Paul had previously done some very nice murine studies with the probiotic Lactobacillus rhamnosus GG, or LGG.

He showed, in a murine model of pseudomonas pneumonia, that giving LGG to mice would help modulate their microbiome and, in turn, their immune system, leading to decreased inflammation, decreased TNF-alpha, IL [interleukin]-2, and IL-6, [and] increased Treg cells [Clin Nutr. 2017;36[6]:1549-57]. This also helped prevent lung injury, and it actually significantly improved survival in mice receiving LGG [Shock. 2013;40[6]:496-503].

In addition, there has been a randomized clinical trial of LGG showing that its administration would help prevent ventilator-associated pneumonia, or VAP [Am J Respir Crit Care Med. 2010 Oct 15;182[8]:1058-64].

And a few years ago, there was another RCT [randomized, controlled trial], published in Nature, showing that another Lactobacillus product significantly decreased the combined endpoint of sepsis and mortality, primarily by reducing lower respiratory tract infection [Nature. 2017 Aug 24;548[7668]:407-12].
 

Dr. Henry: And how is that working? What is the bacillus doing to help us?

Dr. Sung: We think it’s through modulating the immune system. As mentioned in Paul’s studies, we saw significantly decreased amounts of TNF-alpha, IL-2, and IL-6, which are the same cytokines that have been implicated in COVID-19 and associated with increased lung injury in patients during this pandemic.

And we believe that by giving individuals this probiotic, LGG, we may help modulate the immune system, decrease lung injury and symptoms, and maybe even prevent COVID-19.

So with support from the Duke Microbiome Center, as well as private donations and philanthropy, we are conducting a randomized clinical trial of LGG to prevent COVID-19 in household contacts who’ve been exposed to the disease. In other words, if someone in the house gets COVID-19, we want to try to prophylax everybody else living in that house and prevent them from coming down with the same infection.
 

Dr. Henry: And this is an oral administration?

Dr. Sung: Correct. This is an oral pill, two pills once a day.

Dr. Henry: And it’s an ongoing study, of course, in COVID right now?

Dr. Sung: Correct. So we have an IND [investigational new drug application] from the FDA [Food and Drug Administration], and we are actively recruiting subjects both at Duke University, but also due to the unique study design, we can enroll patients anywhere across the country. Because of the importance of social distancing, everything is done remotely.

So a household contact can hear about us, either through your podcast or one of our Facebook ads or through other media. They can reach out to our study website, which is https://sites.duke.edu/protectehc, or reach out to us at our study email, [email protected].

And we can go ahead and screen them for eligibility in our trial. And if they are eligible and they consent to participate, we will mail them a package basically overnight, FedEx, containing either LGG or placebo, as well as kits so that they can self-collect their stool and nasal swabs so we can test it for SARS-CoV-2 by PCR [polymerase chain reaction] and look at the microbiome.

Dr. Sung and Dr. Henry have no relevant disclosures. Funding for the trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

Can receiving all posttransplant care at home improve outcomes for patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.

Anthony D. Sung, MD, of Duke University, Durham, N.C., described this research to David H. Henry, MD, of Penn Medicine in Philadelphia, host of the Blood & Cancer podcast.

On the Nov. 12 episode of Blood & Cancer, Dr. Sung outlined the process of receiving post-HSCT care at home and discussed Duke’s clinical trials assessing the impact of home care on costs, quality of life, the microbiome, graft-versus-host disease (GVHD), and other outcomes. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Welcome to this podcast. We’re delighted to have you listening today because we’re going to be speaking with Dr. Anthony Sung from Duke University, where he is assistant professor of medicine in the division of hematologic malignancies and cellular therapies.

So let’s get right into it. I’m a generalist at Pennsylvania Hospital in Philadelphia, where we do auto [autologous] transplants at the main university hospital, autos and allos [allogeneic], and these patients are in [hospital] anywhere from a little bit to a long time. And I’ve often thought to try and do some of this as outpatient. But I think you have a project, which I’m going to ask you to describe, where you try and do most [treatment] outpatient. So tell me what this project is all about, and we’ll skip through how it works.
 

Anthony Sung, MD: Absolutely. So this is focused on both autologous as well as allogeneic stem cell transplant patients at Duke and a few other centers around the country. Duke University has actually had a long history of an outpatient transplant program. This program is based in a day hospital, which is basically like a high-functioning clinic that’s open 7 days a week. Patients can come into the hospital and receive blood transfusions, IV infusions, and any other therapies that they would need as part of their stem cell transplant treatment in the outpatient setting, returning to their home or to a furnished apartment, temporary lodging, while they’re receiving their care.

What we have done, however, is to take this a step further and deliver care within the patient’s own home. In a sense, we’re returning to an older form of medicine where doctors would make house calls. Within our home-transplant program, instead of the patients having to be in the hospital or instead of having to come back and forth to the outpatient hospital every day, which places additional stresses and strains upon them, our providers will make house calls to the patient’s homes, will draw their labs right there, do a history and physical exam, assess and attend to any of the needs that they have.

Then in the afternoon, the providers will return, have the labs run in the hospital, as they would normally do, a CBC, CMP [comprehensive metabolic panel], and so forth. And then a nurse would return to the patient’s home if needed to deliver any interventions, such as blood transfusions, intravenous fluids, or electrolytes, right there in the comfort of the patient’s own home.
 

Dr. Henry: So let’s then take it through what happens. Say I am a patient with myeloma. I’ve had various therapies, and it’s time for me to get an autotransplant, let’s say. And so I need to do a couple of things. I need to get my stem cells collected. I need to then get my high-dose [conditioning] therapy, and then follows the stem cell therapy reinfusion. So can you take me through each step? Where is that done?

Dr. Sung: Absolutely. So the collection will occur in the outpatient setting, typically after mobilization with G-CSF [granulocyte colony–stimulating factor] and/or plerixafor. That will occur in our outpatient clinic with one of our leukapheresis machines. And the patient will then return to that same outpatient clinic, which is the same building, the same facility as the hospital, to receive melphalan conditioning. And then, following conditioning, about 24 hours after, day 0, that’s the day of their stem cell transplant infusion, which we do in the hospital setting just because of the potential for reactions associated with that.

But everything after that, from day 1 onwards, we try to keep them at home. And as I said, they will stay in their home. One of our nurse practitioners or physician assistants will visit them in the morning, do the assessment and draw the labs. And nurses will return in the afternoon to deliver any supportive care that they need.
 

Dr. Henry: So let’s define “home.” So I’m a Philadelphia resident and I say to you, Dr. Sung, I want to go home. You say, well, Philadelphia is too far. What is close enough and not too far, when you say home?

Dr. Sung: Absolutely. So when we originally conceived the program, we focused on patients who lived within an hour of our transplant center. And in part, that was because, as you know, unfortunately, things can sometimes go wrong during transplant. One of the most concerning ones is infections. And if a patient were to develop a neutropenic fever, we would want them to be seen as urgently as possible within an hour. And that’s where our limitation comes from.

So for our patients who live more than an hour away, those are the ones that we will have relocate to temporary lodging near our transplant center. And we’ve worked with several facilities in the area that have clean, furnished units that are available for rent. Many insurances also include lodging benefits for patients during stem cell transplant, recognizing this need. And historically, those [patients] were not considered part of our transplant patient cohorts.

I have not mentioned, but we initially did this in a phase 1 study, and we’re now studying it in a series of randomized, phase 2 studies that I can go into detail later on. And because they were not necessarily in their home, but a temporary lodging environment, those patients who relocated to Durham were not eligible for a home transplant study.

However, in the setting of the COVID-19 pandemic, we’ve actually pivoted our program in many ways. Specifically, if you think about a patient who’s coming into contact with the medical system, they come to the hospital, they meet someone at the door who is screening them for COVID-19. They see someone who checks them in at the front desk. A medical assistant takes them in the back. Someone calls their labs and phlebotomy. They may encounter other patients and environmental services, other individuals in the setting. You’re talking about dozens of different encounters. Who knows how many surfaces that potentially someone with COVID-19 has coughed on or contaminated?

And in contrast, you have house calls, which even if they are located in the temporary lodging, that’s just one or two individuals going into their living environment. They’re not encountering any different surfaces. And so, in the setting of COVID-19, we felt that this platform had the potential to help protect all our transplant patients who are among the most vulnerable patients, the most immunocompromised patients, and so we expanded our program to include those individuals as well.
 

Dr. Henry: So ... what are the actual outcomes of your patients in terms of how they’re doing, engrafting, and getting cured of their malignancy?

Dr. Sung: So as I mentioned, we first did this in a phase 1 safety and feasibility pilot study of both autologous and allo-transplant patients. This was presented at the annual meeting of the American Society of Hematology [Blood. 2017;130:745]. And we’re actually about ready to submit our manuscript on this.

And we found no difference in outcomes between patients who received care in the home transplant setting versus those who received conventional care either in the day hospital or hospital environment. The process appeared safe. Patients did just as well, if not better. Certainly, anecdotally, patients would talk about feeling so much more comfortable and happier being cared for in that home environment.

And we are now in the process of formally studying these outcomes in two NIH [National Institutes of Health]-funded clinical trials, one focused on allogeneic transplant patients [NCT02218151] and the other focused on autologous transplant patients [NCT01725022].
 

Dr. Henry: So of course, I’m waiting for this next question, which is cost. The services are the same, but you have people traveling, people who are highly skilled caregivers. Have you looked at cost differences from hospital versus home?

Dr. Sung: Absolutely. So you do have increased upfront costs because you have travel time for advanced practice providers and nurses. Not only that, but when a nurse is helping to give a patient a blood transfusion in the home environment, they’re 1:1 with that patient as opposed to the day hospital where a nurse could help with transfusions simultaneously for multiple patients. At the same time, by keeping patients out of the hospital, you have drastic, significant cost savings in that way.

In addition, I should mention, part of why we’re conducting these randomized, phase 2 clinical trials is we believe home care actually has the potential to decrease complications. One area of my research is on the impact of the microbiome, the bacteria in the gut, on transplant outcomes. And we’ve done a number of studies, many in collaboration with Memorial Sloan Kettering, showing that disruption of the microbiota, the bacteria in the gut, is associated with increased infections, graft-versus-host disease, and treatment-related mortality if we’re able to keep patients in their home setting.

However, I actually should go back a step. It’s well known that, if you take an individual from their home setting and put them in a foreign environment such as the hospital, that new environment, that new diet, hospital food as opposed to home food, and so forth, can dramatically shift the microbiome. Our hypothesis is that, by keeping patients in the home environment, their familiar environment will be able to help preserve their microbiome, thus decreasing infections, graft-versus-host disease, and other complications. That’s actually the goal of our studies: to see if we can preserve the microbiome and decrease complications.
 

Dr. Henry: So how will you evaluate that? Are you doing fecal studies, patient culture studies? How are you testing that?

Dr. Sung: So we have a very broad biobank program where we collect stool on our transplantations, pretransplant, day 0, weekly for the first month. And then, in the case of our allogeneic transplant patients, day 60, 90, 180, and 365.

And we do that both in our home transplant patients as well as their matched controls on the phase 2 studies. And we also collect it on a lot of our other transplant patients as part of our biobanking programs and our observational studies to try to understand what’s going on during transplant and how to help improve transplant outcomes.
 

Dr. Henry: Do you have any results of that? You’re probably showing a difference.

Dr. Sung: We think so, on some preliminary results, but those were based on small numbers of patients. And we’re really hoping that these randomized clinical trials with the larger numbers of patients enrolled will help show that difference.

But getting back to your earlier question about cost, a case of graft-versus-host disease, grade 2 or higher, can add about $100,000 to the cost of care. So if you prevent one case of bad gut or liver graft-versus-host disease, those are your cost savings right there.

The randomized, phase 2 trial for allogeneic transplant patients, the primary endpoint is graft-versus-host disease. So we’re looking at the microbiome and those associations and the prevention of GVHD. For the randomized clinical trial in autologous transplant patients – with autologous stem cells, you’re not going to get GVHD – but we do hope to improve quality of life and long-term outcomes in those patients as well.
 

Dr. Henry: Wonderful. Well, Tony, I really want to thank you so much for talking with us today.

Dr. Sung: Thank you very much for this opportunity. And again, I also want to just thank everyone who’s been involved in these studies, the advanced practice providers and nurses who are caring for our patients at home, the study staff who have been involved. Particularly, I’d like to highlight the role of both Nelson Chao, who’s our division chief and my mentor who piloted and first developed home transplant, and Kristin Nichols, our research nurse who has really led the drive forward.

Dr. Sung and Dr. Henry have no relevant disclosures. The trials are funded by grants from the National Institutes of Health.

Can receiving all posttransplant care at home improve outcomes for patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.

Anthony D. Sung, MD, of Duke University, Durham, N.C., described this research to David H. Henry, MD, of Penn Medicine in Philadelphia, host of the Blood & Cancer podcast.

On the Nov. 12 episode of Blood & Cancer, Dr. Sung outlined the process of receiving post-HSCT care at home and discussed Duke’s clinical trials assessing the impact of home care on costs, quality of life, the microbiome, graft-versus-host disease (GVHD), and other outcomes. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Welcome to this podcast. We’re delighted to have you listening today because we’re going to be speaking with Dr. Anthony Sung from Duke University, where he is assistant professor of medicine in the division of hematologic malignancies and cellular therapies.

So let’s get right into it. I’m a generalist at Pennsylvania Hospital in Philadelphia, where we do auto [autologous] transplants at the main university hospital, autos and allos [allogeneic], and these patients are in [hospital] anywhere from a little bit to a long time. And I’ve often thought to try and do some of this as outpatient. But I think you have a project, which I’m going to ask you to describe, where you try and do most [treatment] outpatient. So tell me what this project is all about, and we’ll skip through how it works.
 

Anthony Sung, MD: Absolutely. So this is focused on both autologous as well as allogeneic stem cell transplant patients at Duke and a few other centers around the country. Duke University has actually had a long history of an outpatient transplant program. This program is based in a day hospital, which is basically like a high-functioning clinic that’s open 7 days a week. Patients can come into the hospital and receive blood transfusions, IV infusions, and any other therapies that they would need as part of their stem cell transplant treatment in the outpatient setting, returning to their home or to a furnished apartment, temporary lodging, while they’re receiving their care.

What we have done, however, is to take this a step further and deliver care within the patient’s own home. In a sense, we’re returning to an older form of medicine where doctors would make house calls. Within our home-transplant program, instead of the patients having to be in the hospital or instead of having to come back and forth to the outpatient hospital every day, which places additional stresses and strains upon them, our providers will make house calls to the patient’s homes, will draw their labs right there, do a history and physical exam, assess and attend to any of the needs that they have.

Then in the afternoon, the providers will return, have the labs run in the hospital, as they would normally do, a CBC, CMP [comprehensive metabolic panel], and so forth. And then a nurse would return to the patient’s home if needed to deliver any interventions, such as blood transfusions, intravenous fluids, or electrolytes, right there in the comfort of the patient’s own home.
 

Dr. Henry: So let’s then take it through what happens. Say I am a patient with myeloma. I’ve had various therapies, and it’s time for me to get an autotransplant, let’s say. And so I need to do a couple of things. I need to get my stem cells collected. I need to then get my high-dose [conditioning] therapy, and then follows the stem cell therapy reinfusion. So can you take me through each step? Where is that done?

Dr. Sung: Absolutely. So the collection will occur in the outpatient setting, typically after mobilization with G-CSF [granulocyte colony–stimulating factor] and/or plerixafor. That will occur in our outpatient clinic with one of our leukapheresis machines. And the patient will then return to that same outpatient clinic, which is the same building, the same facility as the hospital, to receive melphalan conditioning. And then, following conditioning, about 24 hours after, day 0, that’s the day of their stem cell transplant infusion, which we do in the hospital setting just because of the potential for reactions associated with that.

But everything after that, from day 1 onwards, we try to keep them at home. And as I said, they will stay in their home. One of our nurse practitioners or physician assistants will visit them in the morning, do the assessment and draw the labs. And nurses will return in the afternoon to deliver any supportive care that they need.
 

Dr. Henry: So let’s define “home.” So I’m a Philadelphia resident and I say to you, Dr. Sung, I want to go home. You say, well, Philadelphia is too far. What is close enough and not too far, when you say home?

Dr. Sung: Absolutely. So when we originally conceived the program, we focused on patients who lived within an hour of our transplant center. And in part, that was because, as you know, unfortunately, things can sometimes go wrong during transplant. One of the most concerning ones is infections. And if a patient were to develop a neutropenic fever, we would want them to be seen as urgently as possible within an hour. And that’s where our limitation comes from.

So for our patients who live more than an hour away, those are the ones that we will have relocate to temporary lodging near our transplant center. And we’ve worked with several facilities in the area that have clean, furnished units that are available for rent. Many insurances also include lodging benefits for patients during stem cell transplant, recognizing this need. And historically, those [patients] were not considered part of our transplant patient cohorts.

I have not mentioned, but we initially did this in a phase 1 study, and we’re now studying it in a series of randomized, phase 2 studies that I can go into detail later on. And because they were not necessarily in their home, but a temporary lodging environment, those patients who relocated to Durham were not eligible for a home transplant study.

However, in the setting of the COVID-19 pandemic, we’ve actually pivoted our program in many ways. Specifically, if you think about a patient who’s coming into contact with the medical system, they come to the hospital, they meet someone at the door who is screening them for COVID-19. They see someone who checks them in at the front desk. A medical assistant takes them in the back. Someone calls their labs and phlebotomy. They may encounter other patients and environmental services, other individuals in the setting. You’re talking about dozens of different encounters. Who knows how many surfaces that potentially someone with COVID-19 has coughed on or contaminated?

And in contrast, you have house calls, which even if they are located in the temporary lodging, that’s just one or two individuals going into their living environment. They’re not encountering any different surfaces. And so, in the setting of COVID-19, we felt that this platform had the potential to help protect all our transplant patients who are among the most vulnerable patients, the most immunocompromised patients, and so we expanded our program to include those individuals as well.
 

Dr. Henry: So ... what are the actual outcomes of your patients in terms of how they’re doing, engrafting, and getting cured of their malignancy?

Dr. Sung: So as I mentioned, we first did this in a phase 1 safety and feasibility pilot study of both autologous and allo-transplant patients. This was presented at the annual meeting of the American Society of Hematology [Blood. 2017;130:745]. And we’re actually about ready to submit our manuscript on this.

And we found no difference in outcomes between patients who received care in the home transplant setting versus those who received conventional care either in the day hospital or hospital environment. The process appeared safe. Patients did just as well, if not better. Certainly, anecdotally, patients would talk about feeling so much more comfortable and happier being cared for in that home environment.

And we are now in the process of formally studying these outcomes in two NIH [National Institutes of Health]-funded clinical trials, one focused on allogeneic transplant patients [NCT02218151] and the other focused on autologous transplant patients [NCT01725022].
 

Dr. Henry: So of course, I’m waiting for this next question, which is cost. The services are the same, but you have people traveling, people who are highly skilled caregivers. Have you looked at cost differences from hospital versus home?

Dr. Sung: Absolutely. So you do have increased upfront costs because you have travel time for advanced practice providers and nurses. Not only that, but when a nurse is helping to give a patient a blood transfusion in the home environment, they’re 1:1 with that patient as opposed to the day hospital where a nurse could help with transfusions simultaneously for multiple patients. At the same time, by keeping patients out of the hospital, you have drastic, significant cost savings in that way.

In addition, I should mention, part of why we’re conducting these randomized, phase 2 clinical trials is we believe home care actually has the potential to decrease complications. One area of my research is on the impact of the microbiome, the bacteria in the gut, on transplant outcomes. And we’ve done a number of studies, many in collaboration with Memorial Sloan Kettering, showing that disruption of the microbiota, the bacteria in the gut, is associated with increased infections, graft-versus-host disease, and treatment-related mortality if we’re able to keep patients in their home setting.

However, I actually should go back a step. It’s well known that, if you take an individual from their home setting and put them in a foreign environment such as the hospital, that new environment, that new diet, hospital food as opposed to home food, and so forth, can dramatically shift the microbiome. Our hypothesis is that, by keeping patients in the home environment, their familiar environment will be able to help preserve their microbiome, thus decreasing infections, graft-versus-host disease, and other complications. That’s actually the goal of our studies: to see if we can preserve the microbiome and decrease complications.
 

Dr. Henry: So how will you evaluate that? Are you doing fecal studies, patient culture studies? How are you testing that?

Dr. Sung: So we have a very broad biobank program where we collect stool on our transplantations, pretransplant, day 0, weekly for the first month. And then, in the case of our allogeneic transplant patients, day 60, 90, 180, and 365.

And we do that both in our home transplant patients as well as their matched controls on the phase 2 studies. And we also collect it on a lot of our other transplant patients as part of our biobanking programs and our observational studies to try to understand what’s going on during transplant and how to help improve transplant outcomes.
 

Dr. Henry: Do you have any results of that? You’re probably showing a difference.

Dr. Sung: We think so, on some preliminary results, but those were based on small numbers of patients. And we’re really hoping that these randomized clinical trials with the larger numbers of patients enrolled will help show that difference.

But getting back to your earlier question about cost, a case of graft-versus-host disease, grade 2 or higher, can add about $100,000 to the cost of care. So if you prevent one case of bad gut or liver graft-versus-host disease, those are your cost savings right there.

The randomized, phase 2 trial for allogeneic transplant patients, the primary endpoint is graft-versus-host disease. So we’re looking at the microbiome and those associations and the prevention of GVHD. For the randomized clinical trial in autologous transplant patients – with autologous stem cells, you’re not going to get GVHD – but we do hope to improve quality of life and long-term outcomes in those patients as well.
 

Dr. Henry: Wonderful. Well, Tony, I really want to thank you so much for talking with us today.

Dr. Sung: Thank you very much for this opportunity. And again, I also want to just thank everyone who’s been involved in these studies, the advanced practice providers and nurses who are caring for our patients at home, the study staff who have been involved. Particularly, I’d like to highlight the role of both Nelson Chao, who’s our division chief and my mentor who piloted and first developed home transplant, and Kristin Nichols, our research nurse who has really led the drive forward.

Dr. Sung and Dr. Henry have no relevant disclosures. The trials are funded by grants from the National Institutes of Health.

Can receiving all posttransplant care at home improve outcomes for patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.

Anthony D. Sung, MD, of Duke University, Durham, N.C., described this research to David H. Henry, MD, of Penn Medicine in Philadelphia, host of the Blood & Cancer podcast.

On the Nov. 12 episode of Blood & Cancer, Dr. Sung outlined the process of receiving post-HSCT care at home and discussed Duke’s clinical trials assessing the impact of home care on costs, quality of life, the microbiome, graft-versus-host disease (GVHD), and other outcomes. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Welcome to this podcast. We’re delighted to have you listening today because we’re going to be speaking with Dr. Anthony Sung from Duke University, where he is assistant professor of medicine in the division of hematologic malignancies and cellular therapies.

So let’s get right into it. I’m a generalist at Pennsylvania Hospital in Philadelphia, where we do auto [autologous] transplants at the main university hospital, autos and allos [allogeneic], and these patients are in [hospital] anywhere from a little bit to a long time. And I’ve often thought to try and do some of this as outpatient. But I think you have a project, which I’m going to ask you to describe, where you try and do most [treatment] outpatient. So tell me what this project is all about, and we’ll skip through how it works.
 

Anthony Sung, MD: Absolutely. So this is focused on both autologous as well as allogeneic stem cell transplant patients at Duke and a few other centers around the country. Duke University has actually had a long history of an outpatient transplant program. This program is based in a day hospital, which is basically like a high-functioning clinic that’s open 7 days a week. Patients can come into the hospital and receive blood transfusions, IV infusions, and any other therapies that they would need as part of their stem cell transplant treatment in the outpatient setting, returning to their home or to a furnished apartment, temporary lodging, while they’re receiving their care.

What we have done, however, is to take this a step further and deliver care within the patient’s own home. In a sense, we’re returning to an older form of medicine where doctors would make house calls. Within our home-transplant program, instead of the patients having to be in the hospital or instead of having to come back and forth to the outpatient hospital every day, which places additional stresses and strains upon them, our providers will make house calls to the patient’s homes, will draw their labs right there, do a history and physical exam, assess and attend to any of the needs that they have.

Then in the afternoon, the providers will return, have the labs run in the hospital, as they would normally do, a CBC, CMP [comprehensive metabolic panel], and so forth. And then a nurse would return to the patient’s home if needed to deliver any interventions, such as blood transfusions, intravenous fluids, or electrolytes, right there in the comfort of the patient’s own home.
 

Dr. Henry: So let’s then take it through what happens. Say I am a patient with myeloma. I’ve had various therapies, and it’s time for me to get an autotransplant, let’s say. And so I need to do a couple of things. I need to get my stem cells collected. I need to then get my high-dose [conditioning] therapy, and then follows the stem cell therapy reinfusion. So can you take me through each step? Where is that done?

Dr. Sung: Absolutely. So the collection will occur in the outpatient setting, typically after mobilization with G-CSF [granulocyte colony–stimulating factor] and/or plerixafor. That will occur in our outpatient clinic with one of our leukapheresis machines. And the patient will then return to that same outpatient clinic, which is the same building, the same facility as the hospital, to receive melphalan conditioning. And then, following conditioning, about 24 hours after, day 0, that’s the day of their stem cell transplant infusion, which we do in the hospital setting just because of the potential for reactions associated with that.

But everything after that, from day 1 onwards, we try to keep them at home. And as I said, they will stay in their home. One of our nurse practitioners or physician assistants will visit them in the morning, do the assessment and draw the labs. And nurses will return in the afternoon to deliver any supportive care that they need.
 

Dr. Henry: So let’s define “home.” So I’m a Philadelphia resident and I say to you, Dr. Sung, I want to go home. You say, well, Philadelphia is too far. What is close enough and not too far, when you say home?

Dr. Sung: Absolutely. So when we originally conceived the program, we focused on patients who lived within an hour of our transplant center. And in part, that was because, as you know, unfortunately, things can sometimes go wrong during transplant. One of the most concerning ones is infections. And if a patient were to develop a neutropenic fever, we would want them to be seen as urgently as possible within an hour. And that’s where our limitation comes from.

So for our patients who live more than an hour away, those are the ones that we will have relocate to temporary lodging near our transplant center. And we’ve worked with several facilities in the area that have clean, furnished units that are available for rent. Many insurances also include lodging benefits for patients during stem cell transplant, recognizing this need. And historically, those [patients] were not considered part of our transplant patient cohorts.

I have not mentioned, but we initially did this in a phase 1 study, and we’re now studying it in a series of randomized, phase 2 studies that I can go into detail later on. And because they were not necessarily in their home, but a temporary lodging environment, those patients who relocated to Durham were not eligible for a home transplant study.

However, in the setting of the COVID-19 pandemic, we’ve actually pivoted our program in many ways. Specifically, if you think about a patient who’s coming into contact with the medical system, they come to the hospital, they meet someone at the door who is screening them for COVID-19. They see someone who checks them in at the front desk. A medical assistant takes them in the back. Someone calls their labs and phlebotomy. They may encounter other patients and environmental services, other individuals in the setting. You’re talking about dozens of different encounters. Who knows how many surfaces that potentially someone with COVID-19 has coughed on or contaminated?

And in contrast, you have house calls, which even if they are located in the temporary lodging, that’s just one or two individuals going into their living environment. They’re not encountering any different surfaces. And so, in the setting of COVID-19, we felt that this platform had the potential to help protect all our transplant patients who are among the most vulnerable patients, the most immunocompromised patients, and so we expanded our program to include those individuals as well.
 

Dr. Henry: So ... what are the actual outcomes of your patients in terms of how they’re doing, engrafting, and getting cured of their malignancy?

Dr. Sung: So as I mentioned, we first did this in a phase 1 safety and feasibility pilot study of both autologous and allo-transplant patients. This was presented at the annual meeting of the American Society of Hematology [Blood. 2017;130:745]. And we’re actually about ready to submit our manuscript on this.

And we found no difference in outcomes between patients who received care in the home transplant setting versus those who received conventional care either in the day hospital or hospital environment. The process appeared safe. Patients did just as well, if not better. Certainly, anecdotally, patients would talk about feeling so much more comfortable and happier being cared for in that home environment.

And we are now in the process of formally studying these outcomes in two NIH [National Institutes of Health]-funded clinical trials, one focused on allogeneic transplant patients [NCT02218151] and the other focused on autologous transplant patients [NCT01725022].
 

Dr. Henry: So of course, I’m waiting for this next question, which is cost. The services are the same, but you have people traveling, people who are highly skilled caregivers. Have you looked at cost differences from hospital versus home?

Dr. Sung: Absolutely. So you do have increased upfront costs because you have travel time for advanced practice providers and nurses. Not only that, but when a nurse is helping to give a patient a blood transfusion in the home environment, they’re 1:1 with that patient as opposed to the day hospital where a nurse could help with transfusions simultaneously for multiple patients. At the same time, by keeping patients out of the hospital, you have drastic, significant cost savings in that way.

In addition, I should mention, part of why we’re conducting these randomized, phase 2 clinical trials is we believe home care actually has the potential to decrease complications. One area of my research is on the impact of the microbiome, the bacteria in the gut, on transplant outcomes. And we’ve done a number of studies, many in collaboration with Memorial Sloan Kettering, showing that disruption of the microbiota, the bacteria in the gut, is associated with increased infections, graft-versus-host disease, and treatment-related mortality if we’re able to keep patients in their home setting.

However, I actually should go back a step. It’s well known that, if you take an individual from their home setting and put them in a foreign environment such as the hospital, that new environment, that new diet, hospital food as opposed to home food, and so forth, can dramatically shift the microbiome. Our hypothesis is that, by keeping patients in the home environment, their familiar environment will be able to help preserve their microbiome, thus decreasing infections, graft-versus-host disease, and other complications. That’s actually the goal of our studies: to see if we can preserve the microbiome and decrease complications.
 

Dr. Henry: So how will you evaluate that? Are you doing fecal studies, patient culture studies? How are you testing that?

Dr. Sung: So we have a very broad biobank program where we collect stool on our transplantations, pretransplant, day 0, weekly for the first month. And then, in the case of our allogeneic transplant patients, day 60, 90, 180, and 365.

And we do that both in our home transplant patients as well as their matched controls on the phase 2 studies. And we also collect it on a lot of our other transplant patients as part of our biobanking programs and our observational studies to try to understand what’s going on during transplant and how to help improve transplant outcomes.
 

Dr. Henry: Do you have any results of that? You’re probably showing a difference.

Dr. Sung: We think so, on some preliminary results, but those were based on small numbers of patients. And we’re really hoping that these randomized clinical trials with the larger numbers of patients enrolled will help show that difference.

But getting back to your earlier question about cost, a case of graft-versus-host disease, grade 2 or higher, can add about $100,000 to the cost of care. So if you prevent one case of bad gut or liver graft-versus-host disease, those are your cost savings right there.

The randomized, phase 2 trial for allogeneic transplant patients, the primary endpoint is graft-versus-host disease. So we’re looking at the microbiome and those associations and the prevention of GVHD. For the randomized clinical trial in autologous transplant patients – with autologous stem cells, you’re not going to get GVHD – but we do hope to improve quality of life and long-term outcomes in those patients as well.
 

Dr. Henry: Wonderful. Well, Tony, I really want to thank you so much for talking with us today.

Dr. Sung: Thank you very much for this opportunity. And again, I also want to just thank everyone who’s been involved in these studies, the advanced practice providers and nurses who are caring for our patients at home, the study staff who have been involved. Particularly, I’d like to highlight the role of both Nelson Chao, who’s our division chief and my mentor who piloted and first developed home transplant, and Kristin Nichols, our research nurse who has really led the drive forward.

Dr. Sung and Dr. Henry have no relevant disclosures. The trials are funded by grants from the National Institutes of Health.

After initial promising interim results on Nov. 9, Pfizer and BioNTech today announced that their mRNA vaccine, in development to prevent COVID-19, is 95% effective.

Final analysis of the randomized, phase 3 study of more than 43,000 people yielded 170 confirmed cases of COVID-19 – with 162 positive cases in the placebo group versus 8 in the BNT162b2 vaccine group.

Researchers reported 10 severe cases of COVID-19 in the trial, 9 of which occurred in the placebo group.

The study was ethnically diverse, and results were consistent across gender and age groups, with a 94% efficacy reported among participants aged older than 65 years.

Pfizer plans to file for an emergency-use authorization with the Food and Drug Administration “within days,” having now met all the FDA data endpoints, according to a news release from the two companies.

The vaccine was well tolerated with no serious safety concerns, the company stated. Two grade 3 adverse events were reported – fatigue in 3.8% of participants and headache in 2%.

The 95% efficacy places the Pfizer vaccine in the same neighborhood as the interim results of the Moderna vaccine, reported at 94.5%. Both products are two-dose mRNA vaccines.

As of Nov. 13, of 43,661 total participants in the Pfizer vaccine phase 3 trial, 41,135 received a second dose. The final results are based on two outcomes measured 7 days after the second dose: vaccine efficacy in people without prior SARS-CoV-2 infection as well as a secondary outcome in people both with and without prior SARS-CoV-2 infection.

The 95% vaccine efficacy was statistically significant, compared with placebo (P < .0001).
 

‘Historic 8-month journey’

The BNT162b2 vaccine candidate is a joint effort between Pfizer and BioNTech. “The study results mark an important step in this historic 8-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” Albert Bourla, DVM, PhD, Pfizer chairman and CEO, said in a statement. “With hundreds of thousands of people around the globe infected every day, we urgently need to get a safe and effective vaccine to the world.”

Ugur Sahin, MD, PhD, cofounder and CEO of BioNTech, added, “we are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30-mcg dose, underscoring the power of BNT162 in providing early protection.”

The two companies expect to produce up to 50 million vaccine doses in 2020 for global distribution. Projections for 2021 include up to 1.3 billion doses.

The companies also designed temperature-controlled thermal shipping containers with dry ice to maintain the required, approximate –70° C (–94° F) conditions. Clinicians can use the containers as temporary storage units for up to 15 days by replacing the dry ice.

This article first appeared on Medscape.com.

After initial promising interim results on Nov. 9, Pfizer and BioNTech today announced that their mRNA vaccine, in development to prevent COVID-19, is 95% effective.

Final analysis of the randomized, phase 3 study of more than 43,000 people yielded 170 confirmed cases of COVID-19 – with 162 positive cases in the placebo group versus 8 in the BNT162b2 vaccine group.

Researchers reported 10 severe cases of COVID-19 in the trial, 9 of which occurred in the placebo group.

The study was ethnically diverse, and results were consistent across gender and age groups, with a 94% efficacy reported among participants aged older than 65 years.

Pfizer plans to file for an emergency-use authorization with the Food and Drug Administration “within days,” having now met all the FDA data endpoints, according to a news release from the two companies.

The vaccine was well tolerated with no serious safety concerns, the company stated. Two grade 3 adverse events were reported – fatigue in 3.8% of participants and headache in 2%.

The 95% efficacy places the Pfizer vaccine in the same neighborhood as the interim results of the Moderna vaccine, reported at 94.5%. Both products are two-dose mRNA vaccines.

As of Nov. 13, of 43,661 total participants in the Pfizer vaccine phase 3 trial, 41,135 received a second dose. The final results are based on two outcomes measured 7 days after the second dose: vaccine efficacy in people without prior SARS-CoV-2 infection as well as a secondary outcome in people both with and without prior SARS-CoV-2 infection.

The 95% vaccine efficacy was statistically significant, compared with placebo (P < .0001).
 

‘Historic 8-month journey’

The BNT162b2 vaccine candidate is a joint effort between Pfizer and BioNTech. “The study results mark an important step in this historic 8-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” Albert Bourla, DVM, PhD, Pfizer chairman and CEO, said in a statement. “With hundreds of thousands of people around the globe infected every day, we urgently need to get a safe and effective vaccine to the world.”

Ugur Sahin, MD, PhD, cofounder and CEO of BioNTech, added, “we are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30-mcg dose, underscoring the power of BNT162 in providing early protection.”

The two companies expect to produce up to 50 million vaccine doses in 2020 for global distribution. Projections for 2021 include up to 1.3 billion doses.

The companies also designed temperature-controlled thermal shipping containers with dry ice to maintain the required, approximate –70° C (–94° F) conditions. Clinicians can use the containers as temporary storage units for up to 15 days by replacing the dry ice.

This article first appeared on Medscape.com.

After initial promising interim results on Nov. 9, Pfizer and BioNTech today announced that their mRNA vaccine, in development to prevent COVID-19, is 95% effective.

Final analysis of the randomized, phase 3 study of more than 43,000 people yielded 170 confirmed cases of COVID-19 – with 162 positive cases in the placebo group versus 8 in the BNT162b2 vaccine group.

Researchers reported 10 severe cases of COVID-19 in the trial, 9 of which occurred in the placebo group.

The study was ethnically diverse, and results were consistent across gender and age groups, with a 94% efficacy reported among participants aged older than 65 years.

Pfizer plans to file for an emergency-use authorization with the Food and Drug Administration “within days,” having now met all the FDA data endpoints, according to a news release from the two companies.

The vaccine was well tolerated with no serious safety concerns, the company stated. Two grade 3 adverse events were reported – fatigue in 3.8% of participants and headache in 2%.

The 95% efficacy places the Pfizer vaccine in the same neighborhood as the interim results of the Moderna vaccine, reported at 94.5%. Both products are two-dose mRNA vaccines.

As of Nov. 13, of 43,661 total participants in the Pfizer vaccine phase 3 trial, 41,135 received a second dose. The final results are based on two outcomes measured 7 days after the second dose: vaccine efficacy in people without prior SARS-CoV-2 infection as well as a secondary outcome in people both with and without prior SARS-CoV-2 infection.

The 95% vaccine efficacy was statistically significant, compared with placebo (P < .0001).
 

‘Historic 8-month journey’

The BNT162b2 vaccine candidate is a joint effort between Pfizer and BioNTech. “The study results mark an important step in this historic 8-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” Albert Bourla, DVM, PhD, Pfizer chairman and CEO, said in a statement. “With hundreds of thousands of people around the globe infected every day, we urgently need to get a safe and effective vaccine to the world.”

Ugur Sahin, MD, PhD, cofounder and CEO of BioNTech, added, “we are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30-mcg dose, underscoring the power of BNT162 in providing early protection.”

The two companies expect to produce up to 50 million vaccine doses in 2020 for global distribution. Projections for 2021 include up to 1.3 billion doses.

The companies also designed temperature-controlled thermal shipping containers with dry ice to maintain the required, approximate –70° C (–94° F) conditions. Clinicians can use the containers as temporary storage units for up to 15 days by replacing the dry ice.

This article first appeared on Medscape.com.