A recent study published in the Journal of Hospital Medicine examined patient discharges from hospitals in Ontario, Canada, to determine if morning discharges were associated with positive outcomes. Some hospitalist programs have embraced discharge before noon (DBN) initiatives like those studied in the article.¹ Unfortunately, the researchers concluded that the Canadian DBNs did not positively impact hospital length of stay, readmissions, or mortality rates.

DBN has been a quality improvement target for hospitals hoping to improve throughput and free up scarce beds, while promoting patient safety by encouraging discharge as soon as patients are ready to leave. Yet other researchers have questioned its actual impact on quality metrics. One author called DBN’s purported impact an “urban legend,”² while a JHM editorial accompanying the Ontario study noted, “Hospitals are delicate organisms; a singular focus on one metric will undoubtedly impact others.”³

Might DBN be an artificial target that doesn’t actually enhance throughput, but leads instead to unintended consequences, such as patients being held over for an additional night in the hospital, rather than being discharged when they are ready to go on the afternoon before, in order to boost DBN rates? A perennial debate in hospital medicine is likely to be reignited by the new findings.
 

‘No significant overall association’

Quality improvement initiatives targeting morning discharges have included stakeholder meetings, incentives programs, discharge-centered breakfast programs, and creation of deadlines for discharge orders, the new study’s authors noted. Although these initiatives have gained support, critics have suggested that their supporting evidence is not robust.

The Canadian researchers retrospectively reviewed all patient admissions to general internal medicine services (GIMs) – largely similar to hospital medicine services in the United States – at seven hospitals in Toronto and Mississauga over a 7-year period ending Oct. 31, 2017, counting all of these patients who were discharged alive between 8 a.m. and noon. DBN averaged 19% of total live discharges across the diverse hospitals, with their diverse discharge practices.

But they found no significant overall association between morning discharge and hospital or emergency department length of stay. “Our findings suggest that increasing the number of morning discharges alone is unlikely to substantially improve patient throughput in GIM, but further research is needed to determine the effectiveness of specific interventions,” they concluded.

“We used a very narrow lens, looking specifically at throughput for the hospitals and emergency departments and whether DBN makes it more efficient,” said corresponding author Amol Verma, MD, MPhil, FRCPC, clinician-scientist at St. Michael’s Hospital, University of Toronto, in a recent interview. “What we found was that, on days when more patients are discharged in the morning, patients do not flow more quickly through the hospital. That suggests that increasing morning discharges is unlikely to make a difference.”
 

What does DBN really mean?

The semantics of DBN deserve further exploration. Is DBN about the actual hour of discharge, or the time when the hospitalist signs a discharge order – which may be well before the patient actually gets a wheelchair ride down to the hospital’s front doors? And if DBN is an organized program promoting morning discharges, how is it incentivized or otherwise rewarded?

Other factors, such as arrival of medications from the pharmacy or results from clinical tests, access to an ambulance if needed, transport to the front door, and bed cleaning will impact how quickly a doctor’s discharge orders get acted upon – and how quickly the newly emptied bed is available for the next occupant.

The clinician’s views on discharge practices may diverge from hospital administrator or health system perspectives, with its imperatives for efficient throughput in order to bring in more patients, Dr. Verma said. The hospitalist is also concerned about whether the patient feels ready to go home. “We can all agree that patients should leave the hospital as soon as they are medically able to do so,” he said. Longer hospital stays are associated with increased rates of hospital-acquired infections and other iatrogenic complications.

But there is not agreement on the components of a safe discharge – or on the other dimensions of effective patient flow and transitions of care. How do we optimize treatments initiated in the hospital? Does the patient need one more CAT scan? And what about the concerns of patient-centered care? Does the patient have a caregiver able to help them when they get home? There is a lot of uncertainty, Dr. Verma said. “These kinds of decisions have to get made many times every day by hospitalists,” he noted.

“We find ourselves trying to mirror the ebbs and flows of the emergency department with what’s happening in the hospital,” said Venkat Gundareddy, MBBS, MPH, associate director of the division of hospital medicine at Johns Hopkins Medicine in Baltimore. “The majority of hospital discharges happen during business hours, but the emergency department doesn’t stop admitting overnight, thus creating a throughput challenge.” Discharges are also based on clinical outcomes and on patients transferring to other facilities that prefer patients to arrive earlier in the day.

“Hospitalists may not fully appreciate these dynamics, because we’re siloed on our units,” Dr. Gundareddy said. “There is a subset of patients who would fit the bill for early discharge, but other patients come into the hospital with greater complexities, and a need for more coordination. Their discharges are harder to predict, although it gets clearer as their care progresses.”

The hospitals included in the Ontario study are at 90% -100% capacity, so their flexibility is constrained and throughput is a critical issue, Dr. Verma said. “But if you start with the target of more efficient throughput, there is no logical or practical reason to assume that discharge before noon would help. If we believe someone is ready for discharge based on physiologic changes, their response to treatment, and the conclusion of medical investigations, none of these conform to the clock. It’s equally likely the patient achieves them in the afternoon or evening.”

Other views on morning discharge

An alternative perspective comes from New York University’s Langone Medical Center, which has published positive results, including earlier subsequent arrivals to the inpatient unit from the emergency department, from increasing its hospital’s DBN rate.⁴

The hospital has continued to encourage morning discharges, which have consistently run 35%-40% or more of total discharges on two acute inpatient units at Langone’s Tisch Hospital. A previous study described the multidisciplinary intervention that resulted in a statistically significant increase in DBN – from 11% to 38% in the first 13 months – while significantly reducing high-frequency admission peaks.⁵

“We’ve been doing DBN for a number of years,” said Benjamin Wertheimer, MD, a hospitalist at Langone Medical Center and one of the studies’ authors. It is an achievable – and sustainable – goal. “Many hospitals around the country have problems with the flow of patients. Many hospitals are full – even before accounting for the COVID pandemic.” There is good evidence that, for a patient who no longer requires hospitalization, getting them out as early as possible, with a safe plan for their discharge, is a good thing, he said. “We see DBN as an important operational metric.”

If the necessary work is done correctly on the afternoon before the discharge, then a DBN approach can push communication, coordination, and advance planning, Dr Wertheimer said. Otherwise, essential discharge tasks may lag until the last minute. “We try to put the pieces in place the day before through a better planned process. But it should never be that DBN takes precedence over when the patient is safely ready to go,” he said.

“Our true measure of success would be how well we are preparing, communicating, putting safe plans into place,” he added. “DBN does not in and of itself answer all the safety and quality concerns. We set priorities around specific quality targets. DBN is just one of our operational and safety measures.”

The DBN intervention at Langone started with a multidisciplinary kickoff event in which all team members received education on its importance, a clear description of roles in the DBN process, and a corresponding checklist of daily responsibilities. The checklist was utilized at newly implemented afternoon interdisciplinary rounds, scripted to identify next-day DBNs, and make sure everything is in place for them, he explained.

“We provide daily feedback to floor staff on the DBN percentage, celebrate success, and offer real-time opportunities for case review,” Dr. Wertheimer said. “We have been careful about how we message this goal. Quality and safety come first, and we want to be prepared for discharge in advance of when the patient is ready.”
 

A boost for discharges

Mark Williams, MD, MHM, recently appointed chief of hospital medicine at Washington University School of Medicine in St. Louis, and a principal investigator for Project BOOST (Better Outcomes by Optimizing Safe Transitions), SHM’s quality improvement mentoring initiative aimed at helping hospitals improve care transitions, said that debates about DBN have gone on for a long time in hospital medicine.

“Around 2002, consultants told the CEO of a community hospital affiliated with Emory Healthcare that if our hospitalists could discharge patients before noon it would improve throughput,” he recalled. The consultants came from the hospitality industry, where DBN is easier to achieve.

But in hospital medicine, he said, “We use the whole day of the discharge in delivering care. I said to the CEO, ‘I can get you 100% discharge before noon – I’ll just hold the patients overnight,’” he explained. “In our initial experience, we pushed DBN up to about 10% -15%, and it opened up a few beds, which rapidly filled.”

Project BOOST encouraged the goal of getting patients ready to go out as soon as they were clinically ready, but did not advocate specifically for DBN, Dr. Williams said. “The problem is that hospital throughput starts to gum up when occupancy goes over 80% or 90%, and many academic medical centers regularly reach occupancy rates greater than 100%, particularly in the afternoon.” The deluge of patients includes transfers from other hospitals, postsurgical patients, and admissions from the emergency department.

“Boarding in the ED is a real issue,” he said. “Right now, it’s a crisis of overoccupancy, and the problem is that the pipeline is pouring patients into the system faster than they can be discharged.”

Dr. Williams believes there needs to be bigger thinking about these issues. Could hospitals, health systems, and hospitalists practice more preventive medicine so that some of these patients don’t need to come to the hospital? “Can you better address high blood pressure to prevent strokes and make sure patients with heart disease risk factors are enrolled in exercise and nutrition programs? What about access to healthy foods and the other social determinants of health? What if we provided adequate, consistent housing and transportation to medical visits?” he wondered.

Hospital at home programs may also offer some relief, he said. “If suddenly there weren’t so many emergency room visits by patients who need to get admitted, we’d have enough beds in the hospital.”
 

A more holistic view

John Nelson, MD, MHM, hospital medicine pioneer and management consultant, has been studying hospital throughput and policies to improve it for a long time. His 2010 column in The Hospitalist, “The Earlier the Better,” said attaching a financial incentive for hospitalists to discharge patients by a preset hour has produced mixed results.⁶ But Dr. Nelson offered some easy steps hospitalists can take to maximize earlier discharges, including to write “probable discharge tomorrow” as an order in the patient’s medical record.

The afternoon before a planned discharge, the hospitalist could talk to a patient’s family members about the discharge plan and order any outstanding tests to be done that evening to be ready for morning rounds – which he suggested should start by 7:00 a.m. The hospitalist could dictate the discharge summary the afternoon before. Even if a discharge can’t proceed as planned, the time isn’t necessarily wasted.

In a recent interview, Dr. Nelson noted that the movement to reduce average length of stay in the hospital has complicated the discharge picture by reducing a hospital’s flexibility. But he added that it’s still worth tracking and collecting data on discharge times, and to keep the conversation going. “Just don’t lose sight of the real goal, which is not DBN but optimal length-of-stay management,” he said.

Dr. Gundareddy said that, as his group has dealt with these issues, some steps have emerged to help manage discharges and throughput. “We didn’t have case management and social work services over the weekend, but when we added that support, it changed how our Mondays went.”

He encourages hospitalists to focus on the actual processes that create bottlenecks preventing throughput. “A good example of effective restructuring is lab testing. It’s amazing to think that you could have lab test results available for 7:00 a.m. rounds. There are areas that deserve more attention and more research regarding DBN. What is the impact of discharge before noon programs on the patients who aren’t being planned for discharge that day? Do they get neglected? I feel that happens sometimes.”

The COVID pandemic has further complicated these questions, Dr. Gundareddy said. “Early on in the pandemic, we were unsure how things were going with discharges, since all of the focus was on the COVID crisis. A lot of outpatient and surgical services came to a standstill, and there weren’t enough of the right kinds of beds for COVID patients. It was hard to align staff appropriately with the new clinical goals and to train them during the crisis.” Now, patients who delayed care during the pandemic are turning up at the hospital with greater acuity.

As with all incentives, DBN can have unintended consequences – especially if you monetize the practice, Dr. Verma said. “Most hospitalists are already working so hard – making so many decisions every day. These incentives could push decisions that aren’t in anybody’s best interests.”

Various groups have created comprehensive packages of protocols for improving transitions of care, he said. Organized programs to maximize efficiency of transitions and patient flow, including Project BOOST and Project RED (Re-Engineered Discharge) at Boston University Medical Center, are important sources of tools and resources. “But we should stop flogging hospitalists to discharge patients before noon,” Dr. Verma said, “Discharge is more complex than that. Instead, we should work to improve discharges in more holistic ways.”
 

References

1. Kirubarajan A et al. Morning discharges and patient length of stay in inpatient general internal medicine. J Hosp Med. 2021 Jun;16(6):333-8. doi: 10.12788/jhm.3605.

2. Shine D. Discharge before noon: An urban legend. Am J Med. 2015 May;128(5):445-6. doi:10.1016/j.amjmed.2014.12.011.

3. Zorian A et al. Discharge by noon: Toward a better understanding of benefits and costs. J Hosp Med. 2021 Jun;16(6):384. doi: 10.12788/jhm.3613.

4. Wertheimer B et al. Discharge before noon: Effect on throughput and sustainability. J Hosp Med. 2015 Oct;10(10):664-9. doi: 10.1002/jhm.2412.

5. Wertheimer B et al. Discharge before noon: an achievable hospital goal. J Hosp Med. 2014 Apr;9(4):210-4. doi: 10.1002/jhm.2154.

6. Nelson J. The earlier, the better. The Hospitalist. 2010 May.

A recent study published in the Journal of Hospital Medicine examined patient discharges from hospitals in Ontario, Canada, to determine if morning discharges were associated with positive outcomes. Some hospitalist programs have embraced discharge before noon (DBN) initiatives like those studied in the article.¹ Unfortunately, the researchers concluded that the Canadian DBNs did not positively impact hospital length of stay, readmissions, or mortality rates.

DBN has been a quality improvement target for hospitals hoping to improve throughput and free up scarce beds, while promoting patient safety by encouraging discharge as soon as patients are ready to leave. Yet other researchers have questioned its actual impact on quality metrics. One author called DBN’s purported impact an “urban legend,”² while a JHM editorial accompanying the Ontario study noted, “Hospitals are delicate organisms; a singular focus on one metric will undoubtedly impact others.”³

Might DBN be an artificial target that doesn’t actually enhance throughput, but leads instead to unintended consequences, such as patients being held over for an additional night in the hospital, rather than being discharged when they are ready to go on the afternoon before, in order to boost DBN rates? A perennial debate in hospital medicine is likely to be reignited by the new findings.
 

‘No significant overall association’

Quality improvement initiatives targeting morning discharges have included stakeholder meetings, incentives programs, discharge-centered breakfast programs, and creation of deadlines for discharge orders, the new study’s authors noted. Although these initiatives have gained support, critics have suggested that their supporting evidence is not robust.

The Canadian researchers retrospectively reviewed all patient admissions to general internal medicine services (GIMs) – largely similar to hospital medicine services in the United States – at seven hospitals in Toronto and Mississauga over a 7-year period ending Oct. 31, 2017, counting all of these patients who were discharged alive between 8 a.m. and noon. DBN averaged 19% of total live discharges across the diverse hospitals, with their diverse discharge practices.

But they found no significant overall association between morning discharge and hospital or emergency department length of stay. “Our findings suggest that increasing the number of morning discharges alone is unlikely to substantially improve patient throughput in GIM, but further research is needed to determine the effectiveness of specific interventions,” they concluded.

“We used a very narrow lens, looking specifically at throughput for the hospitals and emergency departments and whether DBN makes it more efficient,” said corresponding author Amol Verma, MD, MPhil, FRCPC, clinician-scientist at St. Michael’s Hospital, University of Toronto, in a recent interview. “What we found was that, on days when more patients are discharged in the morning, patients do not flow more quickly through the hospital. That suggests that increasing morning discharges is unlikely to make a difference.”
 

What does DBN really mean?

The semantics of DBN deserve further exploration. Is DBN about the actual hour of discharge, or the time when the hospitalist signs a discharge order – which may be well before the patient actually gets a wheelchair ride down to the hospital’s front doors? And if DBN is an organized program promoting morning discharges, how is it incentivized or otherwise rewarded?

Other factors, such as arrival of medications from the pharmacy or results from clinical tests, access to an ambulance if needed, transport to the front door, and bed cleaning will impact how quickly a doctor’s discharge orders get acted upon – and how quickly the newly emptied bed is available for the next occupant.

The clinician’s views on discharge practices may diverge from hospital administrator or health system perspectives, with its imperatives for efficient throughput in order to bring in more patients, Dr. Verma said. The hospitalist is also concerned about whether the patient feels ready to go home. “We can all agree that patients should leave the hospital as soon as they are medically able to do so,” he said. Longer hospital stays are associated with increased rates of hospital-acquired infections and other iatrogenic complications.

But there is not agreement on the components of a safe discharge – or on the other dimensions of effective patient flow and transitions of care. How do we optimize treatments initiated in the hospital? Does the patient need one more CAT scan? And what about the concerns of patient-centered care? Does the patient have a caregiver able to help them when they get home? There is a lot of uncertainty, Dr. Verma said. “These kinds of decisions have to get made many times every day by hospitalists,” he noted.

“We find ourselves trying to mirror the ebbs and flows of the emergency department with what’s happening in the hospital,” said Venkat Gundareddy, MBBS, MPH, associate director of the division of hospital medicine at Johns Hopkins Medicine in Baltimore. “The majority of hospital discharges happen during business hours, but the emergency department doesn’t stop admitting overnight, thus creating a throughput challenge.” Discharges are also based on clinical outcomes and on patients transferring to other facilities that prefer patients to arrive earlier in the day.

“Hospitalists may not fully appreciate these dynamics, because we’re siloed on our units,” Dr. Gundareddy said. “There is a subset of patients who would fit the bill for early discharge, but other patients come into the hospital with greater complexities, and a need for more coordination. Their discharges are harder to predict, although it gets clearer as their care progresses.”

The hospitals included in the Ontario study are at 90% -100% capacity, so their flexibility is constrained and throughput is a critical issue, Dr. Verma said. “But if you start with the target of more efficient throughput, there is no logical or practical reason to assume that discharge before noon would help. If we believe someone is ready for discharge based on physiologic changes, their response to treatment, and the conclusion of medical investigations, none of these conform to the clock. It’s equally likely the patient achieves them in the afternoon or evening.”

Other views on morning discharge

An alternative perspective comes from New York University’s Langone Medical Center, which has published positive results, including earlier subsequent arrivals to the inpatient unit from the emergency department, from increasing its hospital’s DBN rate.⁴

The hospital has continued to encourage morning discharges, which have consistently run 35%-40% or more of total discharges on two acute inpatient units at Langone’s Tisch Hospital. A previous study described the multidisciplinary intervention that resulted in a statistically significant increase in DBN – from 11% to 38% in the first 13 months – while significantly reducing high-frequency admission peaks.⁵

“We’ve been doing DBN for a number of years,” said Benjamin Wertheimer, MD, a hospitalist at Langone Medical Center and one of the studies’ authors. It is an achievable – and sustainable – goal. “Many hospitals around the country have problems with the flow of patients. Many hospitals are full – even before accounting for the COVID pandemic.” There is good evidence that, for a patient who no longer requires hospitalization, getting them out as early as possible, with a safe plan for their discharge, is a good thing, he said. “We see DBN as an important operational metric.”

If the necessary work is done correctly on the afternoon before the discharge, then a DBN approach can push communication, coordination, and advance planning, Dr Wertheimer said. Otherwise, essential discharge tasks may lag until the last minute. “We try to put the pieces in place the day before through a better planned process. But it should never be that DBN takes precedence over when the patient is safely ready to go,” he said.

“Our true measure of success would be how well we are preparing, communicating, putting safe plans into place,” he added. “DBN does not in and of itself answer all the safety and quality concerns. We set priorities around specific quality targets. DBN is just one of our operational and safety measures.”

The DBN intervention at Langone started with a multidisciplinary kickoff event in which all team members received education on its importance, a clear description of roles in the DBN process, and a corresponding checklist of daily responsibilities. The checklist was utilized at newly implemented afternoon interdisciplinary rounds, scripted to identify next-day DBNs, and make sure everything is in place for them, he explained.

“We provide daily feedback to floor staff on the DBN percentage, celebrate success, and offer real-time opportunities for case review,” Dr. Wertheimer said. “We have been careful about how we message this goal. Quality and safety come first, and we want to be prepared for discharge in advance of when the patient is ready.”
 

A boost for discharges

Mark Williams, MD, MHM, recently appointed chief of hospital medicine at Washington University School of Medicine in St. Louis, and a principal investigator for Project BOOST (Better Outcomes by Optimizing Safe Transitions), SHM’s quality improvement mentoring initiative aimed at helping hospitals improve care transitions, said that debates about DBN have gone on for a long time in hospital medicine.

“Around 2002, consultants told the CEO of a community hospital affiliated with Emory Healthcare that if our hospitalists could discharge patients before noon it would improve throughput,” he recalled. The consultants came from the hospitality industry, where DBN is easier to achieve.

But in hospital medicine, he said, “We use the whole day of the discharge in delivering care. I said to the CEO, ‘I can get you 100% discharge before noon – I’ll just hold the patients overnight,’” he explained. “In our initial experience, we pushed DBN up to about 10% -15%, and it opened up a few beds, which rapidly filled.”

Project BOOST encouraged the goal of getting patients ready to go out as soon as they were clinically ready, but did not advocate specifically for DBN, Dr. Williams said. “The problem is that hospital throughput starts to gum up when occupancy goes over 80% or 90%, and many academic medical centers regularly reach occupancy rates greater than 100%, particularly in the afternoon.” The deluge of patients includes transfers from other hospitals, postsurgical patients, and admissions from the emergency department.

“Boarding in the ED is a real issue,” he said. “Right now, it’s a crisis of overoccupancy, and the problem is that the pipeline is pouring patients into the system faster than they can be discharged.”

Dr. Williams believes there needs to be bigger thinking about these issues. Could hospitals, health systems, and hospitalists practice more preventive medicine so that some of these patients don’t need to come to the hospital? “Can you better address high blood pressure to prevent strokes and make sure patients with heart disease risk factors are enrolled in exercise and nutrition programs? What about access to healthy foods and the other social determinants of health? What if we provided adequate, consistent housing and transportation to medical visits?” he wondered.

Hospital at home programs may also offer some relief, he said. “If suddenly there weren’t so many emergency room visits by patients who need to get admitted, we’d have enough beds in the hospital.”
 

A more holistic view

John Nelson, MD, MHM, hospital medicine pioneer and management consultant, has been studying hospital throughput and policies to improve it for a long time. His 2010 column in The Hospitalist, “The Earlier the Better,” said attaching a financial incentive for hospitalists to discharge patients by a preset hour has produced mixed results.⁶ But Dr. Nelson offered some easy steps hospitalists can take to maximize earlier discharges, including to write “probable discharge tomorrow” as an order in the patient’s medical record.

The afternoon before a planned discharge, the hospitalist could talk to a patient’s family members about the discharge plan and order any outstanding tests to be done that evening to be ready for morning rounds – which he suggested should start by 7:00 a.m. The hospitalist could dictate the discharge summary the afternoon before. Even if a discharge can’t proceed as planned, the time isn’t necessarily wasted.

In a recent interview, Dr. Nelson noted that the movement to reduce average length of stay in the hospital has complicated the discharge picture by reducing a hospital’s flexibility. But he added that it’s still worth tracking and collecting data on discharge times, and to keep the conversation going. “Just don’t lose sight of the real goal, which is not DBN but optimal length-of-stay management,” he said.

Dr. Gundareddy said that, as his group has dealt with these issues, some steps have emerged to help manage discharges and throughput. “We didn’t have case management and social work services over the weekend, but when we added that support, it changed how our Mondays went.”

He encourages hospitalists to focus on the actual processes that create bottlenecks preventing throughput. “A good example of effective restructuring is lab testing. It’s amazing to think that you could have lab test results available for 7:00 a.m. rounds. There are areas that deserve more attention and more research regarding DBN. What is the impact of discharge before noon programs on the patients who aren’t being planned for discharge that day? Do they get neglected? I feel that happens sometimes.”

The COVID pandemic has further complicated these questions, Dr. Gundareddy said. “Early on in the pandemic, we were unsure how things were going with discharges, since all of the focus was on the COVID crisis. A lot of outpatient and surgical services came to a standstill, and there weren’t enough of the right kinds of beds for COVID patients. It was hard to align staff appropriately with the new clinical goals and to train them during the crisis.” Now, patients who delayed care during the pandemic are turning up at the hospital with greater acuity.

As with all incentives, DBN can have unintended consequences – especially if you monetize the practice, Dr. Verma said. “Most hospitalists are already working so hard – making so many decisions every day. These incentives could push decisions that aren’t in anybody’s best interests.”

Various groups have created comprehensive packages of protocols for improving transitions of care, he said. Organized programs to maximize efficiency of transitions and patient flow, including Project BOOST and Project RED (Re-Engineered Discharge) at Boston University Medical Center, are important sources of tools and resources. “But we should stop flogging hospitalists to discharge patients before noon,” Dr. Verma said, “Discharge is more complex than that. Instead, we should work to improve discharges in more holistic ways.”
 

References

1. Kirubarajan A et al. Morning discharges and patient length of stay in inpatient general internal medicine. J Hosp Med. 2021 Jun;16(6):333-8. doi: 10.12788/jhm.3605.

2. Shine D. Discharge before noon: An urban legend. Am J Med. 2015 May;128(5):445-6. doi:10.1016/j.amjmed.2014.12.011.

3. Zorian A et al. Discharge by noon: Toward a better understanding of benefits and costs. J Hosp Med. 2021 Jun;16(6):384. doi: 10.12788/jhm.3613.

4. Wertheimer B et al. Discharge before noon: Effect on throughput and sustainability. J Hosp Med. 2015 Oct;10(10):664-9. doi: 10.1002/jhm.2412.

5. Wertheimer B et al. Discharge before noon: an achievable hospital goal. J Hosp Med. 2014 Apr;9(4):210-4. doi: 10.1002/jhm.2154.

6. Nelson J. The earlier, the better. The Hospitalist. 2010 May.

A recent study published in the Journal of Hospital Medicine examined patient discharges from hospitals in Ontario, Canada, to determine if morning discharges were associated with positive outcomes. Some hospitalist programs have embraced discharge before noon (DBN) initiatives like those studied in the article.¹ Unfortunately, the researchers concluded that the Canadian DBNs did not positively impact hospital length of stay, readmissions, or mortality rates.

DBN has been a quality improvement target for hospitals hoping to improve throughput and free up scarce beds, while promoting patient safety by encouraging discharge as soon as patients are ready to leave. Yet other researchers have questioned its actual impact on quality metrics. One author called DBN’s purported impact an “urban legend,”² while a JHM editorial accompanying the Ontario study noted, “Hospitals are delicate organisms; a singular focus on one metric will undoubtedly impact others.”³

Might DBN be an artificial target that doesn’t actually enhance throughput, but leads instead to unintended consequences, such as patients being held over for an additional night in the hospital, rather than being discharged when they are ready to go on the afternoon before, in order to boost DBN rates? A perennial debate in hospital medicine is likely to be reignited by the new findings.
 

‘No significant overall association’

Quality improvement initiatives targeting morning discharges have included stakeholder meetings, incentives programs, discharge-centered breakfast programs, and creation of deadlines for discharge orders, the new study’s authors noted. Although these initiatives have gained support, critics have suggested that their supporting evidence is not robust.

The Canadian researchers retrospectively reviewed all patient admissions to general internal medicine services (GIMs) – largely similar to hospital medicine services in the United States – at seven hospitals in Toronto and Mississauga over a 7-year period ending Oct. 31, 2017, counting all of these patients who were discharged alive between 8 a.m. and noon. DBN averaged 19% of total live discharges across the diverse hospitals, with their diverse discharge practices.

But they found no significant overall association between morning discharge and hospital or emergency department length of stay. “Our findings suggest that increasing the number of morning discharges alone is unlikely to substantially improve patient throughput in GIM, but further research is needed to determine the effectiveness of specific interventions,” they concluded.

“We used a very narrow lens, looking specifically at throughput for the hospitals and emergency departments and whether DBN makes it more efficient,” said corresponding author Amol Verma, MD, MPhil, FRCPC, clinician-scientist at St. Michael’s Hospital, University of Toronto, in a recent interview. “What we found was that, on days when more patients are discharged in the morning, patients do not flow more quickly through the hospital. That suggests that increasing morning discharges is unlikely to make a difference.”
 

What does DBN really mean?

The semantics of DBN deserve further exploration. Is DBN about the actual hour of discharge, or the time when the hospitalist signs a discharge order – which may be well before the patient actually gets a wheelchair ride down to the hospital’s front doors? And if DBN is an organized program promoting morning discharges, how is it incentivized or otherwise rewarded?

Other factors, such as arrival of medications from the pharmacy or results from clinical tests, access to an ambulance if needed, transport to the front door, and bed cleaning will impact how quickly a doctor’s discharge orders get acted upon – and how quickly the newly emptied bed is available for the next occupant.

The clinician’s views on discharge practices may diverge from hospital administrator or health system perspectives, with its imperatives for efficient throughput in order to bring in more patients, Dr. Verma said. The hospitalist is also concerned about whether the patient feels ready to go home. “We can all agree that patients should leave the hospital as soon as they are medically able to do so,” he said. Longer hospital stays are associated with increased rates of hospital-acquired infections and other iatrogenic complications.

But there is not agreement on the components of a safe discharge – or on the other dimensions of effective patient flow and transitions of care. How do we optimize treatments initiated in the hospital? Does the patient need one more CAT scan? And what about the concerns of patient-centered care? Does the patient have a caregiver able to help them when they get home? There is a lot of uncertainty, Dr. Verma said. “These kinds of decisions have to get made many times every day by hospitalists,” he noted.

“We find ourselves trying to mirror the ebbs and flows of the emergency department with what’s happening in the hospital,” said Venkat Gundareddy, MBBS, MPH, associate director of the division of hospital medicine at Johns Hopkins Medicine in Baltimore. “The majority of hospital discharges happen during business hours, but the emergency department doesn’t stop admitting overnight, thus creating a throughput challenge.” Discharges are also based on clinical outcomes and on patients transferring to other facilities that prefer patients to arrive earlier in the day.

“Hospitalists may not fully appreciate these dynamics, because we’re siloed on our units,” Dr. Gundareddy said. “There is a subset of patients who would fit the bill for early discharge, but other patients come into the hospital with greater complexities, and a need for more coordination. Their discharges are harder to predict, although it gets clearer as their care progresses.”

The hospitals included in the Ontario study are at 90% -100% capacity, so their flexibility is constrained and throughput is a critical issue, Dr. Verma said. “But if you start with the target of more efficient throughput, there is no logical or practical reason to assume that discharge before noon would help. If we believe someone is ready for discharge based on physiologic changes, their response to treatment, and the conclusion of medical investigations, none of these conform to the clock. It’s equally likely the patient achieves them in the afternoon or evening.”

Other views on morning discharge

An alternative perspective comes from New York University’s Langone Medical Center, which has published positive results, including earlier subsequent arrivals to the inpatient unit from the emergency department, from increasing its hospital’s DBN rate.⁴

The hospital has continued to encourage morning discharges, which have consistently run 35%-40% or more of total discharges on two acute inpatient units at Langone’s Tisch Hospital. A previous study described the multidisciplinary intervention that resulted in a statistically significant increase in DBN – from 11% to 38% in the first 13 months – while significantly reducing high-frequency admission peaks.⁵

“We’ve been doing DBN for a number of years,” said Benjamin Wertheimer, MD, a hospitalist at Langone Medical Center and one of the studies’ authors. It is an achievable – and sustainable – goal. “Many hospitals around the country have problems with the flow of patients. Many hospitals are full – even before accounting for the COVID pandemic.” There is good evidence that, for a patient who no longer requires hospitalization, getting them out as early as possible, with a safe plan for their discharge, is a good thing, he said. “We see DBN as an important operational metric.”

If the necessary work is done correctly on the afternoon before the discharge, then a DBN approach can push communication, coordination, and advance planning, Dr Wertheimer said. Otherwise, essential discharge tasks may lag until the last minute. “We try to put the pieces in place the day before through a better planned process. But it should never be that DBN takes precedence over when the patient is safely ready to go,” he said.

“Our true measure of success would be how well we are preparing, communicating, putting safe plans into place,” he added. “DBN does not in and of itself answer all the safety and quality concerns. We set priorities around specific quality targets. DBN is just one of our operational and safety measures.”

The DBN intervention at Langone started with a multidisciplinary kickoff event in which all team members received education on its importance, a clear description of roles in the DBN process, and a corresponding checklist of daily responsibilities. The checklist was utilized at newly implemented afternoon interdisciplinary rounds, scripted to identify next-day DBNs, and make sure everything is in place for them, he explained.

“We provide daily feedback to floor staff on the DBN percentage, celebrate success, and offer real-time opportunities for case review,” Dr. Wertheimer said. “We have been careful about how we message this goal. Quality and safety come first, and we want to be prepared for discharge in advance of when the patient is ready.”
 

A boost for discharges

Mark Williams, MD, MHM, recently appointed chief of hospital medicine at Washington University School of Medicine in St. Louis, and a principal investigator for Project BOOST (Better Outcomes by Optimizing Safe Transitions), SHM’s quality improvement mentoring initiative aimed at helping hospitals improve care transitions, said that debates about DBN have gone on for a long time in hospital medicine.

“Around 2002, consultants told the CEO of a community hospital affiliated with Emory Healthcare that if our hospitalists could discharge patients before noon it would improve throughput,” he recalled. The consultants came from the hospitality industry, where DBN is easier to achieve.

But in hospital medicine, he said, “We use the whole day of the discharge in delivering care. I said to the CEO, ‘I can get you 100% discharge before noon – I’ll just hold the patients overnight,’” he explained. “In our initial experience, we pushed DBN up to about 10% -15%, and it opened up a few beds, which rapidly filled.”

Project BOOST encouraged the goal of getting patients ready to go out as soon as they were clinically ready, but did not advocate specifically for DBN, Dr. Williams said. “The problem is that hospital throughput starts to gum up when occupancy goes over 80% or 90%, and many academic medical centers regularly reach occupancy rates greater than 100%, particularly in the afternoon.” The deluge of patients includes transfers from other hospitals, postsurgical patients, and admissions from the emergency department.

“Boarding in the ED is a real issue,” he said. “Right now, it’s a crisis of overoccupancy, and the problem is that the pipeline is pouring patients into the system faster than they can be discharged.”

Dr. Williams believes there needs to be bigger thinking about these issues. Could hospitals, health systems, and hospitalists practice more preventive medicine so that some of these patients don’t need to come to the hospital? “Can you better address high blood pressure to prevent strokes and make sure patients with heart disease risk factors are enrolled in exercise and nutrition programs? What about access to healthy foods and the other social determinants of health? What if we provided adequate, consistent housing and transportation to medical visits?” he wondered.

Hospital at home programs may also offer some relief, he said. “If suddenly there weren’t so many emergency room visits by patients who need to get admitted, we’d have enough beds in the hospital.”
 

A more holistic view

John Nelson, MD, MHM, hospital medicine pioneer and management consultant, has been studying hospital throughput and policies to improve it for a long time. His 2010 column in The Hospitalist, “The Earlier the Better,” said attaching a financial incentive for hospitalists to discharge patients by a preset hour has produced mixed results.⁶ But Dr. Nelson offered some easy steps hospitalists can take to maximize earlier discharges, including to write “probable discharge tomorrow” as an order in the patient’s medical record.

The afternoon before a planned discharge, the hospitalist could talk to a patient’s family members about the discharge plan and order any outstanding tests to be done that evening to be ready for morning rounds – which he suggested should start by 7:00 a.m. The hospitalist could dictate the discharge summary the afternoon before. Even if a discharge can’t proceed as planned, the time isn’t necessarily wasted.

In a recent interview, Dr. Nelson noted that the movement to reduce average length of stay in the hospital has complicated the discharge picture by reducing a hospital’s flexibility. But he added that it’s still worth tracking and collecting data on discharge times, and to keep the conversation going. “Just don’t lose sight of the real goal, which is not DBN but optimal length-of-stay management,” he said.

Dr. Gundareddy said that, as his group has dealt with these issues, some steps have emerged to help manage discharges and throughput. “We didn’t have case management and social work services over the weekend, but when we added that support, it changed how our Mondays went.”

He encourages hospitalists to focus on the actual processes that create bottlenecks preventing throughput. “A good example of effective restructuring is lab testing. It’s amazing to think that you could have lab test results available for 7:00 a.m. rounds. There are areas that deserve more attention and more research regarding DBN. What is the impact of discharge before noon programs on the patients who aren’t being planned for discharge that day? Do they get neglected? I feel that happens sometimes.”

The COVID pandemic has further complicated these questions, Dr. Gundareddy said. “Early on in the pandemic, we were unsure how things were going with discharges, since all of the focus was on the COVID crisis. A lot of outpatient and surgical services came to a standstill, and there weren’t enough of the right kinds of beds for COVID patients. It was hard to align staff appropriately with the new clinical goals and to train them during the crisis.” Now, patients who delayed care during the pandemic are turning up at the hospital with greater acuity.

As with all incentives, DBN can have unintended consequences – especially if you monetize the practice, Dr. Verma said. “Most hospitalists are already working so hard – making so many decisions every day. These incentives could push decisions that aren’t in anybody’s best interests.”

Various groups have created comprehensive packages of protocols for improving transitions of care, he said. Organized programs to maximize efficiency of transitions and patient flow, including Project BOOST and Project RED (Re-Engineered Discharge) at Boston University Medical Center, are important sources of tools and resources. “But we should stop flogging hospitalists to discharge patients before noon,” Dr. Verma said, “Discharge is more complex than that. Instead, we should work to improve discharges in more holistic ways.”
 

References

1. Kirubarajan A et al. Morning discharges and patient length of stay in inpatient general internal medicine. J Hosp Med. 2021 Jun;16(6):333-8. doi: 10.12788/jhm.3605.

2. Shine D. Discharge before noon: An urban legend. Am J Med. 2015 May;128(5):445-6. doi:10.1016/j.amjmed.2014.12.011.

3. Zorian A et al. Discharge by noon: Toward a better understanding of benefits and costs. J Hosp Med. 2021 Jun;16(6):384. doi: 10.12788/jhm.3613.

4. Wertheimer B et al. Discharge before noon: Effect on throughput and sustainability. J Hosp Med. 2015 Oct;10(10):664-9. doi: 10.1002/jhm.2412.

5. Wertheimer B et al. Discharge before noon: an achievable hospital goal. J Hosp Med. 2014 Apr;9(4):210-4. doi: 10.1002/jhm.2154.

6. Nelson J. The earlier, the better. The Hospitalist. 2010 May.

Only 12 state medical boards have taken action against physicians who have spread false or misleading information about COVID-19, according to a new survey from the Federation of State Medical Boards (FSMB).

The FSMB reports that in its 2021 annual survey two-thirds of its 71 member boards (which includes the United States, its territories, and Washington, DC) reported an increase in complaints about doctors spreading false or misleading information.

“The staggering number of state medical boards that have seen an increase in COVID-19 disinformation complaints is a sign of how widespread the issue has become,” said Humayun J. Chaudhry, DO, MACP, president and CEO of the FSMB, in a statement.

The FSMB board of directors warned physicians in July that they risked disciplinary action if they spread COVID-19 vaccine misinformation or disinformation.

The organization said 15 state boards have now adopted similar statements.

Dr. Chaudhry said the FSMB was “encouraged by the number of boards that have already taken action to combat COVID-19 disinformation by disciplining physicians who engage in that behavior and by reminding all physicians that their words and actions matter, and they should think twice before spreading disinformation that may harm patients.”

This news organization asked the FSMB for further comment on why more physicians have not been disciplined, but did not receive a response before publication.

Misinformation policies a new battleground

The FSMB and member board policies on COVID-19 around the country have become a new front in the war against mandates and restrictions.

The Tennessee Board of Medical Examiners voted just recently to remove its statement of policy against the spread of misinformation from its website after a Republican lawmaker allegedly threatened to dissolve the board.

The vote came just a few months after the board had approved the policy. The board did not rescind the policy, however, according to a report by the Associated Press.

In California, the president of the state’s medical board tweeted on December 8 about what she said was an incident of harassment by a group that has promoted “fake COVID-19 treatments.”Ms. Kristina Lawson said she observed four men sitting in front of her house in a truck. They flew a drone over her residence, and then followed her to work, parking nose-to-nose with her vehicle.

Ms. Lawson claimed that when she went to drive home the four men ambushed her in what was by then a dark parking garage. She said her “concern turned to terror” as they jumped out, cameras and recording equipment in hand.

The men told law enforcement called to the scene that they were just trying to interview her, according to a statement emailed by Ms. Lawson.

They had not made such a request to the California Medical Board.

Ms. Lawson tweeted that she would continue to volunteer for the board. “That means protecting Californians from bad doctors, and ensuring disinformation and misinformation do not detract from our work to protect patients and consumers,” she wrote.

The men who ambushed Ms. Larson allegedly identified themselves and were wearing clothing emblazoned with the logo of “America’s Frontline Doctors,” an organization that has trafficked in COVID-19 conspiracy theories and promoted unproven treatments like hydroxychloroquine and ivermectin, according to Time. It is led by Simone Gold, MD, who was arrested for breaching the U.S. Capitol on January 6.

Despite her activities, on November 30, the California Medical Board renewed Ms. Gold’s 2-year license to practice.

Who’s being disciplined, who’s not

Dr. Gold is not alone. An investigation by NPRin September found that 15 of 16 physicians who have spread false information in a high-profile manner have medical licenses in good standing.

Sherri Tenpenny, DO, who has claimed that COVID-19 vaccines magnetize people and “interface” with 5G cell phone towers, was able to renew her license with the Ohio State Medical Board on October 1, according to the Cincinnati Enquirer.

Some boards have acted. The Oregon Medical Board revoked the license of Steven LaTulippe, MD, and fined him $10,000 for spreading misinformation about masks and overprescribing opioids.

In August, Rhode Island’s Board of Medical Licensure suspended Mark Brody’s license for 5 years after finding that the doctor spread falsehoods about COVID-19 vaccines, according to board documents.

Maine physician Paul Gosselin, DO, is on temporary suspension until a February hearing, while the osteopathic board investigates his issuance of vaccine exemption letters and the promotion of unproven COVID-19 therapies.

The board found that Gosselin had “engaged in conduct that constitutes fraud or deceit,” according to official documents.

The Washington State Medical Board has opened an investigation into Ryan N. Cole, MD, a physician who has claimed that COVID vaccines are “fake,” and was appointed to a regional health board in Idaho in September, according to the Washington Post.

The Idaho Capital Sun reported that Dr. Cole claims he is licensed in 11 states, including Washington. The Idaho Medical Association has also filed a complaint about Dr. Cole with the Idaho Board of Medicine, according to the paper.

New FSMB guidance coming

The FSMB said it expects more disciplinary actions as investigations continue to unfold.

The organization is drafting a new policy document that will include further guidelines and recommendations for state medical boards “to help address the spread of disinformation,” it said. The final document would be released in April 2022.

In the meantime, some states, like Tennessee and others, are trying to find ways to counter the current policy — a development the FSMB called “troubling.”

“The FSMB strongly opposes any effort to restrict a board’s authority to evaluate the standard of care and assess risk for patient harm,” the organization said in its statement.

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

Only 12 state medical boards have taken action against physicians who have spread false or misleading information about COVID-19, according to a new survey from the Federation of State Medical Boards (FSMB).

The FSMB reports that in its 2021 annual survey two-thirds of its 71 member boards (which includes the United States, its territories, and Washington, DC) reported an increase in complaints about doctors spreading false or misleading information.

“The staggering number of state medical boards that have seen an increase in COVID-19 disinformation complaints is a sign of how widespread the issue has become,” said Humayun J. Chaudhry, DO, MACP, president and CEO of the FSMB, in a statement.

The FSMB board of directors warned physicians in July that they risked disciplinary action if they spread COVID-19 vaccine misinformation or disinformation.

The organization said 15 state boards have now adopted similar statements.

Dr. Chaudhry said the FSMB was “encouraged by the number of boards that have already taken action to combat COVID-19 disinformation by disciplining physicians who engage in that behavior and by reminding all physicians that their words and actions matter, and they should think twice before spreading disinformation that may harm patients.”

This news organization asked the FSMB for further comment on why more physicians have not been disciplined, but did not receive a response before publication.

Misinformation policies a new battleground

The FSMB and member board policies on COVID-19 around the country have become a new front in the war against mandates and restrictions.

The Tennessee Board of Medical Examiners voted just recently to remove its statement of policy against the spread of misinformation from its website after a Republican lawmaker allegedly threatened to dissolve the board.

The vote came just a few months after the board had approved the policy. The board did not rescind the policy, however, according to a report by the Associated Press.

In California, the president of the state’s medical board tweeted on December 8 about what she said was an incident of harassment by a group that has promoted “fake COVID-19 treatments.”Ms. Kristina Lawson said she observed four men sitting in front of her house in a truck. They flew a drone over her residence, and then followed her to work, parking nose-to-nose with her vehicle.

Ms. Lawson claimed that when she went to drive home the four men ambushed her in what was by then a dark parking garage. She said her “concern turned to terror” as they jumped out, cameras and recording equipment in hand.

The men told law enforcement called to the scene that they were just trying to interview her, according to a statement emailed by Ms. Lawson.

They had not made such a request to the California Medical Board.

Ms. Lawson tweeted that she would continue to volunteer for the board. “That means protecting Californians from bad doctors, and ensuring disinformation and misinformation do not detract from our work to protect patients and consumers,” she wrote.

The men who ambushed Ms. Larson allegedly identified themselves and were wearing clothing emblazoned with the logo of “America’s Frontline Doctors,” an organization that has trafficked in COVID-19 conspiracy theories and promoted unproven treatments like hydroxychloroquine and ivermectin, according to Time. It is led by Simone Gold, MD, who was arrested for breaching the U.S. Capitol on January 6.

Despite her activities, on November 30, the California Medical Board renewed Ms. Gold’s 2-year license to practice.

Who’s being disciplined, who’s not

Dr. Gold is not alone. An investigation by NPRin September found that 15 of 16 physicians who have spread false information in a high-profile manner have medical licenses in good standing.

Sherri Tenpenny, DO, who has claimed that COVID-19 vaccines magnetize people and “interface” with 5G cell phone towers, was able to renew her license with the Ohio State Medical Board on October 1, according to the Cincinnati Enquirer.

Some boards have acted. The Oregon Medical Board revoked the license of Steven LaTulippe, MD, and fined him $10,000 for spreading misinformation about masks and overprescribing opioids.

In August, Rhode Island’s Board of Medical Licensure suspended Mark Brody’s license for 5 years after finding that the doctor spread falsehoods about COVID-19 vaccines, according to board documents.

Maine physician Paul Gosselin, DO, is on temporary suspension until a February hearing, while the osteopathic board investigates his issuance of vaccine exemption letters and the promotion of unproven COVID-19 therapies.

The board found that Gosselin had “engaged in conduct that constitutes fraud or deceit,” according to official documents.

The Washington State Medical Board has opened an investigation into Ryan N. Cole, MD, a physician who has claimed that COVID vaccines are “fake,” and was appointed to a regional health board in Idaho in September, according to the Washington Post.

The Idaho Capital Sun reported that Dr. Cole claims he is licensed in 11 states, including Washington. The Idaho Medical Association has also filed a complaint about Dr. Cole with the Idaho Board of Medicine, according to the paper.

New FSMB guidance coming

The FSMB said it expects more disciplinary actions as investigations continue to unfold.

The organization is drafting a new policy document that will include further guidelines and recommendations for state medical boards “to help address the spread of disinformation,” it said. The final document would be released in April 2022.

In the meantime, some states, like Tennessee and others, are trying to find ways to counter the current policy — a development the FSMB called “troubling.”

“The FSMB strongly opposes any effort to restrict a board’s authority to evaluate the standard of care and assess risk for patient harm,” the organization said in its statement.

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

Only 12 state medical boards have taken action against physicians who have spread false or misleading information about COVID-19, according to a new survey from the Federation of State Medical Boards (FSMB).

The FSMB reports that in its 2021 annual survey two-thirds of its 71 member boards (which includes the United States, its territories, and Washington, DC) reported an increase in complaints about doctors spreading false or misleading information.

“The staggering number of state medical boards that have seen an increase in COVID-19 disinformation complaints is a sign of how widespread the issue has become,” said Humayun J. Chaudhry, DO, MACP, president and CEO of the FSMB, in a statement.

The FSMB board of directors warned physicians in July that they risked disciplinary action if they spread COVID-19 vaccine misinformation or disinformation.

The organization said 15 state boards have now adopted similar statements.

Dr. Chaudhry said the FSMB was “encouraged by the number of boards that have already taken action to combat COVID-19 disinformation by disciplining physicians who engage in that behavior and by reminding all physicians that their words and actions matter, and they should think twice before spreading disinformation that may harm patients.”

This news organization asked the FSMB for further comment on why more physicians have not been disciplined, but did not receive a response before publication.

Misinformation policies a new battleground

The FSMB and member board policies on COVID-19 around the country have become a new front in the war against mandates and restrictions.

The Tennessee Board of Medical Examiners voted just recently to remove its statement of policy against the spread of misinformation from its website after a Republican lawmaker allegedly threatened to dissolve the board.

The vote came just a few months after the board had approved the policy. The board did not rescind the policy, however, according to a report by the Associated Press.

In California, the president of the state’s medical board tweeted on December 8 about what she said was an incident of harassment by a group that has promoted “fake COVID-19 treatments.”Ms. Kristina Lawson said she observed four men sitting in front of her house in a truck. They flew a drone over her residence, and then followed her to work, parking nose-to-nose with her vehicle.

Ms. Lawson claimed that when she went to drive home the four men ambushed her in what was by then a dark parking garage. She said her “concern turned to terror” as they jumped out, cameras and recording equipment in hand.

The men told law enforcement called to the scene that they were just trying to interview her, according to a statement emailed by Ms. Lawson.

They had not made such a request to the California Medical Board.

Ms. Lawson tweeted that she would continue to volunteer for the board. “That means protecting Californians from bad doctors, and ensuring disinformation and misinformation do not detract from our work to protect patients and consumers,” she wrote.

The men who ambushed Ms. Larson allegedly identified themselves and were wearing clothing emblazoned with the logo of “America’s Frontline Doctors,” an organization that has trafficked in COVID-19 conspiracy theories and promoted unproven treatments like hydroxychloroquine and ivermectin, according to Time. It is led by Simone Gold, MD, who was arrested for breaching the U.S. Capitol on January 6.

Despite her activities, on November 30, the California Medical Board renewed Ms. Gold’s 2-year license to practice.

Who’s being disciplined, who’s not

Dr. Gold is not alone. An investigation by NPRin September found that 15 of 16 physicians who have spread false information in a high-profile manner have medical licenses in good standing.

Sherri Tenpenny, DO, who has claimed that COVID-19 vaccines magnetize people and “interface” with 5G cell phone towers, was able to renew her license with the Ohio State Medical Board on October 1, according to the Cincinnati Enquirer.

Some boards have acted. The Oregon Medical Board revoked the license of Steven LaTulippe, MD, and fined him $10,000 for spreading misinformation about masks and overprescribing opioids.

In August, Rhode Island’s Board of Medical Licensure suspended Mark Brody’s license for 5 years after finding that the doctor spread falsehoods about COVID-19 vaccines, according to board documents.

Maine physician Paul Gosselin, DO, is on temporary suspension until a February hearing, while the osteopathic board investigates his issuance of vaccine exemption letters and the promotion of unproven COVID-19 therapies.

The board found that Gosselin had “engaged in conduct that constitutes fraud or deceit,” according to official documents.

The Washington State Medical Board has opened an investigation into Ryan N. Cole, MD, a physician who has claimed that COVID vaccines are “fake,” and was appointed to a regional health board in Idaho in September, according to the Washington Post.

The Idaho Capital Sun reported that Dr. Cole claims he is licensed in 11 states, including Washington. The Idaho Medical Association has also filed a complaint about Dr. Cole with the Idaho Board of Medicine, according to the paper.

New FSMB guidance coming

The FSMB said it expects more disciplinary actions as investigations continue to unfold.

The organization is drafting a new policy document that will include further guidelines and recommendations for state medical boards “to help address the spread of disinformation,” it said. The final document would be released in April 2022.

In the meantime, some states, like Tennessee and others, are trying to find ways to counter the current policy — a development the FSMB called “troubling.”

“The FSMB strongly opposes any effort to restrict a board’s authority to evaluate the standard of care and assess risk for patient harm,” the organization said in its statement.

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

Macular telangiectasia type 2 (MacTel2) is an uncommon, bilateral, and asymmetric condition that typically presents between the ages of 40 and 60 years without sex predilection.^1-9 Its estimated prevalence ranges from 0.02 to 0.10%.^2,8 The disease can manifest in either a nonproliferative or proliferative phase; the latter is far less common. The etiology of MacTel2 is poorly understood, but it is believed to have neurodegenerative as well as vascular components.^1-6,8-10 We present a case of MacTel2 and highlight the role of diagnostic imaging in early diagnosis prior to development of classic funduscopic features.

Case Presentation

A 66-year-old White male with a 10-year history of type 2 diabetes mellitus (T2DM) presented to the eye clinic for an annual eye examination. The patient was taking metformin, and 6 months prior to presentation, his hemoglobin A_1c was 7.4%. He had a history of mild nonproliferative diabetic retinopathy in the left eye without diabetic macular edema. He reported no ocular concerns.

On examination, best-corrected visual acuity (VA) was 20/20 in each eye. Slit-lamp examination was notable only for bilateral mild nuclear sclerosis. Dilated fundus examination showed a blunted foveal reflex consistent with the appearance of a macular pseudo-hole in the right eye and was unremarkable in the left eye (Figure 1).

Discussion

This case highlights several important management considerations in MacTel2. These include symptoms, disease stage, and diagnostic imaging, which can allow more precise staging of the disease.

The etiology of MacTel2 is unknown.⁶ It is believed to be primarily a neurodegenerative condition that damages Müller cells and photoreceptors, leading to vascular changes.^1-6,8-10 Müller cells may play a role in creating and maintaining the integrity of the blood-retinal barrier, particularly in the deep capillary plexus where the vascular abnormalities begin.^6,10 These early changes in the deep capillary plexus may evolve to include the superficial capillary plexus in intermediate stages with anastomoses forming between the 2 layers.^2,6-10 Late proliferative stages show significant alterations of the juxtafoveal capillary network, subretinal neovascularization and retinochoroidal anastomoses.^6,7,9,11 In one cohort study, 81% of patients with MacTel2 were White, and a genetic link is still under investigation.^2,4-9

Presentation

The most common symptoms of MacTel2 include blurred vision, microscotoma, metamorphopsia, and difficulty reading, with missing or distorted letters a common concern.^1,2,4-8 Best-corrected VA at presentation is usually better than 20/30, and disease progression tends to be slow.^2,6 Microscotomata are best mapped with microperimetry.^1-3,5-7

There are several classic fundus findings (Table). In the early stages, these findings are subtle or entirely absent funduscopically.^1,2,4-10 In intermediate stages, fundus findings become apparent and include a loss of retinal clarity (grayish perifoveal sheen), telangiectatic macular vessels, retinal pigment epithelium hypertrophy, blunted right-angled vessels, and superficial retinal crystalline deposits.^2,4-11 Right-angled vessels may have a greater association with choroidal neovascularization, with growth into the outer retina in particular being a marker of disease progression.⁹ The crystalline deposits have been hypothesized to be the footplates of degenerated Müller cells.⁶

Diagnostic Testing

Diagnostic retinal imaging is invaluable in the diagnosis of MacTel2. The OCT can detect hyporeflectivity within the ellipsoid zone in early disease corresponding to ellipsoid zone loss, which increases as the disease progresses.^1-8,10 This loss most often begins in the temporal parafoveal region and correlates with the progression of both relative and absolute scotomas perceived by affected individuals.^2,3,5,8

Intraretinal foveal hyporeflective spaces on the OCT represent cavity formation after Müller cell and photoreceptor loss and do not correlate with increased thickness.^1,2,4,6,7 This is important in differentiating from diabetic macular edema, which will often show thickening.⁶ In most cases of MacTel2, foveal thickness is decreased.^4-6 The ILM remains intact overlying this space and is referred to as ILM drape.^6,7 This can cause blunting or absence of the foveal light reflex and mimic the appearance of a macular pseudohole.⁴

The OCT-A allows visualization of capillary changes through every layer of the retina, which could not otherwise be appreciated, allowing early detection as well as precise staging of the disease.^2,6-10 Anastomoses present in late-stage disease also can be imaged using OCT-A.^7,9 These anastomoses can be seen as hyperreflective vasculature present between the retinal layers where there is little to no vasculature visible in normal eyes.⁷

A lesser-known occurrence in MacTel2 is the depletion of macular luteal pigment, with many eyes possessing an abnormal distribution.^2,4,6-8,10 This depletion and abnormal distribution can be visualized with FAF. In particular, short wavelength fundus autofluorescence (SW-FAF) is the most effective at highlighting these changes.¹⁰ The characteristic finding is a hyperreflective halo surrounding the fovea.^2,6 Fluorescence life imaging ophthalmoscopy (FLIO) is a recent development in FAF that measures FAF lifetime, which is the duration of time a structure autofluoresces.⁸ A cross-sectional study published in 2018 showed prolonged FAF lifetime in the temporal fovea of patients with early and moderate stage MacTel2 when compared with normal patients.⁸ More advanced stages showed a ring encircling the entire fovea.⁸

Classic FA findings in MacTel2 include early hyperfluorescence of temporal foveal telangiectatic capillaries and late-stage leakage with sparing of the central fovea.^1,2,4,6,7,11

Management and Prognosis

Management of MacTel2 depends on the stage of the disease. In the absence of proven treatment, management in nonproliferative stages is conservative.^2,6 Intravitreal anti-VEGF does not offer any benefit in nonproliferative disease.^2,5,6 Indeed, as VEGF may have a neuroprotective effect on the retina, anti-VEGF may result in more harm than benefit in earlier disease stages.⁵ In proliferative stages, intravitreal anti-VEGF can help limit scarring and prevent vision loss.^2,5

Long-term prognosis of MacTel2 is variable with VA typically better than 20/100.² Vision loss in MacTel2 most often begins paracentrally; it can then progress centrally, leading to significant reduction in VA.¹² The progression of this functional vision loss and corresponding structural damage is typically slow.³ VA worse than 20/100 is usually a result of proliferative disease; in such cases, there is potential for severe central vision loss and legal blindness.¹

Conclusions

This case of MacTel2 underscores the subtle retinal findings in the earliest stages of the disease and the importance of a complete retinal examination and diagnostic imaging with macula OCT, OCT-A, and FAF to establish the correct diagnosis.

Macular telangiectasia type 2 (MacTel2) is an uncommon, bilateral, and asymmetric condition that typically presents between the ages of 40 and 60 years without sex predilection.^1-9 Its estimated prevalence ranges from 0.02 to 0.10%.^2,8 The disease can manifest in either a nonproliferative or proliferative phase; the latter is far less common. The etiology of MacTel2 is poorly understood, but it is believed to have neurodegenerative as well as vascular components.^1-6,8-10 We present a case of MacTel2 and highlight the role of diagnostic imaging in early diagnosis prior to development of classic funduscopic features.

Case Presentation

A 66-year-old White male with a 10-year history of type 2 diabetes mellitus (T2DM) presented to the eye clinic for an annual eye examination. The patient was taking metformin, and 6 months prior to presentation, his hemoglobin A_1c was 7.4%. He had a history of mild nonproliferative diabetic retinopathy in the left eye without diabetic macular edema. He reported no ocular concerns.

On examination, best-corrected visual acuity (VA) was 20/20 in each eye. Slit-lamp examination was notable only for bilateral mild nuclear sclerosis. Dilated fundus examination showed a blunted foveal reflex consistent with the appearance of a macular pseudo-hole in the right eye and was unremarkable in the left eye (Figure 1).

Discussion

This case highlights several important management considerations in MacTel2. These include symptoms, disease stage, and diagnostic imaging, which can allow more precise staging of the disease.

The etiology of MacTel2 is unknown.⁶ It is believed to be primarily a neurodegenerative condition that damages Müller cells and photoreceptors, leading to vascular changes.^1-6,8-10 Müller cells may play a role in creating and maintaining the integrity of the blood-retinal barrier, particularly in the deep capillary plexus where the vascular abnormalities begin.^6,10 These early changes in the deep capillary plexus may evolve to include the superficial capillary plexus in intermediate stages with anastomoses forming between the 2 layers.^2,6-10 Late proliferative stages show significant alterations of the juxtafoveal capillary network, subretinal neovascularization and retinochoroidal anastomoses.^6,7,9,11 In one cohort study, 81% of patients with MacTel2 were White, and a genetic link is still under investigation.^2,4-9

Presentation

The most common symptoms of MacTel2 include blurred vision, microscotoma, metamorphopsia, and difficulty reading, with missing or distorted letters a common concern.^1,2,4-8 Best-corrected VA at presentation is usually better than 20/30, and disease progression tends to be slow.^2,6 Microscotomata are best mapped with microperimetry.^1-3,5-7

There are several classic fundus findings (Table). In the early stages, these findings are subtle or entirely absent funduscopically.^1,2,4-10 In intermediate stages, fundus findings become apparent and include a loss of retinal clarity (grayish perifoveal sheen), telangiectatic macular vessels, retinal pigment epithelium hypertrophy, blunted right-angled vessels, and superficial retinal crystalline deposits.^2,4-11 Right-angled vessels may have a greater association with choroidal neovascularization, with growth into the outer retina in particular being a marker of disease progression.⁹ The crystalline deposits have been hypothesized to be the footplates of degenerated Müller cells.⁶

Diagnostic Testing

Diagnostic retinal imaging is invaluable in the diagnosis of MacTel2. The OCT can detect hyporeflectivity within the ellipsoid zone in early disease corresponding to ellipsoid zone loss, which increases as the disease progresses.^1-8,10 This loss most often begins in the temporal parafoveal region and correlates with the progression of both relative and absolute scotomas perceived by affected individuals.^2,3,5,8

Intraretinal foveal hyporeflective spaces on the OCT represent cavity formation after Müller cell and photoreceptor loss and do not correlate with increased thickness.^1,2,4,6,7 This is important in differentiating from diabetic macular edema, which will often show thickening.⁶ In most cases of MacTel2, foveal thickness is decreased.^4-6 The ILM remains intact overlying this space and is referred to as ILM drape.^6,7 This can cause blunting or absence of the foveal light reflex and mimic the appearance of a macular pseudohole.⁴

The OCT-A allows visualization of capillary changes through every layer of the retina, which could not otherwise be appreciated, allowing early detection as well as precise staging of the disease.^2,6-10 Anastomoses present in late-stage disease also can be imaged using OCT-A.^7,9 These anastomoses can be seen as hyperreflective vasculature present between the retinal layers where there is little to no vasculature visible in normal eyes.⁷

A lesser-known occurrence in MacTel2 is the depletion of macular luteal pigment, with many eyes possessing an abnormal distribution.^2,4,6-8,10 This depletion and abnormal distribution can be visualized with FAF. In particular, short wavelength fundus autofluorescence (SW-FAF) is the most effective at highlighting these changes.¹⁰ The characteristic finding is a hyperreflective halo surrounding the fovea.^2,6 Fluorescence life imaging ophthalmoscopy (FLIO) is a recent development in FAF that measures FAF lifetime, which is the duration of time a structure autofluoresces.⁸ A cross-sectional study published in 2018 showed prolonged FAF lifetime in the temporal fovea of patients with early and moderate stage MacTel2 when compared with normal patients.⁸ More advanced stages showed a ring encircling the entire fovea.⁸

Classic FA findings in MacTel2 include early hyperfluorescence of temporal foveal telangiectatic capillaries and late-stage leakage with sparing of the central fovea.^1,2,4,6,7,11

Management and Prognosis

Management of MacTel2 depends on the stage of the disease. In the absence of proven treatment, management in nonproliferative stages is conservative.^2,6 Intravitreal anti-VEGF does not offer any benefit in nonproliferative disease.^2,5,6 Indeed, as VEGF may have a neuroprotective effect on the retina, anti-VEGF may result in more harm than benefit in earlier disease stages.⁵ In proliferative stages, intravitreal anti-VEGF can help limit scarring and prevent vision loss.^2,5

Long-term prognosis of MacTel2 is variable with VA typically better than 20/100.² Vision loss in MacTel2 most often begins paracentrally; it can then progress centrally, leading to significant reduction in VA.¹² The progression of this functional vision loss and corresponding structural damage is typically slow.³ VA worse than 20/100 is usually a result of proliferative disease; in such cases, there is potential for severe central vision loss and legal blindness.¹

Conclusions

This case of MacTel2 underscores the subtle retinal findings in the earliest stages of the disease and the importance of a complete retinal examination and diagnostic imaging with macula OCT, OCT-A, and FAF to establish the correct diagnosis.

Macular telangiectasia type 2 (MacTel2) is an uncommon, bilateral, and asymmetric condition that typically presents between the ages of 40 and 60 years without sex predilection.^1-9 Its estimated prevalence ranges from 0.02 to 0.10%.^2,8 The disease can manifest in either a nonproliferative or proliferative phase; the latter is far less common. The etiology of MacTel2 is poorly understood, but it is believed to have neurodegenerative as well as vascular components.^1-6,8-10 We present a case of MacTel2 and highlight the role of diagnostic imaging in early diagnosis prior to development of classic funduscopic features.

Case Presentation

A 66-year-old White male with a 10-year history of type 2 diabetes mellitus (T2DM) presented to the eye clinic for an annual eye examination. The patient was taking metformin, and 6 months prior to presentation, his hemoglobin A_1c was 7.4%. He had a history of mild nonproliferative diabetic retinopathy in the left eye without diabetic macular edema. He reported no ocular concerns.

On examination, best-corrected visual acuity (VA) was 20/20 in each eye. Slit-lamp examination was notable only for bilateral mild nuclear sclerosis. Dilated fundus examination showed a blunted foveal reflex consistent with the appearance of a macular pseudo-hole in the right eye and was unremarkable in the left eye (Figure 1).

Discussion

This case highlights several important management considerations in MacTel2. These include symptoms, disease stage, and diagnostic imaging, which can allow more precise staging of the disease.

The etiology of MacTel2 is unknown.⁶ It is believed to be primarily a neurodegenerative condition that damages Müller cells and photoreceptors, leading to vascular changes.^1-6,8-10 Müller cells may play a role in creating and maintaining the integrity of the blood-retinal barrier, particularly in the deep capillary plexus where the vascular abnormalities begin.^6,10 These early changes in the deep capillary plexus may evolve to include the superficial capillary plexus in intermediate stages with anastomoses forming between the 2 layers.^2,6-10 Late proliferative stages show significant alterations of the juxtafoveal capillary network, subretinal neovascularization and retinochoroidal anastomoses.^6,7,9,11 In one cohort study, 81% of patients with MacTel2 were White, and a genetic link is still under investigation.^2,4-9

Presentation

The most common symptoms of MacTel2 include blurred vision, microscotoma, metamorphopsia, and difficulty reading, with missing or distorted letters a common concern.^1,2,4-8 Best-corrected VA at presentation is usually better than 20/30, and disease progression tends to be slow.^2,6 Microscotomata are best mapped with microperimetry.^1-3,5-7

There are several classic fundus findings (Table). In the early stages, these findings are subtle or entirely absent funduscopically.^1,2,4-10 In intermediate stages, fundus findings become apparent and include a loss of retinal clarity (grayish perifoveal sheen), telangiectatic macular vessels, retinal pigment epithelium hypertrophy, blunted right-angled vessels, and superficial retinal crystalline deposits.^2,4-11 Right-angled vessels may have a greater association with choroidal neovascularization, with growth into the outer retina in particular being a marker of disease progression.⁹ The crystalline deposits have been hypothesized to be the footplates of degenerated Müller cells.⁶

Diagnostic Testing

Diagnostic retinal imaging is invaluable in the diagnosis of MacTel2. The OCT can detect hyporeflectivity within the ellipsoid zone in early disease corresponding to ellipsoid zone loss, which increases as the disease progresses.^1-8,10 This loss most often begins in the temporal parafoveal region and correlates with the progression of both relative and absolute scotomas perceived by affected individuals.^2,3,5,8

Intraretinal foveal hyporeflective spaces on the OCT represent cavity formation after Müller cell and photoreceptor loss and do not correlate with increased thickness.^1,2,4,6,7 This is important in differentiating from diabetic macular edema, which will often show thickening.⁶ In most cases of MacTel2, foveal thickness is decreased.^4-6 The ILM remains intact overlying this space and is referred to as ILM drape.^6,7 This can cause blunting or absence of the foveal light reflex and mimic the appearance of a macular pseudohole.⁴

The OCT-A allows visualization of capillary changes through every layer of the retina, which could not otherwise be appreciated, allowing early detection as well as precise staging of the disease.^2,6-10 Anastomoses present in late-stage disease also can be imaged using OCT-A.^7,9 These anastomoses can be seen as hyperreflective vasculature present between the retinal layers where there is little to no vasculature visible in normal eyes.⁷

A lesser-known occurrence in MacTel2 is the depletion of macular luteal pigment, with many eyes possessing an abnormal distribution.^2,4,6-8,10 This depletion and abnormal distribution can be visualized with FAF. In particular, short wavelength fundus autofluorescence (SW-FAF) is the most effective at highlighting these changes.¹⁰ The characteristic finding is a hyperreflective halo surrounding the fovea.^2,6 Fluorescence life imaging ophthalmoscopy (FLIO) is a recent development in FAF that measures FAF lifetime, which is the duration of time a structure autofluoresces.⁸ A cross-sectional study published in 2018 showed prolonged FAF lifetime in the temporal fovea of patients with early and moderate stage MacTel2 when compared with normal patients.⁸ More advanced stages showed a ring encircling the entire fovea.⁸

Classic FA findings in MacTel2 include early hyperfluorescence of temporal foveal telangiectatic capillaries and late-stage leakage with sparing of the central fovea.^1,2,4,6,7,11

Management and Prognosis

Management of MacTel2 depends on the stage of the disease. In the absence of proven treatment, management in nonproliferative stages is conservative.^2,6 Intravitreal anti-VEGF does not offer any benefit in nonproliferative disease.^2,5,6 Indeed, as VEGF may have a neuroprotective effect on the retina, anti-VEGF may result in more harm than benefit in earlier disease stages.⁵ In proliferative stages, intravitreal anti-VEGF can help limit scarring and prevent vision loss.^2,5

Long-term prognosis of MacTel2 is variable with VA typically better than 20/100.² Vision loss in MacTel2 most often begins paracentrally; it can then progress centrally, leading to significant reduction in VA.¹² The progression of this functional vision loss and corresponding structural damage is typically slow.³ VA worse than 20/100 is usually a result of proliferative disease; in such cases, there is potential for severe central vision loss and legal blindness.¹

Conclusions

This case of MacTel2 underscores the subtle retinal findings in the earliest stages of the disease and the importance of a complete retinal examination and diagnostic imaging with macula OCT, OCT-A, and FAF to establish the correct diagnosis.

Thousands of health care professionals who separate from active duty each year now have a route to stay in federal health care jobs, including open positions in US Department of Veterans Affairs (VA) hospitals. President Biden signed the Hire Veteran Health Heroes Act of 2021 into law on November 30, saying, “This new program will build upon existing efforts to create a pipeline for former military health professionals….to allow those professionals to continue their service to each other and to our nation.”

Senators Mike Braun (R, Indiana) and Maggie Hassan (D, New Hampshire) introduced the bill last March; Representatives Robert Latta (Ohio-05) and Kathleen Rice (New York-04) introduced companion legislation in the House.

The Act serves multiple purposes, including to retain the critical experience of doctors, nurses, pharmacists, technicians, and physical therapists who understand the challenges service members face; to give those professionals continued employment; and to fill empty staff positions. Two years ago, the VA Inspector General said staff shortages are a root cause of many of the problems in veterans’ care.

 The bill directs the VA to create a program to recruit military medical personnel who are within 1 year of completing their military service. On average, 13,000 active-duty medical department members separate from the military each year at the end of enlistments or contracts, or through retirement. But until now, there has been no formal program to actively recruit them to stay.

The Act requires VA leaders to work with US Department of Defense officials to identify, refer, and transition service members who have critically needed skills. Moreover, the bill specifically mandates that if a member of the Armed Forces expresses an interest in working in a health care occupation within the VA, the VA Secretary “shall refer the member to a recruiter of the Department for consideration of open positions in the specialty and geography of interest to the member.”

Senator Hassan, in an official statement, said, “[W]e must always ensure that veterans have the support and resources that they need to succeed, and a critical way to do that is by expanding employment opportunities for our nation’s heroes and strengthening their health care.”

In his remarks, President Biden said, “For both our veterans and our military medical personnel, service isn’t just what they do, it’s who they are.”

Thousands of health care professionals who separate from active duty each year now have a route to stay in federal health care jobs, including open positions in US Department of Veterans Affairs (VA) hospitals. President Biden signed the Hire Veteran Health Heroes Act of 2021 into law on November 30, saying, “This new program will build upon existing efforts to create a pipeline for former military health professionals….to allow those professionals to continue their service to each other and to our nation.”

Senators Mike Braun (R, Indiana) and Maggie Hassan (D, New Hampshire) introduced the bill last March; Representatives Robert Latta (Ohio-05) and Kathleen Rice (New York-04) introduced companion legislation in the House.

The Act serves multiple purposes, including to retain the critical experience of doctors, nurses, pharmacists, technicians, and physical therapists who understand the challenges service members face; to give those professionals continued employment; and to fill empty staff positions. Two years ago, the VA Inspector General said staff shortages are a root cause of many of the problems in veterans’ care.

 The bill directs the VA to create a program to recruit military medical personnel who are within 1 year of completing their military service. On average, 13,000 active-duty medical department members separate from the military each year at the end of enlistments or contracts, or through retirement. But until now, there has been no formal program to actively recruit them to stay.

The Act requires VA leaders to work with US Department of Defense officials to identify, refer, and transition service members who have critically needed skills. Moreover, the bill specifically mandates that if a member of the Armed Forces expresses an interest in working in a health care occupation within the VA, the VA Secretary “shall refer the member to a recruiter of the Department for consideration of open positions in the specialty and geography of interest to the member.”

Senator Hassan, in an official statement, said, “[W]e must always ensure that veterans have the support and resources that they need to succeed, and a critical way to do that is by expanding employment opportunities for our nation’s heroes and strengthening their health care.”

In his remarks, President Biden said, “For both our veterans and our military medical personnel, service isn’t just what they do, it’s who they are.”

Thousands of health care professionals who separate from active duty each year now have a route to stay in federal health care jobs, including open positions in US Department of Veterans Affairs (VA) hospitals. President Biden signed the Hire Veteran Health Heroes Act of 2021 into law on November 30, saying, “This new program will build upon existing efforts to create a pipeline for former military health professionals….to allow those professionals to continue their service to each other and to our nation.”

Senators Mike Braun (R, Indiana) and Maggie Hassan (D, New Hampshire) introduced the bill last March; Representatives Robert Latta (Ohio-05) and Kathleen Rice (New York-04) introduced companion legislation in the House.

The Act serves multiple purposes, including to retain the critical experience of doctors, nurses, pharmacists, technicians, and physical therapists who understand the challenges service members face; to give those professionals continued employment; and to fill empty staff positions. Two years ago, the VA Inspector General said staff shortages are a root cause of many of the problems in veterans’ care.

 The bill directs the VA to create a program to recruit military medical personnel who are within 1 year of completing their military service. On average, 13,000 active-duty medical department members separate from the military each year at the end of enlistments or contracts, or through retirement. But until now, there has been no formal program to actively recruit them to stay.

The Act requires VA leaders to work with US Department of Defense officials to identify, refer, and transition service members who have critically needed skills. Moreover, the bill specifically mandates that if a member of the Armed Forces expresses an interest in working in a health care occupation within the VA, the VA Secretary “shall refer the member to a recruiter of the Department for consideration of open positions in the specialty and geography of interest to the member.”

Senator Hassan, in an official statement, said, “[W]e must always ensure that veterans have the support and resources that they need to succeed, and a critical way to do that is by expanding employment opportunities for our nation’s heroes and strengthening their health care.”

In his remarks, President Biden said, “For both our veterans and our military medical personnel, service isn’t just what they do, it’s who they are.”

Data is sparse thus far, but there is concern in lung transplant medicine about the long-term risk of chronic lung allograft dysfunction (CLAD) and a potentially shortened longevity of transplanted lungs in recipients who become ill with COVID-19.

Nephron/Creative Commons 3.0

“My fear is that we’re potentially sitting on this iceberg worth of people who, come 6 months or a year from [the acute phase of] their COVID illness, will in fact have earlier and progressive, chronic rejection,” said Cameron R. Wolfe, MBBS, MPH, associate professor of medicine in transplant infectious disease at Duke University, Durham, N.C.

Lower respiratory viral infections have long been concerning for lung transplant recipients given their propensity to cause scarring, a decline in lung function, and a heightened risk of allograft rejection. Time will tell whether lung transplant recipients who survive COVID-19 follow a similar path, or one that is worse, he said.
 

Short-term data

Outcomes beyond hospitalization and acute illness for lung transplant recipients affected by COVID-19 have been reported in the literature by only a few lung transplant programs. These reports – as well as anecdotal experiences being informally shared among transplant programs – have raised the specter of more severe dysfunction following the acute phase and more early CLAD, said Tathagat Narula, MD, assistant professor of medicine at the Mayo Medical School, Rochester, Minn., and a consultant in lung transplantation at the Mayo Clinic’s Jacksonville program.

“The available data cover only 3-6 months out. We don’t know what will happen in the next 6 months and beyond,” Dr. Narula said in an interview.

The risks of COVID-19 in already-transplanted patients and issues relating to the inadequate antibody responses to vaccination are just some of the challenges of lung transplant medicine in the era of SARS-CoV-2. “COVID-19,” said Dr. Narula, “has completely changed the way we practice lung transplant medicine – the way we’re looking both at our recipients and our donors.”

Potential donors are being evaluated with lower respiratory SARS-CoV-2 testing and an abundance of caution. And patients with severe COVID-19 affecting their own lungs are roundly expected to drive up lung transplant volume in the near future. “The whole paradigm has changed,” Dr. Narula said.
 

Post-acute trajectories

A chart review study published in October by the lung transplant team at the University of Texas Southwestern Medical Center, Dallas, covered 44 consecutive survivors at a median follow-up of 4.5 months from hospital discharge or acute illness (the survival rate was 83.3%). Patients had significantly impaired functional status, and 18 of the 44 (40.9%) had a significant and persistent loss of forced vital capacity or forced expiratory volume in 1 second (>10% from pre–COVID-19 baseline).

Three patients met the criteria for new CLAD after COVID-19 infection, with all three classified as restrictive allograft syndrome (RAS) phenotype.

Moreover, the majority of COVID-19 survivors who had CT chest scans (22 of 28) showed persistent parenchymal opacities – a finding that, regardless of symptomatology, suggests persistent allograft injury, said Amit Banga, MD, associate professor of medicine and medical director of the ex vivo lung perfusion program in UT Southwestern’s lung transplant program.

“The implication is that there may be long-term consequences of COVID-19, perhaps related to some degree of ongoing inflammation and damage,” said Dr. Banga, a coauthor of the postinfection outcomes paper.

The UT Southwestern lung transplant program, which normally performs 60-80 transplants a year, began routine CT scanning 4-5 months into the pandemic, after “stumbling into a few patients who had no symptoms indicative of COVID pneumonia and no changes on an x-ray but significant involvement on a CT,” he said.

Without routine scanning in the general population of COVID-19 patients, Dr. Banga noted, “we’re limited in convincingly saying that COVID is uniquely doing this to lung transplant recipients.” Nor can they conclude that SARS-CoV-2 is unique from other respiratory viruses such as respiratory syncytial virus (RSV) in this regard. (The program has added CT scanning to its protocol for lung transplant recipients afflicted with other respiratory viruses to learn more.)

However, in the big picture, COVID-19 has proven to be far worse for lung transplant recipients than illness with other respiratory viruses, including RSV. “Patients have more frequent and greater loss of lung function, and worse debility from the acute illness,” Dr. Banga said.

“The cornerstones of treatment of both these viruses are very similar, but both the in-hospital course and the postdischarge outcomes are significantly different.”

In an initial paper published in September 2021, Dr. Banga and colleagues compared their first 25 lung transplant patients testing positive for SARS-CoV-2 with a historical cohort of 36 patients with RSV treated during 2016-2018.

Patients with COVID-19 had significantly worse morbidity and mortality, including worse postinfection lung function loss, functional decline, and 3-month survival.

More time, he said, will shed light on the risks of CLAD and the long-term potential for recovery of lung function. Currently, at UT Southwestern, it appears that patients who survive acute illness and the “first 3-6 months after COVID-19, when we’re seeing all the postinfection morbidity, may [enter] a period of stability,” Dr. Banga said.

Overall, he said, patients in their initial cohort are “holding steady” without unusual morbidity, readmissions, or “other setbacks to their allografts.”

At the Mayo Clinic in Jacksonville, which normally performs 40-50 lung transplants a year, transplant physicians have similarly observed significant declines in lung function beyond the acute phase of COVID-19. “Anecdotally, we’re seeing that some patients are beginning to recover some of their lung function, while others have not,” said Dr. Narula. “And we don’t have predictors as to who will progress to CLAD. It’s a big knowledge gap.”

Dr. Narula noted that patients with restrictive allograft syndrome, such as those reported by the UT Southwestern team, “have scarring of the lung and a much worse prognosis than the obstructive type of chronic rejection.” Whether there’s a role for antifibrotic therapy is a question worthy of research.

In UT Southwestern’s analysis, persistently lower absolute lymphocyte counts (< 600/dL) and higher ferritin levels (>150 ng/mL) at the time of hospital discharge were independently associated with significant lung function loss. This finding, reported in their October paper, has helped guide their management practices, Dr. Banga said.

“Persistently elevated ferritin may indicate ongoing inflammation at the allograft level,” he said. “We now send [such patients] home on a longer course of oral corticosteroids.”

At the front end of care for infected lung transplant recipients, Dr. Banga said that his team and physicians at other lung transplant programs are holding the cell-cycle inhibitor component of patients’ maintenance immunosuppression therapy (commonly mycophenolate or azathioprine) once infection is diagnosed to maximize chances of a better outcome.

“There may be variation on how long [the regimens are adjusted],” he said. “We changed our duration from 4 weeks to 2 due to patients developing a rebound worsening in the third and fourth week of acute illness.”

There is significant variation from institution to institution in how viral infections are managed in lung transplant recipients, he and Dr. Narula said. “Our numbers are so small in lung transplant, and we don’t have standardized protocols – it’s one of the biggest challenges in our field,” said Dr. Narula.
 

Vaccination issues, evaluation of donors

Whether or not immunosuppression regimens should be adjusted prior to vaccination is a controversial question, but is “an absolutely valid one” and is currently being studied in at least one National Institutes of Health–funded trial involving solid organ transplant recipients, said Dr. Wolfe.

“Some have jumped to the conclusion [based on some earlier data] that they should reduce immunosuppression regimens for everyone at the time of vaccination ... but I don’t know the answer yet,” he said. “Balancing staying rejection free with potentially gaining more immune response is complicated ... and it may depend on where the pandemic is going in your area and other factors.”

Reductions aside, Dr. Wolfe tells lung transplant recipients that, based on his approximation of a number of different studies in solid organ transplant recipients, approximately 40%-50% of patients who are immunized with two doses of the COVID-19 mRNA vaccines will develop meaningful antibody levels – and that this rises to 50%-60% after a third dose.

It is difficult to glean from available studies the level of vaccine response for lung transplant recipients specifically. But given that their level of maintenance immunosuppression is higher than for recipients of other donor organs, “as a broad sweep, lung transplant recipients tend to be lower in the pecking order of response,” he said.

Still, “there’s a lot to gain,” he said, pointing to a recent study from the Morbidity and Mortality Weekly Report (2021 Nov 5. doi: 10.15585/mmwr.mm7044e3) showing that effectiveness of mRNA vaccination against COVID-19–associated hospitalization was 77% among immunocompromised adults (compared with 90% in immunocompetent adults).

“This is good vindication to keep vaccinating,” he said, “and perhaps speaks to how difficult it is to assess the vaccine response [through measurement of antibody only].”

Neither Duke University’s transplant program, which performed 100-120 lung transplants a year pre-COVID, nor the programs at UT Southwestern or the Mayo Clinic in Jacksonville require that solid organ transplant candidates be vaccinated against SARS-CoV-2 in order to receive transplants, as some other transplant programs have done. (When asked about the issue, Dr. Banga and Dr. Narula each said that they have had no or little trouble convincing patients awaiting lung transplants of the need for COVID-19 vaccination.)

In an August statement, the American Society of Transplantation recommended vaccination for all solid organ transplant recipients, preferably prior to transplantation, and said that it “support[s] the development of institutional policies regarding pretransplant vaccination.”

The Society is not tracking centers’ vaccination policies. But Kaiser Health News reported in October that a growing number of transplant programs, such as UCHealth in Denver and UW Medicine in Seattle, have decided to either bar patients who refuse to be vaccinated from receiving transplants or give them lower priority on waitlists.

Potential lung donors, meanwhile, must be evaluated with lower respiratory COVID-19 testing, with results available prior to transplantation, according to policy developed by the Organ Procurement and Transplantation Network and effective in May 2021. The policy followed three published cases of donor-derived COVID-19 in lung transplant recipients, said Dr. Wolfe, who wrote about use of COVID-positive donors in an editorial published in October.

In each case, the donor had a negative COVID-19 nasopharyngeal swab at the time of organ procurement but was later found to have the virus on bronchoalveolar lavage, he said.

(The use of other organs from COVID-positive donors is appearing thus far to be safe, Dr. Wolfe noted. In the editorial, he references 13 cases of solid organ transplantation from SARS-CoV-2–infected donors into noninfected recipients; none of the 13 transplant recipients developed COVID-19).

Some questions remain, such as how many lower respiratory tests should be run, and how donors should be evaluated in cases of discordant results. Dr. Banga shared the case of a donor with one positive lower respiratory test result followed by two negative results. After internal debate, and consideration of potential false positives and other issues, the team at UT Southwestern decided to decline the donor, Dr. Banga said.

Other programs are likely making similar, appropriately cautious decisions, said Dr. Wolfe. “There’s no way in real-time donor evaluation to know whether the positive test is active virus that could infect the recipient and replicate ... or whether it’s [picking up] inactive or dead fragments of virus that was there several weeks ago. Our tests don’t differentiate that.”

Transplants in COVID-19 patients

Decision-making about lung transplant candidacy among patients with COVID-19 acute respiratory distress syndrome is complex and in need of a new paradigm.

“Some of these patients have the potential to recover, and they’re going to recover way later than what we’re used to,” said Dr. Banga. “We can’t extrapolate for COVID ARDS what we’ve learned for any other virus-related ARDS.”

Dr. Narula also has recently seen at least one COVID-19 patient on ECMO and under evaluation for transplantation recover. “We do not want to transplant too early,” he said, noting that there is consensus that lung transplant should be pursued only when the damage is deemed irreversible clinically and radiologically in the best judgment of the team. Still, “for many of these patients the only exit route will be lung transplants. For the next 12-24 months, a significant proportion of our lung transplant patients will have had post-COVID–related lung damage.”

As of October 2021, 233 lung transplants had been performed in the United States in recipients whose primary diagnosis was reported as COVID related, said Anne Paschke, media relations specialist with the United Network for Organ Sharing.

Dr. Banga, Dr. Wolfe, and Dr. Narula reported that they have no relevant disclosures.

Data is sparse thus far, but there is concern in lung transplant medicine about the long-term risk of chronic lung allograft dysfunction (CLAD) and a potentially shortened longevity of transplanted lungs in recipients who become ill with COVID-19.

Nephron/Creative Commons 3.0

“My fear is that we’re potentially sitting on this iceberg worth of people who, come 6 months or a year from [the acute phase of] their COVID illness, will in fact have earlier and progressive, chronic rejection,” said Cameron R. Wolfe, MBBS, MPH, associate professor of medicine in transplant infectious disease at Duke University, Durham, N.C.

Lower respiratory viral infections have long been concerning for lung transplant recipients given their propensity to cause scarring, a decline in lung function, and a heightened risk of allograft rejection. Time will tell whether lung transplant recipients who survive COVID-19 follow a similar path, or one that is worse, he said.
 

Short-term data

Outcomes beyond hospitalization and acute illness for lung transplant recipients affected by COVID-19 have been reported in the literature by only a few lung transplant programs. These reports – as well as anecdotal experiences being informally shared among transplant programs – have raised the specter of more severe dysfunction following the acute phase and more early CLAD, said Tathagat Narula, MD, assistant professor of medicine at the Mayo Medical School, Rochester, Minn., and a consultant in lung transplantation at the Mayo Clinic’s Jacksonville program.

“The available data cover only 3-6 months out. We don’t know what will happen in the next 6 months and beyond,” Dr. Narula said in an interview.

The risks of COVID-19 in already-transplanted patients and issues relating to the inadequate antibody responses to vaccination are just some of the challenges of lung transplant medicine in the era of SARS-CoV-2. “COVID-19,” said Dr. Narula, “has completely changed the way we practice lung transplant medicine – the way we’re looking both at our recipients and our donors.”

Potential donors are being evaluated with lower respiratory SARS-CoV-2 testing and an abundance of caution. And patients with severe COVID-19 affecting their own lungs are roundly expected to drive up lung transplant volume in the near future. “The whole paradigm has changed,” Dr. Narula said.
 

Post-acute trajectories

A chart review study published in October by the lung transplant team at the University of Texas Southwestern Medical Center, Dallas, covered 44 consecutive survivors at a median follow-up of 4.5 months from hospital discharge or acute illness (the survival rate was 83.3%). Patients had significantly impaired functional status, and 18 of the 44 (40.9%) had a significant and persistent loss of forced vital capacity or forced expiratory volume in 1 second (>10% from pre–COVID-19 baseline).

Three patients met the criteria for new CLAD after COVID-19 infection, with all three classified as restrictive allograft syndrome (RAS) phenotype.

Moreover, the majority of COVID-19 survivors who had CT chest scans (22 of 28) showed persistent parenchymal opacities – a finding that, regardless of symptomatology, suggests persistent allograft injury, said Amit Banga, MD, associate professor of medicine and medical director of the ex vivo lung perfusion program in UT Southwestern’s lung transplant program.

“The implication is that there may be long-term consequences of COVID-19, perhaps related to some degree of ongoing inflammation and damage,” said Dr. Banga, a coauthor of the postinfection outcomes paper.

The UT Southwestern lung transplant program, which normally performs 60-80 transplants a year, began routine CT scanning 4-5 months into the pandemic, after “stumbling into a few patients who had no symptoms indicative of COVID pneumonia and no changes on an x-ray but significant involvement on a CT,” he said.

Without routine scanning in the general population of COVID-19 patients, Dr. Banga noted, “we’re limited in convincingly saying that COVID is uniquely doing this to lung transplant recipients.” Nor can they conclude that SARS-CoV-2 is unique from other respiratory viruses such as respiratory syncytial virus (RSV) in this regard. (The program has added CT scanning to its protocol for lung transplant recipients afflicted with other respiratory viruses to learn more.)

However, in the big picture, COVID-19 has proven to be far worse for lung transplant recipients than illness with other respiratory viruses, including RSV. “Patients have more frequent and greater loss of lung function, and worse debility from the acute illness,” Dr. Banga said.

“The cornerstones of treatment of both these viruses are very similar, but both the in-hospital course and the postdischarge outcomes are significantly different.”

In an initial paper published in September 2021, Dr. Banga and colleagues compared their first 25 lung transplant patients testing positive for SARS-CoV-2 with a historical cohort of 36 patients with RSV treated during 2016-2018.

Patients with COVID-19 had significantly worse morbidity and mortality, including worse postinfection lung function loss, functional decline, and 3-month survival.

More time, he said, will shed light on the risks of CLAD and the long-term potential for recovery of lung function. Currently, at UT Southwestern, it appears that patients who survive acute illness and the “first 3-6 months after COVID-19, when we’re seeing all the postinfection morbidity, may [enter] a period of stability,” Dr. Banga said.

Overall, he said, patients in their initial cohort are “holding steady” without unusual morbidity, readmissions, or “other setbacks to their allografts.”

At the Mayo Clinic in Jacksonville, which normally performs 40-50 lung transplants a year, transplant physicians have similarly observed significant declines in lung function beyond the acute phase of COVID-19. “Anecdotally, we’re seeing that some patients are beginning to recover some of their lung function, while others have not,” said Dr. Narula. “And we don’t have predictors as to who will progress to CLAD. It’s a big knowledge gap.”

Dr. Narula noted that patients with restrictive allograft syndrome, such as those reported by the UT Southwestern team, “have scarring of the lung and a much worse prognosis than the obstructive type of chronic rejection.” Whether there’s a role for antifibrotic therapy is a question worthy of research.

In UT Southwestern’s analysis, persistently lower absolute lymphocyte counts (< 600/dL) and higher ferritin levels (>150 ng/mL) at the time of hospital discharge were independently associated with significant lung function loss. This finding, reported in their October paper, has helped guide their management practices, Dr. Banga said.

“Persistently elevated ferritin may indicate ongoing inflammation at the allograft level,” he said. “We now send [such patients] home on a longer course of oral corticosteroids.”

At the front end of care for infected lung transplant recipients, Dr. Banga said that his team and physicians at other lung transplant programs are holding the cell-cycle inhibitor component of patients’ maintenance immunosuppression therapy (commonly mycophenolate or azathioprine) once infection is diagnosed to maximize chances of a better outcome.

“There may be variation on how long [the regimens are adjusted],” he said. “We changed our duration from 4 weeks to 2 due to patients developing a rebound worsening in the third and fourth week of acute illness.”

There is significant variation from institution to institution in how viral infections are managed in lung transplant recipients, he and Dr. Narula said. “Our numbers are so small in lung transplant, and we don’t have standardized protocols – it’s one of the biggest challenges in our field,” said Dr. Narula.
 

Vaccination issues, evaluation of donors

Whether or not immunosuppression regimens should be adjusted prior to vaccination is a controversial question, but is “an absolutely valid one” and is currently being studied in at least one National Institutes of Health–funded trial involving solid organ transplant recipients, said Dr. Wolfe.

“Some have jumped to the conclusion [based on some earlier data] that they should reduce immunosuppression regimens for everyone at the time of vaccination ... but I don’t know the answer yet,” he said. “Balancing staying rejection free with potentially gaining more immune response is complicated ... and it may depend on where the pandemic is going in your area and other factors.”

Reductions aside, Dr. Wolfe tells lung transplant recipients that, based on his approximation of a number of different studies in solid organ transplant recipients, approximately 40%-50% of patients who are immunized with two doses of the COVID-19 mRNA vaccines will develop meaningful antibody levels – and that this rises to 50%-60% after a third dose.

It is difficult to glean from available studies the level of vaccine response for lung transplant recipients specifically. But given that their level of maintenance immunosuppression is higher than for recipients of other donor organs, “as a broad sweep, lung transplant recipients tend to be lower in the pecking order of response,” he said.

Still, “there’s a lot to gain,” he said, pointing to a recent study from the Morbidity and Mortality Weekly Report (2021 Nov 5. doi: 10.15585/mmwr.mm7044e3) showing that effectiveness of mRNA vaccination against COVID-19–associated hospitalization was 77% among immunocompromised adults (compared with 90% in immunocompetent adults).

“This is good vindication to keep vaccinating,” he said, “and perhaps speaks to how difficult it is to assess the vaccine response [through measurement of antibody only].”

Neither Duke University’s transplant program, which performed 100-120 lung transplants a year pre-COVID, nor the programs at UT Southwestern or the Mayo Clinic in Jacksonville require that solid organ transplant candidates be vaccinated against SARS-CoV-2 in order to receive transplants, as some other transplant programs have done. (When asked about the issue, Dr. Banga and Dr. Narula each said that they have had no or little trouble convincing patients awaiting lung transplants of the need for COVID-19 vaccination.)

In an August statement, the American Society of Transplantation recommended vaccination for all solid organ transplant recipients, preferably prior to transplantation, and said that it “support[s] the development of institutional policies regarding pretransplant vaccination.”

The Society is not tracking centers’ vaccination policies. But Kaiser Health News reported in October that a growing number of transplant programs, such as UCHealth in Denver and UW Medicine in Seattle, have decided to either bar patients who refuse to be vaccinated from receiving transplants or give them lower priority on waitlists.

Potential lung donors, meanwhile, must be evaluated with lower respiratory COVID-19 testing, with results available prior to transplantation, according to policy developed by the Organ Procurement and Transplantation Network and effective in May 2021. The policy followed three published cases of donor-derived COVID-19 in lung transplant recipients, said Dr. Wolfe, who wrote about use of COVID-positive donors in an editorial published in October.

In each case, the donor had a negative COVID-19 nasopharyngeal swab at the time of organ procurement but was later found to have the virus on bronchoalveolar lavage, he said.

(The use of other organs from COVID-positive donors is appearing thus far to be safe, Dr. Wolfe noted. In the editorial, he references 13 cases of solid organ transplantation from SARS-CoV-2–infected donors into noninfected recipients; none of the 13 transplant recipients developed COVID-19).

Some questions remain, such as how many lower respiratory tests should be run, and how donors should be evaluated in cases of discordant results. Dr. Banga shared the case of a donor with one positive lower respiratory test result followed by two negative results. After internal debate, and consideration of potential false positives and other issues, the team at UT Southwestern decided to decline the donor, Dr. Banga said.

Other programs are likely making similar, appropriately cautious decisions, said Dr. Wolfe. “There’s no way in real-time donor evaluation to know whether the positive test is active virus that could infect the recipient and replicate ... or whether it’s [picking up] inactive or dead fragments of virus that was there several weeks ago. Our tests don’t differentiate that.”

Transplants in COVID-19 patients

Decision-making about lung transplant candidacy among patients with COVID-19 acute respiratory distress syndrome is complex and in need of a new paradigm.

“Some of these patients have the potential to recover, and they’re going to recover way later than what we’re used to,” said Dr. Banga. “We can’t extrapolate for COVID ARDS what we’ve learned for any other virus-related ARDS.”

Dr. Narula also has recently seen at least one COVID-19 patient on ECMO and under evaluation for transplantation recover. “We do not want to transplant too early,” he said, noting that there is consensus that lung transplant should be pursued only when the damage is deemed irreversible clinically and radiologically in the best judgment of the team. Still, “for many of these patients the only exit route will be lung transplants. For the next 12-24 months, a significant proportion of our lung transplant patients will have had post-COVID–related lung damage.”

As of October 2021, 233 lung transplants had been performed in the United States in recipients whose primary diagnosis was reported as COVID related, said Anne Paschke, media relations specialist with the United Network for Organ Sharing.

Dr. Banga, Dr. Wolfe, and Dr. Narula reported that they have no relevant disclosures.

Data is sparse thus far, but there is concern in lung transplant medicine about the long-term risk of chronic lung allograft dysfunction (CLAD) and a potentially shortened longevity of transplanted lungs in recipients who become ill with COVID-19.

Nephron/Creative Commons 3.0

“My fear is that we’re potentially sitting on this iceberg worth of people who, come 6 months or a year from [the acute phase of] their COVID illness, will in fact have earlier and progressive, chronic rejection,” said Cameron R. Wolfe, MBBS, MPH, associate professor of medicine in transplant infectious disease at Duke University, Durham, N.C.

Lower respiratory viral infections have long been concerning for lung transplant recipients given their propensity to cause scarring, a decline in lung function, and a heightened risk of allograft rejection. Time will tell whether lung transplant recipients who survive COVID-19 follow a similar path, or one that is worse, he said.
 

Short-term data

Outcomes beyond hospitalization and acute illness for lung transplant recipients affected by COVID-19 have been reported in the literature by only a few lung transplant programs. These reports – as well as anecdotal experiences being informally shared among transplant programs – have raised the specter of more severe dysfunction following the acute phase and more early CLAD, said Tathagat Narula, MD, assistant professor of medicine at the Mayo Medical School, Rochester, Minn., and a consultant in lung transplantation at the Mayo Clinic’s Jacksonville program.

“The available data cover only 3-6 months out. We don’t know what will happen in the next 6 months and beyond,” Dr. Narula said in an interview.

The risks of COVID-19 in already-transplanted patients and issues relating to the inadequate antibody responses to vaccination are just some of the challenges of lung transplant medicine in the era of SARS-CoV-2. “COVID-19,” said Dr. Narula, “has completely changed the way we practice lung transplant medicine – the way we’re looking both at our recipients and our donors.”

Potential donors are being evaluated with lower respiratory SARS-CoV-2 testing and an abundance of caution. And patients with severe COVID-19 affecting their own lungs are roundly expected to drive up lung transplant volume in the near future. “The whole paradigm has changed,” Dr. Narula said.
 

Post-acute trajectories

A chart review study published in October by the lung transplant team at the University of Texas Southwestern Medical Center, Dallas, covered 44 consecutive survivors at a median follow-up of 4.5 months from hospital discharge or acute illness (the survival rate was 83.3%). Patients had significantly impaired functional status, and 18 of the 44 (40.9%) had a significant and persistent loss of forced vital capacity or forced expiratory volume in 1 second (>10% from pre–COVID-19 baseline).

Three patients met the criteria for new CLAD after COVID-19 infection, with all three classified as restrictive allograft syndrome (RAS) phenotype.

Moreover, the majority of COVID-19 survivors who had CT chest scans (22 of 28) showed persistent parenchymal opacities – a finding that, regardless of symptomatology, suggests persistent allograft injury, said Amit Banga, MD, associate professor of medicine and medical director of the ex vivo lung perfusion program in UT Southwestern’s lung transplant program.

“The implication is that there may be long-term consequences of COVID-19, perhaps related to some degree of ongoing inflammation and damage,” said Dr. Banga, a coauthor of the postinfection outcomes paper.

The UT Southwestern lung transplant program, which normally performs 60-80 transplants a year, began routine CT scanning 4-5 months into the pandemic, after “stumbling into a few patients who had no symptoms indicative of COVID pneumonia and no changes on an x-ray but significant involvement on a CT,” he said.

Without routine scanning in the general population of COVID-19 patients, Dr. Banga noted, “we’re limited in convincingly saying that COVID is uniquely doing this to lung transplant recipients.” Nor can they conclude that SARS-CoV-2 is unique from other respiratory viruses such as respiratory syncytial virus (RSV) in this regard. (The program has added CT scanning to its protocol for lung transplant recipients afflicted with other respiratory viruses to learn more.)

However, in the big picture, COVID-19 has proven to be far worse for lung transplant recipients than illness with other respiratory viruses, including RSV. “Patients have more frequent and greater loss of lung function, and worse debility from the acute illness,” Dr. Banga said.

“The cornerstones of treatment of both these viruses are very similar, but both the in-hospital course and the postdischarge outcomes are significantly different.”

In an initial paper published in September 2021, Dr. Banga and colleagues compared their first 25 lung transplant patients testing positive for SARS-CoV-2 with a historical cohort of 36 patients with RSV treated during 2016-2018.

Patients with COVID-19 had significantly worse morbidity and mortality, including worse postinfection lung function loss, functional decline, and 3-month survival.

More time, he said, will shed light on the risks of CLAD and the long-term potential for recovery of lung function. Currently, at UT Southwestern, it appears that patients who survive acute illness and the “first 3-6 months after COVID-19, when we’re seeing all the postinfection morbidity, may [enter] a period of stability,” Dr. Banga said.

Overall, he said, patients in their initial cohort are “holding steady” without unusual morbidity, readmissions, or “other setbacks to their allografts.”

At the Mayo Clinic in Jacksonville, which normally performs 40-50 lung transplants a year, transplant physicians have similarly observed significant declines in lung function beyond the acute phase of COVID-19. “Anecdotally, we’re seeing that some patients are beginning to recover some of their lung function, while others have not,” said Dr. Narula. “And we don’t have predictors as to who will progress to CLAD. It’s a big knowledge gap.”

Dr. Narula noted that patients with restrictive allograft syndrome, such as those reported by the UT Southwestern team, “have scarring of the lung and a much worse prognosis than the obstructive type of chronic rejection.” Whether there’s a role for antifibrotic therapy is a question worthy of research.

In UT Southwestern’s analysis, persistently lower absolute lymphocyte counts (< 600/dL) and higher ferritin levels (>150 ng/mL) at the time of hospital discharge were independently associated with significant lung function loss. This finding, reported in their October paper, has helped guide their management practices, Dr. Banga said.

“Persistently elevated ferritin may indicate ongoing inflammation at the allograft level,” he said. “We now send [such patients] home on a longer course of oral corticosteroids.”

At the front end of care for infected lung transplant recipients, Dr. Banga said that his team and physicians at other lung transplant programs are holding the cell-cycle inhibitor component of patients’ maintenance immunosuppression therapy (commonly mycophenolate or azathioprine) once infection is diagnosed to maximize chances of a better outcome.

“There may be variation on how long [the regimens are adjusted],” he said. “We changed our duration from 4 weeks to 2 due to patients developing a rebound worsening in the third and fourth week of acute illness.”

There is significant variation from institution to institution in how viral infections are managed in lung transplant recipients, he and Dr. Narula said. “Our numbers are so small in lung transplant, and we don’t have standardized protocols – it’s one of the biggest challenges in our field,” said Dr. Narula.
 

Vaccination issues, evaluation of donors

Whether or not immunosuppression regimens should be adjusted prior to vaccination is a controversial question, but is “an absolutely valid one” and is currently being studied in at least one National Institutes of Health–funded trial involving solid organ transplant recipients, said Dr. Wolfe.

“Some have jumped to the conclusion [based on some earlier data] that they should reduce immunosuppression regimens for everyone at the time of vaccination ... but I don’t know the answer yet,” he said. “Balancing staying rejection free with potentially gaining more immune response is complicated ... and it may depend on where the pandemic is going in your area and other factors.”

Reductions aside, Dr. Wolfe tells lung transplant recipients that, based on his approximation of a number of different studies in solid organ transplant recipients, approximately 40%-50% of patients who are immunized with two doses of the COVID-19 mRNA vaccines will develop meaningful antibody levels – and that this rises to 50%-60% after a third dose.

It is difficult to glean from available studies the level of vaccine response for lung transplant recipients specifically. But given that their level of maintenance immunosuppression is higher than for recipients of other donor organs, “as a broad sweep, lung transplant recipients tend to be lower in the pecking order of response,” he said.

Still, “there’s a lot to gain,” he said, pointing to a recent study from the Morbidity and Mortality Weekly Report (2021 Nov 5. doi: 10.15585/mmwr.mm7044e3) showing that effectiveness of mRNA vaccination against COVID-19–associated hospitalization was 77% among immunocompromised adults (compared with 90% in immunocompetent adults).

“This is good vindication to keep vaccinating,” he said, “and perhaps speaks to how difficult it is to assess the vaccine response [through measurement of antibody only].”

Neither Duke University’s transplant program, which performed 100-120 lung transplants a year pre-COVID, nor the programs at UT Southwestern or the Mayo Clinic in Jacksonville require that solid organ transplant candidates be vaccinated against SARS-CoV-2 in order to receive transplants, as some other transplant programs have done. (When asked about the issue, Dr. Banga and Dr. Narula each said that they have had no or little trouble convincing patients awaiting lung transplants of the need for COVID-19 vaccination.)

In an August statement, the American Society of Transplantation recommended vaccination for all solid organ transplant recipients, preferably prior to transplantation, and said that it “support[s] the development of institutional policies regarding pretransplant vaccination.”

The Society is not tracking centers’ vaccination policies. But Kaiser Health News reported in October that a growing number of transplant programs, such as UCHealth in Denver and UW Medicine in Seattle, have decided to either bar patients who refuse to be vaccinated from receiving transplants or give them lower priority on waitlists.

Potential lung donors, meanwhile, must be evaluated with lower respiratory COVID-19 testing, with results available prior to transplantation, according to policy developed by the Organ Procurement and Transplantation Network and effective in May 2021. The policy followed three published cases of donor-derived COVID-19 in lung transplant recipients, said Dr. Wolfe, who wrote about use of COVID-positive donors in an editorial published in October.

In each case, the donor had a negative COVID-19 nasopharyngeal swab at the time of organ procurement but was later found to have the virus on bronchoalveolar lavage, he said.

(The use of other organs from COVID-positive donors is appearing thus far to be safe, Dr. Wolfe noted. In the editorial, he references 13 cases of solid organ transplantation from SARS-CoV-2–infected donors into noninfected recipients; none of the 13 transplant recipients developed COVID-19).

Some questions remain, such as how many lower respiratory tests should be run, and how donors should be evaluated in cases of discordant results. Dr. Banga shared the case of a donor with one positive lower respiratory test result followed by two negative results. After internal debate, and consideration of potential false positives and other issues, the team at UT Southwestern decided to decline the donor, Dr. Banga said.

Other programs are likely making similar, appropriately cautious decisions, said Dr. Wolfe. “There’s no way in real-time donor evaluation to know whether the positive test is active virus that could infect the recipient and replicate ... or whether it’s [picking up] inactive or dead fragments of virus that was there several weeks ago. Our tests don’t differentiate that.”

Transplants in COVID-19 patients

Decision-making about lung transplant candidacy among patients with COVID-19 acute respiratory distress syndrome is complex and in need of a new paradigm.

“Some of these patients have the potential to recover, and they’re going to recover way later than what we’re used to,” said Dr. Banga. “We can’t extrapolate for COVID ARDS what we’ve learned for any other virus-related ARDS.”

Dr. Narula also has recently seen at least one COVID-19 patient on ECMO and under evaluation for transplantation recover. “We do not want to transplant too early,” he said, noting that there is consensus that lung transplant should be pursued only when the damage is deemed irreversible clinically and radiologically in the best judgment of the team. Still, “for many of these patients the only exit route will be lung transplants. For the next 12-24 months, a significant proportion of our lung transplant patients will have had post-COVID–related lung damage.”

As of October 2021, 233 lung transplants had been performed in the United States in recipients whose primary diagnosis was reported as COVID related, said Anne Paschke, media relations specialist with the United Network for Organ Sharing.

Dr. Banga, Dr. Wolfe, and Dr. Narula reported that they have no relevant disclosures.

Background: The standard of care for IE has been a prolonged course of IV antibiotics. Recent literature has suggested that oral antibiotics might be a safe and effective step-down therapy for IE.

In studies wherein IV antibiotics alone were compared with IV antibiotics with oral step-down therapy, there was no difference in clinical cure rate. Those given oral step-down therapy had a statistically significant lower mortality rate than patients who received only IV therapy.

Limitations include inconclusive data regarding duration of IV lead-in therapy, with the variance before conversion to oral antibiotics amongst the studies ranging from 0 to 24 days. The limited number of patients with MRSA infections makes it difficult to draw conclusions regarding this particular pathogen.

Bottom line: Highly orally bioavailable antibiotics should be considered for patients with IE who have cleared bacteremia and achieved clinical stability with IV regimens.

Citation: Spellberg B et al. Evaluation of a paradigm shift from intravenous antibiotics to oral step-down therapy for the treatment of infective endocarditis: a narrative review. JAMA Intern Med. 2020;180(5):769-77. doi: 10.1001/jamainternmed.2020.0555.

Dr. Yoo is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: The standard of care for IE has been a prolonged course of IV antibiotics. Recent literature has suggested that oral antibiotics might be a safe and effective step-down therapy for IE.

In studies wherein IV antibiotics alone were compared with IV antibiotics with oral step-down therapy, there was no difference in clinical cure rate. Those given oral step-down therapy had a statistically significant lower mortality rate than patients who received only IV therapy.

Limitations include inconclusive data regarding duration of IV lead-in therapy, with the variance before conversion to oral antibiotics amongst the studies ranging from 0 to 24 days. The limited number of patients with MRSA infections makes it difficult to draw conclusions regarding this particular pathogen.

Bottom line: Highly orally bioavailable antibiotics should be considered for patients with IE who have cleared bacteremia and achieved clinical stability with IV regimens.

Citation: Spellberg B et al. Evaluation of a paradigm shift from intravenous antibiotics to oral step-down therapy for the treatment of infective endocarditis: a narrative review. JAMA Intern Med. 2020;180(5):769-77. doi: 10.1001/jamainternmed.2020.0555.

Dr. Yoo is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: The standard of care for IE has been a prolonged course of IV antibiotics. Recent literature has suggested that oral antibiotics might be a safe and effective step-down therapy for IE.

In studies wherein IV antibiotics alone were compared with IV antibiotics with oral step-down therapy, there was no difference in clinical cure rate. Those given oral step-down therapy had a statistically significant lower mortality rate than patients who received only IV therapy.

Limitations include inconclusive data regarding duration of IV lead-in therapy, with the variance before conversion to oral antibiotics amongst the studies ranging from 0 to 24 days. The limited number of patients with MRSA infections makes it difficult to draw conclusions regarding this particular pathogen.

Bottom line: Highly orally bioavailable antibiotics should be considered for patients with IE who have cleared bacteremia and achieved clinical stability with IV regimens.

Citation: Spellberg B et al. Evaluation of a paradigm shift from intravenous antibiotics to oral step-down therapy for the treatment of infective endocarditis: a narrative review. JAMA Intern Med. 2020;180(5):769-77. doi: 10.1001/jamainternmed.2020.0555.

Dr. Yoo is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

ATLANTA - A new drug recently introduced for use in the treatment of refractory/relapsed multiple myeloma looks like it will also find a role in the treatment of patients with newly diagnosed transplant-eligible multiple myeloma.

The drug is isatuximab (Sarclisa, Sanofi), an anti-CD38 antibody that was approved last year for use in patients with advanced disease.

Now it has shown benefit in patients who have been newly diagnosed with the disease. When isatuximab was added onto a usual triplet therapy for myeloma, it increased the likelihood that patients would be negative for minimal residual disease (MRD) at the end of the induction phase of treatment, thereby increasing their chances for a successful autologous stem cell transplant (ASCT).

The new results come from the GMMG-HD7 trial, in which all patients were treated with the triplet combination of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd).

Some patients, after randomization, also received isatuximab, and in this group, the MRD-negativity rate was 50.1% at the end of induction therapy compared with 35.6% for patients treated with RVd alone.  

Patients who are MRD-negative at the time of ASCT have significantly better outcomes than patients who remain MRD-positive.

“Isa-RVd is the first regimen to demonstrate significant MRD-negativity benefit at the end of induction versus RVd in a phase 3 trial,” reported Hartmut Goldschmidt, MD, from University Hospital Heidelberg, Germany.

“The benefits of the addition of Isa to RVd versus RVd regarding MRD negativity after induction therapy was consistent in all subgroups,” he added.

Dr. Goldschmidt spoke at a press briefing prior to his presentation of the data here at the annual meeting of the American Society of Hematology (ASH).

“I think that these data are encouraging, but they are preliminary, and we need mature data to be absolutely certain about whether this presents a major advance in treatment,” commented Ravi Vij, MD, from the Siteman Cancer Center and Washington University School of Medicine in St. Louis. Dr. Vij was not involved in the study.

“We know that for transplant-eligible patients, for whom this trial was conducted, the field is moving toward giving four drugs for induction,” he said in an interview with this news organization.

He noted that the combination of RVd with the other currently available anti-CD38 antibody, daratumumab (Darzalex), was approved for this indication in the United States in Jan. 2021.

Dr. Vij said that isatuximab has been slow to catch on in the United States both because it was approved after clinicians had already become familiar with daratumumab and because it is given intravenously, compared with subcutaneous administration of the latest formulation of daratumumab.

“Whereas isatuximab can take an hour-and-a-half with each infusion, daratumumab takes 5 minutes for an injection and the patient is out of there, so it is convenient both for the patient and the treating institution,” he said.
 

MRD vs. CR?

Dr. Goldschmidt was asked during the briefing about whether MRD-negativity or complete response rates are better predictors of progression-free survival (PFS). He replied that with current standardized sequencing techniques and sensitivity down to 10-6, “it’s a big benefit to analyze MRD negativity, and there is ongoing discussion between colleagues from the myeloma group with the Food and Drug Administration about how we can merge the data and predict PFS and overall survival.”

Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer, Vancouver, who moderated the briefing, commented that “we’re desperately looking for surrogate markers to speed up answers to clinical trials, and I think MRD in myeloma is quickly becoming a very important surrogate marker.”
 

GMMG-7 results

For their trial, Dr. Goldschmidt and colleagues enrolled 662 patients with newly diagnosed multiple myeloma who were candidates for high-dose therapy and ASCT and after stratification by revised International Staging System (r-ISS) criteria, randomly assigned them six three-week cycles of induction therapy with Isa-RVd or RVd alone.

Following ASCT, patients were again randomized to maintenance with either isatuximab plus lenalidomide or lenalidomide alone.

As noted before, MRD rates at the end of induction were 50.1% with Isa-RVd versus 35.6% with RVd alone, translating to a hazard ratio favoring the four-drug combination of 1.83 (P < .001).

Treatment with Isa-RVd was the only significant predictor for the likelihood of MRD negativity in a multivariate analysis controlling for treatment group, r-ISS status, performance status, renal impairment, age, and sex.

Although the rate of complete responses at the end of induction was similar between the treatment groups, the rate of very good partial response or better was higher with the isatuximab-containing combination (77.3% vs. 60.5%; P < .001).

The respective rates of disease progression at the end of induction in the Isa-RVd and RVd groups were 1.5% versus 4.0%.

The rates of adverse events were generally similar between the groups, except a higher proportion of patients had leukocytopenia or neutropenia in the Isa-RVd than the RVdgroup (26.4% vs. 9.1%). There were four deaths in the Isa-RVd group and eight in the RVd group. Most of the deaths were attributable to disease progression or COVID-19, said Dr. Goldschmidt.

The study was funded by Sanofi. Dr. Goldschmidt has disclosed honoraria and research grants from Sanofi and others. Dr. Vij has disclosed honoraria or advisory board activities from various companies, including Sanofi. Dr. Sehn is a consultant for and has received honoraria from various companies, not including Sanofi.

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

ATLANTA - A new drug recently introduced for use in the treatment of refractory/relapsed multiple myeloma looks like it will also find a role in the treatment of patients with newly diagnosed transplant-eligible multiple myeloma.

The drug is isatuximab (Sarclisa, Sanofi), an anti-CD38 antibody that was approved last year for use in patients with advanced disease.

Now it has shown benefit in patients who have been newly diagnosed with the disease. When isatuximab was added onto a usual triplet therapy for myeloma, it increased the likelihood that patients would be negative for minimal residual disease (MRD) at the end of the induction phase of treatment, thereby increasing their chances for a successful autologous stem cell transplant (ASCT).

The new results come from the GMMG-HD7 trial, in which all patients were treated with the triplet combination of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd).

Some patients, after randomization, also received isatuximab, and in this group, the MRD-negativity rate was 50.1% at the end of induction therapy compared with 35.6% for patients treated with RVd alone.  

Patients who are MRD-negative at the time of ASCT have significantly better outcomes than patients who remain MRD-positive.

“Isa-RVd is the first regimen to demonstrate significant MRD-negativity benefit at the end of induction versus RVd in a phase 3 trial,” reported Hartmut Goldschmidt, MD, from University Hospital Heidelberg, Germany.

“The benefits of the addition of Isa to RVd versus RVd regarding MRD negativity after induction therapy was consistent in all subgroups,” he added.

Dr. Goldschmidt spoke at a press briefing prior to his presentation of the data here at the annual meeting of the American Society of Hematology (ASH).

“I think that these data are encouraging, but they are preliminary, and we need mature data to be absolutely certain about whether this presents a major advance in treatment,” commented Ravi Vij, MD, from the Siteman Cancer Center and Washington University School of Medicine in St. Louis. Dr. Vij was not involved in the study.

“We know that for transplant-eligible patients, for whom this trial was conducted, the field is moving toward giving four drugs for induction,” he said in an interview with this news organization.

He noted that the combination of RVd with the other currently available anti-CD38 antibody, daratumumab (Darzalex), was approved for this indication in the United States in Jan. 2021.

Dr. Vij said that isatuximab has been slow to catch on in the United States both because it was approved after clinicians had already become familiar with daratumumab and because it is given intravenously, compared with subcutaneous administration of the latest formulation of daratumumab.

“Whereas isatuximab can take an hour-and-a-half with each infusion, daratumumab takes 5 minutes for an injection and the patient is out of there, so it is convenient both for the patient and the treating institution,” he said.
 

MRD vs. CR?

Dr. Goldschmidt was asked during the briefing about whether MRD-negativity or complete response rates are better predictors of progression-free survival (PFS). He replied that with current standardized sequencing techniques and sensitivity down to 10-6, “it’s a big benefit to analyze MRD negativity, and there is ongoing discussion between colleagues from the myeloma group with the Food and Drug Administration about how we can merge the data and predict PFS and overall survival.”

Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer, Vancouver, who moderated the briefing, commented that “we’re desperately looking for surrogate markers to speed up answers to clinical trials, and I think MRD in myeloma is quickly becoming a very important surrogate marker.”
 

GMMG-7 results

For their trial, Dr. Goldschmidt and colleagues enrolled 662 patients with newly diagnosed multiple myeloma who were candidates for high-dose therapy and ASCT and after stratification by revised International Staging System (r-ISS) criteria, randomly assigned them six three-week cycles of induction therapy with Isa-RVd or RVd alone.

Following ASCT, patients were again randomized to maintenance with either isatuximab plus lenalidomide or lenalidomide alone.

As noted before, MRD rates at the end of induction were 50.1% with Isa-RVd versus 35.6% with RVd alone, translating to a hazard ratio favoring the four-drug combination of 1.83 (P < .001).

Treatment with Isa-RVd was the only significant predictor for the likelihood of MRD negativity in a multivariate analysis controlling for treatment group, r-ISS status, performance status, renal impairment, age, and sex.

Although the rate of complete responses at the end of induction was similar between the treatment groups, the rate of very good partial response or better was higher with the isatuximab-containing combination (77.3% vs. 60.5%; P < .001).

The respective rates of disease progression at the end of induction in the Isa-RVd and RVd groups were 1.5% versus 4.0%.

The rates of adverse events were generally similar between the groups, except a higher proportion of patients had leukocytopenia or neutropenia in the Isa-RVd than the RVdgroup (26.4% vs. 9.1%). There were four deaths in the Isa-RVd group and eight in the RVd group. Most of the deaths were attributable to disease progression or COVID-19, said Dr. Goldschmidt.

The study was funded by Sanofi. Dr. Goldschmidt has disclosed honoraria and research grants from Sanofi and others. Dr. Vij has disclosed honoraria or advisory board activities from various companies, including Sanofi. Dr. Sehn is a consultant for and has received honoraria from various companies, not including Sanofi.

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

ATLANTA - A new drug recently introduced for use in the treatment of refractory/relapsed multiple myeloma looks like it will also find a role in the treatment of patients with newly diagnosed transplant-eligible multiple myeloma.

The drug is isatuximab (Sarclisa, Sanofi), an anti-CD38 antibody that was approved last year for use in patients with advanced disease.

Now it has shown benefit in patients who have been newly diagnosed with the disease. When isatuximab was added onto a usual triplet therapy for myeloma, it increased the likelihood that patients would be negative for minimal residual disease (MRD) at the end of the induction phase of treatment, thereby increasing their chances for a successful autologous stem cell transplant (ASCT).

The new results come from the GMMG-HD7 trial, in which all patients were treated with the triplet combination of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd).

Some patients, after randomization, also received isatuximab, and in this group, the MRD-negativity rate was 50.1% at the end of induction therapy compared with 35.6% for patients treated with RVd alone.  

Patients who are MRD-negative at the time of ASCT have significantly better outcomes than patients who remain MRD-positive.

“Isa-RVd is the first regimen to demonstrate significant MRD-negativity benefit at the end of induction versus RVd in a phase 3 trial,” reported Hartmut Goldschmidt, MD, from University Hospital Heidelberg, Germany.

“The benefits of the addition of Isa to RVd versus RVd regarding MRD negativity after induction therapy was consistent in all subgroups,” he added.

Dr. Goldschmidt spoke at a press briefing prior to his presentation of the data here at the annual meeting of the American Society of Hematology (ASH).

“I think that these data are encouraging, but they are preliminary, and we need mature data to be absolutely certain about whether this presents a major advance in treatment,” commented Ravi Vij, MD, from the Siteman Cancer Center and Washington University School of Medicine in St. Louis. Dr. Vij was not involved in the study.

“We know that for transplant-eligible patients, for whom this trial was conducted, the field is moving toward giving four drugs for induction,” he said in an interview with this news organization.

He noted that the combination of RVd with the other currently available anti-CD38 antibody, daratumumab (Darzalex), was approved for this indication in the United States in Jan. 2021.

Dr. Vij said that isatuximab has been slow to catch on in the United States both because it was approved after clinicians had already become familiar with daratumumab and because it is given intravenously, compared with subcutaneous administration of the latest formulation of daratumumab.

“Whereas isatuximab can take an hour-and-a-half with each infusion, daratumumab takes 5 minutes for an injection and the patient is out of there, so it is convenient both for the patient and the treating institution,” he said.
 

MRD vs. CR?

Dr. Goldschmidt was asked during the briefing about whether MRD-negativity or complete response rates are better predictors of progression-free survival (PFS). He replied that with current standardized sequencing techniques and sensitivity down to 10-6, “it’s a big benefit to analyze MRD negativity, and there is ongoing discussion between colleagues from the myeloma group with the Food and Drug Administration about how we can merge the data and predict PFS and overall survival.”

Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer, Vancouver, who moderated the briefing, commented that “we’re desperately looking for surrogate markers to speed up answers to clinical trials, and I think MRD in myeloma is quickly becoming a very important surrogate marker.”
 

GMMG-7 results

For their trial, Dr. Goldschmidt and colleagues enrolled 662 patients with newly diagnosed multiple myeloma who were candidates for high-dose therapy and ASCT and after stratification by revised International Staging System (r-ISS) criteria, randomly assigned them six three-week cycles of induction therapy with Isa-RVd or RVd alone.

Following ASCT, patients were again randomized to maintenance with either isatuximab plus lenalidomide or lenalidomide alone.

As noted before, MRD rates at the end of induction were 50.1% with Isa-RVd versus 35.6% with RVd alone, translating to a hazard ratio favoring the four-drug combination of 1.83 (P < .001).

Treatment with Isa-RVd was the only significant predictor for the likelihood of MRD negativity in a multivariate analysis controlling for treatment group, r-ISS status, performance status, renal impairment, age, and sex.

Although the rate of complete responses at the end of induction was similar between the treatment groups, the rate of very good partial response or better was higher with the isatuximab-containing combination (77.3% vs. 60.5%; P < .001).

The respective rates of disease progression at the end of induction in the Isa-RVd and RVd groups were 1.5% versus 4.0%.

The rates of adverse events were generally similar between the groups, except a higher proportion of patients had leukocytopenia or neutropenia in the Isa-RVd than the RVdgroup (26.4% vs. 9.1%). There were four deaths in the Isa-RVd group and eight in the RVd group. Most of the deaths were attributable to disease progression or COVID-19, said Dr. Goldschmidt.

The study was funded by Sanofi. Dr. Goldschmidt has disclosed honoraria and research grants from Sanofi and others. Dr. Vij has disclosed honoraria or advisory board activities from various companies, including Sanofi. Dr. Sehn is a consultant for and has received honoraria from various companies, not including Sanofi.

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

Most of the United States will see significant growth in COVID-19 cases during the next four weeks, according to the latest forecasting models by the PolicyLab at Children’s Hospital of Philadelphia.

Courtesy NIAID-RML

Large metropolitan areas, especially those in the Northeast, are already seeing a major increase in cases following Thanksgiving, and that trend is expected to continue.

“Why? Simply stated, the large amount of Thanksgiving travel and gatherings undermined the nation’s pandemic footing and has elevated disease burden in areas of the country that were fortunate to have lower case rates before the holidays,” the forecasters wrote.

Case numbers in New York City are expected to double throughout December, the forecasters said. Similar growth could happen across Boston, Philadelphia, and Baltimore.

Overall, COVID-19 cases, hospitalizations, and deaths are rising across the United States but remain below levels seen during the summer and last winter’s surges, according to the New York Times. The increase is still being driven by the Delta variant, though it remains unclear how the Omicron variant, which has been detected in 27 states, could affect the trends in the coming weeks.

During the past week, the United States has reported an average of more than 120,000 new cases each day, the newspaper reported, which is an increase of 38% from two weeks ago.

The daily average of COVID-19 hospitalizations is around 64,000, which marks an increase of 22% from two weeks ago. More than 1,300 deaths are being reported each day, which is up 26%.

Numerous states are reporting double the cases from two weeks ago, stretching across the country from states in the Northeast such as Connecticut and Rhode Island to southern states such as North Carolina and Texas and western states such as California.

The Great Lakes region and the Northeast are seeing some of the most severe increases, the newspaper reported. New Hampshire leads the United States in recent cases per capita, and Maine has reported more cases in the past week than in any other seven-day period during the pandemic.

Michigan has the country’s highest hospitalization rate, and federal medical teams have been sent to the state to help with the surge in patients, according to The Detroit News. Michigan’s top public health officials described the surge as a “critical” and “deeply concerning” situation on Dec. 10, and they requested 200 more ventilators from the Strategic National Stockpile.

Indiana, Maine, and New York have also requested aid from the National Guard, according to USA Today. Health officials in those states urged residents to get vaccines or booster shots and wear masks in indoor public settings.

The Omicron variant can evade some vaccine protection, but booster shots can increase efficacy and offer more coverage, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said Dec. 12.

“If you want to be optimally protected, absolutely get a booster,” he said on ABC’s “This Week.”

In addition, New York Gov. Kathy Hochul has announced a statewide mask mandate, which will take effect Dec. 13. Masks will be required in all indoor public spaces and businesses, unless the location implements a vaccine requirement instead, the news outlet reported.

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

Most of the United States will see significant growth in COVID-19 cases during the next four weeks, according to the latest forecasting models by the PolicyLab at Children’s Hospital of Philadelphia.

Courtesy NIAID-RML

Large metropolitan areas, especially those in the Northeast, are already seeing a major increase in cases following Thanksgiving, and that trend is expected to continue.

“Why? Simply stated, the large amount of Thanksgiving travel and gatherings undermined the nation’s pandemic footing and has elevated disease burden in areas of the country that were fortunate to have lower case rates before the holidays,” the forecasters wrote.

Case numbers in New York City are expected to double throughout December, the forecasters said. Similar growth could happen across Boston, Philadelphia, and Baltimore.

Overall, COVID-19 cases, hospitalizations, and deaths are rising across the United States but remain below levels seen during the summer and last winter’s surges, according to the New York Times. The increase is still being driven by the Delta variant, though it remains unclear how the Omicron variant, which has been detected in 27 states, could affect the trends in the coming weeks.

During the past week, the United States has reported an average of more than 120,000 new cases each day, the newspaper reported, which is an increase of 38% from two weeks ago.

The daily average of COVID-19 hospitalizations is around 64,000, which marks an increase of 22% from two weeks ago. More than 1,300 deaths are being reported each day, which is up 26%.

Numerous states are reporting double the cases from two weeks ago, stretching across the country from states in the Northeast such as Connecticut and Rhode Island to southern states such as North Carolina and Texas and western states such as California.

The Great Lakes region and the Northeast are seeing some of the most severe increases, the newspaper reported. New Hampshire leads the United States in recent cases per capita, and Maine has reported more cases in the past week than in any other seven-day period during the pandemic.

Michigan has the country’s highest hospitalization rate, and federal medical teams have been sent to the state to help with the surge in patients, according to The Detroit News. Michigan’s top public health officials described the surge as a “critical” and “deeply concerning” situation on Dec. 10, and they requested 200 more ventilators from the Strategic National Stockpile.

Indiana, Maine, and New York have also requested aid from the National Guard, according to USA Today. Health officials in those states urged residents to get vaccines or booster shots and wear masks in indoor public settings.

The Omicron variant can evade some vaccine protection, but booster shots can increase efficacy and offer more coverage, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said Dec. 12.

“If you want to be optimally protected, absolutely get a booster,” he said on ABC’s “This Week.”

In addition, New York Gov. Kathy Hochul has announced a statewide mask mandate, which will take effect Dec. 13. Masks will be required in all indoor public spaces and businesses, unless the location implements a vaccine requirement instead, the news outlet reported.

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

Most of the United States will see significant growth in COVID-19 cases during the next four weeks, according to the latest forecasting models by the PolicyLab at Children’s Hospital of Philadelphia.

Courtesy NIAID-RML

Large metropolitan areas, especially those in the Northeast, are already seeing a major increase in cases following Thanksgiving, and that trend is expected to continue.

“Why? Simply stated, the large amount of Thanksgiving travel and gatherings undermined the nation’s pandemic footing and has elevated disease burden in areas of the country that were fortunate to have lower case rates before the holidays,” the forecasters wrote.

Case numbers in New York City are expected to double throughout December, the forecasters said. Similar growth could happen across Boston, Philadelphia, and Baltimore.

Overall, COVID-19 cases, hospitalizations, and deaths are rising across the United States but remain below levels seen during the summer and last winter’s surges, according to the New York Times. The increase is still being driven by the Delta variant, though it remains unclear how the Omicron variant, which has been detected in 27 states, could affect the trends in the coming weeks.

During the past week, the United States has reported an average of more than 120,000 new cases each day, the newspaper reported, which is an increase of 38% from two weeks ago.

The daily average of COVID-19 hospitalizations is around 64,000, which marks an increase of 22% from two weeks ago. More than 1,300 deaths are being reported each day, which is up 26%.

Numerous states are reporting double the cases from two weeks ago, stretching across the country from states in the Northeast such as Connecticut and Rhode Island to southern states such as North Carolina and Texas and western states such as California.

The Great Lakes region and the Northeast are seeing some of the most severe increases, the newspaper reported. New Hampshire leads the United States in recent cases per capita, and Maine has reported more cases in the past week than in any other seven-day period during the pandemic.

Michigan has the country’s highest hospitalization rate, and federal medical teams have been sent to the state to help with the surge in patients, according to The Detroit News. Michigan’s top public health officials described the surge as a “critical” and “deeply concerning” situation on Dec. 10, and they requested 200 more ventilators from the Strategic National Stockpile.

Indiana, Maine, and New York have also requested aid from the National Guard, according to USA Today. Health officials in those states urged residents to get vaccines or booster shots and wear masks in indoor public settings.

The Omicron variant can evade some vaccine protection, but booster shots can increase efficacy and offer more coverage, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said Dec. 12.

“If you want to be optimally protected, absolutely get a booster,” he said on ABC’s “This Week.”

In addition, New York Gov. Kathy Hochul has announced a statewide mask mandate, which will take effect Dec. 13. Masks will be required in all indoor public spaces and businesses, unless the location implements a vaccine requirement instead, the news outlet reported.

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

The oral Janus kinase 1 inhibitor abrocitinib has been approved in Europe for the treatment of moderate to severe atopic dermatitis (AD) in adults, who are candidates for systemic therapy, the manufacturer announced.

Approval by the European Commission was based on the results of studies that include four phase 3 clinical trials (JADE MONO-1, JADE-MONO-2, JADE COMPARE, JADE REGIMEN) and an ongoing open-label extension study (JADE EXTEND) in over 2,800 patients, according to the Pfizer press release announcing the approval. The approved doses are 100 and 200 mg a day; a 50-mg dose was approved for patients with moderate and severe renal impairment and “ certain patients receiving treatment with inhibitors of cytochrome P450 (CYP) 2C19,” the release said.

The approval follows a positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency supporting marketing authorization for treating AD, issued in October. It will be marketed as Cibinqo.

Abrocitinib is under review at the Food and Drug Administration. It was approved earlier in 2021 for treating AD in the United Kingdom, Japan, and Korea.

[email protected]

The oral Janus kinase 1 inhibitor abrocitinib has been approved in Europe for the treatment of moderate to severe atopic dermatitis (AD) in adults, who are candidates for systemic therapy, the manufacturer announced.

Approval by the European Commission was based on the results of studies that include four phase 3 clinical trials (JADE MONO-1, JADE-MONO-2, JADE COMPARE, JADE REGIMEN) and an ongoing open-label extension study (JADE EXTEND) in over 2,800 patients, according to the Pfizer press release announcing the approval. The approved doses are 100 and 200 mg a day; a 50-mg dose was approved for patients with moderate and severe renal impairment and “ certain patients receiving treatment with inhibitors of cytochrome P450 (CYP) 2C19,” the release said.

The approval follows a positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency supporting marketing authorization for treating AD, issued in October. It will be marketed as Cibinqo.

Abrocitinib is under review at the Food and Drug Administration. It was approved earlier in 2021 for treating AD in the United Kingdom, Japan, and Korea.

[email protected]

The oral Janus kinase 1 inhibitor abrocitinib has been approved in Europe for the treatment of moderate to severe atopic dermatitis (AD) in adults, who are candidates for systemic therapy, the manufacturer announced.

Approval by the European Commission was based on the results of studies that include four phase 3 clinical trials (JADE MONO-1, JADE-MONO-2, JADE COMPARE, JADE REGIMEN) and an ongoing open-label extension study (JADE EXTEND) in over 2,800 patients, according to the Pfizer press release announcing the approval. The approved doses are 100 and 200 mg a day; a 50-mg dose was approved for patients with moderate and severe renal impairment and “ certain patients receiving treatment with inhibitors of cytochrome P450 (CYP) 2C19,” the release said.

The approval follows a positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency supporting marketing authorization for treating AD, issued in October. It will be marketed as Cibinqo.

Abrocitinib is under review at the Food and Drug Administration. It was approved earlier in 2021 for treating AD in the United Kingdom, Japan, and Korea.

[email protected]

SAN ANTONIO – A small study suggests the frequent use of antibiotics among women with triple-negative breast cancer, may have an impact on overall and breast cancer–specific mortality.

The study was recently presented at the San Antonio Breast Cancer Symposium by Julia D. Ransohoff, MD, of Stanford (Calif.) University.

Gut-associated lymphoid tissues are the largest component of the immune system. They influence both local and systemic immune responses, but the use of antimicrobials can decrease circulating and tumor-infiltrating lymphocytes that effect the immune repertoire and in turn, the survival of women with triple-negative breast cancer.

Dr. Ransohoff and colleagues hypothesized that increasing antimicrobial exposure in the presence of time-varying absolute lymphocyte counts may lead to higher overall and breast cancer–specific mortality. Their analysis is based on data from the population-based Surveillance, Epidemiology, and End Results registry and electronic medical records from Stanford University and Sutter Health. It included 772 women who were treated for triple-negative breast cancer between 2000 and 2014. The women were followed for an average of 104 months.

In an earlier analysis of this same group, Dr. Ransohoff found that higher minimum absolute lymphocyte counts were associated with lower overall mortality (hazard ratio, 0.23; 95% confidence interval, 0.16-0.35) and breast cancer mortality (HR, 0.19; 95% CI, 0.11-0.34) The association between higher peripheral lymphocyte counts and tumor-infiltrating lymphocytes was significant.

In the analysis of relationships between antibiotic use and mortality, 85% of women (n = 654) were prescribed antibiotics after having been diagnosed with triple-negative breast cancer. The death rate among patients who were prescribed antibiotics was 23% (153/654), compared with 20% (24/118) among the patients who were not treated with antibiotics (which accounts for 15% of the entire group).

For total antibiotic exposure, the HR for overall mortality was 1.06 (95% CI, 1.03-1.09; P < .001) and 1.07 for breast cancer–specific mortality (95% CI, 1.04-1.10; P < .001). For unique antibiotic exposure (not counting repeat prescriptions of the same antibiotic), the HR for overall mortality was 1.17 (95% CI, 1.12-1.22; P < .001) and 1.18 for breast cancer–specific mortality (95% CI, 1.12-1.24; P < .001). 

“These were all statistically significant associations derived from a statistical model that takes into account baseline patient characteristics, so the reported hazard ratios, to the best of our ability, represent the risk of death associated with antibiotic use adjusted for other baseline covariates. We’ve attempted to account for differences at baseline that may indicate patients are sicker, and so the reported risk represents mortality related with antibiotic exposure,” Dr. Ransohoff said.

Elucidating the role of the microbiome in mediating absolute lymphocyte counts and immune response may inform interventions to reduce triple-negative mortality, she said.

SAN ANTONIO – A small study suggests the frequent use of antibiotics among women with triple-negative breast cancer, may have an impact on overall and breast cancer–specific mortality.

The study was recently presented at the San Antonio Breast Cancer Symposium by Julia D. Ransohoff, MD, of Stanford (Calif.) University.

Gut-associated lymphoid tissues are the largest component of the immune system. They influence both local and systemic immune responses, but the use of antimicrobials can decrease circulating and tumor-infiltrating lymphocytes that effect the immune repertoire and in turn, the survival of women with triple-negative breast cancer.

Dr. Ransohoff and colleagues hypothesized that increasing antimicrobial exposure in the presence of time-varying absolute lymphocyte counts may lead to higher overall and breast cancer–specific mortality. Their analysis is based on data from the population-based Surveillance, Epidemiology, and End Results registry and electronic medical records from Stanford University and Sutter Health. It included 772 women who were treated for triple-negative breast cancer between 2000 and 2014. The women were followed for an average of 104 months.

In an earlier analysis of this same group, Dr. Ransohoff found that higher minimum absolute lymphocyte counts were associated with lower overall mortality (hazard ratio, 0.23; 95% confidence interval, 0.16-0.35) and breast cancer mortality (HR, 0.19; 95% CI, 0.11-0.34) The association between higher peripheral lymphocyte counts and tumor-infiltrating lymphocytes was significant.

In the analysis of relationships between antibiotic use and mortality, 85% of women (n = 654) were prescribed antibiotics after having been diagnosed with triple-negative breast cancer. The death rate among patients who were prescribed antibiotics was 23% (153/654), compared with 20% (24/118) among the patients who were not treated with antibiotics (which accounts for 15% of the entire group).

For total antibiotic exposure, the HR for overall mortality was 1.06 (95% CI, 1.03-1.09; P < .001) and 1.07 for breast cancer–specific mortality (95% CI, 1.04-1.10; P < .001). For unique antibiotic exposure (not counting repeat prescriptions of the same antibiotic), the HR for overall mortality was 1.17 (95% CI, 1.12-1.22; P < .001) and 1.18 for breast cancer–specific mortality (95% CI, 1.12-1.24; P < .001). 

“These were all statistically significant associations derived from a statistical model that takes into account baseline patient characteristics, so the reported hazard ratios, to the best of our ability, represent the risk of death associated with antibiotic use adjusted for other baseline covariates. We’ve attempted to account for differences at baseline that may indicate patients are sicker, and so the reported risk represents mortality related with antibiotic exposure,” Dr. Ransohoff said.

Elucidating the role of the microbiome in mediating absolute lymphocyte counts and immune response may inform interventions to reduce triple-negative mortality, she said.

SAN ANTONIO – A small study suggests the frequent use of antibiotics among women with triple-negative breast cancer, may have an impact on overall and breast cancer–specific mortality.

The study was recently presented at the San Antonio Breast Cancer Symposium by Julia D. Ransohoff, MD, of Stanford (Calif.) University.

Gut-associated lymphoid tissues are the largest component of the immune system. They influence both local and systemic immune responses, but the use of antimicrobials can decrease circulating and tumor-infiltrating lymphocytes that effect the immune repertoire and in turn, the survival of women with triple-negative breast cancer.

Dr. Ransohoff and colleagues hypothesized that increasing antimicrobial exposure in the presence of time-varying absolute lymphocyte counts may lead to higher overall and breast cancer–specific mortality. Their analysis is based on data from the population-based Surveillance, Epidemiology, and End Results registry and electronic medical records from Stanford University and Sutter Health. It included 772 women who were treated for triple-negative breast cancer between 2000 and 2014. The women were followed for an average of 104 months.

In an earlier analysis of this same group, Dr. Ransohoff found that higher minimum absolute lymphocyte counts were associated with lower overall mortality (hazard ratio, 0.23; 95% confidence interval, 0.16-0.35) and breast cancer mortality (HR, 0.19; 95% CI, 0.11-0.34) The association between higher peripheral lymphocyte counts and tumor-infiltrating lymphocytes was significant.

In the analysis of relationships between antibiotic use and mortality, 85% of women (n = 654) were prescribed antibiotics after having been diagnosed with triple-negative breast cancer. The death rate among patients who were prescribed antibiotics was 23% (153/654), compared with 20% (24/118) among the patients who were not treated with antibiotics (which accounts for 15% of the entire group).

For total antibiotic exposure, the HR for overall mortality was 1.06 (95% CI, 1.03-1.09; P < .001) and 1.07 for breast cancer–specific mortality (95% CI, 1.04-1.10; P < .001). For unique antibiotic exposure (not counting repeat prescriptions of the same antibiotic), the HR for overall mortality was 1.17 (95% CI, 1.12-1.22; P < .001) and 1.18 for breast cancer–specific mortality (95% CI, 1.12-1.24; P < .001). 

“These were all statistically significant associations derived from a statistical model that takes into account baseline patient characteristics, so the reported hazard ratios, to the best of our ability, represent the risk of death associated with antibiotic use adjusted for other baseline covariates. We’ve attempted to account for differences at baseline that may indicate patients are sicker, and so the reported risk represents mortality related with antibiotic exposure,” Dr. Ransohoff said.

Elucidating the role of the microbiome in mediating absolute lymphocyte counts and immune response may inform interventions to reduce triple-negative mortality, she said.