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Progressive multifocal leukoencephalopathy
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Feds to states: Give COVID-19 vaccine to 65+ and those with comorbidities
Federal health officials are urging states to vaccinate all Americans over age 65 and those aged 16-64 who have a documented underlying health condition that makes them more vulnerable to COVID-19.
U.S. Department of Health and Human Services (HHS) Secretary Alex Azar and Centers for Disease Control and Prevention Director Robert Redfield, MD, made the recommendation in a briefing with reporters on Jan. 12, saying that the current vaccine supply was sufficient to meet demand for the next phase of immunization as recommended by the CDC’s Advisory Committee on Immunization Practices.
“We are ready for a transition that we outlined last September in the playbook we sent to states,” Mr. Azar said. Both he and U.S. Army General Gustave F. Perna, chief operations officer for Operation Warp Speed, said that confidence in the distribution system had led to the decision to urge wider access.
The federal government will also increase the number of sites eligible to receive vaccine – including some 13,000 federally qualified community health centers – and will not keep doses in reserve as insurance against issues that might prevent people from receiving a second dose on a timely basis.
“We don’t need to hold back reserve doses,” Mr. Azar said, noting that if there were any “glitches in production” the federal government would move to fulfill obligations for second doses first and delay initial doses.
Azar: Use it or lose it
In a move that is sure to generate pushback, Mr. Azar said that states that don’t quickly administer vaccines will receive fewer doses in the future. That policy will not go into effect until later in February, which leaves open the possibility that it could be reversed by the incoming Biden administration.
“We have too much vaccine sitting in freezers at hospitals with hospitals not using it,” said Mr. Azar, who also blamed the slow administration process on a reporting lag and states being what he called “overly prescriptive” in who has been eligible to receive a shot.
“I would rather have people working to get appointments to get vaccinated than having vaccine going to waste sitting in freezers,” he told reporters.
Mr. Azar had already been pushing for broader vaccination, telling states to do so in an Operation Warp Speed briefing on Jan. 6. At that briefing, he also said that the federal government would be stepping up vaccination through an “early launch” of a federal partnership with 19 pharmacy chains, which will let states allocate vaccines directly to some 40,000 pharmacy sites.
Gen. Perna said during the Jan. 12 briefing that the aim is to further expand that to some 70,000 locations total.
The CDC reported that as of Jan. 11 some 25.4 million doses have been distributed, with 8.9 million administered. An additional 4.2 million doses were distributed to long-term care facilities, and 937,000 residents and staff have received a dose.
“Pace of administration”
Alaska, Connecticut, North Dakota, South Dakota, the District of Columbia, West Virginia, and the Northern Mariana Islands have administered the most vaccines per capita, according to the CDC. But even these locations have immunized only 4%-5% of their populations, the New York Times reports. At the bottom: Alabama, Arizona, Arkansas, Georgia, Mississippi, and South Carolina.
The federal government can encourage but not require states to move on to new phases of vaccination.
“States ultimately determine how they will proceed with vaccination,” said Marcus Plescia, MD, MPH, chief medical officer for the Association of State and Territorial Health Officials. “Most will be cautious about assuring there are doses for those needing a second dose,” he said in an interview.
Dr. Plescia said that ensuring a second dose is available is especially important for health care workers “who need to be confident that they are protected and not inadvertently transmitting the disease themselves.”
He added that “once we reach a steady state of supply and administration, the rate-limiting factor will be supply of vaccine.”
That supply could now be threatened if states don’t comply with a just-announced federal action that will change how doses are allocated.
Beginning in late February, vaccine allocations to states will be based on “the pace of administration reported by states,” and the size of the 65-and-older population, said Mr. Azar, who has previously criticized New York Governor Andrew Cuomo for fining hospitals that didn’t use up vaccine supply within a week.
“This new system gives states a strong incentive to ensure that all vaccinations are being promptly reported, which they currently are not,” he said.
Currently, allocations are based on a state’s or territory’s population.
Prepandemic, states were required to report vaccinations within 30 days. Since COVID-19 vaccines became available, the CDC has required reporting of shots within 72 hours.
Dr. Redfield said the requirement has caused some difficulty, and that the CDC is investigating why some states have reported using only 15% of doses while others have used 80%.
States have been scrambling to ramp up vaccinations.
Just ahead of the federal briefing, Gov. Cuomo tweeted that New York would be opening up vaccinations to anyone older than 65.
The Associated Press is reporting that some states have started mass vaccination sites.
Arizona has begun operating a 24/7 appointment-only vaccination program at State Farm Stadium outside of Phoenix, with the aim of immunizing 6,000 people each day, according to local radio station KJZZ.
California and Florida have also taken steps to use stadiums, while Michigan, New Jersey, New York, and Texas will use convention centers and fairgrounds, Axios has reported.
In Florida, Palm Beach County Health Director Alina Alonso, MD, told county commissioners on Jan. 12 that there isn’t enough vaccine to meet demand, WPTV reported. “We need to realize that there’s a shortage of vaccine. So it’s not the plan, it’s not our ability to do it. It’s simply supply and demand at this point,” Dr. Alonso said, according to the TV station report.
A version of this article first appeared on Medscape.com.
Federal health officials are urging states to vaccinate all Americans over age 65 and those aged 16-64 who have a documented underlying health condition that makes them more vulnerable to COVID-19.
U.S. Department of Health and Human Services (HHS) Secretary Alex Azar and Centers for Disease Control and Prevention Director Robert Redfield, MD, made the recommendation in a briefing with reporters on Jan. 12, saying that the current vaccine supply was sufficient to meet demand for the next phase of immunization as recommended by the CDC’s Advisory Committee on Immunization Practices.
“We are ready for a transition that we outlined last September in the playbook we sent to states,” Mr. Azar said. Both he and U.S. Army General Gustave F. Perna, chief operations officer for Operation Warp Speed, said that confidence in the distribution system had led to the decision to urge wider access.
The federal government will also increase the number of sites eligible to receive vaccine – including some 13,000 federally qualified community health centers – and will not keep doses in reserve as insurance against issues that might prevent people from receiving a second dose on a timely basis.
“We don’t need to hold back reserve doses,” Mr. Azar said, noting that if there were any “glitches in production” the federal government would move to fulfill obligations for second doses first and delay initial doses.
Azar: Use it or lose it
In a move that is sure to generate pushback, Mr. Azar said that states that don’t quickly administer vaccines will receive fewer doses in the future. That policy will not go into effect until later in February, which leaves open the possibility that it could be reversed by the incoming Biden administration.
“We have too much vaccine sitting in freezers at hospitals with hospitals not using it,” said Mr. Azar, who also blamed the slow administration process on a reporting lag and states being what he called “overly prescriptive” in who has been eligible to receive a shot.
“I would rather have people working to get appointments to get vaccinated than having vaccine going to waste sitting in freezers,” he told reporters.
Mr. Azar had already been pushing for broader vaccination, telling states to do so in an Operation Warp Speed briefing on Jan. 6. At that briefing, he also said that the federal government would be stepping up vaccination through an “early launch” of a federal partnership with 19 pharmacy chains, which will let states allocate vaccines directly to some 40,000 pharmacy sites.
Gen. Perna said during the Jan. 12 briefing that the aim is to further expand that to some 70,000 locations total.
The CDC reported that as of Jan. 11 some 25.4 million doses have been distributed, with 8.9 million administered. An additional 4.2 million doses were distributed to long-term care facilities, and 937,000 residents and staff have received a dose.
“Pace of administration”
Alaska, Connecticut, North Dakota, South Dakota, the District of Columbia, West Virginia, and the Northern Mariana Islands have administered the most vaccines per capita, according to the CDC. But even these locations have immunized only 4%-5% of their populations, the New York Times reports. At the bottom: Alabama, Arizona, Arkansas, Georgia, Mississippi, and South Carolina.
The federal government can encourage but not require states to move on to new phases of vaccination.
“States ultimately determine how they will proceed with vaccination,” said Marcus Plescia, MD, MPH, chief medical officer for the Association of State and Territorial Health Officials. “Most will be cautious about assuring there are doses for those needing a second dose,” he said in an interview.
Dr. Plescia said that ensuring a second dose is available is especially important for health care workers “who need to be confident that they are protected and not inadvertently transmitting the disease themselves.”
He added that “once we reach a steady state of supply and administration, the rate-limiting factor will be supply of vaccine.”
That supply could now be threatened if states don’t comply with a just-announced federal action that will change how doses are allocated.
Beginning in late February, vaccine allocations to states will be based on “the pace of administration reported by states,” and the size of the 65-and-older population, said Mr. Azar, who has previously criticized New York Governor Andrew Cuomo for fining hospitals that didn’t use up vaccine supply within a week.
“This new system gives states a strong incentive to ensure that all vaccinations are being promptly reported, which they currently are not,” he said.
Currently, allocations are based on a state’s or territory’s population.
Prepandemic, states were required to report vaccinations within 30 days. Since COVID-19 vaccines became available, the CDC has required reporting of shots within 72 hours.
Dr. Redfield said the requirement has caused some difficulty, and that the CDC is investigating why some states have reported using only 15% of doses while others have used 80%.
States have been scrambling to ramp up vaccinations.
Just ahead of the federal briefing, Gov. Cuomo tweeted that New York would be opening up vaccinations to anyone older than 65.
The Associated Press is reporting that some states have started mass vaccination sites.
Arizona has begun operating a 24/7 appointment-only vaccination program at State Farm Stadium outside of Phoenix, with the aim of immunizing 6,000 people each day, according to local radio station KJZZ.
California and Florida have also taken steps to use stadiums, while Michigan, New Jersey, New York, and Texas will use convention centers and fairgrounds, Axios has reported.
In Florida, Palm Beach County Health Director Alina Alonso, MD, told county commissioners on Jan. 12 that there isn’t enough vaccine to meet demand, WPTV reported. “We need to realize that there’s a shortage of vaccine. So it’s not the plan, it’s not our ability to do it. It’s simply supply and demand at this point,” Dr. Alonso said, according to the TV station report.
A version of this article first appeared on Medscape.com.
Federal health officials are urging states to vaccinate all Americans over age 65 and those aged 16-64 who have a documented underlying health condition that makes them more vulnerable to COVID-19.
U.S. Department of Health and Human Services (HHS) Secretary Alex Azar and Centers for Disease Control and Prevention Director Robert Redfield, MD, made the recommendation in a briefing with reporters on Jan. 12, saying that the current vaccine supply was sufficient to meet demand for the next phase of immunization as recommended by the CDC’s Advisory Committee on Immunization Practices.
“We are ready for a transition that we outlined last September in the playbook we sent to states,” Mr. Azar said. Both he and U.S. Army General Gustave F. Perna, chief operations officer for Operation Warp Speed, said that confidence in the distribution system had led to the decision to urge wider access.
The federal government will also increase the number of sites eligible to receive vaccine – including some 13,000 federally qualified community health centers – and will not keep doses in reserve as insurance against issues that might prevent people from receiving a second dose on a timely basis.
“We don’t need to hold back reserve doses,” Mr. Azar said, noting that if there were any “glitches in production” the federal government would move to fulfill obligations for second doses first and delay initial doses.
Azar: Use it or lose it
In a move that is sure to generate pushback, Mr. Azar said that states that don’t quickly administer vaccines will receive fewer doses in the future. That policy will not go into effect until later in February, which leaves open the possibility that it could be reversed by the incoming Biden administration.
“We have too much vaccine sitting in freezers at hospitals with hospitals not using it,” said Mr. Azar, who also blamed the slow administration process on a reporting lag and states being what he called “overly prescriptive” in who has been eligible to receive a shot.
“I would rather have people working to get appointments to get vaccinated than having vaccine going to waste sitting in freezers,” he told reporters.
Mr. Azar had already been pushing for broader vaccination, telling states to do so in an Operation Warp Speed briefing on Jan. 6. At that briefing, he also said that the federal government would be stepping up vaccination through an “early launch” of a federal partnership with 19 pharmacy chains, which will let states allocate vaccines directly to some 40,000 pharmacy sites.
Gen. Perna said during the Jan. 12 briefing that the aim is to further expand that to some 70,000 locations total.
The CDC reported that as of Jan. 11 some 25.4 million doses have been distributed, with 8.9 million administered. An additional 4.2 million doses were distributed to long-term care facilities, and 937,000 residents and staff have received a dose.
“Pace of administration”
Alaska, Connecticut, North Dakota, South Dakota, the District of Columbia, West Virginia, and the Northern Mariana Islands have administered the most vaccines per capita, according to the CDC. But even these locations have immunized only 4%-5% of their populations, the New York Times reports. At the bottom: Alabama, Arizona, Arkansas, Georgia, Mississippi, and South Carolina.
The federal government can encourage but not require states to move on to new phases of vaccination.
“States ultimately determine how they will proceed with vaccination,” said Marcus Plescia, MD, MPH, chief medical officer for the Association of State and Territorial Health Officials. “Most will be cautious about assuring there are doses for those needing a second dose,” he said in an interview.
Dr. Plescia said that ensuring a second dose is available is especially important for health care workers “who need to be confident that they are protected and not inadvertently transmitting the disease themselves.”
He added that “once we reach a steady state of supply and administration, the rate-limiting factor will be supply of vaccine.”
That supply could now be threatened if states don’t comply with a just-announced federal action that will change how doses are allocated.
Beginning in late February, vaccine allocations to states will be based on “the pace of administration reported by states,” and the size of the 65-and-older population, said Mr. Azar, who has previously criticized New York Governor Andrew Cuomo for fining hospitals that didn’t use up vaccine supply within a week.
“This new system gives states a strong incentive to ensure that all vaccinations are being promptly reported, which they currently are not,” he said.
Currently, allocations are based on a state’s or territory’s population.
Prepandemic, states were required to report vaccinations within 30 days. Since COVID-19 vaccines became available, the CDC has required reporting of shots within 72 hours.
Dr. Redfield said the requirement has caused some difficulty, and that the CDC is investigating why some states have reported using only 15% of doses while others have used 80%.
States have been scrambling to ramp up vaccinations.
Just ahead of the federal briefing, Gov. Cuomo tweeted that New York would be opening up vaccinations to anyone older than 65.
The Associated Press is reporting that some states have started mass vaccination sites.
Arizona has begun operating a 24/7 appointment-only vaccination program at State Farm Stadium outside of Phoenix, with the aim of immunizing 6,000 people each day, according to local radio station KJZZ.
California and Florida have also taken steps to use stadiums, while Michigan, New Jersey, New York, and Texas will use convention centers and fairgrounds, Axios has reported.
In Florida, Palm Beach County Health Director Alina Alonso, MD, told county commissioners on Jan. 12 that there isn’t enough vaccine to meet demand, WPTV reported. “We need to realize that there’s a shortage of vaccine. So it’s not the plan, it’s not our ability to do it. It’s simply supply and demand at this point,” Dr. Alonso said, according to the TV station report.
A version of this article first appeared on Medscape.com.
Overcoming the challenges of COVID-19 for Alzheimer’s patients in long-term care, research
An alarming number of additional Alzheimer’s disease (AD) deaths have been reported across various states within the past several months, according to the Alzheimer’s Association. Centers for Disease Control and Prevention data indicate that no less than 31,000 additional people with the neurodegenerative condition had died from the beginning of the pandemic through the end of September 2020. We know that long-term care facilities have been hit hardest, and access to adequate and/or prompt testing has been cited as the most pressing issue during the onset of the pandemic.1
When ADLs become a matter of survival
For individuals affected with Alzheimer’s disease and other types of dementia, performing routine tasks may seem cumbersome and overwhelming. Many of these patients are dependent upon caregivers and family support to facilitate their activities of daily living (ADLs).
Transitioning into the “new normal” set by the pandemic milieu is not an easy task for the average AD individual, because they are now expected to comply with numerous safety instructions (for example, maintaining hygiene, social distancing, etc.). They are also expected to monitor and communicate information about the onset of any suspected symptom to their caregiver or health care clinician.
The additional tasks added to their list of ADLs are particularly distressing given their already compromised short-term memory and overall cognitive decline. Individuals with AD may also be dealing with a host of psychobehavioral challenges, such as the presence of depression, anxiety, and/or agitation amid self-isolation. Enforced social isolation tied to COVID-19 may compound those issues.
Resource diversion and mitigation strategies
Unfortunately, any disruption in services within a long-term care setting may lead to a suboptimal therapeutic environment for patients. The Washington State LTC, for example, reported experiencing a case fatality rate (CFR) exceeding more than a third of its residents; essential staff and health care clinicians were duly affected from exposure to the virus (the risk of transmission increases considerably during transport between facilities). Access to personal protective equipment (PPE) might have been hindered by availability.
Another issue with far-reaching consequences is diversion of resources for urgent care. Health care professionals may simply not be readily available for those with chronic care needs because of the enormous scale of the impact of COVID-19 upon health care systems.
Continuity of therapy might include evaluations or follow-up services via teleconferencing modalities, but an exhaustive initial onsite physical examination is often necessary for accurate diagnostics and care. Medication management for the newly diagnosed AD or dementia patient necessitates a thorough screening process involving appropriate in-person blood or laboratory work. It is for this reason that clinicians will need to plan ahead by preparing a contingency plan with the corresponding mitigation strategies (for example, telemedicine, proposed solutions to anticipated disruption of services, extended support, and feedback from family members, etc.).2
Resilience and recovery in a retrospective study
A research team from Wuhan Red Cross Hospital in China performed a retrospective cohort study on a sample of patients (n = 42) to determine the severity and prognostic features of COVID-19 pneumonia; 19 AD patients (as per National Institute on Aging/Alzheimer’s Association diagnostic guidelines) were directly compared with 23 age-matched non-AD COVID-19 patients in a similar treatment context.
The study yielded some rather unexpected findings, namely, AD patients experienced remarkably shorter hospital stays and better appetites, especially with respect to their non-AD counterparts. This is even more puzzling when considering that previous studies indicated that dementia patients with concomitant COVID-19 pneumonia are twice as likely to die as those without neurodegenerative compromise.
Aside from a seemingly inexplicable interest in food, the observable positive changes may be attributable to such factors that are particular to the nursing home – residents have immediate access to health care services, which generally allows for timely diagnosis and care. However, the authors of the study speculate that the pathophysiological response of angiotensin-converting enzyme 2 (ACE2) confers to AD patients a therapeutic advantage as they have reduced expression.3 Despite the notoriously high mortality rates of COVID-19 pneumonia among the elderly population, , which underscores the importance of early diagnosis and intervention.
Genetic and environmental susceptibility
One of the more devastating observations about the ongoing pandemic environment is that a whopping 80% of dying patients committed to a long-term facility also include those with AD; it has been reported that almost half of all patients in nursing homes and related services have the neurodegenerative condition. The grim scenario is brought about by several factors, chief of which is the proximity of shared living arrangements within the context of a residential care setting. It should be noted that patients with AD exhibit comorbid conditions (for example, diabetes, cardiovascular disease, and/or respiratory issues) that immediately put them at high risk for COVID exposure. Interestingly enough, the ApoE4 genotype, which is associated with an increased susceptibility for AD, is also correlated with COVID-19 prognosis and severity. Although exact numbers are difficult to come by, it is of utmost importance for clinicians to evaluate the overall scope of the situation, identify at-risk patients such as individuals with AD and related dementias, and work with caregivers to afford care to patients who need it the most.4
Transcending research design
The elderly population, unsurprisingly, experiences the highest COVID-19 mortality rate because of the presence of multiple risk factors, namely, compromised immunity and difficulties maintaining ADLs, and thereby adhering to safety protocols. As far as Alzheimer’s patients are concerned, numerous hurdles affect the domain of neurodegenerative research.
To safeguard the health and well-being of the participants and caregivers, site sponsors and investigators must explore various communication avenues with the goal of facilitating health education (for example, mitigation strategies, adverse effects monitoring, etc.), as well as implementing contingency plans in the event that a site becomes inaccessible (for example, site closure, traveling regulations, lockdowns, etc.).
Alternatives such as telemedicine present viable solutions for ensuring completion of studies. Given the nature of the pandemic, there is a possibility that a research participant may contract the virus, necessitating a break from the established protocol. It is for this reason that site sponsors and corresponding regulatory bodies are advised to proactively engage in dialogue and transparent communications with respect to ensuing protocol deviations. Institutional Review Boards can expedite the review process by making the necessary changes in a timely manner.5
References
1. Ritchie K. KJZZ. 2020 Nov 16.
2. Brown EE et al. Am J Geriatr Psychiatry. 2020 Jul;28(7):712-21.
3. Li J et al. J Alzheimers Dis. 2020;77(1):67-73.
4. Perry G. J Alzheimers Dis. 2020 Jan 1;76(1):1.
5. Alzheimers Dement. 2020 Apr;16(4):587-8.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston. Dr. Dhillon is currently on the speaker bureau/advisory board for Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He has no disclosures.
An alarming number of additional Alzheimer’s disease (AD) deaths have been reported across various states within the past several months, according to the Alzheimer’s Association. Centers for Disease Control and Prevention data indicate that no less than 31,000 additional people with the neurodegenerative condition had died from the beginning of the pandemic through the end of September 2020. We know that long-term care facilities have been hit hardest, and access to adequate and/or prompt testing has been cited as the most pressing issue during the onset of the pandemic.1
When ADLs become a matter of survival
For individuals affected with Alzheimer’s disease and other types of dementia, performing routine tasks may seem cumbersome and overwhelming. Many of these patients are dependent upon caregivers and family support to facilitate their activities of daily living (ADLs).
Transitioning into the “new normal” set by the pandemic milieu is not an easy task for the average AD individual, because they are now expected to comply with numerous safety instructions (for example, maintaining hygiene, social distancing, etc.). They are also expected to monitor and communicate information about the onset of any suspected symptom to their caregiver or health care clinician.
The additional tasks added to their list of ADLs are particularly distressing given their already compromised short-term memory and overall cognitive decline. Individuals with AD may also be dealing with a host of psychobehavioral challenges, such as the presence of depression, anxiety, and/or agitation amid self-isolation. Enforced social isolation tied to COVID-19 may compound those issues.
Resource diversion and mitigation strategies
Unfortunately, any disruption in services within a long-term care setting may lead to a suboptimal therapeutic environment for patients. The Washington State LTC, for example, reported experiencing a case fatality rate (CFR) exceeding more than a third of its residents; essential staff and health care clinicians were duly affected from exposure to the virus (the risk of transmission increases considerably during transport between facilities). Access to personal protective equipment (PPE) might have been hindered by availability.
Another issue with far-reaching consequences is diversion of resources for urgent care. Health care professionals may simply not be readily available for those with chronic care needs because of the enormous scale of the impact of COVID-19 upon health care systems.
Continuity of therapy might include evaluations or follow-up services via teleconferencing modalities, but an exhaustive initial onsite physical examination is often necessary for accurate diagnostics and care. Medication management for the newly diagnosed AD or dementia patient necessitates a thorough screening process involving appropriate in-person blood or laboratory work. It is for this reason that clinicians will need to plan ahead by preparing a contingency plan with the corresponding mitigation strategies (for example, telemedicine, proposed solutions to anticipated disruption of services, extended support, and feedback from family members, etc.).2
Resilience and recovery in a retrospective study
A research team from Wuhan Red Cross Hospital in China performed a retrospective cohort study on a sample of patients (n = 42) to determine the severity and prognostic features of COVID-19 pneumonia; 19 AD patients (as per National Institute on Aging/Alzheimer’s Association diagnostic guidelines) were directly compared with 23 age-matched non-AD COVID-19 patients in a similar treatment context.
The study yielded some rather unexpected findings, namely, AD patients experienced remarkably shorter hospital stays and better appetites, especially with respect to their non-AD counterparts. This is even more puzzling when considering that previous studies indicated that dementia patients with concomitant COVID-19 pneumonia are twice as likely to die as those without neurodegenerative compromise.
Aside from a seemingly inexplicable interest in food, the observable positive changes may be attributable to such factors that are particular to the nursing home – residents have immediate access to health care services, which generally allows for timely diagnosis and care. However, the authors of the study speculate that the pathophysiological response of angiotensin-converting enzyme 2 (ACE2) confers to AD patients a therapeutic advantage as they have reduced expression.3 Despite the notoriously high mortality rates of COVID-19 pneumonia among the elderly population, , which underscores the importance of early diagnosis and intervention.
Genetic and environmental susceptibility
One of the more devastating observations about the ongoing pandemic environment is that a whopping 80% of dying patients committed to a long-term facility also include those with AD; it has been reported that almost half of all patients in nursing homes and related services have the neurodegenerative condition. The grim scenario is brought about by several factors, chief of which is the proximity of shared living arrangements within the context of a residential care setting. It should be noted that patients with AD exhibit comorbid conditions (for example, diabetes, cardiovascular disease, and/or respiratory issues) that immediately put them at high risk for COVID exposure. Interestingly enough, the ApoE4 genotype, which is associated with an increased susceptibility for AD, is also correlated with COVID-19 prognosis and severity. Although exact numbers are difficult to come by, it is of utmost importance for clinicians to evaluate the overall scope of the situation, identify at-risk patients such as individuals with AD and related dementias, and work with caregivers to afford care to patients who need it the most.4
Transcending research design
The elderly population, unsurprisingly, experiences the highest COVID-19 mortality rate because of the presence of multiple risk factors, namely, compromised immunity and difficulties maintaining ADLs, and thereby adhering to safety protocols. As far as Alzheimer’s patients are concerned, numerous hurdles affect the domain of neurodegenerative research.
To safeguard the health and well-being of the participants and caregivers, site sponsors and investigators must explore various communication avenues with the goal of facilitating health education (for example, mitigation strategies, adverse effects monitoring, etc.), as well as implementing contingency plans in the event that a site becomes inaccessible (for example, site closure, traveling regulations, lockdowns, etc.).
Alternatives such as telemedicine present viable solutions for ensuring completion of studies. Given the nature of the pandemic, there is a possibility that a research participant may contract the virus, necessitating a break from the established protocol. It is for this reason that site sponsors and corresponding regulatory bodies are advised to proactively engage in dialogue and transparent communications with respect to ensuing protocol deviations. Institutional Review Boards can expedite the review process by making the necessary changes in a timely manner.5
References
1. Ritchie K. KJZZ. 2020 Nov 16.
2. Brown EE et al. Am J Geriatr Psychiatry. 2020 Jul;28(7):712-21.
3. Li J et al. J Alzheimers Dis. 2020;77(1):67-73.
4. Perry G. J Alzheimers Dis. 2020 Jan 1;76(1):1.
5. Alzheimers Dement. 2020 Apr;16(4):587-8.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston. Dr. Dhillon is currently on the speaker bureau/advisory board for Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He has no disclosures.
An alarming number of additional Alzheimer’s disease (AD) deaths have been reported across various states within the past several months, according to the Alzheimer’s Association. Centers for Disease Control and Prevention data indicate that no less than 31,000 additional people with the neurodegenerative condition had died from the beginning of the pandemic through the end of September 2020. We know that long-term care facilities have been hit hardest, and access to adequate and/or prompt testing has been cited as the most pressing issue during the onset of the pandemic.1
When ADLs become a matter of survival
For individuals affected with Alzheimer’s disease and other types of dementia, performing routine tasks may seem cumbersome and overwhelming. Many of these patients are dependent upon caregivers and family support to facilitate their activities of daily living (ADLs).
Transitioning into the “new normal” set by the pandemic milieu is not an easy task for the average AD individual, because they are now expected to comply with numerous safety instructions (for example, maintaining hygiene, social distancing, etc.). They are also expected to monitor and communicate information about the onset of any suspected symptom to their caregiver or health care clinician.
The additional tasks added to their list of ADLs are particularly distressing given their already compromised short-term memory and overall cognitive decline. Individuals with AD may also be dealing with a host of psychobehavioral challenges, such as the presence of depression, anxiety, and/or agitation amid self-isolation. Enforced social isolation tied to COVID-19 may compound those issues.
Resource diversion and mitigation strategies
Unfortunately, any disruption in services within a long-term care setting may lead to a suboptimal therapeutic environment for patients. The Washington State LTC, for example, reported experiencing a case fatality rate (CFR) exceeding more than a third of its residents; essential staff and health care clinicians were duly affected from exposure to the virus (the risk of transmission increases considerably during transport between facilities). Access to personal protective equipment (PPE) might have been hindered by availability.
Another issue with far-reaching consequences is diversion of resources for urgent care. Health care professionals may simply not be readily available for those with chronic care needs because of the enormous scale of the impact of COVID-19 upon health care systems.
Continuity of therapy might include evaluations or follow-up services via teleconferencing modalities, but an exhaustive initial onsite physical examination is often necessary for accurate diagnostics and care. Medication management for the newly diagnosed AD or dementia patient necessitates a thorough screening process involving appropriate in-person blood or laboratory work. It is for this reason that clinicians will need to plan ahead by preparing a contingency plan with the corresponding mitigation strategies (for example, telemedicine, proposed solutions to anticipated disruption of services, extended support, and feedback from family members, etc.).2
Resilience and recovery in a retrospective study
A research team from Wuhan Red Cross Hospital in China performed a retrospective cohort study on a sample of patients (n = 42) to determine the severity and prognostic features of COVID-19 pneumonia; 19 AD patients (as per National Institute on Aging/Alzheimer’s Association diagnostic guidelines) were directly compared with 23 age-matched non-AD COVID-19 patients in a similar treatment context.
The study yielded some rather unexpected findings, namely, AD patients experienced remarkably shorter hospital stays and better appetites, especially with respect to their non-AD counterparts. This is even more puzzling when considering that previous studies indicated that dementia patients with concomitant COVID-19 pneumonia are twice as likely to die as those without neurodegenerative compromise.
Aside from a seemingly inexplicable interest in food, the observable positive changes may be attributable to such factors that are particular to the nursing home – residents have immediate access to health care services, which generally allows for timely diagnosis and care. However, the authors of the study speculate that the pathophysiological response of angiotensin-converting enzyme 2 (ACE2) confers to AD patients a therapeutic advantage as they have reduced expression.3 Despite the notoriously high mortality rates of COVID-19 pneumonia among the elderly population, , which underscores the importance of early diagnosis and intervention.
Genetic and environmental susceptibility
One of the more devastating observations about the ongoing pandemic environment is that a whopping 80% of dying patients committed to a long-term facility also include those with AD; it has been reported that almost half of all patients in nursing homes and related services have the neurodegenerative condition. The grim scenario is brought about by several factors, chief of which is the proximity of shared living arrangements within the context of a residential care setting. It should be noted that patients with AD exhibit comorbid conditions (for example, diabetes, cardiovascular disease, and/or respiratory issues) that immediately put them at high risk for COVID exposure. Interestingly enough, the ApoE4 genotype, which is associated with an increased susceptibility for AD, is also correlated with COVID-19 prognosis and severity. Although exact numbers are difficult to come by, it is of utmost importance for clinicians to evaluate the overall scope of the situation, identify at-risk patients such as individuals with AD and related dementias, and work with caregivers to afford care to patients who need it the most.4
Transcending research design
The elderly population, unsurprisingly, experiences the highest COVID-19 mortality rate because of the presence of multiple risk factors, namely, compromised immunity and difficulties maintaining ADLs, and thereby adhering to safety protocols. As far as Alzheimer’s patients are concerned, numerous hurdles affect the domain of neurodegenerative research.
To safeguard the health and well-being of the participants and caregivers, site sponsors and investigators must explore various communication avenues with the goal of facilitating health education (for example, mitigation strategies, adverse effects monitoring, etc.), as well as implementing contingency plans in the event that a site becomes inaccessible (for example, site closure, traveling regulations, lockdowns, etc.).
Alternatives such as telemedicine present viable solutions for ensuring completion of studies. Given the nature of the pandemic, there is a possibility that a research participant may contract the virus, necessitating a break from the established protocol. It is for this reason that site sponsors and corresponding regulatory bodies are advised to proactively engage in dialogue and transparent communications with respect to ensuing protocol deviations. Institutional Review Boards can expedite the review process by making the necessary changes in a timely manner.5
References
1. Ritchie K. KJZZ. 2020 Nov 16.
2. Brown EE et al. Am J Geriatr Psychiatry. 2020 Jul;28(7):712-21.
3. Li J et al. J Alzheimers Dis. 2020;77(1):67-73.
4. Perry G. J Alzheimers Dis. 2020 Jan 1;76(1):1.
5. Alzheimers Dement. 2020 Apr;16(4):587-8.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston. Dr. Dhillon is currently on the speaker bureau/advisory board for Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He has no disclosures.
Bedside EEG test aids prognosis in patients with brain injury
results of a new study suggest. The study showed that the use of a paradigm that measures the strength of responses to speech improved the accuracy of prognosis for these patients, compared with prognoses made solely on the basis of standard clinical characteristics.
“What we found is really compelling evidence” of the usefulness of the test, lead study author Rodika Sokoliuk, PhD, a postdoctoral researcher at the Center for Human Brain Health, University of Birmingham (England), said in an interview.
The passive measure of comprehension, which doesn’t require any other response from the patient, can reduce uncertainty at a critical phase of decision-making in the ICU, said Dr. Sokoliuk.
The study was published online Dec. 23, 2020, in Annals of Neurology.
Useful information at a time of ‘considerable prognostic uncertainty’
Accurate, early prognostication is vital for efficient stratification of patients after a TBI, the authors wrote. This can often be achieved from patient behavior and CT at admission, but some patients continue to fail to obey commands after washout of sedation.
These patients pose a significant challenge for neurologic prognostication, they noted. In these cases, clinicians and families must decide whether to “wait and see” or consider treatment withdrawal.
The authors noted that a lack of command following early in the postsedation period is associated with poor outcome, including vegetative state/unresponsive wakefulness syndrome (VS/UWS). This, they said, represents a “window of opportunity” for cessation of life-sustaining therapy at a time of considerable prognostic uncertainty.
Recent research shows that a significant proportion of unresponsive patients retain a level of cognition, and even consciousness, that isn’t evident from their external behavior – the so-called cognitive-motor dissociation.
The new study included 28 adult patients who had experienced a TBI and were admitted to the ICU of the Queen Elizabeth Hospital in Birmingham, England. The patients had a Glasgow Coma Scale motor score less than 6 (i.e., they were incapable of obeying commands). They had been sedation free for 2-7 days.
For the paradigm, researchers constructed 288 English words using the male voice of the Apple synthesizer. The words required the same amount of time to be generated (320 ms) and were monosyllabic, so the rhythms of the sounds were the same.
The words were presented in a specific order: an adjective, then a noun, then a verb, then a noun. Two words – for example, an adjective and noun – “would build a meaningful phrase,” and four words would build a sentence, said Dr. Sokoliuk.
The researchers built 72 of these four-word sentences. A trial comprised 12 of these sentences, resulting in a total of 864 four-word sentences.
Dr. Sokoliuk likened the paradigm to a rap song with a specific beat that is continually repeated. “Basically, we play 12 of these four-word sentences in a row, without any gaps,” she said.
Each sentence was played to patients, in random order, a minimum of eight and a maximum of nine times per patient throughout the experiment. The patients’ brain activity was recorded on EEG.
Dr. Sokoliuk noted that brain activity in healthy people synchronizes only with the rhythm of phrases and sentences when listeners consciously comprehend the speech. The researchers assessed the level of comprehension in the unresponsive patients by measuring the strength of this synchronicity or brain pattern.
After exclusions, 17 patients were available for outcome assessment 3 months post EEG, and 16 patients were available 6 months post EEG.
The analysis showed that outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6; P < .007), quantified by intertrial phase coherence.
Linear regressions revealed that the strength of this comprehension response (beta, 0.603; P = .006) significantly improved the accuracy of prognoses relative to clinical characteristics alone, such as the Glasgow Coma Scale or CT grade.
Previous studies showed that, if there is no understanding of the language used or if the subject is asleep, the brain doesn’t have the “signature” of tracking phrases and sentences, so it doesn’t have the synchronicity or the pattern of individuals with normal cognition, said Dr. Sokoliuk.
“You need a certain level of consciousness, and you need to understand the language, so your brain can actually track sentences or phrases,” she said.
Dr. Sokoliuk explained that the paradigm shows that patients are understanding the sentences and are not just hearing them.
“It’s not showing us that they only hear it, because there are no obvious gaps between the sentences; if there were gaps between sentences, it would probably only show that they hear it. It could be both, that they hear and understand it, but we wouldn’t know.”
A receiver operating characteristics analysis indicated 100% sensitivity and 80% specificity for a distinction between bad outcome (death, VS/UWS) and good outcome at 6 months.
“We could actually define a threshold of the tracking,” said Dr. Sokoliuk. “Patients who had phrases and sentences tracking below this threshold had worse outcome than those whose tracking value was above this threshold.”
The study illustrates that some posttraumatic patients who remain in an unresponsive state despite being sedation free may nevertheless comprehend speech.
The EEG paradigm approach, the authors said, may significantly reduce prognostic uncertainty in a critical phase of medical decision-making. It could also help clinicians make more appropriate decisions about whether or not to continue life-sustaining therapy and ensure more appropriate distribution of limited rehabilitation resources to patients most likely to benefit.
Dr. Sokoliuk stressed that the paradigm could be used at the bedside soon after a brain injury. “The critical thing is, we can actually use it during the acute phase, which is very important for clinical decisions about life-sustaining methods, therapy, and long-term care.”
A prognostic tool
The simple approach promises to be more accessible than fMRI, said Dr. Sokoliuk. “Putting an unresponsive coma patient in a scanner is very difficult and also much more expensive,” she said.
The next step, said Dr. Sokoliuk, is to repeat the study with a larger sample. “The number in the current study was quite small, and we can’t say if the sensitivity of the paradigm is strong enough to use it as a standard prognostic tool.”
To use it in clinical setting, “we really have to have robust measures,” she added.
She aims to conduct a collaborative study involving several institutions and more patients.
The research team plans to eventually build “an open-access toolbox” that would include the auditory streams to be played during EEG recordings and a program to analyze the data, said Dr. Sokoliuk. “Then, in the end, you would get a threshold or a value of tracking for phrases and sentences, and this could then classify a patient to be in a good-outcome or in bad-outcome group.”
She stressed this is a prognostic tool, not a diagnostic tool, and it should not be used in isolation. “It’s important to know that no clinician should only use this paradigm to prognosticate a patient; our paradigm should be part of a bigger battery of tests.”
But it could go a long way toward helping families as well as physicians. “If they know that the patient would be better in 3 months’ time, it’s easier for them to decide what should come next,” she said.
And it’s heartening to know that when families talk to their unresponsive loved one, the patient understands them, she added.
Promising basic research
Commenting on the study in an interview, Christine Blume, PhD, of the Center for Chronobiology, University of Basel (Switzerland), whose research interests include cognitive processing of patients with disorders of consciousness, described it as “very elegant and appealing” and the paradigm it used as “really promising.”
“However, we do, of course, not yet know about the prognostic value on a single-subject level, as the authors performed only group analyses,” said Dr. Blume. “This will require more extensive and perhaps even multicenter studies.”
It would also require developing a “solution” that “allows clinicians with limited time resources and perhaps lacking expert knowledge on the paradigm and the necessary analyses to apply the paradigm at bedside,” said Dr. Blume.
She agreed that a passive paradigm that helps determine whether a patient consciously understands speech, without the need for further processing, “has the potential to really improve the diagnostic process and uncover covert consciousness.”
One should bear in mind, though, that the paradigm “makes one essential assumption: that patients can understand speech,” said Dr. Blume. “For example, an aphasic patient might not understand but still be conscious.”
In this context, she added, “it’s essential to note that while the presence of a response suggests consciousness, the absence of a response does not suggest the absence of consciousness.”
Dr. Blume cautioned that the approach used in the study “is still at the stage of basic research.” Although the paradigm is promising, “I do not think it is ‘around the corner,’ ” she said.
The study was funded by the Medical Research Council. It was further supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Center. Dr. Sokoliuk and Dr. Blume have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
results of a new study suggest. The study showed that the use of a paradigm that measures the strength of responses to speech improved the accuracy of prognosis for these patients, compared with prognoses made solely on the basis of standard clinical characteristics.
“What we found is really compelling evidence” of the usefulness of the test, lead study author Rodika Sokoliuk, PhD, a postdoctoral researcher at the Center for Human Brain Health, University of Birmingham (England), said in an interview.
The passive measure of comprehension, which doesn’t require any other response from the patient, can reduce uncertainty at a critical phase of decision-making in the ICU, said Dr. Sokoliuk.
The study was published online Dec. 23, 2020, in Annals of Neurology.
Useful information at a time of ‘considerable prognostic uncertainty’
Accurate, early prognostication is vital for efficient stratification of patients after a TBI, the authors wrote. This can often be achieved from patient behavior and CT at admission, but some patients continue to fail to obey commands after washout of sedation.
These patients pose a significant challenge for neurologic prognostication, they noted. In these cases, clinicians and families must decide whether to “wait and see” or consider treatment withdrawal.
The authors noted that a lack of command following early in the postsedation period is associated with poor outcome, including vegetative state/unresponsive wakefulness syndrome (VS/UWS). This, they said, represents a “window of opportunity” for cessation of life-sustaining therapy at a time of considerable prognostic uncertainty.
Recent research shows that a significant proportion of unresponsive patients retain a level of cognition, and even consciousness, that isn’t evident from their external behavior – the so-called cognitive-motor dissociation.
The new study included 28 adult patients who had experienced a TBI and were admitted to the ICU of the Queen Elizabeth Hospital in Birmingham, England. The patients had a Glasgow Coma Scale motor score less than 6 (i.e., they were incapable of obeying commands). They had been sedation free for 2-7 days.
For the paradigm, researchers constructed 288 English words using the male voice of the Apple synthesizer. The words required the same amount of time to be generated (320 ms) and were monosyllabic, so the rhythms of the sounds were the same.
The words were presented in a specific order: an adjective, then a noun, then a verb, then a noun. Two words – for example, an adjective and noun – “would build a meaningful phrase,” and four words would build a sentence, said Dr. Sokoliuk.
The researchers built 72 of these four-word sentences. A trial comprised 12 of these sentences, resulting in a total of 864 four-word sentences.
Dr. Sokoliuk likened the paradigm to a rap song with a specific beat that is continually repeated. “Basically, we play 12 of these four-word sentences in a row, without any gaps,” she said.
Each sentence was played to patients, in random order, a minimum of eight and a maximum of nine times per patient throughout the experiment. The patients’ brain activity was recorded on EEG.
Dr. Sokoliuk noted that brain activity in healthy people synchronizes only with the rhythm of phrases and sentences when listeners consciously comprehend the speech. The researchers assessed the level of comprehension in the unresponsive patients by measuring the strength of this synchronicity or brain pattern.
After exclusions, 17 patients were available for outcome assessment 3 months post EEG, and 16 patients were available 6 months post EEG.
The analysis showed that outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6; P < .007), quantified by intertrial phase coherence.
Linear regressions revealed that the strength of this comprehension response (beta, 0.603; P = .006) significantly improved the accuracy of prognoses relative to clinical characteristics alone, such as the Glasgow Coma Scale or CT grade.
Previous studies showed that, if there is no understanding of the language used or if the subject is asleep, the brain doesn’t have the “signature” of tracking phrases and sentences, so it doesn’t have the synchronicity or the pattern of individuals with normal cognition, said Dr. Sokoliuk.
“You need a certain level of consciousness, and you need to understand the language, so your brain can actually track sentences or phrases,” she said.
Dr. Sokoliuk explained that the paradigm shows that patients are understanding the sentences and are not just hearing them.
“It’s not showing us that they only hear it, because there are no obvious gaps between the sentences; if there were gaps between sentences, it would probably only show that they hear it. It could be both, that they hear and understand it, but we wouldn’t know.”
A receiver operating characteristics analysis indicated 100% sensitivity and 80% specificity for a distinction between bad outcome (death, VS/UWS) and good outcome at 6 months.
“We could actually define a threshold of the tracking,” said Dr. Sokoliuk. “Patients who had phrases and sentences tracking below this threshold had worse outcome than those whose tracking value was above this threshold.”
The study illustrates that some posttraumatic patients who remain in an unresponsive state despite being sedation free may nevertheless comprehend speech.
The EEG paradigm approach, the authors said, may significantly reduce prognostic uncertainty in a critical phase of medical decision-making. It could also help clinicians make more appropriate decisions about whether or not to continue life-sustaining therapy and ensure more appropriate distribution of limited rehabilitation resources to patients most likely to benefit.
Dr. Sokoliuk stressed that the paradigm could be used at the bedside soon after a brain injury. “The critical thing is, we can actually use it during the acute phase, which is very important for clinical decisions about life-sustaining methods, therapy, and long-term care.”
A prognostic tool
The simple approach promises to be more accessible than fMRI, said Dr. Sokoliuk. “Putting an unresponsive coma patient in a scanner is very difficult and also much more expensive,” she said.
The next step, said Dr. Sokoliuk, is to repeat the study with a larger sample. “The number in the current study was quite small, and we can’t say if the sensitivity of the paradigm is strong enough to use it as a standard prognostic tool.”
To use it in clinical setting, “we really have to have robust measures,” she added.
She aims to conduct a collaborative study involving several institutions and more patients.
The research team plans to eventually build “an open-access toolbox” that would include the auditory streams to be played during EEG recordings and a program to analyze the data, said Dr. Sokoliuk. “Then, in the end, you would get a threshold or a value of tracking for phrases and sentences, and this could then classify a patient to be in a good-outcome or in bad-outcome group.”
She stressed this is a prognostic tool, not a diagnostic tool, and it should not be used in isolation. “It’s important to know that no clinician should only use this paradigm to prognosticate a patient; our paradigm should be part of a bigger battery of tests.”
But it could go a long way toward helping families as well as physicians. “If they know that the patient would be better in 3 months’ time, it’s easier for them to decide what should come next,” she said.
And it’s heartening to know that when families talk to their unresponsive loved one, the patient understands them, she added.
Promising basic research
Commenting on the study in an interview, Christine Blume, PhD, of the Center for Chronobiology, University of Basel (Switzerland), whose research interests include cognitive processing of patients with disorders of consciousness, described it as “very elegant and appealing” and the paradigm it used as “really promising.”
“However, we do, of course, not yet know about the prognostic value on a single-subject level, as the authors performed only group analyses,” said Dr. Blume. “This will require more extensive and perhaps even multicenter studies.”
It would also require developing a “solution” that “allows clinicians with limited time resources and perhaps lacking expert knowledge on the paradigm and the necessary analyses to apply the paradigm at bedside,” said Dr. Blume.
She agreed that a passive paradigm that helps determine whether a patient consciously understands speech, without the need for further processing, “has the potential to really improve the diagnostic process and uncover covert consciousness.”
One should bear in mind, though, that the paradigm “makes one essential assumption: that patients can understand speech,” said Dr. Blume. “For example, an aphasic patient might not understand but still be conscious.”
In this context, she added, “it’s essential to note that while the presence of a response suggests consciousness, the absence of a response does not suggest the absence of consciousness.”
Dr. Blume cautioned that the approach used in the study “is still at the stage of basic research.” Although the paradigm is promising, “I do not think it is ‘around the corner,’ ” she said.
The study was funded by the Medical Research Council. It was further supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Center. Dr. Sokoliuk and Dr. Blume have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
results of a new study suggest. The study showed that the use of a paradigm that measures the strength of responses to speech improved the accuracy of prognosis for these patients, compared with prognoses made solely on the basis of standard clinical characteristics.
“What we found is really compelling evidence” of the usefulness of the test, lead study author Rodika Sokoliuk, PhD, a postdoctoral researcher at the Center for Human Brain Health, University of Birmingham (England), said in an interview.
The passive measure of comprehension, which doesn’t require any other response from the patient, can reduce uncertainty at a critical phase of decision-making in the ICU, said Dr. Sokoliuk.
The study was published online Dec. 23, 2020, in Annals of Neurology.
Useful information at a time of ‘considerable prognostic uncertainty’
Accurate, early prognostication is vital for efficient stratification of patients after a TBI, the authors wrote. This can often be achieved from patient behavior and CT at admission, but some patients continue to fail to obey commands after washout of sedation.
These patients pose a significant challenge for neurologic prognostication, they noted. In these cases, clinicians and families must decide whether to “wait and see” or consider treatment withdrawal.
The authors noted that a lack of command following early in the postsedation period is associated with poor outcome, including vegetative state/unresponsive wakefulness syndrome (VS/UWS). This, they said, represents a “window of opportunity” for cessation of life-sustaining therapy at a time of considerable prognostic uncertainty.
Recent research shows that a significant proportion of unresponsive patients retain a level of cognition, and even consciousness, that isn’t evident from their external behavior – the so-called cognitive-motor dissociation.
The new study included 28 adult patients who had experienced a TBI and were admitted to the ICU of the Queen Elizabeth Hospital in Birmingham, England. The patients had a Glasgow Coma Scale motor score less than 6 (i.e., they were incapable of obeying commands). They had been sedation free for 2-7 days.
For the paradigm, researchers constructed 288 English words using the male voice of the Apple synthesizer. The words required the same amount of time to be generated (320 ms) and were monosyllabic, so the rhythms of the sounds were the same.
The words were presented in a specific order: an adjective, then a noun, then a verb, then a noun. Two words – for example, an adjective and noun – “would build a meaningful phrase,” and four words would build a sentence, said Dr. Sokoliuk.
The researchers built 72 of these four-word sentences. A trial comprised 12 of these sentences, resulting in a total of 864 four-word sentences.
Dr. Sokoliuk likened the paradigm to a rap song with a specific beat that is continually repeated. “Basically, we play 12 of these four-word sentences in a row, without any gaps,” she said.
Each sentence was played to patients, in random order, a minimum of eight and a maximum of nine times per patient throughout the experiment. The patients’ brain activity was recorded on EEG.
Dr. Sokoliuk noted that brain activity in healthy people synchronizes only with the rhythm of phrases and sentences when listeners consciously comprehend the speech. The researchers assessed the level of comprehension in the unresponsive patients by measuring the strength of this synchronicity or brain pattern.
After exclusions, 17 patients were available for outcome assessment 3 months post EEG, and 16 patients were available 6 months post EEG.
The analysis showed that outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6; P < .007), quantified by intertrial phase coherence.
Linear regressions revealed that the strength of this comprehension response (beta, 0.603; P = .006) significantly improved the accuracy of prognoses relative to clinical characteristics alone, such as the Glasgow Coma Scale or CT grade.
Previous studies showed that, if there is no understanding of the language used or if the subject is asleep, the brain doesn’t have the “signature” of tracking phrases and sentences, so it doesn’t have the synchronicity or the pattern of individuals with normal cognition, said Dr. Sokoliuk.
“You need a certain level of consciousness, and you need to understand the language, so your brain can actually track sentences or phrases,” she said.
Dr. Sokoliuk explained that the paradigm shows that patients are understanding the sentences and are not just hearing them.
“It’s not showing us that they only hear it, because there are no obvious gaps between the sentences; if there were gaps between sentences, it would probably only show that they hear it. It could be both, that they hear and understand it, but we wouldn’t know.”
A receiver operating characteristics analysis indicated 100% sensitivity and 80% specificity for a distinction between bad outcome (death, VS/UWS) and good outcome at 6 months.
“We could actually define a threshold of the tracking,” said Dr. Sokoliuk. “Patients who had phrases and sentences tracking below this threshold had worse outcome than those whose tracking value was above this threshold.”
The study illustrates that some posttraumatic patients who remain in an unresponsive state despite being sedation free may nevertheless comprehend speech.
The EEG paradigm approach, the authors said, may significantly reduce prognostic uncertainty in a critical phase of medical decision-making. It could also help clinicians make more appropriate decisions about whether or not to continue life-sustaining therapy and ensure more appropriate distribution of limited rehabilitation resources to patients most likely to benefit.
Dr. Sokoliuk stressed that the paradigm could be used at the bedside soon after a brain injury. “The critical thing is, we can actually use it during the acute phase, which is very important for clinical decisions about life-sustaining methods, therapy, and long-term care.”
A prognostic tool
The simple approach promises to be more accessible than fMRI, said Dr. Sokoliuk. “Putting an unresponsive coma patient in a scanner is very difficult and also much more expensive,” she said.
The next step, said Dr. Sokoliuk, is to repeat the study with a larger sample. “The number in the current study was quite small, and we can’t say if the sensitivity of the paradigm is strong enough to use it as a standard prognostic tool.”
To use it in clinical setting, “we really have to have robust measures,” she added.
She aims to conduct a collaborative study involving several institutions and more patients.
The research team plans to eventually build “an open-access toolbox” that would include the auditory streams to be played during EEG recordings and a program to analyze the data, said Dr. Sokoliuk. “Then, in the end, you would get a threshold or a value of tracking for phrases and sentences, and this could then classify a patient to be in a good-outcome or in bad-outcome group.”
She stressed this is a prognostic tool, not a diagnostic tool, and it should not be used in isolation. “It’s important to know that no clinician should only use this paradigm to prognosticate a patient; our paradigm should be part of a bigger battery of tests.”
But it could go a long way toward helping families as well as physicians. “If they know that the patient would be better in 3 months’ time, it’s easier for them to decide what should come next,” she said.
And it’s heartening to know that when families talk to their unresponsive loved one, the patient understands them, she added.
Promising basic research
Commenting on the study in an interview, Christine Blume, PhD, of the Center for Chronobiology, University of Basel (Switzerland), whose research interests include cognitive processing of patients with disorders of consciousness, described it as “very elegant and appealing” and the paradigm it used as “really promising.”
“However, we do, of course, not yet know about the prognostic value on a single-subject level, as the authors performed only group analyses,” said Dr. Blume. “This will require more extensive and perhaps even multicenter studies.”
It would also require developing a “solution” that “allows clinicians with limited time resources and perhaps lacking expert knowledge on the paradigm and the necessary analyses to apply the paradigm at bedside,” said Dr. Blume.
She agreed that a passive paradigm that helps determine whether a patient consciously understands speech, without the need for further processing, “has the potential to really improve the diagnostic process and uncover covert consciousness.”
One should bear in mind, though, that the paradigm “makes one essential assumption: that patients can understand speech,” said Dr. Blume. “For example, an aphasic patient might not understand but still be conscious.”
In this context, she added, “it’s essential to note that while the presence of a response suggests consciousness, the absence of a response does not suggest the absence of consciousness.”
Dr. Blume cautioned that the approach used in the study “is still at the stage of basic research.” Although the paradigm is promising, “I do not think it is ‘around the corner,’ ” she said.
The study was funded by the Medical Research Council. It was further supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Center. Dr. Sokoliuk and Dr. Blume have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF NEUROLOGY
Cloth masks provide inferior protection vs. medical masks, suggests evidence review
according to an evidence review published Jan. 11 in Annals of Family Medicine.
Nevertheless, cloth masks may provide some degree of protection, filtration studies indicate. If clinicians use cloth masks, they should take into account the fit, material, and number of layers, the review authors wrote.
And if cloth masks are used as a last resort, such as during shortages of personal protective equipment (PPE), additional measures may help, such as pairing cloth masks with plastic face shields.
“We recommend frequent cloth mask changes to reduce the risk of moisture retention and washing according to hospital laundry standards to decrease the risk of ineffective cleaning,” review author Ariel Kiyomi Daoud, a researcher at the University of Colorado at Denver, Aurora, and colleagues wrote.
The investigators identified and analyzed nine studies related to cloth masks’ ability to prevent respiratory viral infections among health care clinicians. The studies generally were not specific to SARS-CoV-2. They focused on four nonrandomized trials, three laboratory efficacy studies, one single-case experiment, and one randomized controlled trial.
Filtration and fit
“Seven publications addressed the filtration efficacy of commercial cloth masks or materials used to create homemade masks ... in a laboratory setting,” the researchers wrote. These studies found that cloth materials prevent some level of penetration, but generally have “lesser filtration efficiency and greater variability than medical masks” do.
One study found that the materials with the greatest filtration efficacy – vacuum bags and tea towels – had low airflow, which limits their use.
Two studies found that additional layers may increase the viral filtration efficacy of cloth masks.
Several studies that assessed mask fit and airflow found that cloth masks “have worse fit and a greater level of particle leakage, compared to medical masks,” the authors reported. Most studies did not examine cloth masks’ ability to protect wearers from respiratory droplets or contact, which the World Health Organization consider the primary means of SARS-CoV-2 spread, with aerosols playing a smaller role. “Thus, we must interpret these results with caution in the context of COVID-19,” the authors wrote. “For a primary care clinician without access to medical masks, our qualitative synthesis of the literature suggests that it is better to wear a cloth mask than no mask,” as long as other protective measures are considered along with cloth mask use.
Generally consistent guidance
Agencies and researchers have shared similar recommendations about the use of cloth masks in health care settings.
“Health care workers are at the frontline and they need to be protected,” said Abrar Ahmad Chughtai, MBBS, MPH, PhD, an epidemiologist at University of New South Wales, Sydney, in an interview. “Many studies show that respirators are more effective, compared to medical masks, and medical masks are more effective, compared to cloth masks. So ideally, all frontline health care workers should use respirators. If respirators are not available, then medical masks should be used. Cloth masks are not as effective as medical masks and ideally should not be used in health care settings.”
Dr. Chughtai has written about cloth masks for protection against SARS-CoV-2 and was an investigator for a 2015 randomized trial that compared medical masks and cloth masks in health care workers.
In that trial, which was considered in the review, greater rates of influenza-like illness occurred in the cloth mask arm, compared with the medical mask arm.
“Studies show that three or more layers of cloth may reduce the spread of droplets and aerosols from the wearers,” Dr. Chughtai said. “So, cloth masks may be used in community settings to prevent spread of infections from the sick, particularly asymptomatic, people.”
In addition, cloth masks “may be used by health care workers as a last resort, if no other option is available,” he said. In that case, they should have at least three layers, fit to the face, and be washed regularly.
Not considered PPE
According to routine infection prevention and control recommendations for health care personnel from the Centers for Disease Control and Prevention, face masks – often referred to as surgical masks or procedure masks – should be worn by workers “at all times while they are in the healthcare facility, including in break rooms or other spaces where they might encounter coworkers.”
Unlike cloth masks, face masks offer “protection for the wearer against exposure to splashes and sprays of infectious material from others,” as well as source control, the agency says. Health care personnel “should remove their respirator or face mask, perform hand hygiene, and put on their cloth mask when leaving the facility at the end of their shift,” according to the CDC.
“Cloth masks are NOT PPE and should not be worn for the care of patients with suspected or confirmed COVID-19 or other situations where use of a respirator or face mask is recommended,” the agency notes.
When respirators or face masks are unavailable, health care personnel “might use cloth masks as a last resort for care of patients with suspected or confirmed diagnosis for which face mask or respirator use is normally recommended,” according to CDC guidance.
In that scenario, cloth masks “should ideally be used in combination with a face shield that covers the entire front (that extends to the chin or below) and sides of the face,” the CDC says.
Limited data for comparisons
A Dec. 29, 2020, update in Annals of Internal Medicine about masks for prevention of respiratory virus infections highlighted two recent studies in the United States that reported on mask use in health care settings. A study of more than 16,000 health care workers and first responders found that those who used an N95 or surgical mask all of the time were less likely to have SARS-CoV-2 antibodies, compared with workers who did not wear masks all the time. The adjusted odds ratio with consistent N95 use was 0.83, and the aOR with consistent surgical mask use was 0.86.
In the second study, which included more than 20,000 asymptomatic health care workers, risk for infection was reduced with any mask use versus no mask use (OR, 0.58). An N95 mask was associated with decreased risk versus a surgical mask (OR, 0.76). The studies had methodological limitations, however, and “evidence for various comparisons about mask use in health care settings and risk for SARS-CoV-2 remains insufficient,” the authors of the update wrote.
The Annals of Family Medicine review authors had no relevant disclosures. Dr. Chughtai has tested filtration of 3M masks and worked with CleanSpace Technology to research fit testing of respirators, and the 2015 randomized trial was funded by an Australian Research Council Linkage Grant with 3M as a partner on the grant. The Dec. 29, 2020, update was of a review that originally was supported by grants from the Agency for Healthcare Research Quality.
SOURCE: Daoud AK et al. Ann Fam Med. 2020 Jan 11. doi: 10.1370/afm.2640.
according to an evidence review published Jan. 11 in Annals of Family Medicine.
Nevertheless, cloth masks may provide some degree of protection, filtration studies indicate. If clinicians use cloth masks, they should take into account the fit, material, and number of layers, the review authors wrote.
And if cloth masks are used as a last resort, such as during shortages of personal protective equipment (PPE), additional measures may help, such as pairing cloth masks with plastic face shields.
“We recommend frequent cloth mask changes to reduce the risk of moisture retention and washing according to hospital laundry standards to decrease the risk of ineffective cleaning,” review author Ariel Kiyomi Daoud, a researcher at the University of Colorado at Denver, Aurora, and colleagues wrote.
The investigators identified and analyzed nine studies related to cloth masks’ ability to prevent respiratory viral infections among health care clinicians. The studies generally were not specific to SARS-CoV-2. They focused on four nonrandomized trials, three laboratory efficacy studies, one single-case experiment, and one randomized controlled trial.
Filtration and fit
“Seven publications addressed the filtration efficacy of commercial cloth masks or materials used to create homemade masks ... in a laboratory setting,” the researchers wrote. These studies found that cloth materials prevent some level of penetration, but generally have “lesser filtration efficiency and greater variability than medical masks” do.
One study found that the materials with the greatest filtration efficacy – vacuum bags and tea towels – had low airflow, which limits their use.
Two studies found that additional layers may increase the viral filtration efficacy of cloth masks.
Several studies that assessed mask fit and airflow found that cloth masks “have worse fit and a greater level of particle leakage, compared to medical masks,” the authors reported. Most studies did not examine cloth masks’ ability to protect wearers from respiratory droplets or contact, which the World Health Organization consider the primary means of SARS-CoV-2 spread, with aerosols playing a smaller role. “Thus, we must interpret these results with caution in the context of COVID-19,” the authors wrote. “For a primary care clinician without access to medical masks, our qualitative synthesis of the literature suggests that it is better to wear a cloth mask than no mask,” as long as other protective measures are considered along with cloth mask use.
Generally consistent guidance
Agencies and researchers have shared similar recommendations about the use of cloth masks in health care settings.
“Health care workers are at the frontline and they need to be protected,” said Abrar Ahmad Chughtai, MBBS, MPH, PhD, an epidemiologist at University of New South Wales, Sydney, in an interview. “Many studies show that respirators are more effective, compared to medical masks, and medical masks are more effective, compared to cloth masks. So ideally, all frontline health care workers should use respirators. If respirators are not available, then medical masks should be used. Cloth masks are not as effective as medical masks and ideally should not be used in health care settings.”
Dr. Chughtai has written about cloth masks for protection against SARS-CoV-2 and was an investigator for a 2015 randomized trial that compared medical masks and cloth masks in health care workers.
In that trial, which was considered in the review, greater rates of influenza-like illness occurred in the cloth mask arm, compared with the medical mask arm.
“Studies show that three or more layers of cloth may reduce the spread of droplets and aerosols from the wearers,” Dr. Chughtai said. “So, cloth masks may be used in community settings to prevent spread of infections from the sick, particularly asymptomatic, people.”
In addition, cloth masks “may be used by health care workers as a last resort, if no other option is available,” he said. In that case, they should have at least three layers, fit to the face, and be washed regularly.
Not considered PPE
According to routine infection prevention and control recommendations for health care personnel from the Centers for Disease Control and Prevention, face masks – often referred to as surgical masks or procedure masks – should be worn by workers “at all times while they are in the healthcare facility, including in break rooms or other spaces where they might encounter coworkers.”
Unlike cloth masks, face masks offer “protection for the wearer against exposure to splashes and sprays of infectious material from others,” as well as source control, the agency says. Health care personnel “should remove their respirator or face mask, perform hand hygiene, and put on their cloth mask when leaving the facility at the end of their shift,” according to the CDC.
“Cloth masks are NOT PPE and should not be worn for the care of patients with suspected or confirmed COVID-19 or other situations where use of a respirator or face mask is recommended,” the agency notes.
When respirators or face masks are unavailable, health care personnel “might use cloth masks as a last resort for care of patients with suspected or confirmed diagnosis for which face mask or respirator use is normally recommended,” according to CDC guidance.
In that scenario, cloth masks “should ideally be used in combination with a face shield that covers the entire front (that extends to the chin or below) and sides of the face,” the CDC says.
Limited data for comparisons
A Dec. 29, 2020, update in Annals of Internal Medicine about masks for prevention of respiratory virus infections highlighted two recent studies in the United States that reported on mask use in health care settings. A study of more than 16,000 health care workers and first responders found that those who used an N95 or surgical mask all of the time were less likely to have SARS-CoV-2 antibodies, compared with workers who did not wear masks all the time. The adjusted odds ratio with consistent N95 use was 0.83, and the aOR with consistent surgical mask use was 0.86.
In the second study, which included more than 20,000 asymptomatic health care workers, risk for infection was reduced with any mask use versus no mask use (OR, 0.58). An N95 mask was associated with decreased risk versus a surgical mask (OR, 0.76). The studies had methodological limitations, however, and “evidence for various comparisons about mask use in health care settings and risk for SARS-CoV-2 remains insufficient,” the authors of the update wrote.
The Annals of Family Medicine review authors had no relevant disclosures. Dr. Chughtai has tested filtration of 3M masks and worked with CleanSpace Technology to research fit testing of respirators, and the 2015 randomized trial was funded by an Australian Research Council Linkage Grant with 3M as a partner on the grant. The Dec. 29, 2020, update was of a review that originally was supported by grants from the Agency for Healthcare Research Quality.
SOURCE: Daoud AK et al. Ann Fam Med. 2020 Jan 11. doi: 10.1370/afm.2640.
according to an evidence review published Jan. 11 in Annals of Family Medicine.
Nevertheless, cloth masks may provide some degree of protection, filtration studies indicate. If clinicians use cloth masks, they should take into account the fit, material, and number of layers, the review authors wrote.
And if cloth masks are used as a last resort, such as during shortages of personal protective equipment (PPE), additional measures may help, such as pairing cloth masks with plastic face shields.
“We recommend frequent cloth mask changes to reduce the risk of moisture retention and washing according to hospital laundry standards to decrease the risk of ineffective cleaning,” review author Ariel Kiyomi Daoud, a researcher at the University of Colorado at Denver, Aurora, and colleagues wrote.
The investigators identified and analyzed nine studies related to cloth masks’ ability to prevent respiratory viral infections among health care clinicians. The studies generally were not specific to SARS-CoV-2. They focused on four nonrandomized trials, three laboratory efficacy studies, one single-case experiment, and one randomized controlled trial.
Filtration and fit
“Seven publications addressed the filtration efficacy of commercial cloth masks or materials used to create homemade masks ... in a laboratory setting,” the researchers wrote. These studies found that cloth materials prevent some level of penetration, but generally have “lesser filtration efficiency and greater variability than medical masks” do.
One study found that the materials with the greatest filtration efficacy – vacuum bags and tea towels – had low airflow, which limits their use.
Two studies found that additional layers may increase the viral filtration efficacy of cloth masks.
Several studies that assessed mask fit and airflow found that cloth masks “have worse fit and a greater level of particle leakage, compared to medical masks,” the authors reported. Most studies did not examine cloth masks’ ability to protect wearers from respiratory droplets or contact, which the World Health Organization consider the primary means of SARS-CoV-2 spread, with aerosols playing a smaller role. “Thus, we must interpret these results with caution in the context of COVID-19,” the authors wrote. “For a primary care clinician without access to medical masks, our qualitative synthesis of the literature suggests that it is better to wear a cloth mask than no mask,” as long as other protective measures are considered along with cloth mask use.
Generally consistent guidance
Agencies and researchers have shared similar recommendations about the use of cloth masks in health care settings.
“Health care workers are at the frontline and they need to be protected,” said Abrar Ahmad Chughtai, MBBS, MPH, PhD, an epidemiologist at University of New South Wales, Sydney, in an interview. “Many studies show that respirators are more effective, compared to medical masks, and medical masks are more effective, compared to cloth masks. So ideally, all frontline health care workers should use respirators. If respirators are not available, then medical masks should be used. Cloth masks are not as effective as medical masks and ideally should not be used in health care settings.”
Dr. Chughtai has written about cloth masks for protection against SARS-CoV-2 and was an investigator for a 2015 randomized trial that compared medical masks and cloth masks in health care workers.
In that trial, which was considered in the review, greater rates of influenza-like illness occurred in the cloth mask arm, compared with the medical mask arm.
“Studies show that three or more layers of cloth may reduce the spread of droplets and aerosols from the wearers,” Dr. Chughtai said. “So, cloth masks may be used in community settings to prevent spread of infections from the sick, particularly asymptomatic, people.”
In addition, cloth masks “may be used by health care workers as a last resort, if no other option is available,” he said. In that case, they should have at least three layers, fit to the face, and be washed regularly.
Not considered PPE
According to routine infection prevention and control recommendations for health care personnel from the Centers for Disease Control and Prevention, face masks – often referred to as surgical masks or procedure masks – should be worn by workers “at all times while they are in the healthcare facility, including in break rooms or other spaces where they might encounter coworkers.”
Unlike cloth masks, face masks offer “protection for the wearer against exposure to splashes and sprays of infectious material from others,” as well as source control, the agency says. Health care personnel “should remove their respirator or face mask, perform hand hygiene, and put on their cloth mask when leaving the facility at the end of their shift,” according to the CDC.
“Cloth masks are NOT PPE and should not be worn for the care of patients with suspected or confirmed COVID-19 or other situations where use of a respirator or face mask is recommended,” the agency notes.
When respirators or face masks are unavailable, health care personnel “might use cloth masks as a last resort for care of patients with suspected or confirmed diagnosis for which face mask or respirator use is normally recommended,” according to CDC guidance.
In that scenario, cloth masks “should ideally be used in combination with a face shield that covers the entire front (that extends to the chin or below) and sides of the face,” the CDC says.
Limited data for comparisons
A Dec. 29, 2020, update in Annals of Internal Medicine about masks for prevention of respiratory virus infections highlighted two recent studies in the United States that reported on mask use in health care settings. A study of more than 16,000 health care workers and first responders found that those who used an N95 or surgical mask all of the time were less likely to have SARS-CoV-2 antibodies, compared with workers who did not wear masks all the time. The adjusted odds ratio with consistent N95 use was 0.83, and the aOR with consistent surgical mask use was 0.86.
In the second study, which included more than 20,000 asymptomatic health care workers, risk for infection was reduced with any mask use versus no mask use (OR, 0.58). An N95 mask was associated with decreased risk versus a surgical mask (OR, 0.76). The studies had methodological limitations, however, and “evidence for various comparisons about mask use in health care settings and risk for SARS-CoV-2 remains insufficient,” the authors of the update wrote.
The Annals of Family Medicine review authors had no relevant disclosures. Dr. Chughtai has tested filtration of 3M masks and worked with CleanSpace Technology to research fit testing of respirators, and the 2015 randomized trial was funded by an Australian Research Council Linkage Grant with 3M as a partner on the grant. The Dec. 29, 2020, update was of a review that originally was supported by grants from the Agency for Healthcare Research Quality.
SOURCE: Daoud AK et al. Ann Fam Med. 2020 Jan 11. doi: 10.1370/afm.2640.
FROM ANNALS OF FAMILY MEDICINE
Feds authorize $3 billion to boost vaccine rollout
The CDC will send $3 billion to the states to boost a lagging national COVID-19 vaccination program.
The Department of Health and Human Services announced the new funding as only 30% of the more than 22 million doses of vaccine distributed in the U.S. has been injected into Americans’ arms.
Along with the $3 billion, HHS said another $19 billion is headed to states and jurisdictions to boost COVID-19 testing programs. The amount each state will receive will be determined by population.
The news comes days after President-elect Joe Biden said he planned to release all available doses of vaccine after he takes office on Jan. 20. The Trump administration has been holding back millions of doses to ensure supply of vaccine to provide the necessary second dose for those who received the first shot.
“This funding is another timely investment that will strengthen our nation’s efforts to stop the COVID-19 pandemic in America,” CDC Director Robert Redfield, MD, said in a statement. “Particularly now, it is crucial that states and communities have the resources they need to conduct testing, and to distribute and administer safe, high-quality COVID-19 vaccines safely and equitably.”
Federal officials and public health experts, however, expressed concerns this weekend about Biden’s plan.
Outgoing Trump administration officials and others said they worry that doing so will leave providers without enough second doses for people getting the two-shot vaccines.
If Biden releases all available doses and the vaccine-making process has an issue, they said, that could pose a supply risk.
“We have product that is going through QC right now – quality control – for sterility, identity check that we have tens and tens of millions of product. We always will. But batches fail. Sterility fails ... and then you don’t have a product for that second dose,” Alex Azar, secretary of health and human services, told the American Hospital Association on Jan. 8, according to CNN.
“And frankly, talking about that or encouraging that can really undermine a critical public health need, which is that people come back for their second vaccine,” he said.
One of the main roadblocks in the vaccine rollout has been administering the doses that have already been distributed. The U.S. has shipped 22.1 million doses, and 6.6 million first shots have been given, according to the latest CDC data updated Jan. 8. Mr. Azar and other federal health officials have encouraged states to use their current supply and expand vaccine access to more priority groups.
“We would be delighted to learn that jurisdictions have actually administered many more doses than they are presently reporting,” a spokesman for the U.S. Department of Health and Human Services told CNN. “We are encouraging jurisdictions to expand their priority groups as needed to ensure no vaccine is sitting on the shelf after having been delivered to the jurisdiction-directed locations.”
Releasing more vaccines for first doses could create ethical concerns as well, since people getting vaccines expect to get a second dose in the proper amount of time, according to The Week. Biden’s transition team said on Jan. 8 that he won’t delay the second dose but, instead, plans to ramp up production to stay on track.
To do this well, the federal government should create a coordinated vaccine strategy that sets expectations for an around-the-clock operation and help state and local vaccination programs meet their goals, Leana Wen, MD, a professor at George Washington University, wrote in an editorial for The Washington Post.
“The Biden team’s urgency around vaccinations is commendable,” she added in a Twitter post on Jan. 11. “I’d like to see a guarantee that every 1st dose given will be followed with a timely 2nd dose. Otherwise, there are ethical concerns that could add to vaccine hesitancy.”
Biden has pledged that 100 million doses will be administered in his first 100 days in office. He has grown frustrated as concerns grow that his administration could fall short of the promise, according to Politico. His coronavirus response team has noted several challenges, including what they say is a lack of long-term planning by the Trump administration and an initial refusal to share key information.
“We’re uncovering new information each day, and we’re unearthing – of course – more work to be done,” Vivek Murthy, MD, Biden’s nominee for surgeon general, told Politico.
The team has uncovered staffing shortages, technology problems, and issues with health care insurance coverage. The incoming Biden team has developed several initiatives, such as mobile vaccination units and new federal sites to give shots. It could take weeks to get the vaccine rollout on track, the news outlet reported.
“Will this be challenging? Absolutely,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Biden’s incoming chief medical adviser on the coronavirus, told Politico. “This is an unprecedented effort to vaccinate the entire country over a period of time that’s fighting against people dying at record numbers. To say it’s not a challenge would be unrealistic. Do I think it can be done? Yes.”
A version of this article first appeared on WebMD.com.
The CDC will send $3 billion to the states to boost a lagging national COVID-19 vaccination program.
The Department of Health and Human Services announced the new funding as only 30% of the more than 22 million doses of vaccine distributed in the U.S. has been injected into Americans’ arms.
Along with the $3 billion, HHS said another $19 billion is headed to states and jurisdictions to boost COVID-19 testing programs. The amount each state will receive will be determined by population.
The news comes days after President-elect Joe Biden said he planned to release all available doses of vaccine after he takes office on Jan. 20. The Trump administration has been holding back millions of doses to ensure supply of vaccine to provide the necessary second dose for those who received the first shot.
“This funding is another timely investment that will strengthen our nation’s efforts to stop the COVID-19 pandemic in America,” CDC Director Robert Redfield, MD, said in a statement. “Particularly now, it is crucial that states and communities have the resources they need to conduct testing, and to distribute and administer safe, high-quality COVID-19 vaccines safely and equitably.”
Federal officials and public health experts, however, expressed concerns this weekend about Biden’s plan.
Outgoing Trump administration officials and others said they worry that doing so will leave providers without enough second doses for people getting the two-shot vaccines.
If Biden releases all available doses and the vaccine-making process has an issue, they said, that could pose a supply risk.
“We have product that is going through QC right now – quality control – for sterility, identity check that we have tens and tens of millions of product. We always will. But batches fail. Sterility fails ... and then you don’t have a product for that second dose,” Alex Azar, secretary of health and human services, told the American Hospital Association on Jan. 8, according to CNN.
“And frankly, talking about that or encouraging that can really undermine a critical public health need, which is that people come back for their second vaccine,” he said.
One of the main roadblocks in the vaccine rollout has been administering the doses that have already been distributed. The U.S. has shipped 22.1 million doses, and 6.6 million first shots have been given, according to the latest CDC data updated Jan. 8. Mr. Azar and other federal health officials have encouraged states to use their current supply and expand vaccine access to more priority groups.
“We would be delighted to learn that jurisdictions have actually administered many more doses than they are presently reporting,” a spokesman for the U.S. Department of Health and Human Services told CNN. “We are encouraging jurisdictions to expand their priority groups as needed to ensure no vaccine is sitting on the shelf after having been delivered to the jurisdiction-directed locations.”
Releasing more vaccines for first doses could create ethical concerns as well, since people getting vaccines expect to get a second dose in the proper amount of time, according to The Week. Biden’s transition team said on Jan. 8 that he won’t delay the second dose but, instead, plans to ramp up production to stay on track.
To do this well, the federal government should create a coordinated vaccine strategy that sets expectations for an around-the-clock operation and help state and local vaccination programs meet their goals, Leana Wen, MD, a professor at George Washington University, wrote in an editorial for The Washington Post.
“The Biden team’s urgency around vaccinations is commendable,” she added in a Twitter post on Jan. 11. “I’d like to see a guarantee that every 1st dose given will be followed with a timely 2nd dose. Otherwise, there are ethical concerns that could add to vaccine hesitancy.”
Biden has pledged that 100 million doses will be administered in his first 100 days in office. He has grown frustrated as concerns grow that his administration could fall short of the promise, according to Politico. His coronavirus response team has noted several challenges, including what they say is a lack of long-term planning by the Trump administration and an initial refusal to share key information.
“We’re uncovering new information each day, and we’re unearthing – of course – more work to be done,” Vivek Murthy, MD, Biden’s nominee for surgeon general, told Politico.
The team has uncovered staffing shortages, technology problems, and issues with health care insurance coverage. The incoming Biden team has developed several initiatives, such as mobile vaccination units and new federal sites to give shots. It could take weeks to get the vaccine rollout on track, the news outlet reported.
“Will this be challenging? Absolutely,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Biden’s incoming chief medical adviser on the coronavirus, told Politico. “This is an unprecedented effort to vaccinate the entire country over a period of time that’s fighting against people dying at record numbers. To say it’s not a challenge would be unrealistic. Do I think it can be done? Yes.”
A version of this article first appeared on WebMD.com.
The CDC will send $3 billion to the states to boost a lagging national COVID-19 vaccination program.
The Department of Health and Human Services announced the new funding as only 30% of the more than 22 million doses of vaccine distributed in the U.S. has been injected into Americans’ arms.
Along with the $3 billion, HHS said another $19 billion is headed to states and jurisdictions to boost COVID-19 testing programs. The amount each state will receive will be determined by population.
The news comes days after President-elect Joe Biden said he planned to release all available doses of vaccine after he takes office on Jan. 20. The Trump administration has been holding back millions of doses to ensure supply of vaccine to provide the necessary second dose for those who received the first shot.
“This funding is another timely investment that will strengthen our nation’s efforts to stop the COVID-19 pandemic in America,” CDC Director Robert Redfield, MD, said in a statement. “Particularly now, it is crucial that states and communities have the resources they need to conduct testing, and to distribute and administer safe, high-quality COVID-19 vaccines safely and equitably.”
Federal officials and public health experts, however, expressed concerns this weekend about Biden’s plan.
Outgoing Trump administration officials and others said they worry that doing so will leave providers without enough second doses for people getting the two-shot vaccines.
If Biden releases all available doses and the vaccine-making process has an issue, they said, that could pose a supply risk.
“We have product that is going through QC right now – quality control – for sterility, identity check that we have tens and tens of millions of product. We always will. But batches fail. Sterility fails ... and then you don’t have a product for that second dose,” Alex Azar, secretary of health and human services, told the American Hospital Association on Jan. 8, according to CNN.
“And frankly, talking about that or encouraging that can really undermine a critical public health need, which is that people come back for their second vaccine,” he said.
One of the main roadblocks in the vaccine rollout has been administering the doses that have already been distributed. The U.S. has shipped 22.1 million doses, and 6.6 million first shots have been given, according to the latest CDC data updated Jan. 8. Mr. Azar and other federal health officials have encouraged states to use their current supply and expand vaccine access to more priority groups.
“We would be delighted to learn that jurisdictions have actually administered many more doses than they are presently reporting,” a spokesman for the U.S. Department of Health and Human Services told CNN. “We are encouraging jurisdictions to expand their priority groups as needed to ensure no vaccine is sitting on the shelf after having been delivered to the jurisdiction-directed locations.”
Releasing more vaccines for first doses could create ethical concerns as well, since people getting vaccines expect to get a second dose in the proper amount of time, according to The Week. Biden’s transition team said on Jan. 8 that he won’t delay the second dose but, instead, plans to ramp up production to stay on track.
To do this well, the federal government should create a coordinated vaccine strategy that sets expectations for an around-the-clock operation and help state and local vaccination programs meet their goals, Leana Wen, MD, a professor at George Washington University, wrote in an editorial for The Washington Post.
“The Biden team’s urgency around vaccinations is commendable,” she added in a Twitter post on Jan. 11. “I’d like to see a guarantee that every 1st dose given will be followed with a timely 2nd dose. Otherwise, there are ethical concerns that could add to vaccine hesitancy.”
Biden has pledged that 100 million doses will be administered in his first 100 days in office. He has grown frustrated as concerns grow that his administration could fall short of the promise, according to Politico. His coronavirus response team has noted several challenges, including what they say is a lack of long-term planning by the Trump administration and an initial refusal to share key information.
“We’re uncovering new information each day, and we’re unearthing – of course – more work to be done,” Vivek Murthy, MD, Biden’s nominee for surgeon general, told Politico.
The team has uncovered staffing shortages, technology problems, and issues with health care insurance coverage. The incoming Biden team has developed several initiatives, such as mobile vaccination units and new federal sites to give shots. It could take weeks to get the vaccine rollout on track, the news outlet reported.
“Will this be challenging? Absolutely,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Biden’s incoming chief medical adviser on the coronavirus, told Politico. “This is an unprecedented effort to vaccinate the entire country over a period of time that’s fighting against people dying at record numbers. To say it’s not a challenge would be unrealistic. Do I think it can be done? Yes.”
A version of this article first appeared on WebMD.com.
Physicians react: Doctors worry about patients reading their clinical notes
Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.
As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.
The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
Potentially more legal woes for physicians?
A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.
“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.
She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.
Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?
As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”
The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.
“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”
One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”
Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.
One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
Will Open Notes erode patient communication?
One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.
“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
Some physicians envision positive developments
Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.
A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.
“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.
“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”
One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.
Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”
Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”
“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”
“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”
A version of this article first appeared on Medscape.com.
Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.
As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.
The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
Potentially more legal woes for physicians?
A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.
“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.
She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.
Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?
As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”
The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.
“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”
One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”
Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.
One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
Will Open Notes erode patient communication?
One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.
“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
Some physicians envision positive developments
Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.
A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.
“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.
“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”
One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.
Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”
Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”
“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”
“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”
A version of this article first appeared on Medscape.com.
Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.
As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.
The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
Potentially more legal woes for physicians?
A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.
“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.
She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.
Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?
As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”
The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.
“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”
One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”
Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.
One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
Will Open Notes erode patient communication?
One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.
“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
Some physicians envision positive developments
Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.
A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.
“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.
“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”
One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.
Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”
Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”
“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”
“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”
A version of this article first appeared on Medscape.com.
Ultrasound ablation for Parkinson’s disease: Benefit limited by adverse effects
including dyskinesias and other neurologic complications, in a new randomized, sham-controlled trial.
“Longer-term and larger trials are needed to determine the role of focused ultrasound subthalamotomy in the management of Parkinson’s disease and its effect as compared with other available treatments, including deep-brain stimulation,” the authors concluded.
The trial was published online Dec.24, 2020, in the New England Journal of Medicine.
An accompanying editorial concluded that the high rate of adverse events and the lack of ability to modulate treatment over time to treat prominent tremor “raise questions about the appropriate implementation of focused ultrasound–produced lesions for the treatment of Parkinson’s disease.”
A scalpel-free alternative to brain surgery
The study authors, led by Raul Martinez-Fernandez, MD, PhD, University Hospital HM Puerta del Sur, Mostoles, Spain, explained that, in severe cases of refractory motor manifestations such as tremor and motor complications, a neurosurgical approach using deep-brain stimulation of the subthalamic nucleus can be used. But to avoid craniotomy and electrode penetration, MRI-guided focused ultrasound for the ablation of deep-brain structures, including the subthalamic nucleus, is being investigated as a treatment for Parkinson’s disease.
Patients are potential candidates for ultrasound ablation if they have prominently asymmetric parkinsonism, if they are not considered to be clinically suitable candidates for surgery because of contraindications, or if they are reluctant to undergo a brain operation or to have an implanted device.
The current trial involved 40 patients with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery. They were randomly assigned in a 2:1 ratio to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure.
Results showed that the mean Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) motor score for the more affected side – which was the primary endpoint – decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points); and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points). The between-group difference was 8.1 points (P < .001).
The change from baseline in the MDS-UPDRS III score for the more affected side in patients who underwent active treatment varied, ranging from 5% to 95%; the changes were qualitatively more evident for reduction of tremor and rigidity than for bradykinesia.
Adverse events in the active-treatment group were the following:
- Dyskinesia in the off-medication state in six patients and in the on-medication state in six, which persisted in three and one, respectively, at 4 months.
- Weakness on the treated side in five patients, which persisted in two at 4 months.
- Speech disturbance in 15 patients, which persisted in 3 at 4 months.
- Facial weakness in three patients, which persisted in one at 4 months.
- in 13 patients, which persisted in two at 4 months.
In six patients in the active-treatment group, some of these deficits were present at 12 months.
The researchers noted that an approach that has been suggested to reduce the risk of dyskinesias has been to extend ablations dorsal to the subthalamic nucleus in order to interrupt the pallidothalamic-projecting neurons.
The study also showed a greater reduction in the use of dopaminergic medication in the active-treatment group versus the control group, but the researchers noted that the 95% confidence intervals for this and other secondary outcomes were not adjusted for multiple comparisons, so no definite conclusions can be drawn from these data.
They also pointed out that subthalamotomy was performed in one hemisphere, and the natural evolution of Parkinson’s disease eventually leads to motor impairment on both sides of the body in most patients.
“The likely need for an increase in the daily dose of levodopa equivalent to maintain function on the untreated side of the body could lead to the development of dyskinesias on the treated side. However, the few open-label studies of long-term (≥36 months) follow-up of radiofrequency subthalamotomy performed in one hemisphere do not provide support for this concern,” they said.
An important step, but improvements are needed
In an accompanying editorial, Joel S. Perlmutter, MD, and Mwiza Ushe, MD, Washington University, St. Louis, noted that surgical deep brain stimulation of the left and right subthalamic nuclei has shown a reduction in the severity of motor signs of 40%-60% and a reduction in medication use of up to 50%. But this technique involves a small craniotomy with implantation of stimulating electrodes, which has a 1%-5% risk of major adverse events such as hemorrhage, stroke, or infection.
Less severe complications include dystonia, dysarthria, gait impairment, dyskinesia, swallowing dysfunction, or change in verbal fluency; however, modification of the device programming may alleviate these effects. Nevertheless, some patients are wary of the implantation surgery and hardware and therefore decline to undergo deep-brain stimulation, the editorialists explained.
“The development of alternative procedures to deep-brain stimulation is important to the field of Parkinson’s disease treatment. The current trial begins the path to that goal, and improvements in targeting may improve the risk-benefit ratio and permit the use of lesions in both hemispheres, which would widen the population of eligible patients,” Dr. Perlmutter and Dr. Ushe wrote.
They pointed out that limiting the treatment to one side of the brain by ultrasound-produced lesioning constrains the application, since most patients with Parkinson’s disease have progression of symptoms on both sides of the body.
“The potential advantages and limitations of focused ultrasound–produced lesioning should be discussed with patients. We hope that improved technique will reduce the associated risks and increase the applicability of this provocative procedure,” the editorialists concluded.
This study was supported by Insightec, the Focused Ultrasound Foundation, Fundacion MAPFRE, Fundacion Hospitales de Madrid, and the University of Virginia Center of Excellence. Dr. Martinez-Fernandez reported receiving for consultancy fees for Insightec. Dr. Ushe reported non-financial support for Abbott outside the submitted work. Dr. Perlmutter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
including dyskinesias and other neurologic complications, in a new randomized, sham-controlled trial.
“Longer-term and larger trials are needed to determine the role of focused ultrasound subthalamotomy in the management of Parkinson’s disease and its effect as compared with other available treatments, including deep-brain stimulation,” the authors concluded.
The trial was published online Dec.24, 2020, in the New England Journal of Medicine.
An accompanying editorial concluded that the high rate of adverse events and the lack of ability to modulate treatment over time to treat prominent tremor “raise questions about the appropriate implementation of focused ultrasound–produced lesions for the treatment of Parkinson’s disease.”
A scalpel-free alternative to brain surgery
The study authors, led by Raul Martinez-Fernandez, MD, PhD, University Hospital HM Puerta del Sur, Mostoles, Spain, explained that, in severe cases of refractory motor manifestations such as tremor and motor complications, a neurosurgical approach using deep-brain stimulation of the subthalamic nucleus can be used. But to avoid craniotomy and electrode penetration, MRI-guided focused ultrasound for the ablation of deep-brain structures, including the subthalamic nucleus, is being investigated as a treatment for Parkinson’s disease.
Patients are potential candidates for ultrasound ablation if they have prominently asymmetric parkinsonism, if they are not considered to be clinically suitable candidates for surgery because of contraindications, or if they are reluctant to undergo a brain operation or to have an implanted device.
The current trial involved 40 patients with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery. They were randomly assigned in a 2:1 ratio to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure.
Results showed that the mean Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) motor score for the more affected side – which was the primary endpoint – decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points); and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points). The between-group difference was 8.1 points (P < .001).
The change from baseline in the MDS-UPDRS III score for the more affected side in patients who underwent active treatment varied, ranging from 5% to 95%; the changes were qualitatively more evident for reduction of tremor and rigidity than for bradykinesia.
Adverse events in the active-treatment group were the following:
- Dyskinesia in the off-medication state in six patients and in the on-medication state in six, which persisted in three and one, respectively, at 4 months.
- Weakness on the treated side in five patients, which persisted in two at 4 months.
- Speech disturbance in 15 patients, which persisted in 3 at 4 months.
- Facial weakness in three patients, which persisted in one at 4 months.
- in 13 patients, which persisted in two at 4 months.
In six patients in the active-treatment group, some of these deficits were present at 12 months.
The researchers noted that an approach that has been suggested to reduce the risk of dyskinesias has been to extend ablations dorsal to the subthalamic nucleus in order to interrupt the pallidothalamic-projecting neurons.
The study also showed a greater reduction in the use of dopaminergic medication in the active-treatment group versus the control group, but the researchers noted that the 95% confidence intervals for this and other secondary outcomes were not adjusted for multiple comparisons, so no definite conclusions can be drawn from these data.
They also pointed out that subthalamotomy was performed in one hemisphere, and the natural evolution of Parkinson’s disease eventually leads to motor impairment on both sides of the body in most patients.
“The likely need for an increase in the daily dose of levodopa equivalent to maintain function on the untreated side of the body could lead to the development of dyskinesias on the treated side. However, the few open-label studies of long-term (≥36 months) follow-up of radiofrequency subthalamotomy performed in one hemisphere do not provide support for this concern,” they said.
An important step, but improvements are needed
In an accompanying editorial, Joel S. Perlmutter, MD, and Mwiza Ushe, MD, Washington University, St. Louis, noted that surgical deep brain stimulation of the left and right subthalamic nuclei has shown a reduction in the severity of motor signs of 40%-60% and a reduction in medication use of up to 50%. But this technique involves a small craniotomy with implantation of stimulating electrodes, which has a 1%-5% risk of major adverse events such as hemorrhage, stroke, or infection.
Less severe complications include dystonia, dysarthria, gait impairment, dyskinesia, swallowing dysfunction, or change in verbal fluency; however, modification of the device programming may alleviate these effects. Nevertheless, some patients are wary of the implantation surgery and hardware and therefore decline to undergo deep-brain stimulation, the editorialists explained.
“The development of alternative procedures to deep-brain stimulation is important to the field of Parkinson’s disease treatment. The current trial begins the path to that goal, and improvements in targeting may improve the risk-benefit ratio and permit the use of lesions in both hemispheres, which would widen the population of eligible patients,” Dr. Perlmutter and Dr. Ushe wrote.
They pointed out that limiting the treatment to one side of the brain by ultrasound-produced lesioning constrains the application, since most patients with Parkinson’s disease have progression of symptoms on both sides of the body.
“The potential advantages and limitations of focused ultrasound–produced lesioning should be discussed with patients. We hope that improved technique will reduce the associated risks and increase the applicability of this provocative procedure,” the editorialists concluded.
This study was supported by Insightec, the Focused Ultrasound Foundation, Fundacion MAPFRE, Fundacion Hospitales de Madrid, and the University of Virginia Center of Excellence. Dr. Martinez-Fernandez reported receiving for consultancy fees for Insightec. Dr. Ushe reported non-financial support for Abbott outside the submitted work. Dr. Perlmutter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
including dyskinesias and other neurologic complications, in a new randomized, sham-controlled trial.
“Longer-term and larger trials are needed to determine the role of focused ultrasound subthalamotomy in the management of Parkinson’s disease and its effect as compared with other available treatments, including deep-brain stimulation,” the authors concluded.
The trial was published online Dec.24, 2020, in the New England Journal of Medicine.
An accompanying editorial concluded that the high rate of adverse events and the lack of ability to modulate treatment over time to treat prominent tremor “raise questions about the appropriate implementation of focused ultrasound–produced lesions for the treatment of Parkinson’s disease.”
A scalpel-free alternative to brain surgery
The study authors, led by Raul Martinez-Fernandez, MD, PhD, University Hospital HM Puerta del Sur, Mostoles, Spain, explained that, in severe cases of refractory motor manifestations such as tremor and motor complications, a neurosurgical approach using deep-brain stimulation of the subthalamic nucleus can be used. But to avoid craniotomy and electrode penetration, MRI-guided focused ultrasound for the ablation of deep-brain structures, including the subthalamic nucleus, is being investigated as a treatment for Parkinson’s disease.
Patients are potential candidates for ultrasound ablation if they have prominently asymmetric parkinsonism, if they are not considered to be clinically suitable candidates for surgery because of contraindications, or if they are reluctant to undergo a brain operation or to have an implanted device.
The current trial involved 40 patients with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery. They were randomly assigned in a 2:1 ratio to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure.
Results showed that the mean Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) motor score for the more affected side – which was the primary endpoint – decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points); and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points). The between-group difference was 8.1 points (P < .001).
The change from baseline in the MDS-UPDRS III score for the more affected side in patients who underwent active treatment varied, ranging from 5% to 95%; the changes were qualitatively more evident for reduction of tremor and rigidity than for bradykinesia.
Adverse events in the active-treatment group were the following:
- Dyskinesia in the off-medication state in six patients and in the on-medication state in six, which persisted in three and one, respectively, at 4 months.
- Weakness on the treated side in five patients, which persisted in two at 4 months.
- Speech disturbance in 15 patients, which persisted in 3 at 4 months.
- Facial weakness in three patients, which persisted in one at 4 months.
- in 13 patients, which persisted in two at 4 months.
In six patients in the active-treatment group, some of these deficits were present at 12 months.
The researchers noted that an approach that has been suggested to reduce the risk of dyskinesias has been to extend ablations dorsal to the subthalamic nucleus in order to interrupt the pallidothalamic-projecting neurons.
The study also showed a greater reduction in the use of dopaminergic medication in the active-treatment group versus the control group, but the researchers noted that the 95% confidence intervals for this and other secondary outcomes were not adjusted for multiple comparisons, so no definite conclusions can be drawn from these data.
They also pointed out that subthalamotomy was performed in one hemisphere, and the natural evolution of Parkinson’s disease eventually leads to motor impairment on both sides of the body in most patients.
“The likely need for an increase in the daily dose of levodopa equivalent to maintain function on the untreated side of the body could lead to the development of dyskinesias on the treated side. However, the few open-label studies of long-term (≥36 months) follow-up of radiofrequency subthalamotomy performed in one hemisphere do not provide support for this concern,” they said.
An important step, but improvements are needed
In an accompanying editorial, Joel S. Perlmutter, MD, and Mwiza Ushe, MD, Washington University, St. Louis, noted that surgical deep brain stimulation of the left and right subthalamic nuclei has shown a reduction in the severity of motor signs of 40%-60% and a reduction in medication use of up to 50%. But this technique involves a small craniotomy with implantation of stimulating electrodes, which has a 1%-5% risk of major adverse events such as hemorrhage, stroke, or infection.
Less severe complications include dystonia, dysarthria, gait impairment, dyskinesia, swallowing dysfunction, or change in verbal fluency; however, modification of the device programming may alleviate these effects. Nevertheless, some patients are wary of the implantation surgery and hardware and therefore decline to undergo deep-brain stimulation, the editorialists explained.
“The development of alternative procedures to deep-brain stimulation is important to the field of Parkinson’s disease treatment. The current trial begins the path to that goal, and improvements in targeting may improve the risk-benefit ratio and permit the use of lesions in both hemispheres, which would widen the population of eligible patients,” Dr. Perlmutter and Dr. Ushe wrote.
They pointed out that limiting the treatment to one side of the brain by ultrasound-produced lesioning constrains the application, since most patients with Parkinson’s disease have progression of symptoms on both sides of the body.
“The potential advantages and limitations of focused ultrasound–produced lesioning should be discussed with patients. We hope that improved technique will reduce the associated risks and increase the applicability of this provocative procedure,” the editorialists concluded.
This study was supported by Insightec, the Focused Ultrasound Foundation, Fundacion MAPFRE, Fundacion Hospitales de Madrid, and the University of Virginia Center of Excellence. Dr. Martinez-Fernandez reported receiving for consultancy fees for Insightec. Dr. Ushe reported non-financial support for Abbott outside the submitted work. Dr. Perlmutter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Guidance issued on COVID vaccine use in patients with dermal fillers
outlining the potential risk and clinical relevance.
The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.
“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.
The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.
“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.
In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.
The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.
“The good news is that these will go away,” Dr. Cox said.
The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.
Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.
“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.
As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,
Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.
The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.
As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
This article was updated 1/7/21.
outlining the potential risk and clinical relevance.
The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.
“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.
The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.
“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.
In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.
The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.
“The good news is that these will go away,” Dr. Cox said.
The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.
Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.
“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.
As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,
Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.
The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.
As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
This article was updated 1/7/21.
outlining the potential risk and clinical relevance.
The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.
“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.
The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.
“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.
In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.
The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.
“The good news is that these will go away,” Dr. Cox said.
The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.
Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.
“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.
As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,
Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.
The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.
As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.
This article was updated 1/7/21.
Which imaging criteria identify progressive forms of MS?
The role of imaging in diagnosing progressive multiple sclerosis (MS) and in assessing prognosis is the subject of a new review.
MRI is central in the diagnostic work-up of patients suspected of having MS, given its high sensitivity in detecting disease dissemination in space and over time and its notable ability to exclude mimics of MS, the authors noted. However, diagnosis of primary progressive MS remains challenging and is only possible retrospectively on the basis of clinical assessment.
they wrote.
Diagnosis of progressive MS is limited by difficulties in distinguishing accumulating disability caused by inflammatory disease activity from that attributable to degenerative processes associated with secondary progressive MS. Moreover, there are no accepted clinical criteria for diagnosing secondary progressive MS, the authors explained.
This need has promoted extensive research in the field of imaging, facilitated by definition of novel MRI sequences, to identify imaging features reflecting pathophysiological mechanisms relevant to the pathobiology of progressive MS, the authors said.
The current review reports the conclusions of a workshop held in Milan in November 2019, at which an expert panel of neurologists and neuroradiologists addressed the role of MRI in progressive MS.
Massimo Filippi, MD, IRCCS San Raffaele Scientific Institute, Milan, was the lead author of the review, which was published online Dec. 14, 2020, in JAMA Neurology.
The authors concluded that no definitive, qualitative clinical, immunologic, histopathologic, or neuroimaging features differentiate primary progressive and secondary progressive forms of MS; both are characterized by neurodegenerative phenomena and a gradual and irreversible accumulation of clinical disability, which is also affected by aging and comorbidities.
A definitive diagnosis of primary progressive MS is more difficult than a diagnosis of relapsing remitting MS; in part, primary progressive MS is a diagnosis of exclusion because it can be mimicked by other conditions clinically and radiologically, the authors noted.
The writers did report that, although nonspecific, some spinal cord imaging features are typical of primary progressive MS. These include diffuse abnormalities and lesions involving gray matter and two or more white-matter columns, but confirmation of this is required.
In patients with primary progressive MS and those with relapse-onset MS, MRI features at disease onset predict long-term disability and a progressive disease course. These features include lesions in critical central nervous system regions (i.e., spinal cord, infratentorial regions, and gray matter) and high inflammatory activity in the first years after disease onset. These measures are evaluable in clinical practice, the authors said.
In patients with established MS, gray-matter involvement and neurodegeneration are associated with accelerated clinical worsening; however, detection validation and standardization need to be implemented at the individual patient level, they commented.
Novel candidate imaging biomarkers, such as subpial demyelination, and the presence of slowly expanding lesions or paramagnetic rim lesions may identify progressive MS but should be further investigated, they added.
Discovery of MRI markers capable of detecting evolution from relapsing-remitting to secondary progressive MS remains an unmet need that will probably require multiparametric MRI studies, because it is unlikely that a single MRI method will be able to allow clinicians to optimally distinguish among these stages, the authors said.
The contribution of these promising MRI measures combined with other biomarkers, such as quantification of serum neurofilament light chain levels or optical coherence tomography assessment, should be explored to improve the identification of patients with progressive MS, they concluded.
‘A comprehensive review’
In a comment, Jeffrey A. Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, said the article is a comprehensive review of the pathologic mechanisms that underlie progression in MS and the proxy measures of those processes (brain and spinal cord MRI, PET, optical coherence tomography, and biomarkers).
“The paper reports there is no qualitative difference between relapsing remitting and progressive MS; rather, the difference is quantitative,” Dr. Cohen noted. “In other words, the processes that underlie progression are present from the earliest stages of MS, becoming more prominent over time.”
The apparent transition to progressive MS, he added, “rather than representing a ‘transition,’ instead results from the accumulation of pathology over time, a shift from focal lesions to diffuse inflammation and damage, and unmasking of the damage due to decreased resiliency due to aging and failure of compensatory mechanisms (neuroplasticity and remyelination).”
Also commenting, Edward Fox, MD, director, MS Clinic of Central Texas and clinical associate professor, University of Texas, Austin, explained that loss of tissue is the main driver of progressive MS.
“We all look at imaging to confirm that the progressive symptoms expressed by the patient are related to demyelinating disease,” he said. “When I see MRI of the spinal cord showing multifocal lesions, especially if localized atrophy is seen in a region of the cord, I expect to hear a history of progressive deficits in gait and other signs of disability.”
Dr. Fox noted that, on MRI of the brain, gray matter atrophy both cortically and in the deep gray structures usually manifests as cognitive slowing and poorer performance in work and social situations.
“We hope that other biomarkers, such as neurofilament light chain, will add to this body of knowledge and give us a better grasp of the definition of neurodegeneration to confirm the clinical and radiographic findings,” he added.
Dr. Filippi has received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi, Genzyme, Takeda, and Teva Pharmaceutical Industries; and research support from ARiSLA, Biogen Idec, Fondazione Italiana Sclerosi Multipla, Italian Ministry of Health, Merck Serono, Novartis, Roche, and Teva.
A version of this article first appeared on Medscape.com.
The role of imaging in diagnosing progressive multiple sclerosis (MS) and in assessing prognosis is the subject of a new review.
MRI is central in the diagnostic work-up of patients suspected of having MS, given its high sensitivity in detecting disease dissemination in space and over time and its notable ability to exclude mimics of MS, the authors noted. However, diagnosis of primary progressive MS remains challenging and is only possible retrospectively on the basis of clinical assessment.
they wrote.
Diagnosis of progressive MS is limited by difficulties in distinguishing accumulating disability caused by inflammatory disease activity from that attributable to degenerative processes associated with secondary progressive MS. Moreover, there are no accepted clinical criteria for diagnosing secondary progressive MS, the authors explained.
This need has promoted extensive research in the field of imaging, facilitated by definition of novel MRI sequences, to identify imaging features reflecting pathophysiological mechanisms relevant to the pathobiology of progressive MS, the authors said.
The current review reports the conclusions of a workshop held in Milan in November 2019, at which an expert panel of neurologists and neuroradiologists addressed the role of MRI in progressive MS.
Massimo Filippi, MD, IRCCS San Raffaele Scientific Institute, Milan, was the lead author of the review, which was published online Dec. 14, 2020, in JAMA Neurology.
The authors concluded that no definitive, qualitative clinical, immunologic, histopathologic, or neuroimaging features differentiate primary progressive and secondary progressive forms of MS; both are characterized by neurodegenerative phenomena and a gradual and irreversible accumulation of clinical disability, which is also affected by aging and comorbidities.
A definitive diagnosis of primary progressive MS is more difficult than a diagnosis of relapsing remitting MS; in part, primary progressive MS is a diagnosis of exclusion because it can be mimicked by other conditions clinically and radiologically, the authors noted.
The writers did report that, although nonspecific, some spinal cord imaging features are typical of primary progressive MS. These include diffuse abnormalities and lesions involving gray matter and two or more white-matter columns, but confirmation of this is required.
In patients with primary progressive MS and those with relapse-onset MS, MRI features at disease onset predict long-term disability and a progressive disease course. These features include lesions in critical central nervous system regions (i.e., spinal cord, infratentorial regions, and gray matter) and high inflammatory activity in the first years after disease onset. These measures are evaluable in clinical practice, the authors said.
In patients with established MS, gray-matter involvement and neurodegeneration are associated with accelerated clinical worsening; however, detection validation and standardization need to be implemented at the individual patient level, they commented.
Novel candidate imaging biomarkers, such as subpial demyelination, and the presence of slowly expanding lesions or paramagnetic rim lesions may identify progressive MS but should be further investigated, they added.
Discovery of MRI markers capable of detecting evolution from relapsing-remitting to secondary progressive MS remains an unmet need that will probably require multiparametric MRI studies, because it is unlikely that a single MRI method will be able to allow clinicians to optimally distinguish among these stages, the authors said.
The contribution of these promising MRI measures combined with other biomarkers, such as quantification of serum neurofilament light chain levels or optical coherence tomography assessment, should be explored to improve the identification of patients with progressive MS, they concluded.
‘A comprehensive review’
In a comment, Jeffrey A. Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, said the article is a comprehensive review of the pathologic mechanisms that underlie progression in MS and the proxy measures of those processes (brain and spinal cord MRI, PET, optical coherence tomography, and biomarkers).
“The paper reports there is no qualitative difference between relapsing remitting and progressive MS; rather, the difference is quantitative,” Dr. Cohen noted. “In other words, the processes that underlie progression are present from the earliest stages of MS, becoming more prominent over time.”
The apparent transition to progressive MS, he added, “rather than representing a ‘transition,’ instead results from the accumulation of pathology over time, a shift from focal lesions to diffuse inflammation and damage, and unmasking of the damage due to decreased resiliency due to aging and failure of compensatory mechanisms (neuroplasticity and remyelination).”
Also commenting, Edward Fox, MD, director, MS Clinic of Central Texas and clinical associate professor, University of Texas, Austin, explained that loss of tissue is the main driver of progressive MS.
“We all look at imaging to confirm that the progressive symptoms expressed by the patient are related to demyelinating disease,” he said. “When I see MRI of the spinal cord showing multifocal lesions, especially if localized atrophy is seen in a region of the cord, I expect to hear a history of progressive deficits in gait and other signs of disability.”
Dr. Fox noted that, on MRI of the brain, gray matter atrophy both cortically and in the deep gray structures usually manifests as cognitive slowing and poorer performance in work and social situations.
“We hope that other biomarkers, such as neurofilament light chain, will add to this body of knowledge and give us a better grasp of the definition of neurodegeneration to confirm the clinical and radiographic findings,” he added.
Dr. Filippi has received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi, Genzyme, Takeda, and Teva Pharmaceutical Industries; and research support from ARiSLA, Biogen Idec, Fondazione Italiana Sclerosi Multipla, Italian Ministry of Health, Merck Serono, Novartis, Roche, and Teva.
A version of this article first appeared on Medscape.com.
The role of imaging in diagnosing progressive multiple sclerosis (MS) and in assessing prognosis is the subject of a new review.
MRI is central in the diagnostic work-up of patients suspected of having MS, given its high sensitivity in detecting disease dissemination in space and over time and its notable ability to exclude mimics of MS, the authors noted. However, diagnosis of primary progressive MS remains challenging and is only possible retrospectively on the basis of clinical assessment.
they wrote.
Diagnosis of progressive MS is limited by difficulties in distinguishing accumulating disability caused by inflammatory disease activity from that attributable to degenerative processes associated with secondary progressive MS. Moreover, there are no accepted clinical criteria for diagnosing secondary progressive MS, the authors explained.
This need has promoted extensive research in the field of imaging, facilitated by definition of novel MRI sequences, to identify imaging features reflecting pathophysiological mechanisms relevant to the pathobiology of progressive MS, the authors said.
The current review reports the conclusions of a workshop held in Milan in November 2019, at which an expert panel of neurologists and neuroradiologists addressed the role of MRI in progressive MS.
Massimo Filippi, MD, IRCCS San Raffaele Scientific Institute, Milan, was the lead author of the review, which was published online Dec. 14, 2020, in JAMA Neurology.
The authors concluded that no definitive, qualitative clinical, immunologic, histopathologic, or neuroimaging features differentiate primary progressive and secondary progressive forms of MS; both are characterized by neurodegenerative phenomena and a gradual and irreversible accumulation of clinical disability, which is also affected by aging and comorbidities.
A definitive diagnosis of primary progressive MS is more difficult than a diagnosis of relapsing remitting MS; in part, primary progressive MS is a diagnosis of exclusion because it can be mimicked by other conditions clinically and radiologically, the authors noted.
The writers did report that, although nonspecific, some spinal cord imaging features are typical of primary progressive MS. These include diffuse abnormalities and lesions involving gray matter and two or more white-matter columns, but confirmation of this is required.
In patients with primary progressive MS and those with relapse-onset MS, MRI features at disease onset predict long-term disability and a progressive disease course. These features include lesions in critical central nervous system regions (i.e., spinal cord, infratentorial regions, and gray matter) and high inflammatory activity in the first years after disease onset. These measures are evaluable in clinical practice, the authors said.
In patients with established MS, gray-matter involvement and neurodegeneration are associated with accelerated clinical worsening; however, detection validation and standardization need to be implemented at the individual patient level, they commented.
Novel candidate imaging biomarkers, such as subpial demyelination, and the presence of slowly expanding lesions or paramagnetic rim lesions may identify progressive MS but should be further investigated, they added.
Discovery of MRI markers capable of detecting evolution from relapsing-remitting to secondary progressive MS remains an unmet need that will probably require multiparametric MRI studies, because it is unlikely that a single MRI method will be able to allow clinicians to optimally distinguish among these stages, the authors said.
The contribution of these promising MRI measures combined with other biomarkers, such as quantification of serum neurofilament light chain levels or optical coherence tomography assessment, should be explored to improve the identification of patients with progressive MS, they concluded.
‘A comprehensive review’
In a comment, Jeffrey A. Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, said the article is a comprehensive review of the pathologic mechanisms that underlie progression in MS and the proxy measures of those processes (brain and spinal cord MRI, PET, optical coherence tomography, and biomarkers).
“The paper reports there is no qualitative difference between relapsing remitting and progressive MS; rather, the difference is quantitative,” Dr. Cohen noted. “In other words, the processes that underlie progression are present from the earliest stages of MS, becoming more prominent over time.”
The apparent transition to progressive MS, he added, “rather than representing a ‘transition,’ instead results from the accumulation of pathology over time, a shift from focal lesions to diffuse inflammation and damage, and unmasking of the damage due to decreased resiliency due to aging and failure of compensatory mechanisms (neuroplasticity and remyelination).”
Also commenting, Edward Fox, MD, director, MS Clinic of Central Texas and clinical associate professor, University of Texas, Austin, explained that loss of tissue is the main driver of progressive MS.
“We all look at imaging to confirm that the progressive symptoms expressed by the patient are related to demyelinating disease,” he said. “When I see MRI of the spinal cord showing multifocal lesions, especially if localized atrophy is seen in a region of the cord, I expect to hear a history of progressive deficits in gait and other signs of disability.”
Dr. Fox noted that, on MRI of the brain, gray matter atrophy both cortically and in the deep gray structures usually manifests as cognitive slowing and poorer performance in work and social situations.
“We hope that other biomarkers, such as neurofilament light chain, will add to this body of knowledge and give us a better grasp of the definition of neurodegeneration to confirm the clinical and radiographic findings,” he added.
Dr. Filippi has received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi, Genzyme, Takeda, and Teva Pharmaceutical Industries; and research support from ARiSLA, Biogen Idec, Fondazione Italiana Sclerosi Multipla, Italian Ministry of Health, Merck Serono, Novartis, Roche, and Teva.
A version of this article first appeared on Medscape.com.
Microvascular injury of brain, olfactory bulb seen in COVID-19
new research suggests.
Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.
Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.
There was no evidence of viral infection, including SARS-CoV-2.
“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
Interpret with caution
The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.
An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.
Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.
For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.
The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.
In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.
“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.
SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.
In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.
Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.
In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.
The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.
Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.
The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.
A version of this article first appeared on Medscape.com.
new research suggests.
Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.
Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.
There was no evidence of viral infection, including SARS-CoV-2.
“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
Interpret with caution
The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.
An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.
Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.
For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.
The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.
In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.
“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.
SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.
In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.
Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.
In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.
The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.
Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.
The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.
A version of this article first appeared on Medscape.com.
new research suggests.
Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.
Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.
There was no evidence of viral infection, including SARS-CoV-2.
“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
Interpret with caution
The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.
An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.
Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.
For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.
The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.
In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.
“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.
SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.
In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.
Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.
In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.
The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.
Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.
The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.
A version of this article first appeared on Medscape.com.