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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Telemedicine feasible and reliable in Parkinson’s trial
, a 1-year, phase 3 clinical trial has shown. The trial was an add-on study involving a subset of subjects from the STEADY-PD III trial of isradipine in early Parkinson’s disease.
Although the trial was conducted before SARS-CoV-2 arrived on the scene, the findings have particular relevance for being able to conduct a variety of clinical trials in the face of COVID-19 and the need to limit in-person interactions.
The 40 participants used tablets to complete three remote, video-based assessments during 1 year, with each remote visit planned to be completed within 4 weeks of an in-person visit. It was easy to enroll patients, and they completed about 95% of planned visits, said neurologist Christopher Tarolli, MD, of the University of Rochester (N.Y.).
He presented the study findings at the Movement Disorder Society’s 23rd International Congress of Parkinson’s Disease and Movement Disorders (Virtual) 2020.
“The visits were clearly feasible, and we were able to do them [84%] within that 4-week time frame around the in-person visit,” he said. “The visits were also reasonably reliable, particularly so for what we call the nonmotor outcomes and the patient-reported outcomes.”
In-person versus remote assessment
For the remote visits, participants completed primarily the same battery of tests as the in-person visits. Responses on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) subscales demonstrated “that there was excellent correlation between patient-reported and nonmotor outcome measures and moderate correlation between in-person and remote-performed motor assessments,” Dr. Tarolli said.
He explained that the study used modified motor assessments (MDS-UPDRS Part III) that excluded testing of rigidity and postural instability, which require hands-on testing by a trained examiner and thus are impossible to do remotely.
Additionally, the somewhat lower correlation on this subscale was probably the result of different investigators conducting in-person versus remote assessments, with a subset of in-person investigators who tended to rate participants more severely driving down the correlation. “I think if these methods were applied in future trials, the in-person and remote investigators would optimally be the same person,” Dr. Tarolli suggested.
Room for error?
Indu Subramanian, MD, of the department of neurology at the University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education, and Clinical Center at the West Los Angeles Veterans Affairs Hospital, commented that “the reliability of UPDRS [part] III is where I would want to have, for sure, a little bit more of a deep dive. … possibly the same patient be rated by the same person.”
She also noted that doing remote and in-person assessments within 4 weeks of each other leaves a lot of room for variability. “You could see the same patient in the morning and then do UPDRS in the afternoon, and it can be totally different depending on when you meet the person,” she said.
Only so much testing can be done remotely. Nonetheless, she questioned whether it is really a valid UPDRS if rigidity and postural stability measures are eliminated. “[Is] this now a new modified UPDRS that we’re going to use that is as good as the old UPDRS moving forward, a home version of UPDRS or whatever we’re going to call it?”
Dr. Subramanian mentioned that patients have told her that UPDRS part III does not really measure what is most important to them, such as making pastries for their grandchildren rather than rapidly tapping their fingers.
“That speaks a little bit to the fact that we should have more patient-centered outcomes and things that patients can report. … things that are not going to require necessarily an in-person exam as maybe measures that really can be used moving forward in studies,” she suggested.
Patient satisfaction with remote visits
Greater than 90% of the patients were satisfied or very satisfied overall with the remote visits, including the convenience, comfort, and connection (using the devices and Internet connection), with “patients describing enjoying being able to do these visits from the comfort of their own home, not having to travel,” Dr. Tarolli said. Not having to drive in an ‘off’ state “was actually something that some participants identified as a safety benefit from this as well.”
There was also a time benefit to the patients and investigators. The average length of the remote visits was 54.3 minutes each versus 74 minutes of interaction for in-person visits, mainly a result of more efficient hand-offs between the neurologist and the study coordinator during the remote visits, plus being able to pause the remote visit to give a medication dose time to take effect.
For the patient, there was a large amount of time saved when travel time was considered – a total of 190.2 minutes on average for travel and testing for the in-person visits.
About three-quarters (76%) of the study patients said that remote visits would increase their likelihood of participating in future trials. However, that result may be skewed by the fact that these were already people willing to participate in a remote trial, so the generalizability of the result may be affected. Nonetheless, Dr. Tarolli said he thinks that, as technology gets better and older people become more comfortable with it, remote visits within Parkinson’s research studies may become more common.
One caveat he mentioned is that, with remote visits, the neurologist misses a chance to observe a patient’s whole body and construct a global impression of how he or she is moving. On the other hand, remote video gives the investigator the chance to see the living environment of the patient and suggest changes for safety, such as to reduce the risk of falling for a person with unsteadiness of gait living in a crowded house.
“It really allows us to make a more holistic assessment of how our patient is functioning outside the clinic, which I think we’ve traditionally had really no way of doing,” Dr. Tarolli said.
His final suggestion for anyone contemplating conducting studies with remote visits is to develop a team that is comfortable troubleshooting the technological aspects of those visits.
UCLA’s Dr. Subramanian lauded the University of Rochester team for their efforts in moving remote visits forward. “They’re at the cutting edge of these sorts of things,” she said. “So I’m assuming that they’ll come out with more things [for visits] to become better that are going to move this forward, which is exciting.”
Dr. Tarolli has disclosed no relevant financial relationships. Dr. Subramanian has given talks for Acorda Pharmaceuticals and Acadia Pharmaceuticals in the past. The study had only university, government, foundation, and other nonprofit support.
A version of this article originally appeared on Medscape.com.
, a 1-year, phase 3 clinical trial has shown. The trial was an add-on study involving a subset of subjects from the STEADY-PD III trial of isradipine in early Parkinson’s disease.
Although the trial was conducted before SARS-CoV-2 arrived on the scene, the findings have particular relevance for being able to conduct a variety of clinical trials in the face of COVID-19 and the need to limit in-person interactions.
The 40 participants used tablets to complete three remote, video-based assessments during 1 year, with each remote visit planned to be completed within 4 weeks of an in-person visit. It was easy to enroll patients, and they completed about 95% of planned visits, said neurologist Christopher Tarolli, MD, of the University of Rochester (N.Y.).
He presented the study findings at the Movement Disorder Society’s 23rd International Congress of Parkinson’s Disease and Movement Disorders (Virtual) 2020.
“The visits were clearly feasible, and we were able to do them [84%] within that 4-week time frame around the in-person visit,” he said. “The visits were also reasonably reliable, particularly so for what we call the nonmotor outcomes and the patient-reported outcomes.”
In-person versus remote assessment
For the remote visits, participants completed primarily the same battery of tests as the in-person visits. Responses on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) subscales demonstrated “that there was excellent correlation between patient-reported and nonmotor outcome measures and moderate correlation between in-person and remote-performed motor assessments,” Dr. Tarolli said.
He explained that the study used modified motor assessments (MDS-UPDRS Part III) that excluded testing of rigidity and postural instability, which require hands-on testing by a trained examiner and thus are impossible to do remotely.
Additionally, the somewhat lower correlation on this subscale was probably the result of different investigators conducting in-person versus remote assessments, with a subset of in-person investigators who tended to rate participants more severely driving down the correlation. “I think if these methods were applied in future trials, the in-person and remote investigators would optimally be the same person,” Dr. Tarolli suggested.
Room for error?
Indu Subramanian, MD, of the department of neurology at the University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education, and Clinical Center at the West Los Angeles Veterans Affairs Hospital, commented that “the reliability of UPDRS [part] III is where I would want to have, for sure, a little bit more of a deep dive. … possibly the same patient be rated by the same person.”
She also noted that doing remote and in-person assessments within 4 weeks of each other leaves a lot of room for variability. “You could see the same patient in the morning and then do UPDRS in the afternoon, and it can be totally different depending on when you meet the person,” she said.
Only so much testing can be done remotely. Nonetheless, she questioned whether it is really a valid UPDRS if rigidity and postural stability measures are eliminated. “[Is] this now a new modified UPDRS that we’re going to use that is as good as the old UPDRS moving forward, a home version of UPDRS or whatever we’re going to call it?”
Dr. Subramanian mentioned that patients have told her that UPDRS part III does not really measure what is most important to them, such as making pastries for their grandchildren rather than rapidly tapping their fingers.
“That speaks a little bit to the fact that we should have more patient-centered outcomes and things that patients can report. … things that are not going to require necessarily an in-person exam as maybe measures that really can be used moving forward in studies,” she suggested.
Patient satisfaction with remote visits
Greater than 90% of the patients were satisfied or very satisfied overall with the remote visits, including the convenience, comfort, and connection (using the devices and Internet connection), with “patients describing enjoying being able to do these visits from the comfort of their own home, not having to travel,” Dr. Tarolli said. Not having to drive in an ‘off’ state “was actually something that some participants identified as a safety benefit from this as well.”
There was also a time benefit to the patients and investigators. The average length of the remote visits was 54.3 minutes each versus 74 minutes of interaction for in-person visits, mainly a result of more efficient hand-offs between the neurologist and the study coordinator during the remote visits, plus being able to pause the remote visit to give a medication dose time to take effect.
For the patient, there was a large amount of time saved when travel time was considered – a total of 190.2 minutes on average for travel and testing for the in-person visits.
About three-quarters (76%) of the study patients said that remote visits would increase their likelihood of participating in future trials. However, that result may be skewed by the fact that these were already people willing to participate in a remote trial, so the generalizability of the result may be affected. Nonetheless, Dr. Tarolli said he thinks that, as technology gets better and older people become more comfortable with it, remote visits within Parkinson’s research studies may become more common.
One caveat he mentioned is that, with remote visits, the neurologist misses a chance to observe a patient’s whole body and construct a global impression of how he or she is moving. On the other hand, remote video gives the investigator the chance to see the living environment of the patient and suggest changes for safety, such as to reduce the risk of falling for a person with unsteadiness of gait living in a crowded house.
“It really allows us to make a more holistic assessment of how our patient is functioning outside the clinic, which I think we’ve traditionally had really no way of doing,” Dr. Tarolli said.
His final suggestion for anyone contemplating conducting studies with remote visits is to develop a team that is comfortable troubleshooting the technological aspects of those visits.
UCLA’s Dr. Subramanian lauded the University of Rochester team for their efforts in moving remote visits forward. “They’re at the cutting edge of these sorts of things,” she said. “So I’m assuming that they’ll come out with more things [for visits] to become better that are going to move this forward, which is exciting.”
Dr. Tarolli has disclosed no relevant financial relationships. Dr. Subramanian has given talks for Acorda Pharmaceuticals and Acadia Pharmaceuticals in the past. The study had only university, government, foundation, and other nonprofit support.
A version of this article originally appeared on Medscape.com.
, a 1-year, phase 3 clinical trial has shown. The trial was an add-on study involving a subset of subjects from the STEADY-PD III trial of isradipine in early Parkinson’s disease.
Although the trial was conducted before SARS-CoV-2 arrived on the scene, the findings have particular relevance for being able to conduct a variety of clinical trials in the face of COVID-19 and the need to limit in-person interactions.
The 40 participants used tablets to complete three remote, video-based assessments during 1 year, with each remote visit planned to be completed within 4 weeks of an in-person visit. It was easy to enroll patients, and they completed about 95% of planned visits, said neurologist Christopher Tarolli, MD, of the University of Rochester (N.Y.).
He presented the study findings at the Movement Disorder Society’s 23rd International Congress of Parkinson’s Disease and Movement Disorders (Virtual) 2020.
“The visits were clearly feasible, and we were able to do them [84%] within that 4-week time frame around the in-person visit,” he said. “The visits were also reasonably reliable, particularly so for what we call the nonmotor outcomes and the patient-reported outcomes.”
In-person versus remote assessment
For the remote visits, participants completed primarily the same battery of tests as the in-person visits. Responses on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) subscales demonstrated “that there was excellent correlation between patient-reported and nonmotor outcome measures and moderate correlation between in-person and remote-performed motor assessments,” Dr. Tarolli said.
He explained that the study used modified motor assessments (MDS-UPDRS Part III) that excluded testing of rigidity and postural instability, which require hands-on testing by a trained examiner and thus are impossible to do remotely.
Additionally, the somewhat lower correlation on this subscale was probably the result of different investigators conducting in-person versus remote assessments, with a subset of in-person investigators who tended to rate participants more severely driving down the correlation. “I think if these methods were applied in future trials, the in-person and remote investigators would optimally be the same person,” Dr. Tarolli suggested.
Room for error?
Indu Subramanian, MD, of the department of neurology at the University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education, and Clinical Center at the West Los Angeles Veterans Affairs Hospital, commented that “the reliability of UPDRS [part] III is where I would want to have, for sure, a little bit more of a deep dive. … possibly the same patient be rated by the same person.”
She also noted that doing remote and in-person assessments within 4 weeks of each other leaves a lot of room for variability. “You could see the same patient in the morning and then do UPDRS in the afternoon, and it can be totally different depending on when you meet the person,” she said.
Only so much testing can be done remotely. Nonetheless, she questioned whether it is really a valid UPDRS if rigidity and postural stability measures are eliminated. “[Is] this now a new modified UPDRS that we’re going to use that is as good as the old UPDRS moving forward, a home version of UPDRS or whatever we’re going to call it?”
Dr. Subramanian mentioned that patients have told her that UPDRS part III does not really measure what is most important to them, such as making pastries for their grandchildren rather than rapidly tapping their fingers.
“That speaks a little bit to the fact that we should have more patient-centered outcomes and things that patients can report. … things that are not going to require necessarily an in-person exam as maybe measures that really can be used moving forward in studies,” she suggested.
Patient satisfaction with remote visits
Greater than 90% of the patients were satisfied or very satisfied overall with the remote visits, including the convenience, comfort, and connection (using the devices and Internet connection), with “patients describing enjoying being able to do these visits from the comfort of their own home, not having to travel,” Dr. Tarolli said. Not having to drive in an ‘off’ state “was actually something that some participants identified as a safety benefit from this as well.”
There was also a time benefit to the patients and investigators. The average length of the remote visits was 54.3 minutes each versus 74 minutes of interaction for in-person visits, mainly a result of more efficient hand-offs between the neurologist and the study coordinator during the remote visits, plus being able to pause the remote visit to give a medication dose time to take effect.
For the patient, there was a large amount of time saved when travel time was considered – a total of 190.2 minutes on average for travel and testing for the in-person visits.
About three-quarters (76%) of the study patients said that remote visits would increase their likelihood of participating in future trials. However, that result may be skewed by the fact that these were already people willing to participate in a remote trial, so the generalizability of the result may be affected. Nonetheless, Dr. Tarolli said he thinks that, as technology gets better and older people become more comfortable with it, remote visits within Parkinson’s research studies may become more common.
One caveat he mentioned is that, with remote visits, the neurologist misses a chance to observe a patient’s whole body and construct a global impression of how he or she is moving. On the other hand, remote video gives the investigator the chance to see the living environment of the patient and suggest changes for safety, such as to reduce the risk of falling for a person with unsteadiness of gait living in a crowded house.
“It really allows us to make a more holistic assessment of how our patient is functioning outside the clinic, which I think we’ve traditionally had really no way of doing,” Dr. Tarolli said.
His final suggestion for anyone contemplating conducting studies with remote visits is to develop a team that is comfortable troubleshooting the technological aspects of those visits.
UCLA’s Dr. Subramanian lauded the University of Rochester team for their efforts in moving remote visits forward. “They’re at the cutting edge of these sorts of things,” she said. “So I’m assuming that they’ll come out with more things [for visits] to become better that are going to move this forward, which is exciting.”
Dr. Tarolli has disclosed no relevant financial relationships. Dr. Subramanian has given talks for Acorda Pharmaceuticals and Acadia Pharmaceuticals in the past. The study had only university, government, foundation, and other nonprofit support.
A version of this article originally appeared on Medscape.com.
COVID-19 vaccine hesitancy ‘somewhat understandable,’ expert says
“I worry that vaccines are going to be sold like magic powder that we sprinkle across the land and make the virus go away,” Paul Offit, MD, said at the virtual American Academy of Pediatrics (AAP) 2020 National Conference. “That’s not true.”
according to Dr. Offit, director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia.
“I think we can get a vaccine that’s 75%-80% effective at preventing mild to moderate disease, but that means one of every four people can still get moderate to severe disease,” Dr. Offit continued.
And that’s if there is high uptake of the vaccine, which may not be the case. Recent polls have suggested there is considerable concern about the pending vaccines.
“It’s somewhat understandable,” Dr. Offitt acknowledged, especially given the “frightening” language used to describe vaccine development. Terms such as “warp speed” may suggest that haste might trump safety considerations. Before COVID-19, the fastest vaccine ever developed was for mumps, he said, with the virus isolated in 1963 and a commercial product available in 1967.
Addressing hesitancy in clinics
In a wide-ranging livestream plenary presentation, Dr. Offit, coinventor of a rotavirus vaccine, shed light on SARS-CoV-2 vaccine development and his impressions of vaccine hesitancy among patients and families. He also offered advice for how to reassure those skeptical of the safety and efficacy of any SARS-COV-2 vaccine, given the accelerated development process.
With more than 180 different vaccines in various stages of investigation, Dr. Offit called the effort to develop COVID-19 vaccines “unprecedented.” Part of that is a result of governments relieving pharmaceutical companies of much of the typical financial risk – which often climbs to hundreds of millions of dollars – by underwriting the costs of vaccine development to battle the pandemic-inducing virus, he said.
But this very swiftness is also stoking antivaccine sentiment. Dr. Offit, part of vaccine advisory groups for the National Institutes of Health and U.S. Food and Drug Administration, cited recent research reporting nearly half of American adults definitely or probably would not get a COVID-19 vaccine if it were available today.
“One way you convince skeptics is with data presented in a clear, compassionate, and compelling way,” he said.
“The other group is vaccine cynics, who are basically conspiracy theorists who believe pharmaceutical companies control the world, the government, the medical establishment. I think there’s no talking them down from this.”
Numerous strategies are being used in COVID-19 vaccine development, he noted, including messenger RNA, DNA, viral vectors, purified protein, and whole killed virus. Dr. Offit believes any candidates approved for distribution will likely be in the range of 75% effective at preventing mild to moderate symptoms.
But clinicians should be ready to face immediate questions of safety. “Even if this vaccination is given to 20,000 [trial participants] safely, that’s not 20 million,” Dr. Offit said. “Anyone could reasonably ask questions about if it causes rare, serious side effects.
“The good news is, there are systems in place,” such as adverse event reporting systems, to identify rare events, even those that occur in one in a million vaccine recipients. Reminding patients of that continued surveillance can be reassuring.
Another reassuring point is that COVID-19 vaccine trial participants have included people from many diverse populations, he said. But children, notably absent so far, should be added to trials immediately, Dr. Offit contends.
“This is going to be important when you consider strategies to get children universally back into school,” he said, which is a “critical issue” from both learning and wellness standpoints. “It breaks my heart that we’ve been unable to do this when other countries have.”
Transparency will be paramount
While presenting data transparently to patients is key in helping them accept COVID-19 vaccination, Dr. Offit said, he also believes “telling stories” can be just as effective, if not more so. When the varicella vaccine was approved in 1995, he said, the “uptake the first few years was pretty miserable” until public service messaging emphasized that some children die from chickenpox.
“Fear works,” he said. “You always worry about pushback of something being oversold, but hopefully we’re scared enough about this virus” to convince people that vaccination is wise. “I do think personal stories carry weight on both sides,” Dr. Offit said.
Mark Sawyer, MD, of University of California San Diego School of Medicine and Rady Children’s Hospital in San Diego, California, said Offit’s presentation offered important takeaways for clinicians about how to broach the topic of COVID-19 vaccination with patients and families.
“We need to communicate clearly and transparently to patients about what we do and don’t know” about the vaccines, Dr. Sawyer said in an interview. “We will know if they have common side effects, but we will not know about very rare side effects until we have used the vaccines for a while.
“We will know how well the vaccine works over the short-term, but we won’t know over the long term,” added Dr. Sawyer, a member of the AAP Committee on Infectious Diseases.
“We can reassure the community that SARS-CoV-2 vaccines are being evaluated in trials in the same way and with the same thoroughness as other vaccines have been,” he said. “That should give people confidence that shortcuts are not being taken with regard to safety and effectiveness evaluations.”
Dr. Offit and Dr. Sawyer have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
“I worry that vaccines are going to be sold like magic powder that we sprinkle across the land and make the virus go away,” Paul Offit, MD, said at the virtual American Academy of Pediatrics (AAP) 2020 National Conference. “That’s not true.”
according to Dr. Offit, director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia.
“I think we can get a vaccine that’s 75%-80% effective at preventing mild to moderate disease, but that means one of every four people can still get moderate to severe disease,” Dr. Offit continued.
And that’s if there is high uptake of the vaccine, which may not be the case. Recent polls have suggested there is considerable concern about the pending vaccines.
“It’s somewhat understandable,” Dr. Offitt acknowledged, especially given the “frightening” language used to describe vaccine development. Terms such as “warp speed” may suggest that haste might trump safety considerations. Before COVID-19, the fastest vaccine ever developed was for mumps, he said, with the virus isolated in 1963 and a commercial product available in 1967.
Addressing hesitancy in clinics
In a wide-ranging livestream plenary presentation, Dr. Offit, coinventor of a rotavirus vaccine, shed light on SARS-CoV-2 vaccine development and his impressions of vaccine hesitancy among patients and families. He also offered advice for how to reassure those skeptical of the safety and efficacy of any SARS-COV-2 vaccine, given the accelerated development process.
With more than 180 different vaccines in various stages of investigation, Dr. Offit called the effort to develop COVID-19 vaccines “unprecedented.” Part of that is a result of governments relieving pharmaceutical companies of much of the typical financial risk – which often climbs to hundreds of millions of dollars – by underwriting the costs of vaccine development to battle the pandemic-inducing virus, he said.
But this very swiftness is also stoking antivaccine sentiment. Dr. Offit, part of vaccine advisory groups for the National Institutes of Health and U.S. Food and Drug Administration, cited recent research reporting nearly half of American adults definitely or probably would not get a COVID-19 vaccine if it were available today.
“One way you convince skeptics is with data presented in a clear, compassionate, and compelling way,” he said.
“The other group is vaccine cynics, who are basically conspiracy theorists who believe pharmaceutical companies control the world, the government, the medical establishment. I think there’s no talking them down from this.”
Numerous strategies are being used in COVID-19 vaccine development, he noted, including messenger RNA, DNA, viral vectors, purified protein, and whole killed virus. Dr. Offit believes any candidates approved for distribution will likely be in the range of 75% effective at preventing mild to moderate symptoms.
But clinicians should be ready to face immediate questions of safety. “Even if this vaccination is given to 20,000 [trial participants] safely, that’s not 20 million,” Dr. Offit said. “Anyone could reasonably ask questions about if it causes rare, serious side effects.
“The good news is, there are systems in place,” such as adverse event reporting systems, to identify rare events, even those that occur in one in a million vaccine recipients. Reminding patients of that continued surveillance can be reassuring.
Another reassuring point is that COVID-19 vaccine trial participants have included people from many diverse populations, he said. But children, notably absent so far, should be added to trials immediately, Dr. Offit contends.
“This is going to be important when you consider strategies to get children universally back into school,” he said, which is a “critical issue” from both learning and wellness standpoints. “It breaks my heart that we’ve been unable to do this when other countries have.”
Transparency will be paramount
While presenting data transparently to patients is key in helping them accept COVID-19 vaccination, Dr. Offit said, he also believes “telling stories” can be just as effective, if not more so. When the varicella vaccine was approved in 1995, he said, the “uptake the first few years was pretty miserable” until public service messaging emphasized that some children die from chickenpox.
“Fear works,” he said. “You always worry about pushback of something being oversold, but hopefully we’re scared enough about this virus” to convince people that vaccination is wise. “I do think personal stories carry weight on both sides,” Dr. Offit said.
Mark Sawyer, MD, of University of California San Diego School of Medicine and Rady Children’s Hospital in San Diego, California, said Offit’s presentation offered important takeaways for clinicians about how to broach the topic of COVID-19 vaccination with patients and families.
“We need to communicate clearly and transparently to patients about what we do and don’t know” about the vaccines, Dr. Sawyer said in an interview. “We will know if they have common side effects, but we will not know about very rare side effects until we have used the vaccines for a while.
“We will know how well the vaccine works over the short-term, but we won’t know over the long term,” added Dr. Sawyer, a member of the AAP Committee on Infectious Diseases.
“We can reassure the community that SARS-CoV-2 vaccines are being evaluated in trials in the same way and with the same thoroughness as other vaccines have been,” he said. “That should give people confidence that shortcuts are not being taken with regard to safety and effectiveness evaluations.”
Dr. Offit and Dr. Sawyer have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
“I worry that vaccines are going to be sold like magic powder that we sprinkle across the land and make the virus go away,” Paul Offit, MD, said at the virtual American Academy of Pediatrics (AAP) 2020 National Conference. “That’s not true.”
according to Dr. Offit, director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia.
“I think we can get a vaccine that’s 75%-80% effective at preventing mild to moderate disease, but that means one of every four people can still get moderate to severe disease,” Dr. Offit continued.
And that’s if there is high uptake of the vaccine, which may not be the case. Recent polls have suggested there is considerable concern about the pending vaccines.
“It’s somewhat understandable,” Dr. Offitt acknowledged, especially given the “frightening” language used to describe vaccine development. Terms such as “warp speed” may suggest that haste might trump safety considerations. Before COVID-19, the fastest vaccine ever developed was for mumps, he said, with the virus isolated in 1963 and a commercial product available in 1967.
Addressing hesitancy in clinics
In a wide-ranging livestream plenary presentation, Dr. Offit, coinventor of a rotavirus vaccine, shed light on SARS-CoV-2 vaccine development and his impressions of vaccine hesitancy among patients and families. He also offered advice for how to reassure those skeptical of the safety and efficacy of any SARS-COV-2 vaccine, given the accelerated development process.
With more than 180 different vaccines in various stages of investigation, Dr. Offit called the effort to develop COVID-19 vaccines “unprecedented.” Part of that is a result of governments relieving pharmaceutical companies of much of the typical financial risk – which often climbs to hundreds of millions of dollars – by underwriting the costs of vaccine development to battle the pandemic-inducing virus, he said.
But this very swiftness is also stoking antivaccine sentiment. Dr. Offit, part of vaccine advisory groups for the National Institutes of Health and U.S. Food and Drug Administration, cited recent research reporting nearly half of American adults definitely or probably would not get a COVID-19 vaccine if it were available today.
“One way you convince skeptics is with data presented in a clear, compassionate, and compelling way,” he said.
“The other group is vaccine cynics, who are basically conspiracy theorists who believe pharmaceutical companies control the world, the government, the medical establishment. I think there’s no talking them down from this.”
Numerous strategies are being used in COVID-19 vaccine development, he noted, including messenger RNA, DNA, viral vectors, purified protein, and whole killed virus. Dr. Offit believes any candidates approved for distribution will likely be in the range of 75% effective at preventing mild to moderate symptoms.
But clinicians should be ready to face immediate questions of safety. “Even if this vaccination is given to 20,000 [trial participants] safely, that’s not 20 million,” Dr. Offit said. “Anyone could reasonably ask questions about if it causes rare, serious side effects.
“The good news is, there are systems in place,” such as adverse event reporting systems, to identify rare events, even those that occur in one in a million vaccine recipients. Reminding patients of that continued surveillance can be reassuring.
Another reassuring point is that COVID-19 vaccine trial participants have included people from many diverse populations, he said. But children, notably absent so far, should be added to trials immediately, Dr. Offit contends.
“This is going to be important when you consider strategies to get children universally back into school,” he said, which is a “critical issue” from both learning and wellness standpoints. “It breaks my heart that we’ve been unable to do this when other countries have.”
Transparency will be paramount
While presenting data transparently to patients is key in helping them accept COVID-19 vaccination, Dr. Offit said, he also believes “telling stories” can be just as effective, if not more so. When the varicella vaccine was approved in 1995, he said, the “uptake the first few years was pretty miserable” until public service messaging emphasized that some children die from chickenpox.
“Fear works,” he said. “You always worry about pushback of something being oversold, but hopefully we’re scared enough about this virus” to convince people that vaccination is wise. “I do think personal stories carry weight on both sides,” Dr. Offit said.
Mark Sawyer, MD, of University of California San Diego School of Medicine and Rady Children’s Hospital in San Diego, California, said Offit’s presentation offered important takeaways for clinicians about how to broach the topic of COVID-19 vaccination with patients and families.
“We need to communicate clearly and transparently to patients about what we do and don’t know” about the vaccines, Dr. Sawyer said in an interview. “We will know if they have common side effects, but we will not know about very rare side effects until we have used the vaccines for a while.
“We will know how well the vaccine works over the short-term, but we won’t know over the long term,” added Dr. Sawyer, a member of the AAP Committee on Infectious Diseases.
“We can reassure the community that SARS-CoV-2 vaccines are being evaluated in trials in the same way and with the same thoroughness as other vaccines have been,” he said. “That should give people confidence that shortcuts are not being taken with regard to safety and effectiveness evaluations.”
Dr. Offit and Dr. Sawyer have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Flexibility, innovation key to practice management during pandemic
Practice management is the responsibility of every pediatrician, and leadership is more important than ever in a crisis like the COVID-19 pandemic.
“Ultimately you have a critical role in ensuring that your practice remains sustainable so that you can continue to deliver great care,” Sue Kressly, MD, a retired pediatrician from Warrington, Pa., said at the virtual annual meeting of the American Academy of Pediatrics. “None of us escaped some impact of the COVID crisis, and many of us are going to experience lasting change.”
Dr. Kressly and Suzanne Berman, MD, a pediatrician in central Tennessee, presented a live online session on how the pandemic is affecting practices and how pediatricians can effectively address those challenges.
Three ways a crisis impacts practices
“When a practice experiences a crisis, it really exposes what your practice is made of, for better or for worse,” Dr. Berman said. “The COVID crisis has been profound and broad and long enough to really stress the core tensile strength of practices along at least three axes.” Those are staffing, financial health, and partnerships.
It’s a normal human response to enter survival mode during a crisis, so staff management becomes more important than ever. Some things to consider are whether you have a truly collaborative team culture in your practice and whether you’re really listening to the staff’s struggles and suggestions.
“Staffing challenges can be very difficult,” Dr. Berman said. “Permitting staff to work from home is the single biggest thing you can do when staff needs to self-isolate.”
Financially, most medical practices have adequate cash on hand not to have to pay close attention to the numbers, Dr. Kressly said, but if physicians are looking at their books for the first time during a crisis, they have no way of knowing what their baseline expectations should be or how much to worry about their finances. It’s important to understand your practice’s or department’s budget.
Jesse Hackell, MD, a private practice pediatrician in a suburb of New York City and vice president of the New York AAP Chapter 3, attended the session and appreciated this point on finances.
“In order to provide good quality care to kids, you need to be financially successful because otherwise you’ll close your doors,” Dr. Hackell said in an interview. “It’s making yourself available to be able to provide care.”
Stressors among partners during a crisis arise from responding to the challenges of the crisis, such as who should be impacted by pay cuts or furloughs, how to account for overhead, how to distribute revenue and how to divide the work equitably. Other issues include how to protect higher risk providers fairly and how to shift schedules or case load based on unforeseen events, including quarantining.
“There is no ‘fair’ in a crisis,” Dr. Berman said. “We must use the equity paradigm to be sure everyone has what they need to survive and have the best outcome possible.”
The speakers also discussed the importance of a practice’s situation before the pandemic began, a point that resonated with attendee Jason Terk, MD, a pediatrician who practices in a large pediatric health care system near Fort Worth, Texas.
“Just like the pandemic impacts the health of people in different ways based upon their baseline health, the pandemic impacts practices in different ways based on the practice’s baseline health,” he said in an interview. “If you had good operations, a good culture, good communication and all those other good indicators of practice health before, then you stood a much better chance of surviving the pandemic as a practice than practices that had weaknesses before.”
The size of a practice did not necessarily predict the impact of the crisis, Dr. Berman said. Rather, practices with good patient engagement, active recall programs, and good fiscal planning did better.
Dr. Hackell said. “We had never seen anything like this before,” he said in an interview. “From the start we had no idea what was going to work. Try something and see if it works. If it fails, try something else. We were all operating blind here.”
The focus of most practices in the spring was on well visits, chronic care follow-up, and telehealth. Going into fall and winter, innovation will be necessary to provide appropriate care for all children while keeping in mind that the choices pediatricians make will have long-lasting implications for their staff and patients. The speakers stressed the importance of communication and transparency within the office team and to patients and the community.
Dr. Hackell appreciated the speakers’ point that kids need care, and pediatricians need to meet that need.
“Kids need well care and immunizations, and kids get sick and need sick care,” he said. “Parents need a lot more reassurance during times like this. We need to be able to provide that care and be sure that we do it safely. To give the right care at the right time in the right location is key.”
Making practice adaptations
In balancing risk and access to care, Dr. Kressly described the importance of multiple interventions, including managing some patients out of the office and making physical changes, such as putting in physical barriers and eliminating waiting rooms.
“Many practices are highly focused on PPE [personal protective equipment],” Dr. Kressly said, but even Centers for Disease Control and Prevention guidance emphasizes that PPE is the last line of defense. “There are many things we can do to protect our teams and our patients, and we know that not one single adaption is going to be 100% effective. But like the Swiss cheese model indicates, when you layer all of these efforts on top of one another, many defenses allow for the protection of the majority of people.”
Other changes include restricting office visitors to one per patient, implementing social distancing, requiring visitors to wear masks, and considering alternate locations for visits, including car and parking lot visits.
“No idea is too crazy, and some of the best ideas come from your staff,” Dr. Kressly said. She also recommended asking families where they feel most comfortable meeting.
“Don’t make any assumptions about where they want to be seen, but ask and together decide where the patient can most safely and effectively be given appropriate care,” she said.
Dr. Kressly also noted the new CPT code, 99072, that can be used to bill for “additional supplies, materials, and clinical staff time over and above those usually included in an office visit or other nonfacility service(s), when performed during a public health emergency as defined by law, due to respiratory-transmitted infectious disease.”
Pediatricians should think of ways they can remove barriers to access, such as adjusting no-show cancellation penalties and adjusting practice policies as needed when things change. “Avoid creating a culture where families do not disclose all information for fear of not being seen,” Dr. Kressly said.
A slower pace because of delays and hiccups is also normal at this time, Dr. Berman said. “If you feel like you’re just not as efficient as you were prior to COVID, it’s not just you,” she said. “It’s true. Everyone has to grapple with new things now. It takes longer.”
Things that add time include remote check-in and paperwork, more time to don and doff PPE and disinfect, dealing with technology failures, adjusting to new procedures or policies, and the general mental fatigue of adhering to PPE best practices. Patience is vital during this time, Dr. Berman said.
Several ways to improve efficiency include cutting out unnecessary steps, using standing orders and Advance Beneficiary Notice of Noncoverage (ABNs) for flu vaccinations, keeping credit card numbers on file for contactless payment, and considering the clinical and financial value of lab testing before ordering it.
“Effective triage helps patient satisfaction, access to care, and efficiency of your office workload,” Dr. Kressly said. “Use technology where it’s appropriate, but then add people where it’s needed. Connections to caring people matter even more in a time of crisis.”
The speakers also highlighted the importance of early flu vaccinations.
“One of the single biggest things you can do for value in COVID is to get your flu vaccine numbers up,” Dr. Berman said. “Severely reducing the burden of influenza will help flatten the curve, it will reduce febrile respiratory illness, and it will protect your most fragile patients.”
Two ways to do that include flu clinics and making a strong push for immunizations during the first 8 weeks after getting the vaccines. Dr Berman shared numbers from two practices showing how many more total immunizations were done in the practice that began vaccinating in early August versus early September.
A crisis is an opportunity
The speakers closed on an optimistic note that emphasized the opportunities that can grow out of the challenges presented by the pandemic, a point Dr Terk elaborated on.
“One of the most important things is realizing how we can potentially use a crisis to transform our practices,” Dr. Terk said in the interview. “As had been said before, a crisis is a terrible thing to waste. Those practices that have the gumption to innovate and find different ways to improve the way they provide care are probably going to be in better shape as we go forward.”
Critical to that success is taking risks, he added.
“When you’re innovating, failure has to be something you are permissive of because if you’re risk-averse and failure-averse, you’re not going to have the opportunity to grow and innovate, and this is another opportunity to innovate,” Dr. Terk said.
He also stressed the value of learning from one another. “We need to help each other by sharing our good practices, and on the flip side, be open to learning from each other,” he said. “Those pediatricians who are struggling need to be open-minded and open-hearted to understanding how we can operate our practices better and know that the things we think are barriers we can’t change are probably things we probably haven’t allowed ourselves to think about changing.”
Dr. Kressly and Dr. Berman recommended several specific actions for pediatricians to take:
- Creating a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis regarding your practice management response to the pandemic.
- Articulating three goals for improving your understanding or the implementation of management in your practice.
- Creating a working group to identify and implement ways to improve clinical work flow and communication strategies.
“Now is the time to meaningfully address disparities of access to appropriate health care and the impact of social determinants of health,” Dr. Kressly said. It’s also an opportunity to build meaningful relationships with patient families based on trust, science, and “true shared decision-making with health literacy in mind.”
Dr Kressly is the medical director of and owns shares in Office Practicum. Dr. Berman is the assistant medical director of and owns shares in Office Practicum, and is the owner of Script Doctor LLC. Dr. Terk and Dr. Hackell had no relevant financial disclosures.
Practice management is the responsibility of every pediatrician, and leadership is more important than ever in a crisis like the COVID-19 pandemic.
“Ultimately you have a critical role in ensuring that your practice remains sustainable so that you can continue to deliver great care,” Sue Kressly, MD, a retired pediatrician from Warrington, Pa., said at the virtual annual meeting of the American Academy of Pediatrics. “None of us escaped some impact of the COVID crisis, and many of us are going to experience lasting change.”
Dr. Kressly and Suzanne Berman, MD, a pediatrician in central Tennessee, presented a live online session on how the pandemic is affecting practices and how pediatricians can effectively address those challenges.
Three ways a crisis impacts practices
“When a practice experiences a crisis, it really exposes what your practice is made of, for better or for worse,” Dr. Berman said. “The COVID crisis has been profound and broad and long enough to really stress the core tensile strength of practices along at least three axes.” Those are staffing, financial health, and partnerships.
It’s a normal human response to enter survival mode during a crisis, so staff management becomes more important than ever. Some things to consider are whether you have a truly collaborative team culture in your practice and whether you’re really listening to the staff’s struggles and suggestions.
“Staffing challenges can be very difficult,” Dr. Berman said. “Permitting staff to work from home is the single biggest thing you can do when staff needs to self-isolate.”
Financially, most medical practices have adequate cash on hand not to have to pay close attention to the numbers, Dr. Kressly said, but if physicians are looking at their books for the first time during a crisis, they have no way of knowing what their baseline expectations should be or how much to worry about their finances. It’s important to understand your practice’s or department’s budget.
Jesse Hackell, MD, a private practice pediatrician in a suburb of New York City and vice president of the New York AAP Chapter 3, attended the session and appreciated this point on finances.
“In order to provide good quality care to kids, you need to be financially successful because otherwise you’ll close your doors,” Dr. Hackell said in an interview. “It’s making yourself available to be able to provide care.”
Stressors among partners during a crisis arise from responding to the challenges of the crisis, such as who should be impacted by pay cuts or furloughs, how to account for overhead, how to distribute revenue and how to divide the work equitably. Other issues include how to protect higher risk providers fairly and how to shift schedules or case load based on unforeseen events, including quarantining.
“There is no ‘fair’ in a crisis,” Dr. Berman said. “We must use the equity paradigm to be sure everyone has what they need to survive and have the best outcome possible.”
The speakers also discussed the importance of a practice’s situation before the pandemic began, a point that resonated with attendee Jason Terk, MD, a pediatrician who practices in a large pediatric health care system near Fort Worth, Texas.
“Just like the pandemic impacts the health of people in different ways based upon their baseline health, the pandemic impacts practices in different ways based on the practice’s baseline health,” he said in an interview. “If you had good operations, a good culture, good communication and all those other good indicators of practice health before, then you stood a much better chance of surviving the pandemic as a practice than practices that had weaknesses before.”
The size of a practice did not necessarily predict the impact of the crisis, Dr. Berman said. Rather, practices with good patient engagement, active recall programs, and good fiscal planning did better.
Dr. Hackell said. “We had never seen anything like this before,” he said in an interview. “From the start we had no idea what was going to work. Try something and see if it works. If it fails, try something else. We were all operating blind here.”
The focus of most practices in the spring was on well visits, chronic care follow-up, and telehealth. Going into fall and winter, innovation will be necessary to provide appropriate care for all children while keeping in mind that the choices pediatricians make will have long-lasting implications for their staff and patients. The speakers stressed the importance of communication and transparency within the office team and to patients and the community.
Dr. Hackell appreciated the speakers’ point that kids need care, and pediatricians need to meet that need.
“Kids need well care and immunizations, and kids get sick and need sick care,” he said. “Parents need a lot more reassurance during times like this. We need to be able to provide that care and be sure that we do it safely. To give the right care at the right time in the right location is key.”
Making practice adaptations
In balancing risk and access to care, Dr. Kressly described the importance of multiple interventions, including managing some patients out of the office and making physical changes, such as putting in physical barriers and eliminating waiting rooms.
“Many practices are highly focused on PPE [personal protective equipment],” Dr. Kressly said, but even Centers for Disease Control and Prevention guidance emphasizes that PPE is the last line of defense. “There are many things we can do to protect our teams and our patients, and we know that not one single adaption is going to be 100% effective. But like the Swiss cheese model indicates, when you layer all of these efforts on top of one another, many defenses allow for the protection of the majority of people.”
Other changes include restricting office visitors to one per patient, implementing social distancing, requiring visitors to wear masks, and considering alternate locations for visits, including car and parking lot visits.
“No idea is too crazy, and some of the best ideas come from your staff,” Dr. Kressly said. She also recommended asking families where they feel most comfortable meeting.
“Don’t make any assumptions about where they want to be seen, but ask and together decide where the patient can most safely and effectively be given appropriate care,” she said.
Dr. Kressly also noted the new CPT code, 99072, that can be used to bill for “additional supplies, materials, and clinical staff time over and above those usually included in an office visit or other nonfacility service(s), when performed during a public health emergency as defined by law, due to respiratory-transmitted infectious disease.”
Pediatricians should think of ways they can remove barriers to access, such as adjusting no-show cancellation penalties and adjusting practice policies as needed when things change. “Avoid creating a culture where families do not disclose all information for fear of not being seen,” Dr. Kressly said.
A slower pace because of delays and hiccups is also normal at this time, Dr. Berman said. “If you feel like you’re just not as efficient as you were prior to COVID, it’s not just you,” she said. “It’s true. Everyone has to grapple with new things now. It takes longer.”
Things that add time include remote check-in and paperwork, more time to don and doff PPE and disinfect, dealing with technology failures, adjusting to new procedures or policies, and the general mental fatigue of adhering to PPE best practices. Patience is vital during this time, Dr. Berman said.
Several ways to improve efficiency include cutting out unnecessary steps, using standing orders and Advance Beneficiary Notice of Noncoverage (ABNs) for flu vaccinations, keeping credit card numbers on file for contactless payment, and considering the clinical and financial value of lab testing before ordering it.
“Effective triage helps patient satisfaction, access to care, and efficiency of your office workload,” Dr. Kressly said. “Use technology where it’s appropriate, but then add people where it’s needed. Connections to caring people matter even more in a time of crisis.”
The speakers also highlighted the importance of early flu vaccinations.
“One of the single biggest things you can do for value in COVID is to get your flu vaccine numbers up,” Dr. Berman said. “Severely reducing the burden of influenza will help flatten the curve, it will reduce febrile respiratory illness, and it will protect your most fragile patients.”
Two ways to do that include flu clinics and making a strong push for immunizations during the first 8 weeks after getting the vaccines. Dr Berman shared numbers from two practices showing how many more total immunizations were done in the practice that began vaccinating in early August versus early September.
A crisis is an opportunity
The speakers closed on an optimistic note that emphasized the opportunities that can grow out of the challenges presented by the pandemic, a point Dr Terk elaborated on.
“One of the most important things is realizing how we can potentially use a crisis to transform our practices,” Dr. Terk said in the interview. “As had been said before, a crisis is a terrible thing to waste. Those practices that have the gumption to innovate and find different ways to improve the way they provide care are probably going to be in better shape as we go forward.”
Critical to that success is taking risks, he added.
“When you’re innovating, failure has to be something you are permissive of because if you’re risk-averse and failure-averse, you’re not going to have the opportunity to grow and innovate, and this is another opportunity to innovate,” Dr. Terk said.
He also stressed the value of learning from one another. “We need to help each other by sharing our good practices, and on the flip side, be open to learning from each other,” he said. “Those pediatricians who are struggling need to be open-minded and open-hearted to understanding how we can operate our practices better and know that the things we think are barriers we can’t change are probably things we probably haven’t allowed ourselves to think about changing.”
Dr. Kressly and Dr. Berman recommended several specific actions for pediatricians to take:
- Creating a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis regarding your practice management response to the pandemic.
- Articulating three goals for improving your understanding or the implementation of management in your practice.
- Creating a working group to identify and implement ways to improve clinical work flow and communication strategies.
“Now is the time to meaningfully address disparities of access to appropriate health care and the impact of social determinants of health,” Dr. Kressly said. It’s also an opportunity to build meaningful relationships with patient families based on trust, science, and “true shared decision-making with health literacy in mind.”
Dr Kressly is the medical director of and owns shares in Office Practicum. Dr. Berman is the assistant medical director of and owns shares in Office Practicum, and is the owner of Script Doctor LLC. Dr. Terk and Dr. Hackell had no relevant financial disclosures.
Practice management is the responsibility of every pediatrician, and leadership is more important than ever in a crisis like the COVID-19 pandemic.
“Ultimately you have a critical role in ensuring that your practice remains sustainable so that you can continue to deliver great care,” Sue Kressly, MD, a retired pediatrician from Warrington, Pa., said at the virtual annual meeting of the American Academy of Pediatrics. “None of us escaped some impact of the COVID crisis, and many of us are going to experience lasting change.”
Dr. Kressly and Suzanne Berman, MD, a pediatrician in central Tennessee, presented a live online session on how the pandemic is affecting practices and how pediatricians can effectively address those challenges.
Three ways a crisis impacts practices
“When a practice experiences a crisis, it really exposes what your practice is made of, for better or for worse,” Dr. Berman said. “The COVID crisis has been profound and broad and long enough to really stress the core tensile strength of practices along at least three axes.” Those are staffing, financial health, and partnerships.
It’s a normal human response to enter survival mode during a crisis, so staff management becomes more important than ever. Some things to consider are whether you have a truly collaborative team culture in your practice and whether you’re really listening to the staff’s struggles and suggestions.
“Staffing challenges can be very difficult,” Dr. Berman said. “Permitting staff to work from home is the single biggest thing you can do when staff needs to self-isolate.”
Financially, most medical practices have adequate cash on hand not to have to pay close attention to the numbers, Dr. Kressly said, but if physicians are looking at their books for the first time during a crisis, they have no way of knowing what their baseline expectations should be or how much to worry about their finances. It’s important to understand your practice’s or department’s budget.
Jesse Hackell, MD, a private practice pediatrician in a suburb of New York City and vice president of the New York AAP Chapter 3, attended the session and appreciated this point on finances.
“In order to provide good quality care to kids, you need to be financially successful because otherwise you’ll close your doors,” Dr. Hackell said in an interview. “It’s making yourself available to be able to provide care.”
Stressors among partners during a crisis arise from responding to the challenges of the crisis, such as who should be impacted by pay cuts or furloughs, how to account for overhead, how to distribute revenue and how to divide the work equitably. Other issues include how to protect higher risk providers fairly and how to shift schedules or case load based on unforeseen events, including quarantining.
“There is no ‘fair’ in a crisis,” Dr. Berman said. “We must use the equity paradigm to be sure everyone has what they need to survive and have the best outcome possible.”
The speakers also discussed the importance of a practice’s situation before the pandemic began, a point that resonated with attendee Jason Terk, MD, a pediatrician who practices in a large pediatric health care system near Fort Worth, Texas.
“Just like the pandemic impacts the health of people in different ways based upon their baseline health, the pandemic impacts practices in different ways based on the practice’s baseline health,” he said in an interview. “If you had good operations, a good culture, good communication and all those other good indicators of practice health before, then you stood a much better chance of surviving the pandemic as a practice than practices that had weaknesses before.”
The size of a practice did not necessarily predict the impact of the crisis, Dr. Berman said. Rather, practices with good patient engagement, active recall programs, and good fiscal planning did better.
Dr. Hackell said. “We had never seen anything like this before,” he said in an interview. “From the start we had no idea what was going to work. Try something and see if it works. If it fails, try something else. We were all operating blind here.”
The focus of most practices in the spring was on well visits, chronic care follow-up, and telehealth. Going into fall and winter, innovation will be necessary to provide appropriate care for all children while keeping in mind that the choices pediatricians make will have long-lasting implications for their staff and patients. The speakers stressed the importance of communication and transparency within the office team and to patients and the community.
Dr. Hackell appreciated the speakers’ point that kids need care, and pediatricians need to meet that need.
“Kids need well care and immunizations, and kids get sick and need sick care,” he said. “Parents need a lot more reassurance during times like this. We need to be able to provide that care and be sure that we do it safely. To give the right care at the right time in the right location is key.”
Making practice adaptations
In balancing risk and access to care, Dr. Kressly described the importance of multiple interventions, including managing some patients out of the office and making physical changes, such as putting in physical barriers and eliminating waiting rooms.
“Many practices are highly focused on PPE [personal protective equipment],” Dr. Kressly said, but even Centers for Disease Control and Prevention guidance emphasizes that PPE is the last line of defense. “There are many things we can do to protect our teams and our patients, and we know that not one single adaption is going to be 100% effective. But like the Swiss cheese model indicates, when you layer all of these efforts on top of one another, many defenses allow for the protection of the majority of people.”
Other changes include restricting office visitors to one per patient, implementing social distancing, requiring visitors to wear masks, and considering alternate locations for visits, including car and parking lot visits.
“No idea is too crazy, and some of the best ideas come from your staff,” Dr. Kressly said. She also recommended asking families where they feel most comfortable meeting.
“Don’t make any assumptions about where they want to be seen, but ask and together decide where the patient can most safely and effectively be given appropriate care,” she said.
Dr. Kressly also noted the new CPT code, 99072, that can be used to bill for “additional supplies, materials, and clinical staff time over and above those usually included in an office visit or other nonfacility service(s), when performed during a public health emergency as defined by law, due to respiratory-transmitted infectious disease.”
Pediatricians should think of ways they can remove barriers to access, such as adjusting no-show cancellation penalties and adjusting practice policies as needed when things change. “Avoid creating a culture where families do not disclose all information for fear of not being seen,” Dr. Kressly said.
A slower pace because of delays and hiccups is also normal at this time, Dr. Berman said. “If you feel like you’re just not as efficient as you were prior to COVID, it’s not just you,” she said. “It’s true. Everyone has to grapple with new things now. It takes longer.”
Things that add time include remote check-in and paperwork, more time to don and doff PPE and disinfect, dealing with technology failures, adjusting to new procedures or policies, and the general mental fatigue of adhering to PPE best practices. Patience is vital during this time, Dr. Berman said.
Several ways to improve efficiency include cutting out unnecessary steps, using standing orders and Advance Beneficiary Notice of Noncoverage (ABNs) for flu vaccinations, keeping credit card numbers on file for contactless payment, and considering the clinical and financial value of lab testing before ordering it.
“Effective triage helps patient satisfaction, access to care, and efficiency of your office workload,” Dr. Kressly said. “Use technology where it’s appropriate, but then add people where it’s needed. Connections to caring people matter even more in a time of crisis.”
The speakers also highlighted the importance of early flu vaccinations.
“One of the single biggest things you can do for value in COVID is to get your flu vaccine numbers up,” Dr. Berman said. “Severely reducing the burden of influenza will help flatten the curve, it will reduce febrile respiratory illness, and it will protect your most fragile patients.”
Two ways to do that include flu clinics and making a strong push for immunizations during the first 8 weeks after getting the vaccines. Dr Berman shared numbers from two practices showing how many more total immunizations were done in the practice that began vaccinating in early August versus early September.
A crisis is an opportunity
The speakers closed on an optimistic note that emphasized the opportunities that can grow out of the challenges presented by the pandemic, a point Dr Terk elaborated on.
“One of the most important things is realizing how we can potentially use a crisis to transform our practices,” Dr. Terk said in the interview. “As had been said before, a crisis is a terrible thing to waste. Those practices that have the gumption to innovate and find different ways to improve the way they provide care are probably going to be in better shape as we go forward.”
Critical to that success is taking risks, he added.
“When you’re innovating, failure has to be something you are permissive of because if you’re risk-averse and failure-averse, you’re not going to have the opportunity to grow and innovate, and this is another opportunity to innovate,” Dr. Terk said.
He also stressed the value of learning from one another. “We need to help each other by sharing our good practices, and on the flip side, be open to learning from each other,” he said. “Those pediatricians who are struggling need to be open-minded and open-hearted to understanding how we can operate our practices better and know that the things we think are barriers we can’t change are probably things we probably haven’t allowed ourselves to think about changing.”
Dr. Kressly and Dr. Berman recommended several specific actions for pediatricians to take:
- Creating a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis regarding your practice management response to the pandemic.
- Articulating three goals for improving your understanding or the implementation of management in your practice.
- Creating a working group to identify and implement ways to improve clinical work flow and communication strategies.
“Now is the time to meaningfully address disparities of access to appropriate health care and the impact of social determinants of health,” Dr. Kressly said. It’s also an opportunity to build meaningful relationships with patient families based on trust, science, and “true shared decision-making with health literacy in mind.”
Dr Kressly is the medical director of and owns shares in Office Practicum. Dr. Berman is the assistant medical director of and owns shares in Office Practicum, and is the owner of Script Doctor LLC. Dr. Terk and Dr. Hackell had no relevant financial disclosures.
FROM AAP 2020
Pediatric fractures shift during pandemic
Pediatric fractures dropped by 2.5-fold during the early months of the COVID-19 pandemic, but more breaks happened at home and on bicycles, and younger kids were more affected, new research indicates.
The study of 1,745 patients also found that those with distal radius torus fractures were more likely to receive a Velcro splint during the pandemic. Experts said this key trend points toward widespread shifts to streamline treatment, which should persist after the pandemic.
“We expected to see a drop in fracture volume, but what was a bit unexpected was the proportional rise in at-home injuries, which we weren’t immediately aware of,” said senior author Apurva Shah, MD, MBA, of Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania in Philadelphia.
“As time went on, it became more apparent that trampoline and bicycle injuries were on the rise, but at the beginning of the pandemic, we didn’t intuitively expect that,” he added.
“Whenever there’s a major shift in how the world is working, we want to understand how that impacts child safety,” Dr. Shah said in an interview. “The message to get out to parents is that it’s obviously difficult to supervise kids while working from home” during the pandemic “and that supervision obviously is not always working as well as intended.”
Joshua T. Bram, a medical student, presented the study at the virtual American Academy of Pediatrics (AAP) 2020 National Conference.
Dr. Bram, Dr. Shah, and colleagues compared patients with acute fractures who presented at CHOP between March and April 2020 with those who presented during the same months in 2018 and 2019.
Overall, the number of patients with pediatric fractures who presented to CHOP fell to an average of just under 10 per day, compared with more than 22 per day in prior years (P < .001). In addition, the age of the patients fell from an average of 9.4 years to 7.5 years (P < .001), with fewer adolescents affected in 2020.
“I think when you cancel a 14-year-old’s baseball season” because of the pandemic, “unfortunately, that lost outdoor time might be substituted with time on a screen,” he explained. “But canceling a 6-year-old’s soccer season might mean substituting that with more time outside on bikes or on a trampoline.”
As noted, because of the pandemic, a higher proportion of pediatric fractures occurred at home (57.8% vs. 32.5%; P < .001) or on bicycles (18.3% vs. 8.2%; P < .001), but there were fewer organized sports–related (7.2% vs. 26.0%; P < .001) or playground-related injuries (5.2% vs. 9.0%; P < .001).
In the study period this year, the researchers saw no increase in the amount of time between injury and presentation. However, data suggest that, in more recent months, “kids are presenting with fractures late, with sometimes great consequences,” Dr. Shah said.
“What has changed is that a lot of adults have lost their jobs, and as a consequence, a lot of children have lost their access to private insurance,” he said. “But fracture is really a major injury, and this is a reminder for pediatricians and primary care physicians to recognize that families are going through these changes and that delays in care can really be detrimental to children.”
Velcro splints more common
A potential upside to shifts seen during the pandemic, Dr. Shah said, is the finding that distal radius torus fractures were more likely to be treated with a Velcro splint than in previous years (44.2% vs. 25.9%; P = .010).
“This is hitting on something important – that sometimes it’s crisis that forces us as physicians to evolve,” he said. “This is something I think is here to stay.
“Although research had already been there suggesting a close equivalent between splints and casting, culturally, a lot of surgeons hadn’t made that shift when historically the gold standard had been casting,” Dr. Shah added. “But with the pandemic, the shift to minimize contact with the health care system to keep families safe in their COVID bubble helped [usage of] splints take off.
“I suspect – and we’ll only know when we’re on the other side of this – when physicians see good results in splints in their own patients, they’re going to adopt those strategies more permanently,” he said.
Benjamin Shore, MD, MPH, of Boston Children’s Hospital, agreed with Dr. Shah’s prediction that fracture care will be more streamlined after the pandemic. Dr. Shore, who wasn’t involved in the study, said not only are more orthopedic providers treating patients with Velcro splints and bivalve casts, but they are also monitoring patients via telehealth.
“All of these are great examples of innovation, and one of the unique parts of the pandemic is it created a lot of rapid change across healthcare because it caused us to scrutinize the ways we practice and make a change,” Dr. Shore said in an interview.
“It wasn’t a very fancy study, but it’s very important in terms of demonstrating a change in practice,” Dr. Shore said. “The research here basically validated what many of us are seeing and hopefully will help us in future pandemics – which hopefully won’t happen – to tell families what to be proactive about.”
Dr. Shah and Dr. Shore agreed that, because fewer fractures are occurring in kids during the pandemic, there is an opportunity to redeploy orthopedic providers to other clinical areas on the basis of volume and need.
Dr. Shah and Dr. Shore have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Pediatric fractures dropped by 2.5-fold during the early months of the COVID-19 pandemic, but more breaks happened at home and on bicycles, and younger kids were more affected, new research indicates.
The study of 1,745 patients also found that those with distal radius torus fractures were more likely to receive a Velcro splint during the pandemic. Experts said this key trend points toward widespread shifts to streamline treatment, which should persist after the pandemic.
“We expected to see a drop in fracture volume, but what was a bit unexpected was the proportional rise in at-home injuries, which we weren’t immediately aware of,” said senior author Apurva Shah, MD, MBA, of Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania in Philadelphia.
“As time went on, it became more apparent that trampoline and bicycle injuries were on the rise, but at the beginning of the pandemic, we didn’t intuitively expect that,” he added.
“Whenever there’s a major shift in how the world is working, we want to understand how that impacts child safety,” Dr. Shah said in an interview. “The message to get out to parents is that it’s obviously difficult to supervise kids while working from home” during the pandemic “and that supervision obviously is not always working as well as intended.”
Joshua T. Bram, a medical student, presented the study at the virtual American Academy of Pediatrics (AAP) 2020 National Conference.
Dr. Bram, Dr. Shah, and colleagues compared patients with acute fractures who presented at CHOP between March and April 2020 with those who presented during the same months in 2018 and 2019.
Overall, the number of patients with pediatric fractures who presented to CHOP fell to an average of just under 10 per day, compared with more than 22 per day in prior years (P < .001). In addition, the age of the patients fell from an average of 9.4 years to 7.5 years (P < .001), with fewer adolescents affected in 2020.
“I think when you cancel a 14-year-old’s baseball season” because of the pandemic, “unfortunately, that lost outdoor time might be substituted with time on a screen,” he explained. “But canceling a 6-year-old’s soccer season might mean substituting that with more time outside on bikes or on a trampoline.”
As noted, because of the pandemic, a higher proportion of pediatric fractures occurred at home (57.8% vs. 32.5%; P < .001) or on bicycles (18.3% vs. 8.2%; P < .001), but there were fewer organized sports–related (7.2% vs. 26.0%; P < .001) or playground-related injuries (5.2% vs. 9.0%; P < .001).
In the study period this year, the researchers saw no increase in the amount of time between injury and presentation. However, data suggest that, in more recent months, “kids are presenting with fractures late, with sometimes great consequences,” Dr. Shah said.
“What has changed is that a lot of adults have lost their jobs, and as a consequence, a lot of children have lost their access to private insurance,” he said. “But fracture is really a major injury, and this is a reminder for pediatricians and primary care physicians to recognize that families are going through these changes and that delays in care can really be detrimental to children.”
Velcro splints more common
A potential upside to shifts seen during the pandemic, Dr. Shah said, is the finding that distal radius torus fractures were more likely to be treated with a Velcro splint than in previous years (44.2% vs. 25.9%; P = .010).
“This is hitting on something important – that sometimes it’s crisis that forces us as physicians to evolve,” he said. “This is something I think is here to stay.
“Although research had already been there suggesting a close equivalent between splints and casting, culturally, a lot of surgeons hadn’t made that shift when historically the gold standard had been casting,” Dr. Shah added. “But with the pandemic, the shift to minimize contact with the health care system to keep families safe in their COVID bubble helped [usage of] splints take off.
“I suspect – and we’ll only know when we’re on the other side of this – when physicians see good results in splints in their own patients, they’re going to adopt those strategies more permanently,” he said.
Benjamin Shore, MD, MPH, of Boston Children’s Hospital, agreed with Dr. Shah’s prediction that fracture care will be more streamlined after the pandemic. Dr. Shore, who wasn’t involved in the study, said not only are more orthopedic providers treating patients with Velcro splints and bivalve casts, but they are also monitoring patients via telehealth.
“All of these are great examples of innovation, and one of the unique parts of the pandemic is it created a lot of rapid change across healthcare because it caused us to scrutinize the ways we practice and make a change,” Dr. Shore said in an interview.
“It wasn’t a very fancy study, but it’s very important in terms of demonstrating a change in practice,” Dr. Shore said. “The research here basically validated what many of us are seeing and hopefully will help us in future pandemics – which hopefully won’t happen – to tell families what to be proactive about.”
Dr. Shah and Dr. Shore agreed that, because fewer fractures are occurring in kids during the pandemic, there is an opportunity to redeploy orthopedic providers to other clinical areas on the basis of volume and need.
Dr. Shah and Dr. Shore have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Pediatric fractures dropped by 2.5-fold during the early months of the COVID-19 pandemic, but more breaks happened at home and on bicycles, and younger kids were more affected, new research indicates.
The study of 1,745 patients also found that those with distal radius torus fractures were more likely to receive a Velcro splint during the pandemic. Experts said this key trend points toward widespread shifts to streamline treatment, which should persist after the pandemic.
“We expected to see a drop in fracture volume, but what was a bit unexpected was the proportional rise in at-home injuries, which we weren’t immediately aware of,” said senior author Apurva Shah, MD, MBA, of Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania in Philadelphia.
“As time went on, it became more apparent that trampoline and bicycle injuries were on the rise, but at the beginning of the pandemic, we didn’t intuitively expect that,” he added.
“Whenever there’s a major shift in how the world is working, we want to understand how that impacts child safety,” Dr. Shah said in an interview. “The message to get out to parents is that it’s obviously difficult to supervise kids while working from home” during the pandemic “and that supervision obviously is not always working as well as intended.”
Joshua T. Bram, a medical student, presented the study at the virtual American Academy of Pediatrics (AAP) 2020 National Conference.
Dr. Bram, Dr. Shah, and colleagues compared patients with acute fractures who presented at CHOP between March and April 2020 with those who presented during the same months in 2018 and 2019.
Overall, the number of patients with pediatric fractures who presented to CHOP fell to an average of just under 10 per day, compared with more than 22 per day in prior years (P < .001). In addition, the age of the patients fell from an average of 9.4 years to 7.5 years (P < .001), with fewer adolescents affected in 2020.
“I think when you cancel a 14-year-old’s baseball season” because of the pandemic, “unfortunately, that lost outdoor time might be substituted with time on a screen,” he explained. “But canceling a 6-year-old’s soccer season might mean substituting that with more time outside on bikes or on a trampoline.”
As noted, because of the pandemic, a higher proportion of pediatric fractures occurred at home (57.8% vs. 32.5%; P < .001) or on bicycles (18.3% vs. 8.2%; P < .001), but there were fewer organized sports–related (7.2% vs. 26.0%; P < .001) or playground-related injuries (5.2% vs. 9.0%; P < .001).
In the study period this year, the researchers saw no increase in the amount of time between injury and presentation. However, data suggest that, in more recent months, “kids are presenting with fractures late, with sometimes great consequences,” Dr. Shah said.
“What has changed is that a lot of adults have lost their jobs, and as a consequence, a lot of children have lost their access to private insurance,” he said. “But fracture is really a major injury, and this is a reminder for pediatricians and primary care physicians to recognize that families are going through these changes and that delays in care can really be detrimental to children.”
Velcro splints more common
A potential upside to shifts seen during the pandemic, Dr. Shah said, is the finding that distal radius torus fractures were more likely to be treated with a Velcro splint than in previous years (44.2% vs. 25.9%; P = .010).
“This is hitting on something important – that sometimes it’s crisis that forces us as physicians to evolve,” he said. “This is something I think is here to stay.
“Although research had already been there suggesting a close equivalent between splints and casting, culturally, a lot of surgeons hadn’t made that shift when historically the gold standard had been casting,” Dr. Shah added. “But with the pandemic, the shift to minimize contact with the health care system to keep families safe in their COVID bubble helped [usage of] splints take off.
“I suspect – and we’ll only know when we’re on the other side of this – when physicians see good results in splints in their own patients, they’re going to adopt those strategies more permanently,” he said.
Benjamin Shore, MD, MPH, of Boston Children’s Hospital, agreed with Dr. Shah’s prediction that fracture care will be more streamlined after the pandemic. Dr. Shore, who wasn’t involved in the study, said not only are more orthopedic providers treating patients with Velcro splints and bivalve casts, but they are also monitoring patients via telehealth.
“All of these are great examples of innovation, and one of the unique parts of the pandemic is it created a lot of rapid change across healthcare because it caused us to scrutinize the ways we practice and make a change,” Dr. Shore said in an interview.
“It wasn’t a very fancy study, but it’s very important in terms of demonstrating a change in practice,” Dr. Shore said. “The research here basically validated what many of us are seeing and hopefully will help us in future pandemics – which hopefully won’t happen – to tell families what to be proactive about.”
Dr. Shah and Dr. Shore agreed that, because fewer fractures are occurring in kids during the pandemic, there is an opportunity to redeploy orthopedic providers to other clinical areas on the basis of volume and need.
Dr. Shah and Dr. Shore have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Clinical factors and treatment tied to COVID-19 mortality in cancer patients
according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.
Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.
The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.
Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.
Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
Clinical and laboratory factors: Abstract LBA72
The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.
The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.
Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).
Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).
In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).
Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
Treatment-related outcomes: Abstract LBA71
An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.
Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.
Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.
The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).
The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.
An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.
Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.
“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.
This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.
SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.
according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.
Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.
The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.
Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.
Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
Clinical and laboratory factors: Abstract LBA72
The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.
The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.
Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).
Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).
In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).
Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
Treatment-related outcomes: Abstract LBA71
An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.
Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.
Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.
The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).
The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.
An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.
Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.
“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.
This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.
SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.
according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.
Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.
The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.
Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.
Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
Clinical and laboratory factors: Abstract LBA72
The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.
The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.
Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).
Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).
In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).
Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
Treatment-related outcomes: Abstract LBA71
An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.
Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.
Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.
The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).
The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.
An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.
Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.
“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.
This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.
SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.
FROM ESMO 2020
Teen affective disorders raise risk for midlife acute MI
in a Swedish national registry study presented at the virtual annual congress of the European Society of Cardiology.
The association was mediated in part by poor stress resilience and lack of physical fitness among these teenagers with an affective disorder, reported Cecilia Bergh, PhD, of Obrero (Sweden) University.
Her study was made possible by Sweden’s comprehensive national health care registries coupled with the Nordic nation’s compulsory conscription for military service. The mandatory conscription evaluation during the study years included a semistructured interview with a psychologist to assess stress resilience through questions about coping with everyday life, a medical history and physical examination, and a cardiovascular fitness test using a bicycle ergometer.
The study included 238,013 males born in 1952-1956. They were aged 18-19 years when they underwent their conscription examination, at which time 34,503 of them either received or already had a diagnosis of depression or anxiety. During follow-up from 1987 to 2010, a first acute MI occurred in 5,891 of the men. The risk was increased 51% among those with an earlier teen diagnosis of depression or anxiety.
In a Cox regression analysis adjusted for levels of adolescent cardiovascular risk factors, including blood pressure, body mass index, and systemic inflammation, as well as additional potential confounders, such as cognitive function, parental socioeconomic index, and a summary disease score, the midlife MI risk associated with adolescent depression or anxiety was attenuated, but still significant, with a 24% increase. Upon further statistical adjustment incorporating adolescent stress resilience and cardiovascular fitness, the increased risk of acute MI in midlife associated with adolescent depression or anxiety was further attenuated yet remained significant, at 18%.
Dr. Bergh shared her thoughts on preventing this increased risk of acute MI at a relatively young age: “Effective prevention might focus on behavior, lifestyle, and psychosocial stress in early life. If a healthy lifestyle is encouraged as early as possible in childhood and adolescence, it is more likely to persist into adulthood and to improve longterm health. So look for signs of stress, depression, or anxiety that is beyond normal teenager behavior and a persistent problem. Teenagers with poor well-being could benefit from additional support to encourage exercise and also to develop strategies to deal with stress.”
She reported having no financial conflicts regarding her study, conducted free of commercial support.
SOURCE: Bergh C et al. ESC 2020, Abstract 90524.
in a Swedish national registry study presented at the virtual annual congress of the European Society of Cardiology.
The association was mediated in part by poor stress resilience and lack of physical fitness among these teenagers with an affective disorder, reported Cecilia Bergh, PhD, of Obrero (Sweden) University.
Her study was made possible by Sweden’s comprehensive national health care registries coupled with the Nordic nation’s compulsory conscription for military service. The mandatory conscription evaluation during the study years included a semistructured interview with a psychologist to assess stress resilience through questions about coping with everyday life, a medical history and physical examination, and a cardiovascular fitness test using a bicycle ergometer.
The study included 238,013 males born in 1952-1956. They were aged 18-19 years when they underwent their conscription examination, at which time 34,503 of them either received or already had a diagnosis of depression or anxiety. During follow-up from 1987 to 2010, a first acute MI occurred in 5,891 of the men. The risk was increased 51% among those with an earlier teen diagnosis of depression or anxiety.
In a Cox regression analysis adjusted for levels of adolescent cardiovascular risk factors, including blood pressure, body mass index, and systemic inflammation, as well as additional potential confounders, such as cognitive function, parental socioeconomic index, and a summary disease score, the midlife MI risk associated with adolescent depression or anxiety was attenuated, but still significant, with a 24% increase. Upon further statistical adjustment incorporating adolescent stress resilience and cardiovascular fitness, the increased risk of acute MI in midlife associated with adolescent depression or anxiety was further attenuated yet remained significant, at 18%.
Dr. Bergh shared her thoughts on preventing this increased risk of acute MI at a relatively young age: “Effective prevention might focus on behavior, lifestyle, and psychosocial stress in early life. If a healthy lifestyle is encouraged as early as possible in childhood and adolescence, it is more likely to persist into adulthood and to improve longterm health. So look for signs of stress, depression, or anxiety that is beyond normal teenager behavior and a persistent problem. Teenagers with poor well-being could benefit from additional support to encourage exercise and also to develop strategies to deal with stress.”
She reported having no financial conflicts regarding her study, conducted free of commercial support.
SOURCE: Bergh C et al. ESC 2020, Abstract 90524.
in a Swedish national registry study presented at the virtual annual congress of the European Society of Cardiology.
The association was mediated in part by poor stress resilience and lack of physical fitness among these teenagers with an affective disorder, reported Cecilia Bergh, PhD, of Obrero (Sweden) University.
Her study was made possible by Sweden’s comprehensive national health care registries coupled with the Nordic nation’s compulsory conscription for military service. The mandatory conscription evaluation during the study years included a semistructured interview with a psychologist to assess stress resilience through questions about coping with everyday life, a medical history and physical examination, and a cardiovascular fitness test using a bicycle ergometer.
The study included 238,013 males born in 1952-1956. They were aged 18-19 years when they underwent their conscription examination, at which time 34,503 of them either received or already had a diagnosis of depression or anxiety. During follow-up from 1987 to 2010, a first acute MI occurred in 5,891 of the men. The risk was increased 51% among those with an earlier teen diagnosis of depression or anxiety.
In a Cox regression analysis adjusted for levels of adolescent cardiovascular risk factors, including blood pressure, body mass index, and systemic inflammation, as well as additional potential confounders, such as cognitive function, parental socioeconomic index, and a summary disease score, the midlife MI risk associated with adolescent depression or anxiety was attenuated, but still significant, with a 24% increase. Upon further statistical adjustment incorporating adolescent stress resilience and cardiovascular fitness, the increased risk of acute MI in midlife associated with adolescent depression or anxiety was further attenuated yet remained significant, at 18%.
Dr. Bergh shared her thoughts on preventing this increased risk of acute MI at a relatively young age: “Effective prevention might focus on behavior, lifestyle, and psychosocial stress in early life. If a healthy lifestyle is encouraged as early as possible in childhood and adolescence, it is more likely to persist into adulthood and to improve longterm health. So look for signs of stress, depression, or anxiety that is beyond normal teenager behavior and a persistent problem. Teenagers with poor well-being could benefit from additional support to encourage exercise and also to develop strategies to deal with stress.”
She reported having no financial conflicts regarding her study, conducted free of commercial support.
SOURCE: Bergh C et al. ESC 2020, Abstract 90524.
FROM ESC CONGRESS 2020
Hidradenitis suppurativa therapy options should be patient guided
of their most challenging symptoms, according to an expert summary presented at the Skin of Color Update 2020.
“If your patient is only focused on the appearance of the lesions or the presence of sinus tracts, they might not think your treatment is working,” said Ginette A. Okoye, MD, professor and chair, department of dermatology, Howard University, Washington.
Instead, she advised working with patients to define priorities, allowing them to measure and appreciate improvement. The most difficult symptoms for one patient, such as pain or persistent abscess drainage, might not be the same for another.
There is a large array of treatment options for HS. These were once typically employed in stepwise manner, moving from steroids to hormonal therapies, antibiotics, and on to biologics and lasers, but Dr. Okoye reported that she layers on treatments, guided by patient priorities and responses. “Most of my patients are not on just one treatment at a time,” she said.
In addition to patient goals, her treatment choices are also influenced by the presence of comorbidities such as metabolic syndrome, polycystic ovarian syndrome (PCOS), or inflammatory bowel disease (IBD). For example, she reported she is more likely to include metformin among treatment options in patients with central obesity or insulin resistance, whereas she moves more quickly to a biologic for those with another systemic inflammatory disease such as IBD.
Although multiple factors appear to contribute to the symptoms of HS, the pathophysiology remains incompletely understood, but follicular occlusion is often “a primary inciting event,” Dr. Okoye said.
For this reason, laser hair removal can provide substantial benefit, she noted. Not only does it eliminate the occlusion, but the heat generated by the laser eliminates some of the pathogens, such as Porphyromonas gingivalis, associated with HS.
“Lasers work well for preventing new lesions from forming but also in making active lesions go away faster,” said Dr. Okoye, who relies on the Nd:YAG laser when treating this disease in darker skin. She has found lasers to be particularly effective in mild to moderate disease.
When using lasers, one challenge is third-party insurance, according to Dr. Okoye, who reported that she has tried repeatedly to convince payers that this treatment is medically indicated for HS, but claims have been routinely denied. As a result, she has had to significantly discount the cost of laser at her center in order to provide access to “a modality that actually works.”
Incision and drainage of inflamed painful lesions is a common intervention in HS, but Dr. Okoye discourages this approach. Because of the high recurrence rates, the benefits are temporary. Instead, she recommends an intralesional injection of triamcinolone acetonide diluted with equal amounts of lidocaine.
With this injection, “there is immediate pain relief followed by significant resolution of the inflammation,” she said. Because of the likelihood that patients seeking care in the emergency department for acutely inflamed lesions will receive surgical treatment, Dr. Okoye recommends offering patients urgent appointments for steroid injections when painful and inflamed lesions need immediate attention.
In contrast, marsupialization of abscesses or sinus tracts, often called deroofing, is associated with a relatively low risk of recurrence, can be done under local anesthesia in an office, and can lead to resolution of persistent nodules in patients with mild disease.
“This is an easy procedure that takes relatively little time,” advised Dr. Okoye, who provided CPT codes (10060 and 10061) that will provide reimbursement as long as procedural notes describe the rationale.
Metformin is an attractive adjunctive therapy for HS in patients with type 2 diabetes or features that suggest metabolic disturbances, such as central obesity, hypercholesterolemia, hypertension, or hypertriglyceridemia. It should also be considered in patients with PCOS because metformin decreases ovarian androgen production, she said.
When prescribing metformin in HS, which is an off-label indication, “I prefer the extended release formulation. It has a better profile in regard to gastrointestinal side effects and it can be taken once-daily,” Dr. Okoye said.
Citing a study that suggests patients with HS have even worse quality of life scores than do patients with diabetes, Dr. Okoye also emphasized the importance of psychosocial support and lifestyle modification as part of a holistic approach. With multiple manifestations of varying severity, individualizing therapy to control symptoms that the patient finds most bothersome is essential for optimizing patient well being.
Tien Viet Nguyen, MD, who practices dermatology and conducts clinical research in Bellevue, Wash., agrees that a comprehensive treatment program is needed. First author of a recent review article on HS, Dr. Nguyen agreed that common comorbidities like IBD, PCOS, and diabetes are accompanied frequently by a host of mental health and behavioral issues that contribute to impaired quality of life, such as depression, low self-esteem, sexual dysfunction, impaired sleep, and substance use disorders.
“Therefore, addressing these important comorbidities and quality of life issues with other health care professionals as a team is the best approach to improving health outcomes,” he said in an interview.
Dr. Nguyen also recently authored a chapter on quality of life issues associated with HS in the soon-to-be-published Comprehensive Guide to Hidradenitis Suppurativa (1st Edition, Dermatology Clinics). He agreed that optimal outcomes are achieved by an interdisciplinary team of health care providers who can address the sometimes independent but often interrelated comorbidities associated with this disorder.
Dr. Okoye has financial relationships with Pfizer and Unilver, but neither is relevant to this topic.
of their most challenging symptoms, according to an expert summary presented at the Skin of Color Update 2020.
“If your patient is only focused on the appearance of the lesions or the presence of sinus tracts, they might not think your treatment is working,” said Ginette A. Okoye, MD, professor and chair, department of dermatology, Howard University, Washington.
Instead, she advised working with patients to define priorities, allowing them to measure and appreciate improvement. The most difficult symptoms for one patient, such as pain or persistent abscess drainage, might not be the same for another.
There is a large array of treatment options for HS. These were once typically employed in stepwise manner, moving from steroids to hormonal therapies, antibiotics, and on to biologics and lasers, but Dr. Okoye reported that she layers on treatments, guided by patient priorities and responses. “Most of my patients are not on just one treatment at a time,” she said.
In addition to patient goals, her treatment choices are also influenced by the presence of comorbidities such as metabolic syndrome, polycystic ovarian syndrome (PCOS), or inflammatory bowel disease (IBD). For example, she reported she is more likely to include metformin among treatment options in patients with central obesity or insulin resistance, whereas she moves more quickly to a biologic for those with another systemic inflammatory disease such as IBD.
Although multiple factors appear to contribute to the symptoms of HS, the pathophysiology remains incompletely understood, but follicular occlusion is often “a primary inciting event,” Dr. Okoye said.
For this reason, laser hair removal can provide substantial benefit, she noted. Not only does it eliminate the occlusion, but the heat generated by the laser eliminates some of the pathogens, such as Porphyromonas gingivalis, associated with HS.
“Lasers work well for preventing new lesions from forming but also in making active lesions go away faster,” said Dr. Okoye, who relies on the Nd:YAG laser when treating this disease in darker skin. She has found lasers to be particularly effective in mild to moderate disease.
When using lasers, one challenge is third-party insurance, according to Dr. Okoye, who reported that she has tried repeatedly to convince payers that this treatment is medically indicated for HS, but claims have been routinely denied. As a result, she has had to significantly discount the cost of laser at her center in order to provide access to “a modality that actually works.”
Incision and drainage of inflamed painful lesions is a common intervention in HS, but Dr. Okoye discourages this approach. Because of the high recurrence rates, the benefits are temporary. Instead, she recommends an intralesional injection of triamcinolone acetonide diluted with equal amounts of lidocaine.
With this injection, “there is immediate pain relief followed by significant resolution of the inflammation,” she said. Because of the likelihood that patients seeking care in the emergency department for acutely inflamed lesions will receive surgical treatment, Dr. Okoye recommends offering patients urgent appointments for steroid injections when painful and inflamed lesions need immediate attention.
In contrast, marsupialization of abscesses or sinus tracts, often called deroofing, is associated with a relatively low risk of recurrence, can be done under local anesthesia in an office, and can lead to resolution of persistent nodules in patients with mild disease.
“This is an easy procedure that takes relatively little time,” advised Dr. Okoye, who provided CPT codes (10060 and 10061) that will provide reimbursement as long as procedural notes describe the rationale.
Metformin is an attractive adjunctive therapy for HS in patients with type 2 diabetes or features that suggest metabolic disturbances, such as central obesity, hypercholesterolemia, hypertension, or hypertriglyceridemia. It should also be considered in patients with PCOS because metformin decreases ovarian androgen production, she said.
When prescribing metformin in HS, which is an off-label indication, “I prefer the extended release formulation. It has a better profile in regard to gastrointestinal side effects and it can be taken once-daily,” Dr. Okoye said.
Citing a study that suggests patients with HS have even worse quality of life scores than do patients with diabetes, Dr. Okoye also emphasized the importance of psychosocial support and lifestyle modification as part of a holistic approach. With multiple manifestations of varying severity, individualizing therapy to control symptoms that the patient finds most bothersome is essential for optimizing patient well being.
Tien Viet Nguyen, MD, who practices dermatology and conducts clinical research in Bellevue, Wash., agrees that a comprehensive treatment program is needed. First author of a recent review article on HS, Dr. Nguyen agreed that common comorbidities like IBD, PCOS, and diabetes are accompanied frequently by a host of mental health and behavioral issues that contribute to impaired quality of life, such as depression, low self-esteem, sexual dysfunction, impaired sleep, and substance use disorders.
“Therefore, addressing these important comorbidities and quality of life issues with other health care professionals as a team is the best approach to improving health outcomes,” he said in an interview.
Dr. Nguyen also recently authored a chapter on quality of life issues associated with HS in the soon-to-be-published Comprehensive Guide to Hidradenitis Suppurativa (1st Edition, Dermatology Clinics). He agreed that optimal outcomes are achieved by an interdisciplinary team of health care providers who can address the sometimes independent but often interrelated comorbidities associated with this disorder.
Dr. Okoye has financial relationships with Pfizer and Unilver, but neither is relevant to this topic.
of their most challenging symptoms, according to an expert summary presented at the Skin of Color Update 2020.
“If your patient is only focused on the appearance of the lesions or the presence of sinus tracts, they might not think your treatment is working,” said Ginette A. Okoye, MD, professor and chair, department of dermatology, Howard University, Washington.
Instead, she advised working with patients to define priorities, allowing them to measure and appreciate improvement. The most difficult symptoms for one patient, such as pain or persistent abscess drainage, might not be the same for another.
There is a large array of treatment options for HS. These were once typically employed in stepwise manner, moving from steroids to hormonal therapies, antibiotics, and on to biologics and lasers, but Dr. Okoye reported that she layers on treatments, guided by patient priorities and responses. “Most of my patients are not on just one treatment at a time,” she said.
In addition to patient goals, her treatment choices are also influenced by the presence of comorbidities such as metabolic syndrome, polycystic ovarian syndrome (PCOS), or inflammatory bowel disease (IBD). For example, she reported she is more likely to include metformin among treatment options in patients with central obesity or insulin resistance, whereas she moves more quickly to a biologic for those with another systemic inflammatory disease such as IBD.
Although multiple factors appear to contribute to the symptoms of HS, the pathophysiology remains incompletely understood, but follicular occlusion is often “a primary inciting event,” Dr. Okoye said.
For this reason, laser hair removal can provide substantial benefit, she noted. Not only does it eliminate the occlusion, but the heat generated by the laser eliminates some of the pathogens, such as Porphyromonas gingivalis, associated with HS.
“Lasers work well for preventing new lesions from forming but also in making active lesions go away faster,” said Dr. Okoye, who relies on the Nd:YAG laser when treating this disease in darker skin. She has found lasers to be particularly effective in mild to moderate disease.
When using lasers, one challenge is third-party insurance, according to Dr. Okoye, who reported that she has tried repeatedly to convince payers that this treatment is medically indicated for HS, but claims have been routinely denied. As a result, she has had to significantly discount the cost of laser at her center in order to provide access to “a modality that actually works.”
Incision and drainage of inflamed painful lesions is a common intervention in HS, but Dr. Okoye discourages this approach. Because of the high recurrence rates, the benefits are temporary. Instead, she recommends an intralesional injection of triamcinolone acetonide diluted with equal amounts of lidocaine.
With this injection, “there is immediate pain relief followed by significant resolution of the inflammation,” she said. Because of the likelihood that patients seeking care in the emergency department for acutely inflamed lesions will receive surgical treatment, Dr. Okoye recommends offering patients urgent appointments for steroid injections when painful and inflamed lesions need immediate attention.
In contrast, marsupialization of abscesses or sinus tracts, often called deroofing, is associated with a relatively low risk of recurrence, can be done under local anesthesia in an office, and can lead to resolution of persistent nodules in patients with mild disease.
“This is an easy procedure that takes relatively little time,” advised Dr. Okoye, who provided CPT codes (10060 and 10061) that will provide reimbursement as long as procedural notes describe the rationale.
Metformin is an attractive adjunctive therapy for HS in patients with type 2 diabetes or features that suggest metabolic disturbances, such as central obesity, hypercholesterolemia, hypertension, or hypertriglyceridemia. It should also be considered in patients with PCOS because metformin decreases ovarian androgen production, she said.
When prescribing metformin in HS, which is an off-label indication, “I prefer the extended release formulation. It has a better profile in regard to gastrointestinal side effects and it can be taken once-daily,” Dr. Okoye said.
Citing a study that suggests patients with HS have even worse quality of life scores than do patients with diabetes, Dr. Okoye also emphasized the importance of psychosocial support and lifestyle modification as part of a holistic approach. With multiple manifestations of varying severity, individualizing therapy to control symptoms that the patient finds most bothersome is essential for optimizing patient well being.
Tien Viet Nguyen, MD, who practices dermatology and conducts clinical research in Bellevue, Wash., agrees that a comprehensive treatment program is needed. First author of a recent review article on HS, Dr. Nguyen agreed that common comorbidities like IBD, PCOS, and diabetes are accompanied frequently by a host of mental health and behavioral issues that contribute to impaired quality of life, such as depression, low self-esteem, sexual dysfunction, impaired sleep, and substance use disorders.
“Therefore, addressing these important comorbidities and quality of life issues with other health care professionals as a team is the best approach to improving health outcomes,” he said in an interview.
Dr. Nguyen also recently authored a chapter on quality of life issues associated with HS in the soon-to-be-published Comprehensive Guide to Hidradenitis Suppurativa (1st Edition, Dermatology Clinics). He agreed that optimal outcomes are achieved by an interdisciplinary team of health care providers who can address the sometimes independent but often interrelated comorbidities associated with this disorder.
Dr. Okoye has financial relationships with Pfizer and Unilver, but neither is relevant to this topic.
FROM SOC 2020
Expert offers tips for combining lasers and injectables on the same day
While if it involves the same area.
“Swelling from the laser can potentially make the toxin migrate and cause ptosis,” Arisa E. Ortiz, MD, said at the virtual annual Masters of Aesthetics Symposium. “Even though this is temporary, your patient’s not going to be very happy with you. I would separate these at least 1 day apart, and then you should be OK.”
When using a filler on the same day as a laser treatment, Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego, performs the laser procedure after injecting the filler, “because you may get some swelling, which can distort your need for filler,” she said. “I like to do the filler first to make sure I can assess how much volume loss they have. Then I’ll do the laser procedure right after.”
Another general rule of thumb is that, when combining lasers on the same day, consider lowering the device settings, “because it’s going to be a more aggressive treatment when you’re combining various laser procedures,” she said. “Treat vascular lesions first to not exacerbate nonspecific erythema. Then treat pigment, then resurfacing, followed by liquid nitrogen if needed to treat seborrheic keratoses.”
For periorbital rejuvenation, Dr. Ortiz likes to use a neurotoxin 1 week before performing the laser-resurfacing or skin-tightening procedure, followed by injection of a filler. “This augments your results,” she said. “Studies have shown that, if you start with a neuromodulator, you can get more improvement with your resurfacing procedure,” she said. “That makes sense, because you’re not contracting the muscle while you’re healing from the laser, so you get more effective collagen remodeling.”
When using a neuromodulator for dynamic periorbital rhytides, place it superficially to avoid bruising and stay superior to the maxillary prominence to avoid the zygomaticus major “so you don’t get a droopy smile,” she said. “The approved dosing is 24 units, 12 on each side. Less may be required for younger patients and more for more severe rhytides.”
For static rhytides, fractional resurfacing procedures will provide a more modest result with less downtime, while fully ablative laser resurfacing procedures will provide more dramatic improvement with more downtime. “You’re really going to tailor your treatment to what the patient is looking for,” Dr. Ortiz said. “If you use a fractional device you may need multiple treatments. Using a corneal shield when you’re resurfacing within the periorbital rim is a must, so you need to know how to place these if you’re going to be resurfacing in that area.”
For anesthesia, Dr. Ortiz likes to use injectable lidocaine, “because if you use a topical it can creep into the eye, and then you get a chemical corneal abrasion. This resolves after a few days but it’s really painful and your patient won’t be very happy.”
For tear troughs, use a hyaluronic acid filler with a low G prime. “If you use a thicker filler it can look lumpy or too full,” she said. While some clinicians use a needle to administer the filler, Dr. Ortiz prefers to use a blunt-tipped cannula. “It’s less painful and there’s less risk of bruising or swelling,” she said. “There’s also less risk of cannulizing a vessel. This is not zero risk. It’s been shown that the 27-gauge can actually cannulize the vessel, so it shouldn’t give you a false sense of security, but there is less risk, compared with using a needle. You can use the cannula to thread. If you’re using a needle you can inject a bolus and then massage it in, or you can use the microdroplet technique.”
With the cannula technique, bruising or swelling can occur even in the most experienced hands, “so make sure your patients don’t have an important event coming up,” Dr. Ortiz said. “With filler, not only do you improve the volume loss, but sometimes you improve the dark circles. I tend to see this more in lighter-skinned patients. In darker-skinned patients, the dark circles can be caused by racial pigmentation. That’s hard to fix, so I never promise that we can improve dark circles, but sometimes it does improve.”
For dynamic perioral rhytides, Dr. Ortiz generally treats with a neuromodulator 1 week in advance of laser resurfacing, followed by a filler for any etched-in lines. Use of a neuromodulator in the perioral region of musicians or singers is contraindicated “because it can affect their phonation,” she said. “Also, older patients might complain that it’s difficult for them to pucker their lips when they’re putting on a lip liner or lipstick. There are four injection sites on the upper lip and two on the lower lip. I do 1 unit at each injection site, with a max of 6-8 units. Any more than that and they’ll have difficulty puckering.”
Two main options for treating submental fullness include cryolipolysis or deoxycholic acid. “If you have a lot of volume, you want to use cryolipolysis,” Dr. Ortiz said. “The general rule is, if it fits in the cup [of the applicator], hook them up.” Use deoxycholic acid for areas of smaller volume, or to fine-tune, she added.
For platysmal bands, Dr. Ortiz favors injecting 2 units of botulinum toxin at three to four sites along the band. She pulls away and injects superficially and limits the treatment dose to 40 units in one session “because excessive doses can cause dysphagia,” she said. “If they need additional units, I’ll have them come back in 2 weeks.”
The Nefertiti lift combines the treatment of the platysma with the insertion point of the platysma along the jawline. Treatment of the patient along the lateral jawline with 2 units of botulinum toxin every centimeter or so can actually improve the definition of the jawline, “because your platysma is pulling down on your lower face,” Dr. Ortiz explained. “So, if you relax that, it can help to define the jawline. By treating the platysma, you can also prevent or soften the horizontal bands that occur across the neck.”
For necklace creases, she likes to inject 1-2 units of a low-HA filler along the crease – evenly spaced all along. “I’ll dilute it even further with 0.5 cc of lidocaine with epinephrine,” she said. “Then you can do serial punctures or you can thread along that line.”
For treating static rhytides on the neck, laser-resurfacing procedures work best, but at low settings. “Because there are fewer adnexal structures, the neck is at increased risk for scarring,” Dr. Ortiz said. “You want to use a lower fluence because your neck skin is thin. Your fluence determines your depth with resurfacing. Most importantly, use a lower density for a more conservative setting”
Options for treating poikiloderma of Civatte include the vascular laser, an IPL [intense pulsed light device], or a 1927-nm thulium laser. To avoid footprinting, or a “chicken wire” appearance to the treated area, Dr. Ortiz recommends using a large spot size with the pulsed dye laser or the IPL.
She concluded her presentation by underscoring the importance of communicating realistic expectations with patients. “There is some delayed gratification here,” she said. “For procedures that take time to see results, consider adding another procedure that will give them immediate results.”
Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also cochair of the MOA.
While if it involves the same area.
“Swelling from the laser can potentially make the toxin migrate and cause ptosis,” Arisa E. Ortiz, MD, said at the virtual annual Masters of Aesthetics Symposium. “Even though this is temporary, your patient’s not going to be very happy with you. I would separate these at least 1 day apart, and then you should be OK.”
When using a filler on the same day as a laser treatment, Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego, performs the laser procedure after injecting the filler, “because you may get some swelling, which can distort your need for filler,” she said. “I like to do the filler first to make sure I can assess how much volume loss they have. Then I’ll do the laser procedure right after.”
Another general rule of thumb is that, when combining lasers on the same day, consider lowering the device settings, “because it’s going to be a more aggressive treatment when you’re combining various laser procedures,” she said. “Treat vascular lesions first to not exacerbate nonspecific erythema. Then treat pigment, then resurfacing, followed by liquid nitrogen if needed to treat seborrheic keratoses.”
For periorbital rejuvenation, Dr. Ortiz likes to use a neurotoxin 1 week before performing the laser-resurfacing or skin-tightening procedure, followed by injection of a filler. “This augments your results,” she said. “Studies have shown that, if you start with a neuromodulator, you can get more improvement with your resurfacing procedure,” she said. “That makes sense, because you’re not contracting the muscle while you’re healing from the laser, so you get more effective collagen remodeling.”
When using a neuromodulator for dynamic periorbital rhytides, place it superficially to avoid bruising and stay superior to the maxillary prominence to avoid the zygomaticus major “so you don’t get a droopy smile,” she said. “The approved dosing is 24 units, 12 on each side. Less may be required for younger patients and more for more severe rhytides.”
For static rhytides, fractional resurfacing procedures will provide a more modest result with less downtime, while fully ablative laser resurfacing procedures will provide more dramatic improvement with more downtime. “You’re really going to tailor your treatment to what the patient is looking for,” Dr. Ortiz said. “If you use a fractional device you may need multiple treatments. Using a corneal shield when you’re resurfacing within the periorbital rim is a must, so you need to know how to place these if you’re going to be resurfacing in that area.”
For anesthesia, Dr. Ortiz likes to use injectable lidocaine, “because if you use a topical it can creep into the eye, and then you get a chemical corneal abrasion. This resolves after a few days but it’s really painful and your patient won’t be very happy.”
For tear troughs, use a hyaluronic acid filler with a low G prime. “If you use a thicker filler it can look lumpy or too full,” she said. While some clinicians use a needle to administer the filler, Dr. Ortiz prefers to use a blunt-tipped cannula. “It’s less painful and there’s less risk of bruising or swelling,” she said. “There’s also less risk of cannulizing a vessel. This is not zero risk. It’s been shown that the 27-gauge can actually cannulize the vessel, so it shouldn’t give you a false sense of security, but there is less risk, compared with using a needle. You can use the cannula to thread. If you’re using a needle you can inject a bolus and then massage it in, or you can use the microdroplet technique.”
With the cannula technique, bruising or swelling can occur even in the most experienced hands, “so make sure your patients don’t have an important event coming up,” Dr. Ortiz said. “With filler, not only do you improve the volume loss, but sometimes you improve the dark circles. I tend to see this more in lighter-skinned patients. In darker-skinned patients, the dark circles can be caused by racial pigmentation. That’s hard to fix, so I never promise that we can improve dark circles, but sometimes it does improve.”
For dynamic perioral rhytides, Dr. Ortiz generally treats with a neuromodulator 1 week in advance of laser resurfacing, followed by a filler for any etched-in lines. Use of a neuromodulator in the perioral region of musicians or singers is contraindicated “because it can affect their phonation,” she said. “Also, older patients might complain that it’s difficult for them to pucker their lips when they’re putting on a lip liner or lipstick. There are four injection sites on the upper lip and two on the lower lip. I do 1 unit at each injection site, with a max of 6-8 units. Any more than that and they’ll have difficulty puckering.”
Two main options for treating submental fullness include cryolipolysis or deoxycholic acid. “If you have a lot of volume, you want to use cryolipolysis,” Dr. Ortiz said. “The general rule is, if it fits in the cup [of the applicator], hook them up.” Use deoxycholic acid for areas of smaller volume, or to fine-tune, she added.
For platysmal bands, Dr. Ortiz favors injecting 2 units of botulinum toxin at three to four sites along the band. She pulls away and injects superficially and limits the treatment dose to 40 units in one session “because excessive doses can cause dysphagia,” she said. “If they need additional units, I’ll have them come back in 2 weeks.”
The Nefertiti lift combines the treatment of the platysma with the insertion point of the platysma along the jawline. Treatment of the patient along the lateral jawline with 2 units of botulinum toxin every centimeter or so can actually improve the definition of the jawline, “because your platysma is pulling down on your lower face,” Dr. Ortiz explained. “So, if you relax that, it can help to define the jawline. By treating the platysma, you can also prevent or soften the horizontal bands that occur across the neck.”
For necklace creases, she likes to inject 1-2 units of a low-HA filler along the crease – evenly spaced all along. “I’ll dilute it even further with 0.5 cc of lidocaine with epinephrine,” she said. “Then you can do serial punctures or you can thread along that line.”
For treating static rhytides on the neck, laser-resurfacing procedures work best, but at low settings. “Because there are fewer adnexal structures, the neck is at increased risk for scarring,” Dr. Ortiz said. “You want to use a lower fluence because your neck skin is thin. Your fluence determines your depth with resurfacing. Most importantly, use a lower density for a more conservative setting”
Options for treating poikiloderma of Civatte include the vascular laser, an IPL [intense pulsed light device], or a 1927-nm thulium laser. To avoid footprinting, or a “chicken wire” appearance to the treated area, Dr. Ortiz recommends using a large spot size with the pulsed dye laser or the IPL.
She concluded her presentation by underscoring the importance of communicating realistic expectations with patients. “There is some delayed gratification here,” she said. “For procedures that take time to see results, consider adding another procedure that will give them immediate results.”
Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also cochair of the MOA.
While if it involves the same area.
“Swelling from the laser can potentially make the toxin migrate and cause ptosis,” Arisa E. Ortiz, MD, said at the virtual annual Masters of Aesthetics Symposium. “Even though this is temporary, your patient’s not going to be very happy with you. I would separate these at least 1 day apart, and then you should be OK.”
When using a filler on the same day as a laser treatment, Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego, performs the laser procedure after injecting the filler, “because you may get some swelling, which can distort your need for filler,” she said. “I like to do the filler first to make sure I can assess how much volume loss they have. Then I’ll do the laser procedure right after.”
Another general rule of thumb is that, when combining lasers on the same day, consider lowering the device settings, “because it’s going to be a more aggressive treatment when you’re combining various laser procedures,” she said. “Treat vascular lesions first to not exacerbate nonspecific erythema. Then treat pigment, then resurfacing, followed by liquid nitrogen if needed to treat seborrheic keratoses.”
For periorbital rejuvenation, Dr. Ortiz likes to use a neurotoxin 1 week before performing the laser-resurfacing or skin-tightening procedure, followed by injection of a filler. “This augments your results,” she said. “Studies have shown that, if you start with a neuromodulator, you can get more improvement with your resurfacing procedure,” she said. “That makes sense, because you’re not contracting the muscle while you’re healing from the laser, so you get more effective collagen remodeling.”
When using a neuromodulator for dynamic periorbital rhytides, place it superficially to avoid bruising and stay superior to the maxillary prominence to avoid the zygomaticus major “so you don’t get a droopy smile,” she said. “The approved dosing is 24 units, 12 on each side. Less may be required for younger patients and more for more severe rhytides.”
For static rhytides, fractional resurfacing procedures will provide a more modest result with less downtime, while fully ablative laser resurfacing procedures will provide more dramatic improvement with more downtime. “You’re really going to tailor your treatment to what the patient is looking for,” Dr. Ortiz said. “If you use a fractional device you may need multiple treatments. Using a corneal shield when you’re resurfacing within the periorbital rim is a must, so you need to know how to place these if you’re going to be resurfacing in that area.”
For anesthesia, Dr. Ortiz likes to use injectable lidocaine, “because if you use a topical it can creep into the eye, and then you get a chemical corneal abrasion. This resolves after a few days but it’s really painful and your patient won’t be very happy.”
For tear troughs, use a hyaluronic acid filler with a low G prime. “If you use a thicker filler it can look lumpy or too full,” she said. While some clinicians use a needle to administer the filler, Dr. Ortiz prefers to use a blunt-tipped cannula. “It’s less painful and there’s less risk of bruising or swelling,” she said. “There’s also less risk of cannulizing a vessel. This is not zero risk. It’s been shown that the 27-gauge can actually cannulize the vessel, so it shouldn’t give you a false sense of security, but there is less risk, compared with using a needle. You can use the cannula to thread. If you’re using a needle you can inject a bolus and then massage it in, or you can use the microdroplet technique.”
With the cannula technique, bruising or swelling can occur even in the most experienced hands, “so make sure your patients don’t have an important event coming up,” Dr. Ortiz said. “With filler, not only do you improve the volume loss, but sometimes you improve the dark circles. I tend to see this more in lighter-skinned patients. In darker-skinned patients, the dark circles can be caused by racial pigmentation. That’s hard to fix, so I never promise that we can improve dark circles, but sometimes it does improve.”
For dynamic perioral rhytides, Dr. Ortiz generally treats with a neuromodulator 1 week in advance of laser resurfacing, followed by a filler for any etched-in lines. Use of a neuromodulator in the perioral region of musicians or singers is contraindicated “because it can affect their phonation,” she said. “Also, older patients might complain that it’s difficult for them to pucker their lips when they’re putting on a lip liner or lipstick. There are four injection sites on the upper lip and two on the lower lip. I do 1 unit at each injection site, with a max of 6-8 units. Any more than that and they’ll have difficulty puckering.”
Two main options for treating submental fullness include cryolipolysis or deoxycholic acid. “If you have a lot of volume, you want to use cryolipolysis,” Dr. Ortiz said. “The general rule is, if it fits in the cup [of the applicator], hook them up.” Use deoxycholic acid for areas of smaller volume, or to fine-tune, she added.
For platysmal bands, Dr. Ortiz favors injecting 2 units of botulinum toxin at three to four sites along the band. She pulls away and injects superficially and limits the treatment dose to 40 units in one session “because excessive doses can cause dysphagia,” she said. “If they need additional units, I’ll have them come back in 2 weeks.”
The Nefertiti lift combines the treatment of the platysma with the insertion point of the platysma along the jawline. Treatment of the patient along the lateral jawline with 2 units of botulinum toxin every centimeter or so can actually improve the definition of the jawline, “because your platysma is pulling down on your lower face,” Dr. Ortiz explained. “So, if you relax that, it can help to define the jawline. By treating the platysma, you can also prevent or soften the horizontal bands that occur across the neck.”
For necklace creases, she likes to inject 1-2 units of a low-HA filler along the crease – evenly spaced all along. “I’ll dilute it even further with 0.5 cc of lidocaine with epinephrine,” she said. “Then you can do serial punctures or you can thread along that line.”
For treating static rhytides on the neck, laser-resurfacing procedures work best, but at low settings. “Because there are fewer adnexal structures, the neck is at increased risk for scarring,” Dr. Ortiz said. “You want to use a lower fluence because your neck skin is thin. Your fluence determines your depth with resurfacing. Most importantly, use a lower density for a more conservative setting”
Options for treating poikiloderma of Civatte include the vascular laser, an IPL [intense pulsed light device], or a 1927-nm thulium laser. To avoid footprinting, or a “chicken wire” appearance to the treated area, Dr. Ortiz recommends using a large spot size with the pulsed dye laser or the IPL.
She concluded her presentation by underscoring the importance of communicating realistic expectations with patients. “There is some delayed gratification here,” she said. “For procedures that take time to see results, consider adding another procedure that will give them immediate results.”
Dr. Ortiz disclosed having financial relationships with numerous pharmaceutical and device companies. She is also cochair of the MOA.
EXPERT ANALYSIS FROM MOA 2020
Optimal sedation strategies for COVID-19 ICU patients: A work in progress
According to the best available evidence, analagosedation remains the focus for managing COVID-19 ICU patients, according to Steven B. Greenberg, MD, FCCP, FCCM.
“The choice of sedation and analgesia is important,” Dr. Greenberg, vice chair of education in the department of anesthesiology at Evanston Hospital, part of NorthShore University Health System, Chicago, said at a Society for Critical Care virtual meeting: COVID-19: What’s Next. “We know that the right choice of these two components may increase liberation from ventilators, earlier ICU discharge, and return to normal brain function and independent functional status.”
Analgesia first
Prior to the current pandemic, the approach to sedation of patients in the ICU was based on the PADIS Guidelines of 2018, which call for an assessment-driven, protocol-based stepwise approach to pain and sedation management in critically ill adults (Crit Care Med. 2018;46:e825-73). “” Dr. Greenberg said. “We know that pain management should be a priority of sedation, because pain may increase the risk of delirium, anxiety, and endocrine suppression, and may increase the risk of release of endogenous catecholamines, ischemia, and hypermetabolic states.”
Fentanyl appears to be the most common opioid analgesic used for patients in the ICU, “but fentanyl is a very lipophilic drug and has a long context-sensitive half-life,” he said. “There are components to fentanyl that allow it to become a very long-acting drug upon days and days of infusion. Another opioid used is remifentanil, which is typically short-acting because it is broken down in the blood by esterases, but may cause rigidity at higher doses. Dilaudid seems to be the least affected by organ dysfunction. In our very critically ill, prolonged mechanically ventilated COVID-19 patients, we’ve been using methadone for its NMDA [N-methyl-D-aspartate] antagonistic effect and its opioid-sparing effects.”
As for nonopioid analgesics, Dr. Greenberg said that clinicians have shied away from using NSAIDs because of their side effects. “Tramadol indirectly inhibits reuptake of norepinephrine and serotonin, and ketamine is being used a lot more because of its NMDA antagonist effect,” he said. “Lidocaine and gabapentin have also been used.”
In a recent systematic review and meta-analysis, researchers assessed 34 trials that examined adjuvant analgesic use with an opioid in critically ill patients versus an opioid alone (Crit Care Expl. 2020;2:e0157). They found that when using an adjuvant such as acetaminophen, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium, nefopam, NSAIDs, pregabalin, and tramadol, there was a reduction in pain scores as well as a reduction in opioid consumption. “So, clinicians should consider using adjuvant agents to limit opioid exposure and improve pain scores in the critically ill,” Dr. Greenberg said.
ICU delirium: Risk factors, prevention
Delirium in COVID-19 patients treated in the ICU of particular concern. According to a systematic review of 33 studies, 11 risk factors for delirium in the ICU were supported by strong or moderate levels of evidence (Crit Care Med. 2015;43:40-7). These include age, dementia, hypertension, emergency surgery, trauma, APACHE score of II, need for mechanical ventilation, metabolic acidosis, delirium on prior day, coma, and dexmedetomidine use. Risk factors for ICU delirium among COVID-19 patients, however, “are far different,” Dr. Greenberg said. “Why? First and foremost, we are restricting visitation of family,” he said. “That family connection largely can be lost. Second, there are limitations of nonpharmacologic interventions. There is less mobility and physical therapy employed because of the risk of health care workers’ exposure to the virus. There’s also uncertainty about the global pandemic. Anxiety and depression come with that, as well as disruptions to spiritual and religious services.”
Strategies for preventing delirium remain the same as before the pandemic and in accord with recent clinical practice guidelines: Reduce the use of certain drugs such as benzodiazepines and narcotics, reorient the patients, treat dehydration, use hearing aids and eyeglasses in patients who have them, use ear plugs to cancel noise, mobilize patients, maintain sleep/awake cycles, and encourage sedation holidays (Crit Care Med. 2018;46[9]:e825-73).
A recent study from France found that among 58 patients with COVID-19, 65% had positive Confusion Assessment Method (CAM)–ICU findings and 69% had agitation (N Engl J Med 2020;382:2268-70). Most of the patients (86%) received midazolam, 47% received propofol, and all received sufentanil. “In the pre-COVID days, we would use midazolam as a second-line agent for many of these patients,” Dr. Greenberg said. “So, times really have changed.”
The fate of COVID-19 patients following discharge from the ICU remains a concern, continued Dr. Greenberg, clinical professor of anesthesiology at the University of Chicago. A recent journal article by Michelle Biehl, MD, and Denise Sese, MD, noted that post–intensive care syndrome (PICS) or new or worsening impairment in any physical, cognitive, or mental domain is of significant concern among COVID-19 patients following their ICU stay (Cleveland Clin J Med 2020 Aug doi: 10.3949/ccjm.87a.ccc055). The authors stated that COVID-19 patients may face a higher risk of PICS because of restricted family visitation, prolonged mechanical ventilation, exposure to higher amounts of sedatives, and limited physical therapy during hospital stay.
No ideal sedative agent
The 2018 PADIS Guidelines on the use of ICU sedation suggested strong evidence for modifiable risk factors producing delirium in the context of benzodiazepines and blood transfusion. They recommend a light level of sedation and the use of propofol or dexmedetomidine over benzodiazepines. They also recommend routine delirium testing such as using the CAM-ICU or Intensive Care Delirium Screening Checklist (ICDSC) and nonpharmacologic therapies such as reorientation, cognitive stimulation, sleep improvement, and mobilization.
Several sedation-related factors may be related to an increased risk of delirium. “The type, dose, duration, and mode of delivery are very important,” Dr. Greenberg said. “The ideal sedative agent has a rapid, predictable onset; is short-acting; has anxiolytic, amnestic, and analgesic properties; is soluble; has a high therapeutic index; and no toxicity. The ideal sedative is also easy to administrate, contains no active metabolites, has minimal actions with other drugs, is reversible, and is cost effective. The problem is, there really is no ideal sedative agent. There is inadequate knowledge about the drugs [used to treat COVID-19 in the ICU] available to us, the dosage, and importantly, the pharmacokinetics and dynamics of these medications.”
The classic types of sedation being used in the ICU, he said, include the benzodiazepines midazolam, lorazepam, and diazepam, as well as propofol. Alternatives include dexmedetomidine, clonidine, ketamine, and the neuroleptics – haloperidol, quetiapine, olanzapine, ziprasidone, and risperidone. “The advantages of benzos are that they are anxiolytics, amnestics, and they are good sedatives with minimal hemodynamic effects,” Dr. Greenberg said.
Advantages of propofol include its sedative, hypnotic, and anxiolytic properties, he said. It reduces the cerebral metabolic rate and can relieve bronchospasm. “However, small studies have found that its use may be associated with an increased risk of delirium,” he said. “It is a respiratory depressant, and it can cause hypotension and decreased contractility. It has no analgesic properties, and two of the big concerns of its use in COVID-19 are the potential for hypertriglyceridemia and propofol infusion syndrome, particularly at doses of greater than 5 mg/kg per hour for greater than 48 hours. It is being given in high doses because patients are requiring higher doses to maintain ventilator synchrony.”
Choosing the right drug
The keys to success for sedation of ICU patients are choosing the right drug at the right dose for the right duration and the right mode of delivery, and applying them to the right population. However, as noted in a recent study, the pandemic poses unique challenges to clinicians in how they care for critically ill COVID-19 patients who require sedation (Anesth Analg. 2020 Apr 22. doi: 10.1213/ANE.0000000000004887). The use of provisional work areas “has escalated because of the amount of patients we’ve had to care for over the past nine months,” Dr. Greenberg said. “We’ve used alternate providers who are not necessarily familiar with the sedation and analgesic protocols and how to use these specific medications. Drug shortages have been on the rise, so there’s a need to understand alternative agents that can be used.”
COVID-19 patients face the potential risk for an increase in drug-drug interactions and side effects due to the polypharmacy that is often required to provide adequate sedation during mechanical ventilation. He noted that these patients may have “unusually high” analgesia and sedation requirements, particularly when they’re mechanically ventilated. A hypothesis as to why patients with COVID-19 require so much sedation and analgesia is that they often have a high respiratory drive and ventilator dyssynchrony, which requires increased neuromuscular blockade. “They also have an intense inflammatory response, which may be linked to tolerance of specific opioids and other medications,” Dr. Greenberg said. “Many ventilated COVID-19 patients are of younger age and previously in good health, and therefore, have an excellent metabolism. Health care providers are concerned about self-extubation. This prompts bedside providers to administer more sedatives to prevent this unwanted complication. There may also be a reduction of drip modifications by health care workers because of the potential risk of contracting COVID-19 when going into the room multiple times and for long periods of time” (Anesth Analg. 2020;131[1]:e34-e35).
According to a sedation resource on the SCCM website, about 5% of COVID-19 patients require mechanical ventilation. “There has been a massive shortage of the usual drugs that we use,” Dr. Greenberg said. “The demand for sedatives has increased by approximately 91%, while the demand for analgesics has increased by 79%, and neuromuscular blocker demand has increased by 105%.”
A retrospective study of 24 COVID-19 patients who required ventilation in the ICU found that the median daily dose of benzodiazepines was significantly higher, compared with the median daily dose used in the OSCILLATE trial (a median of 270 mg vs. 199 mg, respectively; Anesth Analg. 2020;131[4]e198-e200. doi: 10.1213/ane.0000000000005131). In addition, their median daily dose of opioid was approximately three times higher, compared with patients in the OSCILLATE trial (a median of 775 mg vs. 289 mg). Other agents used included propofol (84%), dexmedetomidine (53%), and ketamine (11%).
“A potential strategy for COVID-19 ICU patient sedation should be analgesia first, as indicated in the 2018 PADIS guidelines,” Dr. Greenberg advised. “We should also apply nonpharmacologic measures to reduce delirium. In nonintubated patients, we should use light to moderate sedation, targeting a RASS of –2 to +1, using hydromorphone or fentanyl boluses for analgesia and midazolam boluses or dexmedetomidine for sedation,.”
For intubated patients, he continued, target a RASS of –3 to –4, or –4 to –5 in those who require neuromuscular blockade. “Use propofol first then intermittent boluses of benzodiazepines,” said Dr. Greenberg, editor-in-chief of the Anesthesia Patient Safety Foundation newsletter. “For heavy sedation, use midazolam and supplement with ketamine and other analgesics and sedatives such as barbiturates, methadone, and even inhalation anesthetics in some cases.”
For analgesia in intubated patients, use fentanyl boluses then infusion. “Patients can easily become tachyphylactic to fentanyl, and it has a long context-sensitive half time,” he said. “Hydromorphone may be least affected by organ dysfunction.”
Dr. Greenberg concluded his presentation by stating that more studies are required “to delineate the best analgesia/sedation strategies and monitoring modalities for COVID-19 ICU patients.”
In commenting on the presentation, Mangala Narasimhan, DO, FCCP, senior vice president and director of critical care services at Northwell Health, said that the recommendations regarding sedation highlight a struggle that ICU providers have been dealing with during the COVID-19 epidemic.
“There have been unique challenges with COVID-19 and intubated patients. We have seen severe ventilator dyssynchrony and prolonged duration of mechanical ventilation. I think we can all agree that these patients have extremely high metabolic rates, have required high levels of sedation, have an increased need for neuromuscular blockade, and have high levels of delirium for extended periods of time. The recommendations provided here are reasonable. Strategies to prevent delirium should be employed, pain management should be prioritized, analgesics can help reduce the need for opioids. Alternatives to sedation are useful in this patient population and are well tolerated. Drug shortages have provided additional challenges to these strategies and have required us to think about the use of alternative agents. The recommendations echo the experience we have had with large numbers of intubated COVID-19 patients.”
Dr. Greenberg disclosed that he receives a stipend from the Anesthesia Patient Safety Foundation for serving as editor-in-chief of the foundation’s newsletter.
According to the best available evidence, analagosedation remains the focus for managing COVID-19 ICU patients, according to Steven B. Greenberg, MD, FCCP, FCCM.
“The choice of sedation and analgesia is important,” Dr. Greenberg, vice chair of education in the department of anesthesiology at Evanston Hospital, part of NorthShore University Health System, Chicago, said at a Society for Critical Care virtual meeting: COVID-19: What’s Next. “We know that the right choice of these two components may increase liberation from ventilators, earlier ICU discharge, and return to normal brain function and independent functional status.”
Analgesia first
Prior to the current pandemic, the approach to sedation of patients in the ICU was based on the PADIS Guidelines of 2018, which call for an assessment-driven, protocol-based stepwise approach to pain and sedation management in critically ill adults (Crit Care Med. 2018;46:e825-73). “” Dr. Greenberg said. “We know that pain management should be a priority of sedation, because pain may increase the risk of delirium, anxiety, and endocrine suppression, and may increase the risk of release of endogenous catecholamines, ischemia, and hypermetabolic states.”
Fentanyl appears to be the most common opioid analgesic used for patients in the ICU, “but fentanyl is a very lipophilic drug and has a long context-sensitive half-life,” he said. “There are components to fentanyl that allow it to become a very long-acting drug upon days and days of infusion. Another opioid used is remifentanil, which is typically short-acting because it is broken down in the blood by esterases, but may cause rigidity at higher doses. Dilaudid seems to be the least affected by organ dysfunction. In our very critically ill, prolonged mechanically ventilated COVID-19 patients, we’ve been using methadone for its NMDA [N-methyl-D-aspartate] antagonistic effect and its opioid-sparing effects.”
As for nonopioid analgesics, Dr. Greenberg said that clinicians have shied away from using NSAIDs because of their side effects. “Tramadol indirectly inhibits reuptake of norepinephrine and serotonin, and ketamine is being used a lot more because of its NMDA antagonist effect,” he said. “Lidocaine and gabapentin have also been used.”
In a recent systematic review and meta-analysis, researchers assessed 34 trials that examined adjuvant analgesic use with an opioid in critically ill patients versus an opioid alone (Crit Care Expl. 2020;2:e0157). They found that when using an adjuvant such as acetaminophen, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium, nefopam, NSAIDs, pregabalin, and tramadol, there was a reduction in pain scores as well as a reduction in opioid consumption. “So, clinicians should consider using adjuvant agents to limit opioid exposure and improve pain scores in the critically ill,” Dr. Greenberg said.
ICU delirium: Risk factors, prevention
Delirium in COVID-19 patients treated in the ICU of particular concern. According to a systematic review of 33 studies, 11 risk factors for delirium in the ICU were supported by strong or moderate levels of evidence (Crit Care Med. 2015;43:40-7). These include age, dementia, hypertension, emergency surgery, trauma, APACHE score of II, need for mechanical ventilation, metabolic acidosis, delirium on prior day, coma, and dexmedetomidine use. Risk factors for ICU delirium among COVID-19 patients, however, “are far different,” Dr. Greenberg said. “Why? First and foremost, we are restricting visitation of family,” he said. “That family connection largely can be lost. Second, there are limitations of nonpharmacologic interventions. There is less mobility and physical therapy employed because of the risk of health care workers’ exposure to the virus. There’s also uncertainty about the global pandemic. Anxiety and depression come with that, as well as disruptions to spiritual and religious services.”
Strategies for preventing delirium remain the same as before the pandemic and in accord with recent clinical practice guidelines: Reduce the use of certain drugs such as benzodiazepines and narcotics, reorient the patients, treat dehydration, use hearing aids and eyeglasses in patients who have them, use ear plugs to cancel noise, mobilize patients, maintain sleep/awake cycles, and encourage sedation holidays (Crit Care Med. 2018;46[9]:e825-73).
A recent study from France found that among 58 patients with COVID-19, 65% had positive Confusion Assessment Method (CAM)–ICU findings and 69% had agitation (N Engl J Med 2020;382:2268-70). Most of the patients (86%) received midazolam, 47% received propofol, and all received sufentanil. “In the pre-COVID days, we would use midazolam as a second-line agent for many of these patients,” Dr. Greenberg said. “So, times really have changed.”
The fate of COVID-19 patients following discharge from the ICU remains a concern, continued Dr. Greenberg, clinical professor of anesthesiology at the University of Chicago. A recent journal article by Michelle Biehl, MD, and Denise Sese, MD, noted that post–intensive care syndrome (PICS) or new or worsening impairment in any physical, cognitive, or mental domain is of significant concern among COVID-19 patients following their ICU stay (Cleveland Clin J Med 2020 Aug doi: 10.3949/ccjm.87a.ccc055). The authors stated that COVID-19 patients may face a higher risk of PICS because of restricted family visitation, prolonged mechanical ventilation, exposure to higher amounts of sedatives, and limited physical therapy during hospital stay.
No ideal sedative agent
The 2018 PADIS Guidelines on the use of ICU sedation suggested strong evidence for modifiable risk factors producing delirium in the context of benzodiazepines and blood transfusion. They recommend a light level of sedation and the use of propofol or dexmedetomidine over benzodiazepines. They also recommend routine delirium testing such as using the CAM-ICU or Intensive Care Delirium Screening Checklist (ICDSC) and nonpharmacologic therapies such as reorientation, cognitive stimulation, sleep improvement, and mobilization.
Several sedation-related factors may be related to an increased risk of delirium. “The type, dose, duration, and mode of delivery are very important,” Dr. Greenberg said. “The ideal sedative agent has a rapid, predictable onset; is short-acting; has anxiolytic, amnestic, and analgesic properties; is soluble; has a high therapeutic index; and no toxicity. The ideal sedative is also easy to administrate, contains no active metabolites, has minimal actions with other drugs, is reversible, and is cost effective. The problem is, there really is no ideal sedative agent. There is inadequate knowledge about the drugs [used to treat COVID-19 in the ICU] available to us, the dosage, and importantly, the pharmacokinetics and dynamics of these medications.”
The classic types of sedation being used in the ICU, he said, include the benzodiazepines midazolam, lorazepam, and diazepam, as well as propofol. Alternatives include dexmedetomidine, clonidine, ketamine, and the neuroleptics – haloperidol, quetiapine, olanzapine, ziprasidone, and risperidone. “The advantages of benzos are that they are anxiolytics, amnestics, and they are good sedatives with minimal hemodynamic effects,” Dr. Greenberg said.
Advantages of propofol include its sedative, hypnotic, and anxiolytic properties, he said. It reduces the cerebral metabolic rate and can relieve bronchospasm. “However, small studies have found that its use may be associated with an increased risk of delirium,” he said. “It is a respiratory depressant, and it can cause hypotension and decreased contractility. It has no analgesic properties, and two of the big concerns of its use in COVID-19 are the potential for hypertriglyceridemia and propofol infusion syndrome, particularly at doses of greater than 5 mg/kg per hour for greater than 48 hours. It is being given in high doses because patients are requiring higher doses to maintain ventilator synchrony.”
Choosing the right drug
The keys to success for sedation of ICU patients are choosing the right drug at the right dose for the right duration and the right mode of delivery, and applying them to the right population. However, as noted in a recent study, the pandemic poses unique challenges to clinicians in how they care for critically ill COVID-19 patients who require sedation (Anesth Analg. 2020 Apr 22. doi: 10.1213/ANE.0000000000004887). The use of provisional work areas “has escalated because of the amount of patients we’ve had to care for over the past nine months,” Dr. Greenberg said. “We’ve used alternate providers who are not necessarily familiar with the sedation and analgesic protocols and how to use these specific medications. Drug shortages have been on the rise, so there’s a need to understand alternative agents that can be used.”
COVID-19 patients face the potential risk for an increase in drug-drug interactions and side effects due to the polypharmacy that is often required to provide adequate sedation during mechanical ventilation. He noted that these patients may have “unusually high” analgesia and sedation requirements, particularly when they’re mechanically ventilated. A hypothesis as to why patients with COVID-19 require so much sedation and analgesia is that they often have a high respiratory drive and ventilator dyssynchrony, which requires increased neuromuscular blockade. “They also have an intense inflammatory response, which may be linked to tolerance of specific opioids and other medications,” Dr. Greenberg said. “Many ventilated COVID-19 patients are of younger age and previously in good health, and therefore, have an excellent metabolism. Health care providers are concerned about self-extubation. This prompts bedside providers to administer more sedatives to prevent this unwanted complication. There may also be a reduction of drip modifications by health care workers because of the potential risk of contracting COVID-19 when going into the room multiple times and for long periods of time” (Anesth Analg. 2020;131[1]:e34-e35).
According to a sedation resource on the SCCM website, about 5% of COVID-19 patients require mechanical ventilation. “There has been a massive shortage of the usual drugs that we use,” Dr. Greenberg said. “The demand for sedatives has increased by approximately 91%, while the demand for analgesics has increased by 79%, and neuromuscular blocker demand has increased by 105%.”
A retrospective study of 24 COVID-19 patients who required ventilation in the ICU found that the median daily dose of benzodiazepines was significantly higher, compared with the median daily dose used in the OSCILLATE trial (a median of 270 mg vs. 199 mg, respectively; Anesth Analg. 2020;131[4]e198-e200. doi: 10.1213/ane.0000000000005131). In addition, their median daily dose of opioid was approximately three times higher, compared with patients in the OSCILLATE trial (a median of 775 mg vs. 289 mg). Other agents used included propofol (84%), dexmedetomidine (53%), and ketamine (11%).
“A potential strategy for COVID-19 ICU patient sedation should be analgesia first, as indicated in the 2018 PADIS guidelines,” Dr. Greenberg advised. “We should also apply nonpharmacologic measures to reduce delirium. In nonintubated patients, we should use light to moderate sedation, targeting a RASS of –2 to +1, using hydromorphone or fentanyl boluses for analgesia and midazolam boluses or dexmedetomidine for sedation,.”
For intubated patients, he continued, target a RASS of –3 to –4, or –4 to –5 in those who require neuromuscular blockade. “Use propofol first then intermittent boluses of benzodiazepines,” said Dr. Greenberg, editor-in-chief of the Anesthesia Patient Safety Foundation newsletter. “For heavy sedation, use midazolam and supplement with ketamine and other analgesics and sedatives such as barbiturates, methadone, and even inhalation anesthetics in some cases.”
For analgesia in intubated patients, use fentanyl boluses then infusion. “Patients can easily become tachyphylactic to fentanyl, and it has a long context-sensitive half time,” he said. “Hydromorphone may be least affected by organ dysfunction.”
Dr. Greenberg concluded his presentation by stating that more studies are required “to delineate the best analgesia/sedation strategies and monitoring modalities for COVID-19 ICU patients.”
In commenting on the presentation, Mangala Narasimhan, DO, FCCP, senior vice president and director of critical care services at Northwell Health, said that the recommendations regarding sedation highlight a struggle that ICU providers have been dealing with during the COVID-19 epidemic.
“There have been unique challenges with COVID-19 and intubated patients. We have seen severe ventilator dyssynchrony and prolonged duration of mechanical ventilation. I think we can all agree that these patients have extremely high metabolic rates, have required high levels of sedation, have an increased need for neuromuscular blockade, and have high levels of delirium for extended periods of time. The recommendations provided here are reasonable. Strategies to prevent delirium should be employed, pain management should be prioritized, analgesics can help reduce the need for opioids. Alternatives to sedation are useful in this patient population and are well tolerated. Drug shortages have provided additional challenges to these strategies and have required us to think about the use of alternative agents. The recommendations echo the experience we have had with large numbers of intubated COVID-19 patients.”
Dr. Greenberg disclosed that he receives a stipend from the Anesthesia Patient Safety Foundation for serving as editor-in-chief of the foundation’s newsletter.
According to the best available evidence, analagosedation remains the focus for managing COVID-19 ICU patients, according to Steven B. Greenberg, MD, FCCP, FCCM.
“The choice of sedation and analgesia is important,” Dr. Greenberg, vice chair of education in the department of anesthesiology at Evanston Hospital, part of NorthShore University Health System, Chicago, said at a Society for Critical Care virtual meeting: COVID-19: What’s Next. “We know that the right choice of these two components may increase liberation from ventilators, earlier ICU discharge, and return to normal brain function and independent functional status.”
Analgesia first
Prior to the current pandemic, the approach to sedation of patients in the ICU was based on the PADIS Guidelines of 2018, which call for an assessment-driven, protocol-based stepwise approach to pain and sedation management in critically ill adults (Crit Care Med. 2018;46:e825-73). “” Dr. Greenberg said. “We know that pain management should be a priority of sedation, because pain may increase the risk of delirium, anxiety, and endocrine suppression, and may increase the risk of release of endogenous catecholamines, ischemia, and hypermetabolic states.”
Fentanyl appears to be the most common opioid analgesic used for patients in the ICU, “but fentanyl is a very lipophilic drug and has a long context-sensitive half-life,” he said. “There are components to fentanyl that allow it to become a very long-acting drug upon days and days of infusion. Another opioid used is remifentanil, which is typically short-acting because it is broken down in the blood by esterases, but may cause rigidity at higher doses. Dilaudid seems to be the least affected by organ dysfunction. In our very critically ill, prolonged mechanically ventilated COVID-19 patients, we’ve been using methadone for its NMDA [N-methyl-D-aspartate] antagonistic effect and its opioid-sparing effects.”
As for nonopioid analgesics, Dr. Greenberg said that clinicians have shied away from using NSAIDs because of their side effects. “Tramadol indirectly inhibits reuptake of norepinephrine and serotonin, and ketamine is being used a lot more because of its NMDA antagonist effect,” he said. “Lidocaine and gabapentin have also been used.”
In a recent systematic review and meta-analysis, researchers assessed 34 trials that examined adjuvant analgesic use with an opioid in critically ill patients versus an opioid alone (Crit Care Expl. 2020;2:e0157). They found that when using an adjuvant such as acetaminophen, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium, nefopam, NSAIDs, pregabalin, and tramadol, there was a reduction in pain scores as well as a reduction in opioid consumption. “So, clinicians should consider using adjuvant agents to limit opioid exposure and improve pain scores in the critically ill,” Dr. Greenberg said.
ICU delirium: Risk factors, prevention
Delirium in COVID-19 patients treated in the ICU of particular concern. According to a systematic review of 33 studies, 11 risk factors for delirium in the ICU were supported by strong or moderate levels of evidence (Crit Care Med. 2015;43:40-7). These include age, dementia, hypertension, emergency surgery, trauma, APACHE score of II, need for mechanical ventilation, metabolic acidosis, delirium on prior day, coma, and dexmedetomidine use. Risk factors for ICU delirium among COVID-19 patients, however, “are far different,” Dr. Greenberg said. “Why? First and foremost, we are restricting visitation of family,” he said. “That family connection largely can be lost. Second, there are limitations of nonpharmacologic interventions. There is less mobility and physical therapy employed because of the risk of health care workers’ exposure to the virus. There’s also uncertainty about the global pandemic. Anxiety and depression come with that, as well as disruptions to spiritual and religious services.”
Strategies for preventing delirium remain the same as before the pandemic and in accord with recent clinical practice guidelines: Reduce the use of certain drugs such as benzodiazepines and narcotics, reorient the patients, treat dehydration, use hearing aids and eyeglasses in patients who have them, use ear plugs to cancel noise, mobilize patients, maintain sleep/awake cycles, and encourage sedation holidays (Crit Care Med. 2018;46[9]:e825-73).
A recent study from France found that among 58 patients with COVID-19, 65% had positive Confusion Assessment Method (CAM)–ICU findings and 69% had agitation (N Engl J Med 2020;382:2268-70). Most of the patients (86%) received midazolam, 47% received propofol, and all received sufentanil. “In the pre-COVID days, we would use midazolam as a second-line agent for many of these patients,” Dr. Greenberg said. “So, times really have changed.”
The fate of COVID-19 patients following discharge from the ICU remains a concern, continued Dr. Greenberg, clinical professor of anesthesiology at the University of Chicago. A recent journal article by Michelle Biehl, MD, and Denise Sese, MD, noted that post–intensive care syndrome (PICS) or new or worsening impairment in any physical, cognitive, or mental domain is of significant concern among COVID-19 patients following their ICU stay (Cleveland Clin J Med 2020 Aug doi: 10.3949/ccjm.87a.ccc055). The authors stated that COVID-19 patients may face a higher risk of PICS because of restricted family visitation, prolonged mechanical ventilation, exposure to higher amounts of sedatives, and limited physical therapy during hospital stay.
No ideal sedative agent
The 2018 PADIS Guidelines on the use of ICU sedation suggested strong evidence for modifiable risk factors producing delirium in the context of benzodiazepines and blood transfusion. They recommend a light level of sedation and the use of propofol or dexmedetomidine over benzodiazepines. They also recommend routine delirium testing such as using the CAM-ICU or Intensive Care Delirium Screening Checklist (ICDSC) and nonpharmacologic therapies such as reorientation, cognitive stimulation, sleep improvement, and mobilization.
Several sedation-related factors may be related to an increased risk of delirium. “The type, dose, duration, and mode of delivery are very important,” Dr. Greenberg said. “The ideal sedative agent has a rapid, predictable onset; is short-acting; has anxiolytic, amnestic, and analgesic properties; is soluble; has a high therapeutic index; and no toxicity. The ideal sedative is also easy to administrate, contains no active metabolites, has minimal actions with other drugs, is reversible, and is cost effective. The problem is, there really is no ideal sedative agent. There is inadequate knowledge about the drugs [used to treat COVID-19 in the ICU] available to us, the dosage, and importantly, the pharmacokinetics and dynamics of these medications.”
The classic types of sedation being used in the ICU, he said, include the benzodiazepines midazolam, lorazepam, and diazepam, as well as propofol. Alternatives include dexmedetomidine, clonidine, ketamine, and the neuroleptics – haloperidol, quetiapine, olanzapine, ziprasidone, and risperidone. “The advantages of benzos are that they are anxiolytics, amnestics, and they are good sedatives with minimal hemodynamic effects,” Dr. Greenberg said.
Advantages of propofol include its sedative, hypnotic, and anxiolytic properties, he said. It reduces the cerebral metabolic rate and can relieve bronchospasm. “However, small studies have found that its use may be associated with an increased risk of delirium,” he said. “It is a respiratory depressant, and it can cause hypotension and decreased contractility. It has no analgesic properties, and two of the big concerns of its use in COVID-19 are the potential for hypertriglyceridemia and propofol infusion syndrome, particularly at doses of greater than 5 mg/kg per hour for greater than 48 hours. It is being given in high doses because patients are requiring higher doses to maintain ventilator synchrony.”
Choosing the right drug
The keys to success for sedation of ICU patients are choosing the right drug at the right dose for the right duration and the right mode of delivery, and applying them to the right population. However, as noted in a recent study, the pandemic poses unique challenges to clinicians in how they care for critically ill COVID-19 patients who require sedation (Anesth Analg. 2020 Apr 22. doi: 10.1213/ANE.0000000000004887). The use of provisional work areas “has escalated because of the amount of patients we’ve had to care for over the past nine months,” Dr. Greenberg said. “We’ve used alternate providers who are not necessarily familiar with the sedation and analgesic protocols and how to use these specific medications. Drug shortages have been on the rise, so there’s a need to understand alternative agents that can be used.”
COVID-19 patients face the potential risk for an increase in drug-drug interactions and side effects due to the polypharmacy that is often required to provide adequate sedation during mechanical ventilation. He noted that these patients may have “unusually high” analgesia and sedation requirements, particularly when they’re mechanically ventilated. A hypothesis as to why patients with COVID-19 require so much sedation and analgesia is that they often have a high respiratory drive and ventilator dyssynchrony, which requires increased neuromuscular blockade. “They also have an intense inflammatory response, which may be linked to tolerance of specific opioids and other medications,” Dr. Greenberg said. “Many ventilated COVID-19 patients are of younger age and previously in good health, and therefore, have an excellent metabolism. Health care providers are concerned about self-extubation. This prompts bedside providers to administer more sedatives to prevent this unwanted complication. There may also be a reduction of drip modifications by health care workers because of the potential risk of contracting COVID-19 when going into the room multiple times and for long periods of time” (Anesth Analg. 2020;131[1]:e34-e35).
According to a sedation resource on the SCCM website, about 5% of COVID-19 patients require mechanical ventilation. “There has been a massive shortage of the usual drugs that we use,” Dr. Greenberg said. “The demand for sedatives has increased by approximately 91%, while the demand for analgesics has increased by 79%, and neuromuscular blocker demand has increased by 105%.”
A retrospective study of 24 COVID-19 patients who required ventilation in the ICU found that the median daily dose of benzodiazepines was significantly higher, compared with the median daily dose used in the OSCILLATE trial (a median of 270 mg vs. 199 mg, respectively; Anesth Analg. 2020;131[4]e198-e200. doi: 10.1213/ane.0000000000005131). In addition, their median daily dose of opioid was approximately three times higher, compared with patients in the OSCILLATE trial (a median of 775 mg vs. 289 mg). Other agents used included propofol (84%), dexmedetomidine (53%), and ketamine (11%).
“A potential strategy for COVID-19 ICU patient sedation should be analgesia first, as indicated in the 2018 PADIS guidelines,” Dr. Greenberg advised. “We should also apply nonpharmacologic measures to reduce delirium. In nonintubated patients, we should use light to moderate sedation, targeting a RASS of –2 to +1, using hydromorphone or fentanyl boluses for analgesia and midazolam boluses or dexmedetomidine for sedation,.”
For intubated patients, he continued, target a RASS of –3 to –4, or –4 to –5 in those who require neuromuscular blockade. “Use propofol first then intermittent boluses of benzodiazepines,” said Dr. Greenberg, editor-in-chief of the Anesthesia Patient Safety Foundation newsletter. “For heavy sedation, use midazolam and supplement with ketamine and other analgesics and sedatives such as barbiturates, methadone, and even inhalation anesthetics in some cases.”
For analgesia in intubated patients, use fentanyl boluses then infusion. “Patients can easily become tachyphylactic to fentanyl, and it has a long context-sensitive half time,” he said. “Hydromorphone may be least affected by organ dysfunction.”
Dr. Greenberg concluded his presentation by stating that more studies are required “to delineate the best analgesia/sedation strategies and monitoring modalities for COVID-19 ICU patients.”
In commenting on the presentation, Mangala Narasimhan, DO, FCCP, senior vice president and director of critical care services at Northwell Health, said that the recommendations regarding sedation highlight a struggle that ICU providers have been dealing with during the COVID-19 epidemic.
“There have been unique challenges with COVID-19 and intubated patients. We have seen severe ventilator dyssynchrony and prolonged duration of mechanical ventilation. I think we can all agree that these patients have extremely high metabolic rates, have required high levels of sedation, have an increased need for neuromuscular blockade, and have high levels of delirium for extended periods of time. The recommendations provided here are reasonable. Strategies to prevent delirium should be employed, pain management should be prioritized, analgesics can help reduce the need for opioids. Alternatives to sedation are useful in this patient population and are well tolerated. Drug shortages have provided additional challenges to these strategies and have required us to think about the use of alternative agents. The recommendations echo the experience we have had with large numbers of intubated COVID-19 patients.”
Dr. Greenberg disclosed that he receives a stipend from the Anesthesia Patient Safety Foundation for serving as editor-in-chief of the foundation’s newsletter.
FROM AN SCCM VIRTUAL MEETING
Bacteria may be associated with risk of MS relapse
No broad differences in gut bacterial composition, however, are associated with risk of relapse, according to the investigators. The findings were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Previous research has found an association between Blautia stercoris and disease activity in other immune-mediated diseases such as systemic lupus. Although the current study is the largest in patients with MS that includes data about the microbiome and relapses, its findings require replication, said Mary Horton, a doctoral candidate in epidemiology at the University of California, Berkeley.
Gut microbes digest food, produce vitamins (for example, B12 and K), create a barrier against pathogens, and regulate the immune system, among other tasks. Most current knowledge about the gut microbiome in MS comes from studies of patients with adult-onset MS. In 2016, Tremlett et al. found an increase in Desulfovibrionaceae and a decrease in Lachnospiraceae and Ruminococcaceae in patients with pediatric-onset MS. They also found that a decrease in Fusobacteria was associated with risk of relapse in this population.
Advanced analytical methods
Using a larger sample size and newer analytical methods than in the study by Tremlett and colleagues, Ms. Horton’s group sought to determine whether features of the gut microbiome are associated with relapse. From 2014 to 2018, the investigators recruited 53 patients with pediatric-onset MS from the University of California, San Francisco, and six centers in the U.S. Network of Pediatric MS Centers. At baseline, they collected stool samples, blood samples, information about past relapses, medication records, demographics, and environmental factors. At each relapse, the investigators collected information about the patient’s current and past medication use and about relapses that the patient had had since the previous visit.
Ms. Horton and colleagues analyzed the stool samples using 16S rRNA sequencing of the V4 region. They identified amplicon sequence variants (ASVs), which are used to define species of bacteria, with the Divisive Amplicon Denoising Algorithm-2 (DADA2). Taxonomies were assigned using the naive Bayesian classifier method, and the read count was normalized using multiple rarefaction.
The investigators identified ASV clusters using weighted genetic correlation network analysis (WGCNA). To evaluate whether individual ASVs were associated with relapse, they used a Prentice, Williams, and Peterson (PWP) recurrent event model, an extension of the Cox proportional hazards model.
The role of methanogenesis
Ms. Horton and colleagues included 53 patients (72% girls) in their study. The population’s mean age was 14.3 years at disease onset and 15.5 years at stool sample collection. About 70% of patients were White, and about 36% were Hispanic. Mean disease duration was 1.3 years, and median Expanded Disability Status Scale score was 1.0.
Approximately 45% of participants had one relapse, and 30% had more than one relapse during the subsequent mean follow-up of 2.5 years. About 91% of patients used a disease-modifying therapy during follow-up.
Gut bacterial abundance was broadly similar between patients who relapsed during the study period and those who did not. Of 270 ASVs included in the analyses, 20 were nominally associated with risk of relapse. Blautia stercoris had the most significant association with relapse risk (hazard ratio, 2.50). Blautia massiliensis also was among the 20 ASVs associated with risk of relapse.
WGCNA identified six ASV clusters. Higher values of one cluster’s eigengene were significantly associated with higher relapse risk (HR, 1.23). The following four ASVs nominally associated with higher relapse risk were in this cluster: Blautia massiliensis, Dorea longicatena, Coprococcus comes, and an unknown species in genus Subdoligranulum.
When Ms. Horton and colleagues examined the pathways from these bacterial species, they found 10 that were significantly associated with the risk of relapse. Four of these 10 pathways are involved in methane production, which suggests the involvement of methanogenesis pathways in relapse.
Although the investigators used advanced techniques for genetic and statistical analysis, the study’s sample size is small, Ms. Horton acknowledged. In addition, the conclusions that can be drawn from observational data are limited.
These suggest several avenues for future research. “There is a big question about how the different treatments that people are on when they are experiencing relapses might impact the microbiome,” said Ms. Horton. “Is the microbiome impacting your treatment response, or is it the reverse?” Investigators also could examine why the methane production pathway is overrepresented among people with MS who have relapses. “Which specific archaea might be leading to that increase in methane is a ripe future study question. Just what that means for health is really unknown.”
The National MS Society and the National Institute of Neurological Disorders and Stroke provided funding for the study. Ms. Horton had no disclosures.
SOURCE: Horton M et al. MSVirtual2020, Abstract LB01.05.
No broad differences in gut bacterial composition, however, are associated with risk of relapse, according to the investigators. The findings were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Previous research has found an association between Blautia stercoris and disease activity in other immune-mediated diseases such as systemic lupus. Although the current study is the largest in patients with MS that includes data about the microbiome and relapses, its findings require replication, said Mary Horton, a doctoral candidate in epidemiology at the University of California, Berkeley.
Gut microbes digest food, produce vitamins (for example, B12 and K), create a barrier against pathogens, and regulate the immune system, among other tasks. Most current knowledge about the gut microbiome in MS comes from studies of patients with adult-onset MS. In 2016, Tremlett et al. found an increase in Desulfovibrionaceae and a decrease in Lachnospiraceae and Ruminococcaceae in patients with pediatric-onset MS. They also found that a decrease in Fusobacteria was associated with risk of relapse in this population.
Advanced analytical methods
Using a larger sample size and newer analytical methods than in the study by Tremlett and colleagues, Ms. Horton’s group sought to determine whether features of the gut microbiome are associated with relapse. From 2014 to 2018, the investigators recruited 53 patients with pediatric-onset MS from the University of California, San Francisco, and six centers in the U.S. Network of Pediatric MS Centers. At baseline, they collected stool samples, blood samples, information about past relapses, medication records, demographics, and environmental factors. At each relapse, the investigators collected information about the patient’s current and past medication use and about relapses that the patient had had since the previous visit.
Ms. Horton and colleagues analyzed the stool samples using 16S rRNA sequencing of the V4 region. They identified amplicon sequence variants (ASVs), which are used to define species of bacteria, with the Divisive Amplicon Denoising Algorithm-2 (DADA2). Taxonomies were assigned using the naive Bayesian classifier method, and the read count was normalized using multiple rarefaction.
The investigators identified ASV clusters using weighted genetic correlation network analysis (WGCNA). To evaluate whether individual ASVs were associated with relapse, they used a Prentice, Williams, and Peterson (PWP) recurrent event model, an extension of the Cox proportional hazards model.
The role of methanogenesis
Ms. Horton and colleagues included 53 patients (72% girls) in their study. The population’s mean age was 14.3 years at disease onset and 15.5 years at stool sample collection. About 70% of patients were White, and about 36% were Hispanic. Mean disease duration was 1.3 years, and median Expanded Disability Status Scale score was 1.0.
Approximately 45% of participants had one relapse, and 30% had more than one relapse during the subsequent mean follow-up of 2.5 years. About 91% of patients used a disease-modifying therapy during follow-up.
Gut bacterial abundance was broadly similar between patients who relapsed during the study period and those who did not. Of 270 ASVs included in the analyses, 20 were nominally associated with risk of relapse. Blautia stercoris had the most significant association with relapse risk (hazard ratio, 2.50). Blautia massiliensis also was among the 20 ASVs associated with risk of relapse.
WGCNA identified six ASV clusters. Higher values of one cluster’s eigengene were significantly associated with higher relapse risk (HR, 1.23). The following four ASVs nominally associated with higher relapse risk were in this cluster: Blautia massiliensis, Dorea longicatena, Coprococcus comes, and an unknown species in genus Subdoligranulum.
When Ms. Horton and colleagues examined the pathways from these bacterial species, they found 10 that were significantly associated with the risk of relapse. Four of these 10 pathways are involved in methane production, which suggests the involvement of methanogenesis pathways in relapse.
Although the investigators used advanced techniques for genetic and statistical analysis, the study’s sample size is small, Ms. Horton acknowledged. In addition, the conclusions that can be drawn from observational data are limited.
These suggest several avenues for future research. “There is a big question about how the different treatments that people are on when they are experiencing relapses might impact the microbiome,” said Ms. Horton. “Is the microbiome impacting your treatment response, or is it the reverse?” Investigators also could examine why the methane production pathway is overrepresented among people with MS who have relapses. “Which specific archaea might be leading to that increase in methane is a ripe future study question. Just what that means for health is really unknown.”
The National MS Society and the National Institute of Neurological Disorders and Stroke provided funding for the study. Ms. Horton had no disclosures.
SOURCE: Horton M et al. MSVirtual2020, Abstract LB01.05.
No broad differences in gut bacterial composition, however, are associated with risk of relapse, according to the investigators. The findings were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
Previous research has found an association between Blautia stercoris and disease activity in other immune-mediated diseases such as systemic lupus. Although the current study is the largest in patients with MS that includes data about the microbiome and relapses, its findings require replication, said Mary Horton, a doctoral candidate in epidemiology at the University of California, Berkeley.
Gut microbes digest food, produce vitamins (for example, B12 and K), create a barrier against pathogens, and regulate the immune system, among other tasks. Most current knowledge about the gut microbiome in MS comes from studies of patients with adult-onset MS. In 2016, Tremlett et al. found an increase in Desulfovibrionaceae and a decrease in Lachnospiraceae and Ruminococcaceae in patients with pediatric-onset MS. They also found that a decrease in Fusobacteria was associated with risk of relapse in this population.
Advanced analytical methods
Using a larger sample size and newer analytical methods than in the study by Tremlett and colleagues, Ms. Horton’s group sought to determine whether features of the gut microbiome are associated with relapse. From 2014 to 2018, the investigators recruited 53 patients with pediatric-onset MS from the University of California, San Francisco, and six centers in the U.S. Network of Pediatric MS Centers. At baseline, they collected stool samples, blood samples, information about past relapses, medication records, demographics, and environmental factors. At each relapse, the investigators collected information about the patient’s current and past medication use and about relapses that the patient had had since the previous visit.
Ms. Horton and colleagues analyzed the stool samples using 16S rRNA sequencing of the V4 region. They identified amplicon sequence variants (ASVs), which are used to define species of bacteria, with the Divisive Amplicon Denoising Algorithm-2 (DADA2). Taxonomies were assigned using the naive Bayesian classifier method, and the read count was normalized using multiple rarefaction.
The investigators identified ASV clusters using weighted genetic correlation network analysis (WGCNA). To evaluate whether individual ASVs were associated with relapse, they used a Prentice, Williams, and Peterson (PWP) recurrent event model, an extension of the Cox proportional hazards model.
The role of methanogenesis
Ms. Horton and colleagues included 53 patients (72% girls) in their study. The population’s mean age was 14.3 years at disease onset and 15.5 years at stool sample collection. About 70% of patients were White, and about 36% were Hispanic. Mean disease duration was 1.3 years, and median Expanded Disability Status Scale score was 1.0.
Approximately 45% of participants had one relapse, and 30% had more than one relapse during the subsequent mean follow-up of 2.5 years. About 91% of patients used a disease-modifying therapy during follow-up.
Gut bacterial abundance was broadly similar between patients who relapsed during the study period and those who did not. Of 270 ASVs included in the analyses, 20 were nominally associated with risk of relapse. Blautia stercoris had the most significant association with relapse risk (hazard ratio, 2.50). Blautia massiliensis also was among the 20 ASVs associated with risk of relapse.
WGCNA identified six ASV clusters. Higher values of one cluster’s eigengene were significantly associated with higher relapse risk (HR, 1.23). The following four ASVs nominally associated with higher relapse risk were in this cluster: Blautia massiliensis, Dorea longicatena, Coprococcus comes, and an unknown species in genus Subdoligranulum.
When Ms. Horton and colleagues examined the pathways from these bacterial species, they found 10 that were significantly associated with the risk of relapse. Four of these 10 pathways are involved in methane production, which suggests the involvement of methanogenesis pathways in relapse.
Although the investigators used advanced techniques for genetic and statistical analysis, the study’s sample size is small, Ms. Horton acknowledged. In addition, the conclusions that can be drawn from observational data are limited.
These suggest several avenues for future research. “There is a big question about how the different treatments that people are on when they are experiencing relapses might impact the microbiome,” said Ms. Horton. “Is the microbiome impacting your treatment response, or is it the reverse?” Investigators also could examine why the methane production pathway is overrepresented among people with MS who have relapses. “Which specific archaea might be leading to that increase in methane is a ripe future study question. Just what that means for health is really unknown.”
The National MS Society and the National Institute of Neurological Disorders and Stroke provided funding for the study. Ms. Horton had no disclosures.
SOURCE: Horton M et al. MSVirtual2020, Abstract LB01.05.
From MSVirtual2020