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Tips for connecting with your patients
It is a tough time to be a doctor. With the stresses of the pandemic, the continued unfettered rise of insurance company BS, and so many medical groups being bought up that we often don’t even know who makes the decisions, the patient can sometimes be hidden in the equation.
Be curious
When physicians are curious about why patients have symptoms, how those symptoms will affect their lives, and how worried the patient is about them, patients feel cared about.
Ascertaining how concerned patients are about their symptoms will help you make decisions on whether symptoms you are not concerned about actually need to be treated.
Limit use of EHRs when possible
Use of the electronic health record during visits is essential, but focusing on it too much can put a barrier between the physician and the patient.
Marmor and colleagues found there is an inverse relationship between time spent on the EHR by a patient’s physician and the patient’s satisfaction.1
Eye contact with the patient is important, especially when patients are sharing concerns they are scared about and upsetting experiences. There can be awkward pauses when looking things up on the EHR. Fill those pauses by explaining to the patient what you are doing, or chatting with the patient.
Consider teaching medical students
When a medical student works with you, it doubles the time the patient gets with a concerned listener. Students also can do a great job with timely follow-up and checking in with worried patients.
By having the student present in the clinic room, with the patient present, the patient can really feel heard. The student shares all the details the patient shared, and now their physician is hearing an organized, thoughtful report of the patients concerns.
In fact, I was involved in a study that showed that patients preferred in room presentations, and that they were more satisfied when students presented in the room.2
Use healing words
Some words carry loaded emotions. The word chronic, for example, has negative connotations, whereas the term persisting does not.
I will often ask patients how long they have been suffering from a symptom to imply my concern for what they are going through. The term “chief complaint” is outdated, and upsets patients when they see it in their medical record.
As a patient of mine once said to me: “I never complained about that problem, I just brought it to your attention.” No one wants to be seen as a complainer. Substituting the word concern for complaint works well.
Explain as you examine
People love to hear the term normal. When you are examining a patient, let them know when findings are normal.
I also find it helpful to explain to patients why I am doing certain physical exam maneuvers. This helps them assess how thorough we are in our thought process.
When patients feel their physicians are thorough, they have more confidence in them.
In summary
- Be curious.
- Do not overly focus on the EHR.
- Consider teaching a medical student.
- Be careful of word choice.
- “Overexplain” the physical exam.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Marmor RA et al. Appl Clin Inform. 2018 Jan;9(1):11-4.
2. Rogers HD et al. Acad Med. 2003 Sep;78(9):945-9.
It is a tough time to be a doctor. With the stresses of the pandemic, the continued unfettered rise of insurance company BS, and so many medical groups being bought up that we often don’t even know who makes the decisions, the patient can sometimes be hidden in the equation.
Be curious
When physicians are curious about why patients have symptoms, how those symptoms will affect their lives, and how worried the patient is about them, patients feel cared about.
Ascertaining how concerned patients are about their symptoms will help you make decisions on whether symptoms you are not concerned about actually need to be treated.
Limit use of EHRs when possible
Use of the electronic health record during visits is essential, but focusing on it too much can put a barrier between the physician and the patient.
Marmor and colleagues found there is an inverse relationship between time spent on the EHR by a patient’s physician and the patient’s satisfaction.1
Eye contact with the patient is important, especially when patients are sharing concerns they are scared about and upsetting experiences. There can be awkward pauses when looking things up on the EHR. Fill those pauses by explaining to the patient what you are doing, or chatting with the patient.
Consider teaching medical students
When a medical student works with you, it doubles the time the patient gets with a concerned listener. Students also can do a great job with timely follow-up and checking in with worried patients.
By having the student present in the clinic room, with the patient present, the patient can really feel heard. The student shares all the details the patient shared, and now their physician is hearing an organized, thoughtful report of the patients concerns.
In fact, I was involved in a study that showed that patients preferred in room presentations, and that they were more satisfied when students presented in the room.2
Use healing words
Some words carry loaded emotions. The word chronic, for example, has negative connotations, whereas the term persisting does not.
I will often ask patients how long they have been suffering from a symptom to imply my concern for what they are going through. The term “chief complaint” is outdated, and upsets patients when they see it in their medical record.
As a patient of mine once said to me: “I never complained about that problem, I just brought it to your attention.” No one wants to be seen as a complainer. Substituting the word concern for complaint works well.
Explain as you examine
People love to hear the term normal. When you are examining a patient, let them know when findings are normal.
I also find it helpful to explain to patients why I am doing certain physical exam maneuvers. This helps them assess how thorough we are in our thought process.
When patients feel their physicians are thorough, they have more confidence in them.
In summary
- Be curious.
- Do not overly focus on the EHR.
- Consider teaching a medical student.
- Be careful of word choice.
- “Overexplain” the physical exam.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Marmor RA et al. Appl Clin Inform. 2018 Jan;9(1):11-4.
2. Rogers HD et al. Acad Med. 2003 Sep;78(9):945-9.
It is a tough time to be a doctor. With the stresses of the pandemic, the continued unfettered rise of insurance company BS, and so many medical groups being bought up that we often don’t even know who makes the decisions, the patient can sometimes be hidden in the equation.
Be curious
When physicians are curious about why patients have symptoms, how those symptoms will affect their lives, and how worried the patient is about them, patients feel cared about.
Ascertaining how concerned patients are about their symptoms will help you make decisions on whether symptoms you are not concerned about actually need to be treated.
Limit use of EHRs when possible
Use of the electronic health record during visits is essential, but focusing on it too much can put a barrier between the physician and the patient.
Marmor and colleagues found there is an inverse relationship between time spent on the EHR by a patient’s physician and the patient’s satisfaction.1
Eye contact with the patient is important, especially when patients are sharing concerns they are scared about and upsetting experiences. There can be awkward pauses when looking things up on the EHR. Fill those pauses by explaining to the patient what you are doing, or chatting with the patient.
Consider teaching medical students
When a medical student works with you, it doubles the time the patient gets with a concerned listener. Students also can do a great job with timely follow-up and checking in with worried patients.
By having the student present in the clinic room, with the patient present, the patient can really feel heard. The student shares all the details the patient shared, and now their physician is hearing an organized, thoughtful report of the patients concerns.
In fact, I was involved in a study that showed that patients preferred in room presentations, and that they were more satisfied when students presented in the room.2
Use healing words
Some words carry loaded emotions. The word chronic, for example, has negative connotations, whereas the term persisting does not.
I will often ask patients how long they have been suffering from a symptom to imply my concern for what they are going through. The term “chief complaint” is outdated, and upsets patients when they see it in their medical record.
As a patient of mine once said to me: “I never complained about that problem, I just brought it to your attention.” No one wants to be seen as a complainer. Substituting the word concern for complaint works well.
Explain as you examine
People love to hear the term normal. When you are examining a patient, let them know when findings are normal.
I also find it helpful to explain to patients why I am doing certain physical exam maneuvers. This helps them assess how thorough we are in our thought process.
When patients feel their physicians are thorough, they have more confidence in them.
In summary
- Be curious.
- Do not overly focus on the EHR.
- Consider teaching a medical student.
- Be careful of word choice.
- “Overexplain” the physical exam.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Marmor RA et al. Appl Clin Inform. 2018 Jan;9(1):11-4.
2. Rogers HD et al. Acad Med. 2003 Sep;78(9):945-9.
New hemophilia treatments: ‘Our cup runneth over’
It’s a problem many clinicians would love to have: A whole variety of new or emerging therapeutic options to use in the care of their patients.
In a session titled “Hemophilia Update: Our Cup Runneth Over,” presented at the 2021 annual meeting of the American Society of Hematology, .
Factor concentrates
Prophylaxis – as opposed to episodic treatment – is the standard of care in the use of factor concentrates in patients with hemophilia, said Ming Y. Lim, MB BChir, from the University of Utah in Salt Lake City.
“Effective prophylaxis is an ongoing collaborative effort that relies on shared decision-making between the patient and the clinician,” she told the audience.
As the complexity of therapeutic options, including gene therapy, continues to increase “it is critical that both patients and clinicians are actively involved in this collaborative process to optimize treatment and overall patient outcomes,” she added.
Historically, clinicians who treat patients with hemophilia aimed for trough levels of factor concentrates of at least 1% to prevent spontaneous joint bleeding. But as updated World Federation of Hemophilia (WFH) guidelines now recommend, trough levels should be sufficient to prevent spontaneous bleeding based on the individual patient’s bleeding phenotype and activity levels, starting in the range between 3% and 5%, and going higher as necessary.
“The appropriate target trough level is that at which a person with hemophilia experiences zero bleeds while pursuing an active or sedentary lifestyle,” she said.
The choice of factor concentrates between standard and extended half-life products will depend on multiple factors, including availability, patient and provider preferences, cost, and access to assays for monitoring extended half-life products.
The prolonged action of extended half-life products translates into dosing twice per week or every 3 days for factor VIII concentrates, and every 7-14 days for factor IX concentrates.
“All available extended half-life products have been shown to be efficacious in the prevention and treatment of bleeds, with no evidence for any clinical safety issues,” Dr. Lim said.
There are theoretical concerns, however, regarding the lifelong use of PEGylated clotting factor concentrates, leading to some variations in the regulatory approval for some PEGylated product intended for bleeding prophylaxis in children with hemophilia, she noted.
The pharmacokinetics of prophylaxis with factor concentrates can vary according to age, body mass, blood type, and von Willebrand factor levels, so WFH guidelines recommend pharmacokinetic assessment of people with hemophilia for optimization of prophylaxis, she said.
Factor mimetic and rebalancing therapies
With the commercial availability of one factor mimetic for treatment of hemophilia A and with other factor mimetics and rebalancing therapies such as fitusiran in the works, it raises the question, “Is this the beginning of the end of the use of factor?” said Alice Ma, MD, FACP, of the University of North Carolina in Chapel Hill.
Factors that may determine the answer to that question include the convenience of subcutaneous administration of factor VIII mimetics compared with intravenous delivery of factor concentrates, relative cost of factors versus nonfactor products, and safety.
She reviewed the current state of alternatives to factor concentrates, including the factor mimetic emicizumab (Hemlibra), which was approved by the Food and Drug Administration in 2018 for bleeding prophylaxis in patients with hemophilia A with inhibitors, and is currently the only FDA-approved and licensed agent in its class.
Although emicizumab is widely regarded as a major advance, there are still unanswered clinical questions about its long-term use, Dr. Ma said. It is unknown, for example, whether it can prevent inhibitor development in previously untreated patients, and whether it can prevent intracranial hemorrhage in early years of life prior to the start of traditional prophylaxis.
It’s also unknown whether the factor VIII mimetic activity of emicizumab provides the same physiological benefits of coagulation factors, and the mechanism of thrombotic adverse events seen with this agent is still unclear, she added.
Other factor VIII mimetics in the pipeline include Mim8, which is being developed in Denmark by Novo Nordisk; this is a next-generation bispecific antibody with enhanced activity over emicizumab in both mouse models and in vitro hemophilia A assays. There are also two others bispecific antibodies designed to generate thrombin in preclinical development: BS-027125 (Bioverativ, U.S.) and NIBX-2101 (Takeda, Japan).
One of the most promising rebalancing factors in development is fitusiran, a small interfering RNA molecule that targets mRNA encoding antithrombin. As reported during ASH 2021, fitusiran was associated with an approximately 90% reduction in annualized bleeding rates in patients with hemophilia A and hemophilia B, both with inhibitors, in two clinical trials. It was described at the meeting “as a great leap forward” in the treatment of hemophilia.
However, during its clinical development fitusiran has been consistently associated with thrombotic complications, Dr. Ma noted.
Also in development are several drugs targeted against tissue factor pathway inhibitor (TFPI), an anticoagulant protein that inhibits early phases of the procoagulant response. These agents included marstacimab (Pfizer, U.S.) which has been reported to normalize coagulation in plasma from hemophilia patients ex vivo and is currently being evaluated in patients with hemophilia A and B. There is also MG1113 (Green Cross Corporation, South Korea), a monoclonal antibody currently being tested in healthy volunteers, and BAX499 (Takeda), an aptamer derived from recombinant human TFPI that has been shown to inhibit TFPI in vitro and in vivo. However, development of this agent is on hold due to bleeding in study subjects, Dr. Ma noted.
“It is really notable that none of the replacements of factor have been free of thrombotic side effects,” Dr. Ma said. “And so I think it shows that you mess with Mother Nature at your peril. If you poke at the hemostasis-thrombosis arm and reduce antithrombotic proteins, and something triggers bleeding and you start to treat with a therapy for hemorrhage, it’s not a surprise that the first patient treated with fitusiran had a thrombosis, and I think we were just not potentially savvy enough to predict that.”
Considerable optimism over gene therapy
“There is now repeated proof of concept success for hemophilia A and B gene therapy. I think this supports the considerable optimism that’s really driving this field,” said Lindsey A. George, MD, of the University of Pennsylvania and Children’s Hospital of Philadelphia.
She reviewed adeno-associated virus (AAV) vector and AAV-mediated gene transfer approaches for hemophilia A and B.
There are currently four clinical trials of gene therapy for patients with hemophilia B, and five for patients with hemophilia A.
Because AAV efficiently targets the liver, most safety considerations about systemic AAV-mediated gene therapy are focused around potential hepatotoxicity, Dr. George said.
“Thankfully, short-term safety in the context of hemophilia has really been quite good,” she said.
Patients who undergo gene therapy for hemophilia are typically monitored twice weekly for 3 months for evidence of a capsid-specific CD8 T cell response, also called a capsid immune response. This presents with transient transaminase elevations (primarily ALT) and a decline in factor VIII and factor IX activity.
In clinical trials for patients with hemophilia, the capsid immune response has limited the efficacy of the therapy in the short term, but has not been a major cause for safety concerns. It is typically managed with glucocorticoids or other immunomodulating agents such as mycophenolate mofetil or tacrolimus.
There have also been reported cases of transaminase elevations without evidence of a capsid immune response, which warrants further investigation, she added.
Regarding efficacy, she noted that across clinical trials, the observed annualized bleeding rate has been less than 1%, despite heterogeneity of vectors and dosing used.
“That’s obviously quite optimistic for the field, but it also sort of raises the point that the heterogeneity at which we’re achieving the same phenotypic observations deserves a bit of a deeper dive,” she said.
Although hemophilia B gene transfer appears to be durable, the same cannot be said as yet for hemophilia A.
In canine models for hemophilia A and B, factor VIII and factor IX expression have been demonstrated for 8-10 years post vector, and in humans factor IX expression in patients with hemophilia B has been reported for up to 8 years.
In contrast, in the three hemophilia A trials in which patients have been followed for a minimum of 2 years, there was an approximately 40% loss of transgene vector from year 1 to year 2 with two vectors, but not a third.
Potential explanations for the loss of expression seen include an unfolded protein response, promoter silence, and an ongoing undetected or unmitigated immune response to AAV or to the transgene.
Regarding the future of gene therapy, Dr. George said that “we anticipate that there will be licensed vectors in the very near future, and predicted that gene therapy “will fulfill its promise to alter the paradigm of hemophilia care.”
Dr. Lim disclosed honoraria from several companies and travel support from Novo Nordisk. Dr. Ma disclosed honoraria and research funding from Takeda. Dr. George disclosed FVIII-QQ patents and royalties, research funding from AskBio, and consulting activities/advisory board participation with others.
A version of this article first appeared on Medscape.com.
It’s a problem many clinicians would love to have: A whole variety of new or emerging therapeutic options to use in the care of their patients.
In a session titled “Hemophilia Update: Our Cup Runneth Over,” presented at the 2021 annual meeting of the American Society of Hematology, .
Factor concentrates
Prophylaxis – as opposed to episodic treatment – is the standard of care in the use of factor concentrates in patients with hemophilia, said Ming Y. Lim, MB BChir, from the University of Utah in Salt Lake City.
“Effective prophylaxis is an ongoing collaborative effort that relies on shared decision-making between the patient and the clinician,” she told the audience.
As the complexity of therapeutic options, including gene therapy, continues to increase “it is critical that both patients and clinicians are actively involved in this collaborative process to optimize treatment and overall patient outcomes,” she added.
Historically, clinicians who treat patients with hemophilia aimed for trough levels of factor concentrates of at least 1% to prevent spontaneous joint bleeding. But as updated World Federation of Hemophilia (WFH) guidelines now recommend, trough levels should be sufficient to prevent spontaneous bleeding based on the individual patient’s bleeding phenotype and activity levels, starting in the range between 3% and 5%, and going higher as necessary.
“The appropriate target trough level is that at which a person with hemophilia experiences zero bleeds while pursuing an active or sedentary lifestyle,” she said.
The choice of factor concentrates between standard and extended half-life products will depend on multiple factors, including availability, patient and provider preferences, cost, and access to assays for monitoring extended half-life products.
The prolonged action of extended half-life products translates into dosing twice per week or every 3 days for factor VIII concentrates, and every 7-14 days for factor IX concentrates.
“All available extended half-life products have been shown to be efficacious in the prevention and treatment of bleeds, with no evidence for any clinical safety issues,” Dr. Lim said.
There are theoretical concerns, however, regarding the lifelong use of PEGylated clotting factor concentrates, leading to some variations in the regulatory approval for some PEGylated product intended for bleeding prophylaxis in children with hemophilia, she noted.
The pharmacokinetics of prophylaxis with factor concentrates can vary according to age, body mass, blood type, and von Willebrand factor levels, so WFH guidelines recommend pharmacokinetic assessment of people with hemophilia for optimization of prophylaxis, she said.
Factor mimetic and rebalancing therapies
With the commercial availability of one factor mimetic for treatment of hemophilia A and with other factor mimetics and rebalancing therapies such as fitusiran in the works, it raises the question, “Is this the beginning of the end of the use of factor?” said Alice Ma, MD, FACP, of the University of North Carolina in Chapel Hill.
Factors that may determine the answer to that question include the convenience of subcutaneous administration of factor VIII mimetics compared with intravenous delivery of factor concentrates, relative cost of factors versus nonfactor products, and safety.
She reviewed the current state of alternatives to factor concentrates, including the factor mimetic emicizumab (Hemlibra), which was approved by the Food and Drug Administration in 2018 for bleeding prophylaxis in patients with hemophilia A with inhibitors, and is currently the only FDA-approved and licensed agent in its class.
Although emicizumab is widely regarded as a major advance, there are still unanswered clinical questions about its long-term use, Dr. Ma said. It is unknown, for example, whether it can prevent inhibitor development in previously untreated patients, and whether it can prevent intracranial hemorrhage in early years of life prior to the start of traditional prophylaxis.
It’s also unknown whether the factor VIII mimetic activity of emicizumab provides the same physiological benefits of coagulation factors, and the mechanism of thrombotic adverse events seen with this agent is still unclear, she added.
Other factor VIII mimetics in the pipeline include Mim8, which is being developed in Denmark by Novo Nordisk; this is a next-generation bispecific antibody with enhanced activity over emicizumab in both mouse models and in vitro hemophilia A assays. There are also two others bispecific antibodies designed to generate thrombin in preclinical development: BS-027125 (Bioverativ, U.S.) and NIBX-2101 (Takeda, Japan).
One of the most promising rebalancing factors in development is fitusiran, a small interfering RNA molecule that targets mRNA encoding antithrombin. As reported during ASH 2021, fitusiran was associated with an approximately 90% reduction in annualized bleeding rates in patients with hemophilia A and hemophilia B, both with inhibitors, in two clinical trials. It was described at the meeting “as a great leap forward” in the treatment of hemophilia.
However, during its clinical development fitusiran has been consistently associated with thrombotic complications, Dr. Ma noted.
Also in development are several drugs targeted against tissue factor pathway inhibitor (TFPI), an anticoagulant protein that inhibits early phases of the procoagulant response. These agents included marstacimab (Pfizer, U.S.) which has been reported to normalize coagulation in plasma from hemophilia patients ex vivo and is currently being evaluated in patients with hemophilia A and B. There is also MG1113 (Green Cross Corporation, South Korea), a monoclonal antibody currently being tested in healthy volunteers, and BAX499 (Takeda), an aptamer derived from recombinant human TFPI that has been shown to inhibit TFPI in vitro and in vivo. However, development of this agent is on hold due to bleeding in study subjects, Dr. Ma noted.
“It is really notable that none of the replacements of factor have been free of thrombotic side effects,” Dr. Ma said. “And so I think it shows that you mess with Mother Nature at your peril. If you poke at the hemostasis-thrombosis arm and reduce antithrombotic proteins, and something triggers bleeding and you start to treat with a therapy for hemorrhage, it’s not a surprise that the first patient treated with fitusiran had a thrombosis, and I think we were just not potentially savvy enough to predict that.”
Considerable optimism over gene therapy
“There is now repeated proof of concept success for hemophilia A and B gene therapy. I think this supports the considerable optimism that’s really driving this field,” said Lindsey A. George, MD, of the University of Pennsylvania and Children’s Hospital of Philadelphia.
She reviewed adeno-associated virus (AAV) vector and AAV-mediated gene transfer approaches for hemophilia A and B.
There are currently four clinical trials of gene therapy for patients with hemophilia B, and five for patients with hemophilia A.
Because AAV efficiently targets the liver, most safety considerations about systemic AAV-mediated gene therapy are focused around potential hepatotoxicity, Dr. George said.
“Thankfully, short-term safety in the context of hemophilia has really been quite good,” she said.
Patients who undergo gene therapy for hemophilia are typically monitored twice weekly for 3 months for evidence of a capsid-specific CD8 T cell response, also called a capsid immune response. This presents with transient transaminase elevations (primarily ALT) and a decline in factor VIII and factor IX activity.
In clinical trials for patients with hemophilia, the capsid immune response has limited the efficacy of the therapy in the short term, but has not been a major cause for safety concerns. It is typically managed with glucocorticoids or other immunomodulating agents such as mycophenolate mofetil or tacrolimus.
There have also been reported cases of transaminase elevations without evidence of a capsid immune response, which warrants further investigation, she added.
Regarding efficacy, she noted that across clinical trials, the observed annualized bleeding rate has been less than 1%, despite heterogeneity of vectors and dosing used.
“That’s obviously quite optimistic for the field, but it also sort of raises the point that the heterogeneity at which we’re achieving the same phenotypic observations deserves a bit of a deeper dive,” she said.
Although hemophilia B gene transfer appears to be durable, the same cannot be said as yet for hemophilia A.
In canine models for hemophilia A and B, factor VIII and factor IX expression have been demonstrated for 8-10 years post vector, and in humans factor IX expression in patients with hemophilia B has been reported for up to 8 years.
In contrast, in the three hemophilia A trials in which patients have been followed for a minimum of 2 years, there was an approximately 40% loss of transgene vector from year 1 to year 2 with two vectors, but not a third.
Potential explanations for the loss of expression seen include an unfolded protein response, promoter silence, and an ongoing undetected or unmitigated immune response to AAV or to the transgene.
Regarding the future of gene therapy, Dr. George said that “we anticipate that there will be licensed vectors in the very near future, and predicted that gene therapy “will fulfill its promise to alter the paradigm of hemophilia care.”
Dr. Lim disclosed honoraria from several companies and travel support from Novo Nordisk. Dr. Ma disclosed honoraria and research funding from Takeda. Dr. George disclosed FVIII-QQ patents and royalties, research funding from AskBio, and consulting activities/advisory board participation with others.
A version of this article first appeared on Medscape.com.
It’s a problem many clinicians would love to have: A whole variety of new or emerging therapeutic options to use in the care of their patients.
In a session titled “Hemophilia Update: Our Cup Runneth Over,” presented at the 2021 annual meeting of the American Society of Hematology, .
Factor concentrates
Prophylaxis – as opposed to episodic treatment – is the standard of care in the use of factor concentrates in patients with hemophilia, said Ming Y. Lim, MB BChir, from the University of Utah in Salt Lake City.
“Effective prophylaxis is an ongoing collaborative effort that relies on shared decision-making between the patient and the clinician,” she told the audience.
As the complexity of therapeutic options, including gene therapy, continues to increase “it is critical that both patients and clinicians are actively involved in this collaborative process to optimize treatment and overall patient outcomes,” she added.
Historically, clinicians who treat patients with hemophilia aimed for trough levels of factor concentrates of at least 1% to prevent spontaneous joint bleeding. But as updated World Federation of Hemophilia (WFH) guidelines now recommend, trough levels should be sufficient to prevent spontaneous bleeding based on the individual patient’s bleeding phenotype and activity levels, starting in the range between 3% and 5%, and going higher as necessary.
“The appropriate target trough level is that at which a person with hemophilia experiences zero bleeds while pursuing an active or sedentary lifestyle,” she said.
The choice of factor concentrates between standard and extended half-life products will depend on multiple factors, including availability, patient and provider preferences, cost, and access to assays for monitoring extended half-life products.
The prolonged action of extended half-life products translates into dosing twice per week or every 3 days for factor VIII concentrates, and every 7-14 days for factor IX concentrates.
“All available extended half-life products have been shown to be efficacious in the prevention and treatment of bleeds, with no evidence for any clinical safety issues,” Dr. Lim said.
There are theoretical concerns, however, regarding the lifelong use of PEGylated clotting factor concentrates, leading to some variations in the regulatory approval for some PEGylated product intended for bleeding prophylaxis in children with hemophilia, she noted.
The pharmacokinetics of prophylaxis with factor concentrates can vary according to age, body mass, blood type, and von Willebrand factor levels, so WFH guidelines recommend pharmacokinetic assessment of people with hemophilia for optimization of prophylaxis, she said.
Factor mimetic and rebalancing therapies
With the commercial availability of one factor mimetic for treatment of hemophilia A and with other factor mimetics and rebalancing therapies such as fitusiran in the works, it raises the question, “Is this the beginning of the end of the use of factor?” said Alice Ma, MD, FACP, of the University of North Carolina in Chapel Hill.
Factors that may determine the answer to that question include the convenience of subcutaneous administration of factor VIII mimetics compared with intravenous delivery of factor concentrates, relative cost of factors versus nonfactor products, and safety.
She reviewed the current state of alternatives to factor concentrates, including the factor mimetic emicizumab (Hemlibra), which was approved by the Food and Drug Administration in 2018 for bleeding prophylaxis in patients with hemophilia A with inhibitors, and is currently the only FDA-approved and licensed agent in its class.
Although emicizumab is widely regarded as a major advance, there are still unanswered clinical questions about its long-term use, Dr. Ma said. It is unknown, for example, whether it can prevent inhibitor development in previously untreated patients, and whether it can prevent intracranial hemorrhage in early years of life prior to the start of traditional prophylaxis.
It’s also unknown whether the factor VIII mimetic activity of emicizumab provides the same physiological benefits of coagulation factors, and the mechanism of thrombotic adverse events seen with this agent is still unclear, she added.
Other factor VIII mimetics in the pipeline include Mim8, which is being developed in Denmark by Novo Nordisk; this is a next-generation bispecific antibody with enhanced activity over emicizumab in both mouse models and in vitro hemophilia A assays. There are also two others bispecific antibodies designed to generate thrombin in preclinical development: BS-027125 (Bioverativ, U.S.) and NIBX-2101 (Takeda, Japan).
One of the most promising rebalancing factors in development is fitusiran, a small interfering RNA molecule that targets mRNA encoding antithrombin. As reported during ASH 2021, fitusiran was associated with an approximately 90% reduction in annualized bleeding rates in patients with hemophilia A and hemophilia B, both with inhibitors, in two clinical trials. It was described at the meeting “as a great leap forward” in the treatment of hemophilia.
However, during its clinical development fitusiran has been consistently associated with thrombotic complications, Dr. Ma noted.
Also in development are several drugs targeted against tissue factor pathway inhibitor (TFPI), an anticoagulant protein that inhibits early phases of the procoagulant response. These agents included marstacimab (Pfizer, U.S.) which has been reported to normalize coagulation in plasma from hemophilia patients ex vivo and is currently being evaluated in patients with hemophilia A and B. There is also MG1113 (Green Cross Corporation, South Korea), a monoclonal antibody currently being tested in healthy volunteers, and BAX499 (Takeda), an aptamer derived from recombinant human TFPI that has been shown to inhibit TFPI in vitro and in vivo. However, development of this agent is on hold due to bleeding in study subjects, Dr. Ma noted.
“It is really notable that none of the replacements of factor have been free of thrombotic side effects,” Dr. Ma said. “And so I think it shows that you mess with Mother Nature at your peril. If you poke at the hemostasis-thrombosis arm and reduce antithrombotic proteins, and something triggers bleeding and you start to treat with a therapy for hemorrhage, it’s not a surprise that the first patient treated with fitusiran had a thrombosis, and I think we were just not potentially savvy enough to predict that.”
Considerable optimism over gene therapy
“There is now repeated proof of concept success for hemophilia A and B gene therapy. I think this supports the considerable optimism that’s really driving this field,” said Lindsey A. George, MD, of the University of Pennsylvania and Children’s Hospital of Philadelphia.
She reviewed adeno-associated virus (AAV) vector and AAV-mediated gene transfer approaches for hemophilia A and B.
There are currently four clinical trials of gene therapy for patients with hemophilia B, and five for patients with hemophilia A.
Because AAV efficiently targets the liver, most safety considerations about systemic AAV-mediated gene therapy are focused around potential hepatotoxicity, Dr. George said.
“Thankfully, short-term safety in the context of hemophilia has really been quite good,” she said.
Patients who undergo gene therapy for hemophilia are typically monitored twice weekly for 3 months for evidence of a capsid-specific CD8 T cell response, also called a capsid immune response. This presents with transient transaminase elevations (primarily ALT) and a decline in factor VIII and factor IX activity.
In clinical trials for patients with hemophilia, the capsid immune response has limited the efficacy of the therapy in the short term, but has not been a major cause for safety concerns. It is typically managed with glucocorticoids or other immunomodulating agents such as mycophenolate mofetil or tacrolimus.
There have also been reported cases of transaminase elevations without evidence of a capsid immune response, which warrants further investigation, she added.
Regarding efficacy, she noted that across clinical trials, the observed annualized bleeding rate has been less than 1%, despite heterogeneity of vectors and dosing used.
“That’s obviously quite optimistic for the field, but it also sort of raises the point that the heterogeneity at which we’re achieving the same phenotypic observations deserves a bit of a deeper dive,” she said.
Although hemophilia B gene transfer appears to be durable, the same cannot be said as yet for hemophilia A.
In canine models for hemophilia A and B, factor VIII and factor IX expression have been demonstrated for 8-10 years post vector, and in humans factor IX expression in patients with hemophilia B has been reported for up to 8 years.
In contrast, in the three hemophilia A trials in which patients have been followed for a minimum of 2 years, there was an approximately 40% loss of transgene vector from year 1 to year 2 with two vectors, but not a third.
Potential explanations for the loss of expression seen include an unfolded protein response, promoter silence, and an ongoing undetected or unmitigated immune response to AAV or to the transgene.
Regarding the future of gene therapy, Dr. George said that “we anticipate that there will be licensed vectors in the very near future, and predicted that gene therapy “will fulfill its promise to alter the paradigm of hemophilia care.”
Dr. Lim disclosed honoraria from several companies and travel support from Novo Nordisk. Dr. Ma disclosed honoraria and research funding from Takeda. Dr. George disclosed FVIII-QQ patents and royalties, research funding from AskBio, and consulting activities/advisory board participation with others.
A version of this article first appeared on Medscape.com.
REPORTING FROM ASH 2021
Long COVID symptoms linked to effects on vagus nerve
Several long COVID symptoms could be linked to the effects of the coronavirus on a vital central nerve, according to new research being released in the spring.
The vagus nerve, which runs from the brain into the body, connects to the heart, lungs, intestines, and several muscles involved with swallowing. It plays a role in several body functions that control heart rate, speech, the gag reflex, sweating, and digestion.
Those with long COVID and vagus nerve problems could face long-term issues with their voice, a hard time swallowing, dizziness, a high heart rate, low blood pressure, and diarrhea, the study authors found.
Their findings will be presented at the 2022 European Congress of Clinical Microbiology and Infectious Diseases in late April.
“Most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing,” the study authors wrote. “Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”
Researchers from the University Hospital Germans Trias i Pujol in Barcelona performed a study to look at vagus nerve functioning in long COVID patients. Among 348 patients, about 66% had at least one symptom that suggested vagus nerve dysfunction. The researchers did a broad evaluation with imaging and functional tests for 22 patients in the university’s Long COVID Clinic from March to June 2021.
Of the 22 patients, 20 were women, and the median age was 44. The most frequent symptoms related to vagus nerve dysfunction were diarrhea (73%), high heart rates (59%), dizziness (45%), swallowing problems (45%), voice problems (45%), and low blood pressure (14%).
Almost all (19 of 22 patients) had three or more symptoms related to vagus nerve dysfunction. The average length of symptoms was 14 months.
Of 22 patients, 6 had a change in the vagus nerve in the neck, which the researchers observed by ultrasound. They had a thickening of the vagus nerve and increased “echogenicity,” which suggests inflammation.
What’s more, 10 of 22 patients had flattened “diaphragmatic curves” during a thoracic ultrasound, which means the diaphragm doesn’t move as well as it should during breathing, and abnormal breathing. In another assessment, 10 of 16 patients had lower maximum inspiration pressures, suggesting a weakness in breathing muscles.
Eating and digestion were also impaired in some patients, with 13 reporting trouble with swallowing. During a gastric and bowel function assessment, eight patients couldn’t move food from the esophagus to the stomach as well as they should, while nine patients had acid reflux. Three patients had a hiatal hernia, which happens when the upper part of the stomach bulges through the diaphragm into the chest cavity.
The voices of some patients changed as well. Eight patients had an abnormal voice handicap index 30 test, which is a standard way to measure voice function. Among those, seven patients had dysphonia, or persistent voice problems.
The study is ongoing, and the research team is continuing to recruit patients to study the links between long COVID and the vagus nerve. The full paper isn’t yet available, and the research hasn’t yet been peer reviewed.
“The study appears to add to a growing collection of data suggesting at least some of the symptoms of long COVID is mediated through a direct impact on the nervous system,” David Strain, MD, a clinical senior lecturer at the University of Exeter (England), told the Science Media Centre.
“Establishing vagal nerve damage is useful information, as there are recognized, albeit not perfect, treatments for other causes of vagal nerve dysfunction that may be extrapolated to be beneficial for people with this type of long COVID,” he said.
A version of this article first appeared on WebMD.com.
Several long COVID symptoms could be linked to the effects of the coronavirus on a vital central nerve, according to new research being released in the spring.
The vagus nerve, which runs from the brain into the body, connects to the heart, lungs, intestines, and several muscles involved with swallowing. It plays a role in several body functions that control heart rate, speech, the gag reflex, sweating, and digestion.
Those with long COVID and vagus nerve problems could face long-term issues with their voice, a hard time swallowing, dizziness, a high heart rate, low blood pressure, and diarrhea, the study authors found.
Their findings will be presented at the 2022 European Congress of Clinical Microbiology and Infectious Diseases in late April.
“Most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing,” the study authors wrote. “Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”
Researchers from the University Hospital Germans Trias i Pujol in Barcelona performed a study to look at vagus nerve functioning in long COVID patients. Among 348 patients, about 66% had at least one symptom that suggested vagus nerve dysfunction. The researchers did a broad evaluation with imaging and functional tests for 22 patients in the university’s Long COVID Clinic from March to June 2021.
Of the 22 patients, 20 were women, and the median age was 44. The most frequent symptoms related to vagus nerve dysfunction were diarrhea (73%), high heart rates (59%), dizziness (45%), swallowing problems (45%), voice problems (45%), and low blood pressure (14%).
Almost all (19 of 22 patients) had three or more symptoms related to vagus nerve dysfunction. The average length of symptoms was 14 months.
Of 22 patients, 6 had a change in the vagus nerve in the neck, which the researchers observed by ultrasound. They had a thickening of the vagus nerve and increased “echogenicity,” which suggests inflammation.
What’s more, 10 of 22 patients had flattened “diaphragmatic curves” during a thoracic ultrasound, which means the diaphragm doesn’t move as well as it should during breathing, and abnormal breathing. In another assessment, 10 of 16 patients had lower maximum inspiration pressures, suggesting a weakness in breathing muscles.
Eating and digestion were also impaired in some patients, with 13 reporting trouble with swallowing. During a gastric and bowel function assessment, eight patients couldn’t move food from the esophagus to the stomach as well as they should, while nine patients had acid reflux. Three patients had a hiatal hernia, which happens when the upper part of the stomach bulges through the diaphragm into the chest cavity.
The voices of some patients changed as well. Eight patients had an abnormal voice handicap index 30 test, which is a standard way to measure voice function. Among those, seven patients had dysphonia, or persistent voice problems.
The study is ongoing, and the research team is continuing to recruit patients to study the links between long COVID and the vagus nerve. The full paper isn’t yet available, and the research hasn’t yet been peer reviewed.
“The study appears to add to a growing collection of data suggesting at least some of the symptoms of long COVID is mediated through a direct impact on the nervous system,” David Strain, MD, a clinical senior lecturer at the University of Exeter (England), told the Science Media Centre.
“Establishing vagal nerve damage is useful information, as there are recognized, albeit not perfect, treatments for other causes of vagal nerve dysfunction that may be extrapolated to be beneficial for people with this type of long COVID,” he said.
A version of this article first appeared on WebMD.com.
Several long COVID symptoms could be linked to the effects of the coronavirus on a vital central nerve, according to new research being released in the spring.
The vagus nerve, which runs from the brain into the body, connects to the heart, lungs, intestines, and several muscles involved with swallowing. It plays a role in several body functions that control heart rate, speech, the gag reflex, sweating, and digestion.
Those with long COVID and vagus nerve problems could face long-term issues with their voice, a hard time swallowing, dizziness, a high heart rate, low blood pressure, and diarrhea, the study authors found.
Their findings will be presented at the 2022 European Congress of Clinical Microbiology and Infectious Diseases in late April.
“Most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing,” the study authors wrote. “Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”
Researchers from the University Hospital Germans Trias i Pujol in Barcelona performed a study to look at vagus nerve functioning in long COVID patients. Among 348 patients, about 66% had at least one symptom that suggested vagus nerve dysfunction. The researchers did a broad evaluation with imaging and functional tests for 22 patients in the university’s Long COVID Clinic from March to June 2021.
Of the 22 patients, 20 were women, and the median age was 44. The most frequent symptoms related to vagus nerve dysfunction were diarrhea (73%), high heart rates (59%), dizziness (45%), swallowing problems (45%), voice problems (45%), and low blood pressure (14%).
Almost all (19 of 22 patients) had three or more symptoms related to vagus nerve dysfunction. The average length of symptoms was 14 months.
Of 22 patients, 6 had a change in the vagus nerve in the neck, which the researchers observed by ultrasound. They had a thickening of the vagus nerve and increased “echogenicity,” which suggests inflammation.
What’s more, 10 of 22 patients had flattened “diaphragmatic curves” during a thoracic ultrasound, which means the diaphragm doesn’t move as well as it should during breathing, and abnormal breathing. In another assessment, 10 of 16 patients had lower maximum inspiration pressures, suggesting a weakness in breathing muscles.
Eating and digestion were also impaired in some patients, with 13 reporting trouble with swallowing. During a gastric and bowel function assessment, eight patients couldn’t move food from the esophagus to the stomach as well as they should, while nine patients had acid reflux. Three patients had a hiatal hernia, which happens when the upper part of the stomach bulges through the diaphragm into the chest cavity.
The voices of some patients changed as well. Eight patients had an abnormal voice handicap index 30 test, which is a standard way to measure voice function. Among those, seven patients had dysphonia, or persistent voice problems.
The study is ongoing, and the research team is continuing to recruit patients to study the links between long COVID and the vagus nerve. The full paper isn’t yet available, and the research hasn’t yet been peer reviewed.
“The study appears to add to a growing collection of data suggesting at least some of the symptoms of long COVID is mediated through a direct impact on the nervous system,” David Strain, MD, a clinical senior lecturer at the University of Exeter (England), told the Science Media Centre.
“Establishing vagal nerve damage is useful information, as there are recognized, albeit not perfect, treatments for other causes of vagal nerve dysfunction that may be extrapolated to be beneficial for people with this type of long COVID,” he said.
A version of this article first appeared on WebMD.com.
Can cancer patients get approved COVID therapies?
In mid-November, Kevin Billingsley, MD, MBA, chief medical officer at Yale Cancer Center, New Haven, Conn., was keeping a close eye on the new COVID variant sweeping across South Africa. Six weeks later, the Omicron variant had become the dominant strain in the U.S. – and the Yale health system was no exception.
“As we entered January, we had a breathtaking rate of infection in our hospital,” said Dr. Billingsley, who also leads clinical care at the Smilow Cancer Hospital. “Some of the newly authorized COVID agents were available but not widely enough to make a clinically meaningful impact to protect all high-risk individuals during this surge.”
That left the team at Yale with difficult decisions about who would receive these treatments and who wouldn’t.
The health system convened a COVID-19 immunocompromised working group to identify which patients should get priority access to one of the promising drugs authorized to treat the infection – the monoclonal antibody sotrovimab and antiviral pills Paxlovid and molnupiravir – or the sole available option to prevent it, Evusheld.
“Although clinically sound, none of these decisions have been easy,” Dr. Billingsley told this news organization. “We have done a lot of case-by-case reviewing and a lot of handwringing. Omicron has been a wild ride for us all, and we have been doing the best we can with limited resources.”
‘We’re seeing incredible variability’
The team at Yale is not alone. The restricted supply of COVID-19 treatments has led many oncologists and other experts across the U.S. to create carefully curated lists of their most vulnerable patients.
In late December, the National Institutes of Health published broad criteria to help clinicians prioritize patients most likely to benefit from these therapies. A handful of state health departments, including those in Michigan and Minnesota, established their own standards. Patients with cancer – specifically those with hematologic malignancies and receiving oncology therapies that compromise the immune system – appeared at the top of everyone’s list.
But ultimately individual decisions about who receives these drugs and how they’re allocated fell to institutions.
“Overall, what we’re seeing is incredible variability across the country, because there’s no uniform agreement on what comprises best practices on allocating scarce resources,” said Matthew Wynia, MD, MPH, professor of medicine and director of the Center for Bioethics and Humanities at the University of Colorado, Aurora. “There are so many people at the top of most lists, and the drugs are in such short supply, that there’s no guarantee even those in the top tier will get it.”
This news organization spoke to experts across the country about their experiences accessing these treatments during the Omicron surge and their strategies prioritizing patients with cancer.
Dealing with limited supply
Overall, the limited supply of COVID-19 drugs means not every patient who’s eligible to receive a treatment will get one.
A snapshot of the past 2 weeks, for instance, shows that the count of new infections hit almost 4.3 million, while distribution of the two antiviral pills Paxlovid and molnupiravir and the monoclonal antibody sotrovimab reached just over 600,000 courses.
Since receiving emergency use authorization in early December, almost 500,000 courses of the pre-exposure prophylactic agent Evusheld – which offers about 6 months of protection for immunocompromised individuals – have been distributed; however, about 7 million adults in the U.S. could potentially benefit from it.
In addition, the distribution of drugs is uneven. The federal government manages the overall distribution to states, but states then decide how to divvy up these allocations to hospitals, pharmacies, and medical centers. In Ohio, for instance, the antivirals go to providers who already receive monoclonal antibodies, while in Tennessee, the supply of antiviral agents only goes to Walmart pharmacies.
This strategy, Dr. Wynia explained, can leave clinicians at the mercy of where and how much states decide to allocate to each location. “I’ve heard of some hospitals and health systems in Colorado that aren’t using all they’ve got, but most don’t have nearly enough,” Dr. Wynia said. However, he noted, “some of that is inevitable. We will never get a perfect distribution of these drugs when there is such variable need and demand.”
And, according to Nicolette Louissaint, PhD, MBA, senior vice president of policy and strategic planning at the Healthcare Distribution Alliance in Arlington, Virginia, “we can take some comfort that the federal government is actively looking at cases from week to week and working with state and local health departments to see who needs these products, which means the process is constantly being reviewed and adjusted.”
Plus, not every positive COVID-19 case, even among immunocompromised individuals, necessarily warrants treatment. “If, for instance, an individual with cancer has a mild case of COVID-19, their provider may not deem it necessary for them to receive treatment,” Dr. Louissaint noted.
Still, given the limited and unpredictable supply, “we have had to be thoughtful about who gets these drugs,” said Derek Raghavan, MD, PhD, president of the Levine Cancer Institute, part of the 40-hospital Atrium Health system in Charlotte, North Carolina.
Dr. Raghavan said the highest priority goes to patients with hematologic malignancies, those receiving or coming off chemotherapy or experiencing myelosuppression and immune paresis, as well as those who have undergone organ transplants. Age and other comorbidities, such as diabetes or obesity, play into the lineup as well.
To further hone their priority list, the Levine Cancer Institute has implemented a cancer-centered Hospital at Home initiative. The program includes 40 oncology nurse navigators who routinely screen and score all cancer patients who test positive for COVID-19 by their symptoms and risk factors. For a time-sensitive treatment like Paxlovid, this close monitoring allows patients with COVID to access the pills within 5 days of symptom onset.
Ultimately, “the decision regarding who gets these drugs is [made] by a team to overcome any risk of personal bias, and some of it just comes down to the interface between clinical judgment and available data,” Dr. Raghavan told this news organization. “Although we’d like to have more COVID drugs available and fewer patients with COVID, we have been able to get adequate supplies for our most at-risk patients.”
Like Dr. Raghavan, Karen Bloch, MD, MPH, the medical director for the COVID Infusion Clinic at Vanderbilt University Medical Center (VUMC), said the clinic has had to be highly selective about which patients would benefit most from the COVID monoclonal antibodies. For patients with cancer, her team prioritizes individuals who would be least able to develop antibodies through vaccination or natural infection – which includes patients with B cell malignancies, acute myeloid leukemia, or multiple myeloma receiving active treatment, as well as those who recently received an allogeneic or autologous stem cell transplant.
“Since our criteria for treatment with therapies such as sotrovimab and Evusheld are pretty stringent, we have had sufficient supply to treat those who meet our internal ‘category 1’ predetermined criteria,” said Dr. Bloch, professor of medicine and associate division director for clinical affairs at VUMC, Nashville. “More recently, as the supply chain has begun to open up, we’ve been able to loosen our criteria for sotrovimab, though not for Evusheld yet.”
The Yale team described a similar evolution. “Initially, only a small subset of oncology patients could get these drugs,” said Osama (Sam) Abdelghany, PharmD, MHA, associate director of Oncology Pharmacy Services at Smilow Cancer Hospital. But as the caseload has diminished, Dr. Abdelghany noted, “we have been able to reach many more patients with COVID-19.”
An equitable system?
Dr. Wynia, who has written many reports on crisis standards of care, has spent thousands of hours delving into the ethics of allocating scarce resources during a disaster.
A core problem arises when there are too many people who need a scarce resource and no way of differentiating among them.
In response to the limited supply of COVID-19 treatments, some institutions, such as the University of Pittsburgh Medical Center and Massachusetts General Hospital, have created a lottery system. Others, such as Johns Hopkins Medicine, have opted for first come, first served. Each strategy comes with caveats.
“First come, first served prioritization may be quicker, but it gives more well-resourced people an advantage and lends itself to people abusing the system or exacerbating existing disparities,” Dr. Wynia said.
While a lottery system may be more equitable, this strategy often comes at the price of efficiency. “The practicality of doing a lottery when you have to make a decision about whether or not to treat the patient sitting in front of you comes with its own challenges,” Dr. Wynia said.
At the University of Colorado, he explained, the health center constantly scans medical records for patients who have been diagnosed with COVID and fall into a high-risk group. That way clinicians can call or email those most likely to benefit from these drugs.
“It ends up being a bit of a first come, first served strategy,” Dr. Wynia said. “But we also do not have a huge supply coming in each week, so reaching out to the most eligible people when we have the drugs in hand means more privileged patients are less likely to game the system.”
To manage the supply of Evusheld, Timothy Kubal, MD, MBA, and colleagues also reach out to patients most likely to benefit – specifically, those who can’t mount an adequate antibody response after vaccination.
“We screen all of our patients who have been receiving anti-CD20 agents and other chemotherapy agents known to suppress antibody response,” Dr. Kubal, a medical oncologist/hematologist at the Moffitt Institute in Tampa, Florida, said in an interview. “We then test those patients for antibodies and deliver Evusheld if they have no evidence of antibodies.”
Fortunately, in the coming months, distribution of these drugs should improve significantly. Pfizer says it expects to deliver 10 million courses of Paxlovid by the end of June, and another 10 million by the end of September. More than 1 million courses of sotrovimab should be distributed by GlaxoSmithKline through the end of March. And, recently, the Biden administration announced it purchased 1.2 million courses of Evusheld from AstraZeneca.
“Every few weeks, because the COVID picture changes, the demand changes,” said Dr. Louissaint. “With vaccination rates going up and cases going down, fewer patients will need these products.”
Still, the constant barrage of supply shortages over the past 2 years – from COVID tests, ventilators, and personal protective equipment early on to COVID vaccines a year later and more recently health care staff and COVID tests once again – has taken its toll.
“We have faced supply challenge after challenge and have had to be creative in each situation,” said Lisa Barbarotta, MSN, APRN, program director of Oncology Education and Clinical Practice at Smilow Cancer Hospital. “Nothing has been easy about this.”
And, Dr. Bloch cautioned, even with broader access to COVID-19 drugs on the horizon, there is still no substitute for vaccination. “Getting vaccinated is the best and first line of defense for most people,” she said.
A version of this article first appeared on Medscape.com.
In mid-November, Kevin Billingsley, MD, MBA, chief medical officer at Yale Cancer Center, New Haven, Conn., was keeping a close eye on the new COVID variant sweeping across South Africa. Six weeks later, the Omicron variant had become the dominant strain in the U.S. – and the Yale health system was no exception.
“As we entered January, we had a breathtaking rate of infection in our hospital,” said Dr. Billingsley, who also leads clinical care at the Smilow Cancer Hospital. “Some of the newly authorized COVID agents were available but not widely enough to make a clinically meaningful impact to protect all high-risk individuals during this surge.”
That left the team at Yale with difficult decisions about who would receive these treatments and who wouldn’t.
The health system convened a COVID-19 immunocompromised working group to identify which patients should get priority access to one of the promising drugs authorized to treat the infection – the monoclonal antibody sotrovimab and antiviral pills Paxlovid and molnupiravir – or the sole available option to prevent it, Evusheld.
“Although clinically sound, none of these decisions have been easy,” Dr. Billingsley told this news organization. “We have done a lot of case-by-case reviewing and a lot of handwringing. Omicron has been a wild ride for us all, and we have been doing the best we can with limited resources.”
‘We’re seeing incredible variability’
The team at Yale is not alone. The restricted supply of COVID-19 treatments has led many oncologists and other experts across the U.S. to create carefully curated lists of their most vulnerable patients.
In late December, the National Institutes of Health published broad criteria to help clinicians prioritize patients most likely to benefit from these therapies. A handful of state health departments, including those in Michigan and Minnesota, established their own standards. Patients with cancer – specifically those with hematologic malignancies and receiving oncology therapies that compromise the immune system – appeared at the top of everyone’s list.
But ultimately individual decisions about who receives these drugs and how they’re allocated fell to institutions.
“Overall, what we’re seeing is incredible variability across the country, because there’s no uniform agreement on what comprises best practices on allocating scarce resources,” said Matthew Wynia, MD, MPH, professor of medicine and director of the Center for Bioethics and Humanities at the University of Colorado, Aurora. “There are so many people at the top of most lists, and the drugs are in such short supply, that there’s no guarantee even those in the top tier will get it.”
This news organization spoke to experts across the country about their experiences accessing these treatments during the Omicron surge and their strategies prioritizing patients with cancer.
Dealing with limited supply
Overall, the limited supply of COVID-19 drugs means not every patient who’s eligible to receive a treatment will get one.
A snapshot of the past 2 weeks, for instance, shows that the count of new infections hit almost 4.3 million, while distribution of the two antiviral pills Paxlovid and molnupiravir and the monoclonal antibody sotrovimab reached just over 600,000 courses.
Since receiving emergency use authorization in early December, almost 500,000 courses of the pre-exposure prophylactic agent Evusheld – which offers about 6 months of protection for immunocompromised individuals – have been distributed; however, about 7 million adults in the U.S. could potentially benefit from it.
In addition, the distribution of drugs is uneven. The federal government manages the overall distribution to states, but states then decide how to divvy up these allocations to hospitals, pharmacies, and medical centers. In Ohio, for instance, the antivirals go to providers who already receive monoclonal antibodies, while in Tennessee, the supply of antiviral agents only goes to Walmart pharmacies.
This strategy, Dr. Wynia explained, can leave clinicians at the mercy of where and how much states decide to allocate to each location. “I’ve heard of some hospitals and health systems in Colorado that aren’t using all they’ve got, but most don’t have nearly enough,” Dr. Wynia said. However, he noted, “some of that is inevitable. We will never get a perfect distribution of these drugs when there is such variable need and demand.”
And, according to Nicolette Louissaint, PhD, MBA, senior vice president of policy and strategic planning at the Healthcare Distribution Alliance in Arlington, Virginia, “we can take some comfort that the federal government is actively looking at cases from week to week and working with state and local health departments to see who needs these products, which means the process is constantly being reviewed and adjusted.”
Plus, not every positive COVID-19 case, even among immunocompromised individuals, necessarily warrants treatment. “If, for instance, an individual with cancer has a mild case of COVID-19, their provider may not deem it necessary for them to receive treatment,” Dr. Louissaint noted.
Still, given the limited and unpredictable supply, “we have had to be thoughtful about who gets these drugs,” said Derek Raghavan, MD, PhD, president of the Levine Cancer Institute, part of the 40-hospital Atrium Health system in Charlotte, North Carolina.
Dr. Raghavan said the highest priority goes to patients with hematologic malignancies, those receiving or coming off chemotherapy or experiencing myelosuppression and immune paresis, as well as those who have undergone organ transplants. Age and other comorbidities, such as diabetes or obesity, play into the lineup as well.
To further hone their priority list, the Levine Cancer Institute has implemented a cancer-centered Hospital at Home initiative. The program includes 40 oncology nurse navigators who routinely screen and score all cancer patients who test positive for COVID-19 by their symptoms and risk factors. For a time-sensitive treatment like Paxlovid, this close monitoring allows patients with COVID to access the pills within 5 days of symptom onset.
Ultimately, “the decision regarding who gets these drugs is [made] by a team to overcome any risk of personal bias, and some of it just comes down to the interface between clinical judgment and available data,” Dr. Raghavan told this news organization. “Although we’d like to have more COVID drugs available and fewer patients with COVID, we have been able to get adequate supplies for our most at-risk patients.”
Like Dr. Raghavan, Karen Bloch, MD, MPH, the medical director for the COVID Infusion Clinic at Vanderbilt University Medical Center (VUMC), said the clinic has had to be highly selective about which patients would benefit most from the COVID monoclonal antibodies. For patients with cancer, her team prioritizes individuals who would be least able to develop antibodies through vaccination or natural infection – which includes patients with B cell malignancies, acute myeloid leukemia, or multiple myeloma receiving active treatment, as well as those who recently received an allogeneic or autologous stem cell transplant.
“Since our criteria for treatment with therapies such as sotrovimab and Evusheld are pretty stringent, we have had sufficient supply to treat those who meet our internal ‘category 1’ predetermined criteria,” said Dr. Bloch, professor of medicine and associate division director for clinical affairs at VUMC, Nashville. “More recently, as the supply chain has begun to open up, we’ve been able to loosen our criteria for sotrovimab, though not for Evusheld yet.”
The Yale team described a similar evolution. “Initially, only a small subset of oncology patients could get these drugs,” said Osama (Sam) Abdelghany, PharmD, MHA, associate director of Oncology Pharmacy Services at Smilow Cancer Hospital. But as the caseload has diminished, Dr. Abdelghany noted, “we have been able to reach many more patients with COVID-19.”
An equitable system?
Dr. Wynia, who has written many reports on crisis standards of care, has spent thousands of hours delving into the ethics of allocating scarce resources during a disaster.
A core problem arises when there are too many people who need a scarce resource and no way of differentiating among them.
In response to the limited supply of COVID-19 treatments, some institutions, such as the University of Pittsburgh Medical Center and Massachusetts General Hospital, have created a lottery system. Others, such as Johns Hopkins Medicine, have opted for first come, first served. Each strategy comes with caveats.
“First come, first served prioritization may be quicker, but it gives more well-resourced people an advantage and lends itself to people abusing the system or exacerbating existing disparities,” Dr. Wynia said.
While a lottery system may be more equitable, this strategy often comes at the price of efficiency. “The practicality of doing a lottery when you have to make a decision about whether or not to treat the patient sitting in front of you comes with its own challenges,” Dr. Wynia said.
At the University of Colorado, he explained, the health center constantly scans medical records for patients who have been diagnosed with COVID and fall into a high-risk group. That way clinicians can call or email those most likely to benefit from these drugs.
“It ends up being a bit of a first come, first served strategy,” Dr. Wynia said. “But we also do not have a huge supply coming in each week, so reaching out to the most eligible people when we have the drugs in hand means more privileged patients are less likely to game the system.”
To manage the supply of Evusheld, Timothy Kubal, MD, MBA, and colleagues also reach out to patients most likely to benefit – specifically, those who can’t mount an adequate antibody response after vaccination.
“We screen all of our patients who have been receiving anti-CD20 agents and other chemotherapy agents known to suppress antibody response,” Dr. Kubal, a medical oncologist/hematologist at the Moffitt Institute in Tampa, Florida, said in an interview. “We then test those patients for antibodies and deliver Evusheld if they have no evidence of antibodies.”
Fortunately, in the coming months, distribution of these drugs should improve significantly. Pfizer says it expects to deliver 10 million courses of Paxlovid by the end of June, and another 10 million by the end of September. More than 1 million courses of sotrovimab should be distributed by GlaxoSmithKline through the end of March. And, recently, the Biden administration announced it purchased 1.2 million courses of Evusheld from AstraZeneca.
“Every few weeks, because the COVID picture changes, the demand changes,” said Dr. Louissaint. “With vaccination rates going up and cases going down, fewer patients will need these products.”
Still, the constant barrage of supply shortages over the past 2 years – from COVID tests, ventilators, and personal protective equipment early on to COVID vaccines a year later and more recently health care staff and COVID tests once again – has taken its toll.
“We have faced supply challenge after challenge and have had to be creative in each situation,” said Lisa Barbarotta, MSN, APRN, program director of Oncology Education and Clinical Practice at Smilow Cancer Hospital. “Nothing has been easy about this.”
And, Dr. Bloch cautioned, even with broader access to COVID-19 drugs on the horizon, there is still no substitute for vaccination. “Getting vaccinated is the best and first line of defense for most people,” she said.
A version of this article first appeared on Medscape.com.
In mid-November, Kevin Billingsley, MD, MBA, chief medical officer at Yale Cancer Center, New Haven, Conn., was keeping a close eye on the new COVID variant sweeping across South Africa. Six weeks later, the Omicron variant had become the dominant strain in the U.S. – and the Yale health system was no exception.
“As we entered January, we had a breathtaking rate of infection in our hospital,” said Dr. Billingsley, who also leads clinical care at the Smilow Cancer Hospital. “Some of the newly authorized COVID agents were available but not widely enough to make a clinically meaningful impact to protect all high-risk individuals during this surge.”
That left the team at Yale with difficult decisions about who would receive these treatments and who wouldn’t.
The health system convened a COVID-19 immunocompromised working group to identify which patients should get priority access to one of the promising drugs authorized to treat the infection – the monoclonal antibody sotrovimab and antiviral pills Paxlovid and molnupiravir – or the sole available option to prevent it, Evusheld.
“Although clinically sound, none of these decisions have been easy,” Dr. Billingsley told this news organization. “We have done a lot of case-by-case reviewing and a lot of handwringing. Omicron has been a wild ride for us all, and we have been doing the best we can with limited resources.”
‘We’re seeing incredible variability’
The team at Yale is not alone. The restricted supply of COVID-19 treatments has led many oncologists and other experts across the U.S. to create carefully curated lists of their most vulnerable patients.
In late December, the National Institutes of Health published broad criteria to help clinicians prioritize patients most likely to benefit from these therapies. A handful of state health departments, including those in Michigan and Minnesota, established their own standards. Patients with cancer – specifically those with hematologic malignancies and receiving oncology therapies that compromise the immune system – appeared at the top of everyone’s list.
But ultimately individual decisions about who receives these drugs and how they’re allocated fell to institutions.
“Overall, what we’re seeing is incredible variability across the country, because there’s no uniform agreement on what comprises best practices on allocating scarce resources,” said Matthew Wynia, MD, MPH, professor of medicine and director of the Center for Bioethics and Humanities at the University of Colorado, Aurora. “There are so many people at the top of most lists, and the drugs are in such short supply, that there’s no guarantee even those in the top tier will get it.”
This news organization spoke to experts across the country about their experiences accessing these treatments during the Omicron surge and their strategies prioritizing patients with cancer.
Dealing with limited supply
Overall, the limited supply of COVID-19 drugs means not every patient who’s eligible to receive a treatment will get one.
A snapshot of the past 2 weeks, for instance, shows that the count of new infections hit almost 4.3 million, while distribution of the two antiviral pills Paxlovid and molnupiravir and the monoclonal antibody sotrovimab reached just over 600,000 courses.
Since receiving emergency use authorization in early December, almost 500,000 courses of the pre-exposure prophylactic agent Evusheld – which offers about 6 months of protection for immunocompromised individuals – have been distributed; however, about 7 million adults in the U.S. could potentially benefit from it.
In addition, the distribution of drugs is uneven. The federal government manages the overall distribution to states, but states then decide how to divvy up these allocations to hospitals, pharmacies, and medical centers. In Ohio, for instance, the antivirals go to providers who already receive monoclonal antibodies, while in Tennessee, the supply of antiviral agents only goes to Walmart pharmacies.
This strategy, Dr. Wynia explained, can leave clinicians at the mercy of where and how much states decide to allocate to each location. “I’ve heard of some hospitals and health systems in Colorado that aren’t using all they’ve got, but most don’t have nearly enough,” Dr. Wynia said. However, he noted, “some of that is inevitable. We will never get a perfect distribution of these drugs when there is such variable need and demand.”
And, according to Nicolette Louissaint, PhD, MBA, senior vice president of policy and strategic planning at the Healthcare Distribution Alliance in Arlington, Virginia, “we can take some comfort that the federal government is actively looking at cases from week to week and working with state and local health departments to see who needs these products, which means the process is constantly being reviewed and adjusted.”
Plus, not every positive COVID-19 case, even among immunocompromised individuals, necessarily warrants treatment. “If, for instance, an individual with cancer has a mild case of COVID-19, their provider may not deem it necessary for them to receive treatment,” Dr. Louissaint noted.
Still, given the limited and unpredictable supply, “we have had to be thoughtful about who gets these drugs,” said Derek Raghavan, MD, PhD, president of the Levine Cancer Institute, part of the 40-hospital Atrium Health system in Charlotte, North Carolina.
Dr. Raghavan said the highest priority goes to patients with hematologic malignancies, those receiving or coming off chemotherapy or experiencing myelosuppression and immune paresis, as well as those who have undergone organ transplants. Age and other comorbidities, such as diabetes or obesity, play into the lineup as well.
To further hone their priority list, the Levine Cancer Institute has implemented a cancer-centered Hospital at Home initiative. The program includes 40 oncology nurse navigators who routinely screen and score all cancer patients who test positive for COVID-19 by their symptoms and risk factors. For a time-sensitive treatment like Paxlovid, this close monitoring allows patients with COVID to access the pills within 5 days of symptom onset.
Ultimately, “the decision regarding who gets these drugs is [made] by a team to overcome any risk of personal bias, and some of it just comes down to the interface between clinical judgment and available data,” Dr. Raghavan told this news organization. “Although we’d like to have more COVID drugs available and fewer patients with COVID, we have been able to get adequate supplies for our most at-risk patients.”
Like Dr. Raghavan, Karen Bloch, MD, MPH, the medical director for the COVID Infusion Clinic at Vanderbilt University Medical Center (VUMC), said the clinic has had to be highly selective about which patients would benefit most from the COVID monoclonal antibodies. For patients with cancer, her team prioritizes individuals who would be least able to develop antibodies through vaccination or natural infection – which includes patients with B cell malignancies, acute myeloid leukemia, or multiple myeloma receiving active treatment, as well as those who recently received an allogeneic or autologous stem cell transplant.
“Since our criteria for treatment with therapies such as sotrovimab and Evusheld are pretty stringent, we have had sufficient supply to treat those who meet our internal ‘category 1’ predetermined criteria,” said Dr. Bloch, professor of medicine and associate division director for clinical affairs at VUMC, Nashville. “More recently, as the supply chain has begun to open up, we’ve been able to loosen our criteria for sotrovimab, though not for Evusheld yet.”
The Yale team described a similar evolution. “Initially, only a small subset of oncology patients could get these drugs,” said Osama (Sam) Abdelghany, PharmD, MHA, associate director of Oncology Pharmacy Services at Smilow Cancer Hospital. But as the caseload has diminished, Dr. Abdelghany noted, “we have been able to reach many more patients with COVID-19.”
An equitable system?
Dr. Wynia, who has written many reports on crisis standards of care, has spent thousands of hours delving into the ethics of allocating scarce resources during a disaster.
A core problem arises when there are too many people who need a scarce resource and no way of differentiating among them.
In response to the limited supply of COVID-19 treatments, some institutions, such as the University of Pittsburgh Medical Center and Massachusetts General Hospital, have created a lottery system. Others, such as Johns Hopkins Medicine, have opted for first come, first served. Each strategy comes with caveats.
“First come, first served prioritization may be quicker, but it gives more well-resourced people an advantage and lends itself to people abusing the system or exacerbating existing disparities,” Dr. Wynia said.
While a lottery system may be more equitable, this strategy often comes at the price of efficiency. “The practicality of doing a lottery when you have to make a decision about whether or not to treat the patient sitting in front of you comes with its own challenges,” Dr. Wynia said.
At the University of Colorado, he explained, the health center constantly scans medical records for patients who have been diagnosed with COVID and fall into a high-risk group. That way clinicians can call or email those most likely to benefit from these drugs.
“It ends up being a bit of a first come, first served strategy,” Dr. Wynia said. “But we also do not have a huge supply coming in each week, so reaching out to the most eligible people when we have the drugs in hand means more privileged patients are less likely to game the system.”
To manage the supply of Evusheld, Timothy Kubal, MD, MBA, and colleagues also reach out to patients most likely to benefit – specifically, those who can’t mount an adequate antibody response after vaccination.
“We screen all of our patients who have been receiving anti-CD20 agents and other chemotherapy agents known to suppress antibody response,” Dr. Kubal, a medical oncologist/hematologist at the Moffitt Institute in Tampa, Florida, said in an interview. “We then test those patients for antibodies and deliver Evusheld if they have no evidence of antibodies.”
Fortunately, in the coming months, distribution of these drugs should improve significantly. Pfizer says it expects to deliver 10 million courses of Paxlovid by the end of June, and another 10 million by the end of September. More than 1 million courses of sotrovimab should be distributed by GlaxoSmithKline through the end of March. And, recently, the Biden administration announced it purchased 1.2 million courses of Evusheld from AstraZeneca.
“Every few weeks, because the COVID picture changes, the demand changes,” said Dr. Louissaint. “With vaccination rates going up and cases going down, fewer patients will need these products.”
Still, the constant barrage of supply shortages over the past 2 years – from COVID tests, ventilators, and personal protective equipment early on to COVID vaccines a year later and more recently health care staff and COVID tests once again – has taken its toll.
“We have faced supply challenge after challenge and have had to be creative in each situation,” said Lisa Barbarotta, MSN, APRN, program director of Oncology Education and Clinical Practice at Smilow Cancer Hospital. “Nothing has been easy about this.”
And, Dr. Bloch cautioned, even with broader access to COVID-19 drugs on the horizon, there is still no substitute for vaccination. “Getting vaccinated is the best and first line of defense for most people,” she said.
A version of this article first appeared on Medscape.com.
New stroke risk score developed for COVID patients
Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.
“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.
The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.
The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.
Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.
Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.
The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.
Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:
- history of stroke
- no fever at the time of hospital admission
- no history of pulmonary disease
- high white blood cell count
- history of hypertension
- high systolic blood pressure at the time of hospital admission
That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.
A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.
In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”
The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.
“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”
The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.
A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.
Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.
“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.
Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.
Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.
Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”
The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”
He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”
Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”
“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.
This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.
“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”
The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.
“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.
The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.
The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.
Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.
Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.
The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.
Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:
- history of stroke
- no fever at the time of hospital admission
- no history of pulmonary disease
- high white blood cell count
- history of hypertension
- high systolic blood pressure at the time of hospital admission
That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.
A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.
In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”
The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.
“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”
The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.
A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.
Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.
“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.
Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.
Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.
Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”
The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”
He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”
Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”
“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.
This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.
“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”
The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.
“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.
The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.
The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.
Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.
Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.
Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.
The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.
Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:
- history of stroke
- no fever at the time of hospital admission
- no history of pulmonary disease
- high white blood cell count
- history of hypertension
- high systolic blood pressure at the time of hospital admission
That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.
A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.
In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”
The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.
“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”
The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.
A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.
Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.
“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.
Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.
Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.
Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”
The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”
He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”
Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”
“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.
This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.
“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”
The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
FDA delays action on Pfizer vaccine for kids under 5
for younger children until data on the effects of three doses is available.
Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said the plan for a meeting the week of Feb. 14 of the FDA’s Vaccines and Related Biological Products Advisory Committee was to “understand if two doses would provide sufficient protection to move forward.”
Pfizer has asked the FDA to authorize the use of its mRNA vaccine for children under the age of 5. But, Dr. Marks said, “in looking through the data we realized now … that at this time it makes sense for us to wait until we have the data of the evaluation of a third dose before taking action.”
“If we feel something doesn’t meet (our) standard, we can’t go forward,” he said. “Rather than an issue of having anyone question the process, I hope this reassures people that the process has a standard.”
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, predicted in January that the Pfizer vaccine for younger kids could be available this month. But, he also predicted three doses would be required.
Pfizer announced in mid-December that it planned to submit data to the FDA during the first half of 2022 if the three-dose study was successful. At that time, Pfizer said it didn’t identify any safety concerns with the 3-microgram dose for children ages 6 months to 4 years, which is much lower than the 30-microgram dose given to adults.
A version of this article first appeared on WebMD.com.
for younger children until data on the effects of three doses is available.
Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said the plan for a meeting the week of Feb. 14 of the FDA’s Vaccines and Related Biological Products Advisory Committee was to “understand if two doses would provide sufficient protection to move forward.”
Pfizer has asked the FDA to authorize the use of its mRNA vaccine for children under the age of 5. But, Dr. Marks said, “in looking through the data we realized now … that at this time it makes sense for us to wait until we have the data of the evaluation of a third dose before taking action.”
“If we feel something doesn’t meet (our) standard, we can’t go forward,” he said. “Rather than an issue of having anyone question the process, I hope this reassures people that the process has a standard.”
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, predicted in January that the Pfizer vaccine for younger kids could be available this month. But, he also predicted three doses would be required.
Pfizer announced in mid-December that it planned to submit data to the FDA during the first half of 2022 if the three-dose study was successful. At that time, Pfizer said it didn’t identify any safety concerns with the 3-microgram dose for children ages 6 months to 4 years, which is much lower than the 30-microgram dose given to adults.
A version of this article first appeared on WebMD.com.
for younger children until data on the effects of three doses is available.
Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said the plan for a meeting the week of Feb. 14 of the FDA’s Vaccines and Related Biological Products Advisory Committee was to “understand if two doses would provide sufficient protection to move forward.”
Pfizer has asked the FDA to authorize the use of its mRNA vaccine for children under the age of 5. But, Dr. Marks said, “in looking through the data we realized now … that at this time it makes sense for us to wait until we have the data of the evaluation of a third dose before taking action.”
“If we feel something doesn’t meet (our) standard, we can’t go forward,” he said. “Rather than an issue of having anyone question the process, I hope this reassures people that the process has a standard.”
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, predicted in January that the Pfizer vaccine for younger kids could be available this month. But, he also predicted three doses would be required.
Pfizer announced in mid-December that it planned to submit data to the FDA during the first half of 2022 if the three-dose study was successful. At that time, Pfizer said it didn’t identify any safety concerns with the 3-microgram dose for children ages 6 months to 4 years, which is much lower than the 30-microgram dose given to adults.
A version of this article first appeared on WebMD.com.
Novel drug targets raised Lp(a): topline results released
Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.
Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.
High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.
SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.
The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.
No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.
Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.
Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.
A version of this article first appeared on Medscape.com.
Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.
Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.
High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.
SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.
The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.
No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.
Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.
Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.
A version of this article first appeared on Medscape.com.
Topline results from the phase 1 APOLLO study of SLN360, a short interfering ribonucleic acid (siRNA) targeting lipoprotein(a), showed it significantly reduced Lp(a) in a dose-dependent manner from 46% to up to 98%.
Reductions of up to 81% were maintained out to 150 days, according to a release from the developer of the drug, Silence Therapeutics.
High Lp(a) affects about one in five people worldwide and is a genetic risk factor for cardiovascular disease. There are no approved medications that selectively lower Lp(a), and levels cannot be significantly modified through lifestyle changes or any approved medications.
SLN360 is a siRNA that is designed to lower Lp(a) production by using the body’s natural process of RNA interference to target and silence messenger RNA transcribed from the LPA gene in liver cells.
The first-in-human APOLLO trial evaluated 32 patients with serum Lp(a) concentrations of at least 150 nmol/L and no cardiovascular disease who received a single subcutaneous dose of SLN360 (30 mg, 100 mg, less than or equal to 300 mg, or less than or equal to 600 mg) or placebo and were followed for up to 150 days.
No clinically important safety concerns were identified, although low-grade adverse events at the injection site occurred, most prominently at the highest dose, according to the company.
Study follow-up has been extended to 1 year. Patient enrollment continues in the multiple-ascending dose portion of the phase 1 study in patients with high Lp(a) and a confirmed history of stable atherosclerotic cardiovascular disease, the company statement notes.
Detailed results from APOLLO will be presented in a late-breaking clinical trials session at the American College of Cardiology Annual Scientific Session on April 3 by principal investigator Steven E. Nissen, MD, Cleveland Clinic.
A version of this article first appeared on Medscape.com.
CDC releases updated draft guidance on opioid prescribing
The Centers for Disease Controls and Prevention has released a draft update of its current Clinical Practice Guidelines for Prescribing Opioids for pain management and is asking for public comment before moving forward.
The last guidance on this topic was released in 2016 and, among other things, noted that clinicians should be cautious when considering increasing dosage of opioids to 50 or more morphine milligram equivalents (MME)/day and should avoid increasing to a dose of 90 or more MME/day. It also noted that 3 days or less “will often be sufficient” regarding the quantity of lowest effective dose of immediate-release opioids to be prescribed for acute pain – and that more than 7 days “will rarely be needed.”
In the new report from the CDC’s National Center for Injury Prevention and Control (NCIPC), those dose limits have been replaced with the suggestion that clinicians use their best judgement – albeit still urging conservative use and even the possibility of nonopioid treatments.
The updated recommendations are now open for public comment via the Federal Register’s website through April 11.
“This comment period provides another critical opportunity for diverse audiences to offer their perspective on the draft clinical practice guideline,” Christopher M. Jones, PharmD, DrPH, acting director for the NCIPC, said in a release.
“We want to hear many voices from the public, including people living with pain and health care providers who help their patients manage pain,” Dr. Jones added.
Outpatient recommendations
The CDC noted that the updated guidance provides “evidence-based recommendations” for treatment of adults with acute, subacute, or chronic pain. It does not include guidance for managing pain related to sickle cell disease, cancer, or palliative care.
It is aimed at primary care clinicians and others who manage pain in an outpatient setting, including in dental and postsurgical practices and for those discharging patients from emergency departments. It does not apply to inpatient care.
The draft guidance includes 12 recommendations focused on four key areas:
- Helping clinicians determine whether or not to initiate opioid treatment for pain
- Opioid selection and dosage
- Duration of use and follow-up
- Assessing risk and addressing potential harms from use
The overall aim “is to ensure people have access to safe, accessible, and effective pain management that improves their function and quality of life while illuminating and reducing risks associated with prescription opioids and ultimately reducing the consequences of prescription opioid misuse and overdose,” the CDC notes.
In addition, the guidance itself “is intended to be a clinical tool to improve communication between providers and patients and empower them to make informed, patient-centered decisions,” the agency said in a press release.
It added that the new recommendations “are not intended to be applied as inflexible standards of care.” Rather, it is intended as a guide to support health care providers in their clinical decisionmaking as they provide individualized patient care.
Patients, caregivers, and providers are invited to submit comments over the next 60 days through the Federal Register docket.
“It is vitally important to CDC that we receive, process, and understand public feedback during the guideline update process,” the agency noted.
“The ultimate goal of this clinical practice guideline is to help people set and achieve personal goals to reduce their pain and improve their function and quality of life. Getting feedback from the public is essential to achieving this goal,” Dr. Jones said.
A version of this article first appeared on Medscape.com.
The Centers for Disease Controls and Prevention has released a draft update of its current Clinical Practice Guidelines for Prescribing Opioids for pain management and is asking for public comment before moving forward.
The last guidance on this topic was released in 2016 and, among other things, noted that clinicians should be cautious when considering increasing dosage of opioids to 50 or more morphine milligram equivalents (MME)/day and should avoid increasing to a dose of 90 or more MME/day. It also noted that 3 days or less “will often be sufficient” regarding the quantity of lowest effective dose of immediate-release opioids to be prescribed for acute pain – and that more than 7 days “will rarely be needed.”
In the new report from the CDC’s National Center for Injury Prevention and Control (NCIPC), those dose limits have been replaced with the suggestion that clinicians use their best judgement – albeit still urging conservative use and even the possibility of nonopioid treatments.
The updated recommendations are now open for public comment via the Federal Register’s website through April 11.
“This comment period provides another critical opportunity for diverse audiences to offer their perspective on the draft clinical practice guideline,” Christopher M. Jones, PharmD, DrPH, acting director for the NCIPC, said in a release.
“We want to hear many voices from the public, including people living with pain and health care providers who help their patients manage pain,” Dr. Jones added.
Outpatient recommendations
The CDC noted that the updated guidance provides “evidence-based recommendations” for treatment of adults with acute, subacute, or chronic pain. It does not include guidance for managing pain related to sickle cell disease, cancer, or palliative care.
It is aimed at primary care clinicians and others who manage pain in an outpatient setting, including in dental and postsurgical practices and for those discharging patients from emergency departments. It does not apply to inpatient care.
The draft guidance includes 12 recommendations focused on four key areas:
- Helping clinicians determine whether or not to initiate opioid treatment for pain
- Opioid selection and dosage
- Duration of use and follow-up
- Assessing risk and addressing potential harms from use
The overall aim “is to ensure people have access to safe, accessible, and effective pain management that improves their function and quality of life while illuminating and reducing risks associated with prescription opioids and ultimately reducing the consequences of prescription opioid misuse and overdose,” the CDC notes.
In addition, the guidance itself “is intended to be a clinical tool to improve communication between providers and patients and empower them to make informed, patient-centered decisions,” the agency said in a press release.
It added that the new recommendations “are not intended to be applied as inflexible standards of care.” Rather, it is intended as a guide to support health care providers in their clinical decisionmaking as they provide individualized patient care.
Patients, caregivers, and providers are invited to submit comments over the next 60 days through the Federal Register docket.
“It is vitally important to CDC that we receive, process, and understand public feedback during the guideline update process,” the agency noted.
“The ultimate goal of this clinical practice guideline is to help people set and achieve personal goals to reduce their pain and improve their function and quality of life. Getting feedback from the public is essential to achieving this goal,” Dr. Jones said.
A version of this article first appeared on Medscape.com.
The Centers for Disease Controls and Prevention has released a draft update of its current Clinical Practice Guidelines for Prescribing Opioids for pain management and is asking for public comment before moving forward.
The last guidance on this topic was released in 2016 and, among other things, noted that clinicians should be cautious when considering increasing dosage of opioids to 50 or more morphine milligram equivalents (MME)/day and should avoid increasing to a dose of 90 or more MME/day. It also noted that 3 days or less “will often be sufficient” regarding the quantity of lowest effective dose of immediate-release opioids to be prescribed for acute pain – and that more than 7 days “will rarely be needed.”
In the new report from the CDC’s National Center for Injury Prevention and Control (NCIPC), those dose limits have been replaced with the suggestion that clinicians use their best judgement – albeit still urging conservative use and even the possibility of nonopioid treatments.
The updated recommendations are now open for public comment via the Federal Register’s website through April 11.
“This comment period provides another critical opportunity for diverse audiences to offer their perspective on the draft clinical practice guideline,” Christopher M. Jones, PharmD, DrPH, acting director for the NCIPC, said in a release.
“We want to hear many voices from the public, including people living with pain and health care providers who help their patients manage pain,” Dr. Jones added.
Outpatient recommendations
The CDC noted that the updated guidance provides “evidence-based recommendations” for treatment of adults with acute, subacute, or chronic pain. It does not include guidance for managing pain related to sickle cell disease, cancer, or palliative care.
It is aimed at primary care clinicians and others who manage pain in an outpatient setting, including in dental and postsurgical practices and for those discharging patients from emergency departments. It does not apply to inpatient care.
The draft guidance includes 12 recommendations focused on four key areas:
- Helping clinicians determine whether or not to initiate opioid treatment for pain
- Opioid selection and dosage
- Duration of use and follow-up
- Assessing risk and addressing potential harms from use
The overall aim “is to ensure people have access to safe, accessible, and effective pain management that improves their function and quality of life while illuminating and reducing risks associated with prescription opioids and ultimately reducing the consequences of prescription opioid misuse and overdose,” the CDC notes.
In addition, the guidance itself “is intended to be a clinical tool to improve communication between providers and patients and empower them to make informed, patient-centered decisions,” the agency said in a press release.
It added that the new recommendations “are not intended to be applied as inflexible standards of care.” Rather, it is intended as a guide to support health care providers in their clinical decisionmaking as they provide individualized patient care.
Patients, caregivers, and providers are invited to submit comments over the next 60 days through the Federal Register docket.
“It is vitally important to CDC that we receive, process, and understand public feedback during the guideline update process,” the agency noted.
“The ultimate goal of this clinical practice guideline is to help people set and achieve personal goals to reduce their pain and improve their function and quality of life. Getting feedback from the public is essential to achieving this goal,” Dr. Jones said.
A version of this article first appeared on Medscape.com.
Omicron death rate higher than during Delta surge
With the Omicron variant now accounting for almost 100% of COVID-19 cases in the United States, the Washington Post reported.
That’s higher than the approximately 2,000 daily deaths in fall 2021 during the Delta surge, but less than the 3,000 daily deaths in January 2021, when COVID vaccines were not widely available, the Post’s data analysis said.
The Omicron variant generally causes less severe disease than other strains of COVID, but because it is so transmissible, Omicron is infecting higher raw numbers of people that previous strains.
“Even if on a per-case basis fewer people develop severe illness and die, when you apply a small percentage to a very large number, you get a substantial number,” Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins University, Baltimore, told the Post.
The unvaccinated, people over 75, and people with underlying medical conditions are the groups most endangered by Omicron, the Post said. About half of the deaths in January 2022 were among people over 75, compared with about a third in September 2021 during the Delta surge.
The age trend is seen in Florida, said Jason Salemi, PhD, an epidemiologist at the University of South Florida, Tampa. He told the Post that seniors accounted for about 85% of deaths in the winter of 2020-2021, about 60% during the Delta surge, and about 80% now during the Omicron surge.
The uptick in senior deaths may have occurred because seniors who got vaccinated in early 2021 didn’t get boosted ahead of the Omicron surge, he said.
“Omicron may be less severe for younger people, but it will still find vulnerable seniors in our community,” Dr. Salemi said. “That vaccination back in February isn’t as effective now if you aren’t boosted.”
CDC data shows that 95% of people in the United States over 65 have gotten at least one dose of vaccine, 88.5% are fully vaccinated, but only 62.5% have gotten a booster dose.
The COVID death rate is highest in the Midwest. During the last 2 months, Chicago reported more than 1,000 COVID deaths, almost as much as the December 2020 peak, The Post said. Minorities have been hit hard. About third of the city’s population is Black but about half the COVID victims are Black, the Post said.
“It’s been challenging because it goes up against the national narrative that omicron is nothing dangerous,” said Allison Arwady, commissioner of the Chicago Department of Public Health.
In a Feb. 9 news briefing at the White House, CDC Director Rochelle Walensky, MD, provided slightly different statistics on COVID-related deaths. She said that the 7-day average of daily deaths was about 2,400, up 3% from the previous week.
The 7-day daily average of cases is about 247,300 cases per day, down 44% from the previous week, she said. Hospital admissions are about 13,000 daily, down 25% from the previous week.
Dr. Walensky said the Omicron variant now accounts for almost 100% of COVID viruses circulating in the United States.
A version of this article first appeared on WebMD.com.
With the Omicron variant now accounting for almost 100% of COVID-19 cases in the United States, the Washington Post reported.
That’s higher than the approximately 2,000 daily deaths in fall 2021 during the Delta surge, but less than the 3,000 daily deaths in January 2021, when COVID vaccines were not widely available, the Post’s data analysis said.
The Omicron variant generally causes less severe disease than other strains of COVID, but because it is so transmissible, Omicron is infecting higher raw numbers of people that previous strains.
“Even if on a per-case basis fewer people develop severe illness and die, when you apply a small percentage to a very large number, you get a substantial number,” Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins University, Baltimore, told the Post.
The unvaccinated, people over 75, and people with underlying medical conditions are the groups most endangered by Omicron, the Post said. About half of the deaths in January 2022 were among people over 75, compared with about a third in September 2021 during the Delta surge.
The age trend is seen in Florida, said Jason Salemi, PhD, an epidemiologist at the University of South Florida, Tampa. He told the Post that seniors accounted for about 85% of deaths in the winter of 2020-2021, about 60% during the Delta surge, and about 80% now during the Omicron surge.
The uptick in senior deaths may have occurred because seniors who got vaccinated in early 2021 didn’t get boosted ahead of the Omicron surge, he said.
“Omicron may be less severe for younger people, but it will still find vulnerable seniors in our community,” Dr. Salemi said. “That vaccination back in February isn’t as effective now if you aren’t boosted.”
CDC data shows that 95% of people in the United States over 65 have gotten at least one dose of vaccine, 88.5% are fully vaccinated, but only 62.5% have gotten a booster dose.
The COVID death rate is highest in the Midwest. During the last 2 months, Chicago reported more than 1,000 COVID deaths, almost as much as the December 2020 peak, The Post said. Minorities have been hit hard. About third of the city’s population is Black but about half the COVID victims are Black, the Post said.
“It’s been challenging because it goes up against the national narrative that omicron is nothing dangerous,” said Allison Arwady, commissioner of the Chicago Department of Public Health.
In a Feb. 9 news briefing at the White House, CDC Director Rochelle Walensky, MD, provided slightly different statistics on COVID-related deaths. She said that the 7-day average of daily deaths was about 2,400, up 3% from the previous week.
The 7-day daily average of cases is about 247,300 cases per day, down 44% from the previous week, she said. Hospital admissions are about 13,000 daily, down 25% from the previous week.
Dr. Walensky said the Omicron variant now accounts for almost 100% of COVID viruses circulating in the United States.
A version of this article first appeared on WebMD.com.
With the Omicron variant now accounting for almost 100% of COVID-19 cases in the United States, the Washington Post reported.
That’s higher than the approximately 2,000 daily deaths in fall 2021 during the Delta surge, but less than the 3,000 daily deaths in January 2021, when COVID vaccines were not widely available, the Post’s data analysis said.
The Omicron variant generally causes less severe disease than other strains of COVID, but because it is so transmissible, Omicron is infecting higher raw numbers of people that previous strains.
“Even if on a per-case basis fewer people develop severe illness and die, when you apply a small percentage to a very large number, you get a substantial number,” Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins University, Baltimore, told the Post.
The unvaccinated, people over 75, and people with underlying medical conditions are the groups most endangered by Omicron, the Post said. About half of the deaths in January 2022 were among people over 75, compared with about a third in September 2021 during the Delta surge.
The age trend is seen in Florida, said Jason Salemi, PhD, an epidemiologist at the University of South Florida, Tampa. He told the Post that seniors accounted for about 85% of deaths in the winter of 2020-2021, about 60% during the Delta surge, and about 80% now during the Omicron surge.
The uptick in senior deaths may have occurred because seniors who got vaccinated in early 2021 didn’t get boosted ahead of the Omicron surge, he said.
“Omicron may be less severe for younger people, but it will still find vulnerable seniors in our community,” Dr. Salemi said. “That vaccination back in February isn’t as effective now if you aren’t boosted.”
CDC data shows that 95% of people in the United States over 65 have gotten at least one dose of vaccine, 88.5% are fully vaccinated, but only 62.5% have gotten a booster dose.
The COVID death rate is highest in the Midwest. During the last 2 months, Chicago reported more than 1,000 COVID deaths, almost as much as the December 2020 peak, The Post said. Minorities have been hit hard. About third of the city’s population is Black but about half the COVID victims are Black, the Post said.
“It’s been challenging because it goes up against the national narrative that omicron is nothing dangerous,” said Allison Arwady, commissioner of the Chicago Department of Public Health.
In a Feb. 9 news briefing at the White House, CDC Director Rochelle Walensky, MD, provided slightly different statistics on COVID-related deaths. She said that the 7-day average of daily deaths was about 2,400, up 3% from the previous week.
The 7-day daily average of cases is about 247,300 cases per day, down 44% from the previous week, she said. Hospital admissions are about 13,000 daily, down 25% from the previous week.
Dr. Walensky said the Omicron variant now accounts for almost 100% of COVID viruses circulating in the United States.
A version of this article first appeared on WebMD.com.
Scientists see hope in new therapy for COVID-19 brain fog patients
People with long-COVID “brain fog” may be able to recover mental abilities that were dulled or stolen from them by the virus through an approach that has improved the effects of stroke, traumatic brain injury, and other post-viral disorders, doctors and scientists say.
For a lucky portion of the population, COVID-19 lasts a handful of days with minor symptoms. But for an estimated 37% who contract the virus, symptoms can linger for weeks, months, or even years. One of the most common symptoms of long COVID is brain fog: a life-altering condition characterized by slow thinking, confusion, difficulty remembering things, and poor concentration.
The approaches are based on the concept of neuroplasticity: The ability of neural networks in the brain to change, adapt, and strengthen, much like a muscle in the body that has been trained and exercised.
“The brain’s ability to bounce back from injury is what neuroplasticity is, and I’ve worked with people in our rehab clinic who have had brain tumors or suffer the effects of surgery or radiation on the brain, and people who have had West Nile virus, HIV, and meningitis,” said Tom Bergquist, PhD, clinical neuropsychologist at Mayo Clinic in Rochester, Minn. “There’s not a week that goes by that I don’t see someone recovering from COVID-19.”
One of the approaches used in the clinic is errorless learning, or having a patient with memory problems repeat information a certain number of times without error. The repetition helps rebuild those memory skills that were weakened during infection, Dr. Bergquist says.
People who have experienced brain fog after other viral infections have seen improvements with these approaches. Ben Ahrens, co-founder and CEO of re-origin – a company that offers neuroplasticity therapy – says he had long-term cognitive issues after a Lyme disease infection. Posttreatment Lyme disease syndrome, or chronic Lyme disease, occurs in about 1 in 10 people who are infected.
Mr. Ahrens says he was struck with Lyme 10 years ago and had brain fog, joint pain, and brain lesions detectable on scans for several years after infection.
According to Mr. Ahrens, neuroplasticity-based therapies help combat what researchers have found may be a lingering memory of past infections that lead to a heightened immune response, causing lingering symptoms.
“Essentially, what we believe is happening here, is the brain has learned that these symptoms are life-threatening – because, in fact, they can be,” Mr. Ahrens said. “The brain’s one job is to protect the body, and once it’s learned to associate these symptoms with that potentially very dangerous pathogen, even after it’s gone, things like a normal headache can trigger an immune cascade.”
Studies are underway at the University of Alabama at Birmingham to examine whether constraint-induced therapy – an approach rooted in neuroplasticity and historically used for loss of limb and speech function – is also effective for cognitive impairments like brain fog.
One technique they use is called shaping, which requires a person to repeatedly carry out their personal best function of impaired use – for example, remembering household tasks they have previously forgotten. That is done multiple times over several weeks in the clinic, and patients are given ways to transfer those skills to real-life use.
So far, the results are promising, said Edward Taub, PhD, researcher and professor of psychology at the University of Alabama at Birmingham.
When used in the past for physical impairments, researchers have noted not just clinical improvements, but structural changes. It led to an increase in the brain’s gray matter – which allows individuals to control movement, memory, and emotions – and improved white matter, which helps communication between gray matter areas.
Though results of the cognitive studies have not been published, Dr. Taub said patients with brain fog have shown improvement after just 35 hours of therapy and are nearly 100% improved after 6 months.
“The idea behind this is that the brain is responsive to use,” Dr. Taub said. “The amount of brain territory that’s dedicated to supporting or mediating a given behavioral function depends on the demands placed on the brain.”
A version of this article first appeared on WebMD.com.
People with long-COVID “brain fog” may be able to recover mental abilities that were dulled or stolen from them by the virus through an approach that has improved the effects of stroke, traumatic brain injury, and other post-viral disorders, doctors and scientists say.
For a lucky portion of the population, COVID-19 lasts a handful of days with minor symptoms. But for an estimated 37% who contract the virus, symptoms can linger for weeks, months, or even years. One of the most common symptoms of long COVID is brain fog: a life-altering condition characterized by slow thinking, confusion, difficulty remembering things, and poor concentration.
The approaches are based on the concept of neuroplasticity: The ability of neural networks in the brain to change, adapt, and strengthen, much like a muscle in the body that has been trained and exercised.
“The brain’s ability to bounce back from injury is what neuroplasticity is, and I’ve worked with people in our rehab clinic who have had brain tumors or suffer the effects of surgery or radiation on the brain, and people who have had West Nile virus, HIV, and meningitis,” said Tom Bergquist, PhD, clinical neuropsychologist at Mayo Clinic in Rochester, Minn. “There’s not a week that goes by that I don’t see someone recovering from COVID-19.”
One of the approaches used in the clinic is errorless learning, or having a patient with memory problems repeat information a certain number of times without error. The repetition helps rebuild those memory skills that were weakened during infection, Dr. Bergquist says.
People who have experienced brain fog after other viral infections have seen improvements with these approaches. Ben Ahrens, co-founder and CEO of re-origin – a company that offers neuroplasticity therapy – says he had long-term cognitive issues after a Lyme disease infection. Posttreatment Lyme disease syndrome, or chronic Lyme disease, occurs in about 1 in 10 people who are infected.
Mr. Ahrens says he was struck with Lyme 10 years ago and had brain fog, joint pain, and brain lesions detectable on scans for several years after infection.
According to Mr. Ahrens, neuroplasticity-based therapies help combat what researchers have found may be a lingering memory of past infections that lead to a heightened immune response, causing lingering symptoms.
“Essentially, what we believe is happening here, is the brain has learned that these symptoms are life-threatening – because, in fact, they can be,” Mr. Ahrens said. “The brain’s one job is to protect the body, and once it’s learned to associate these symptoms with that potentially very dangerous pathogen, even after it’s gone, things like a normal headache can trigger an immune cascade.”
Studies are underway at the University of Alabama at Birmingham to examine whether constraint-induced therapy – an approach rooted in neuroplasticity and historically used for loss of limb and speech function – is also effective for cognitive impairments like brain fog.
One technique they use is called shaping, which requires a person to repeatedly carry out their personal best function of impaired use – for example, remembering household tasks they have previously forgotten. That is done multiple times over several weeks in the clinic, and patients are given ways to transfer those skills to real-life use.
So far, the results are promising, said Edward Taub, PhD, researcher and professor of psychology at the University of Alabama at Birmingham.
When used in the past for physical impairments, researchers have noted not just clinical improvements, but structural changes. It led to an increase in the brain’s gray matter – which allows individuals to control movement, memory, and emotions – and improved white matter, which helps communication between gray matter areas.
Though results of the cognitive studies have not been published, Dr. Taub said patients with brain fog have shown improvement after just 35 hours of therapy and are nearly 100% improved after 6 months.
“The idea behind this is that the brain is responsive to use,” Dr. Taub said. “The amount of brain territory that’s dedicated to supporting or mediating a given behavioral function depends on the demands placed on the brain.”
A version of this article first appeared on WebMD.com.
People with long-COVID “brain fog” may be able to recover mental abilities that were dulled or stolen from them by the virus through an approach that has improved the effects of stroke, traumatic brain injury, and other post-viral disorders, doctors and scientists say.
For a lucky portion of the population, COVID-19 lasts a handful of days with minor symptoms. But for an estimated 37% who contract the virus, symptoms can linger for weeks, months, or even years. One of the most common symptoms of long COVID is brain fog: a life-altering condition characterized by slow thinking, confusion, difficulty remembering things, and poor concentration.
The approaches are based on the concept of neuroplasticity: The ability of neural networks in the brain to change, adapt, and strengthen, much like a muscle in the body that has been trained and exercised.
“The brain’s ability to bounce back from injury is what neuroplasticity is, and I’ve worked with people in our rehab clinic who have had brain tumors or suffer the effects of surgery or radiation on the brain, and people who have had West Nile virus, HIV, and meningitis,” said Tom Bergquist, PhD, clinical neuropsychologist at Mayo Clinic in Rochester, Minn. “There’s not a week that goes by that I don’t see someone recovering from COVID-19.”
One of the approaches used in the clinic is errorless learning, or having a patient with memory problems repeat information a certain number of times without error. The repetition helps rebuild those memory skills that were weakened during infection, Dr. Bergquist says.
People who have experienced brain fog after other viral infections have seen improvements with these approaches. Ben Ahrens, co-founder and CEO of re-origin – a company that offers neuroplasticity therapy – says he had long-term cognitive issues after a Lyme disease infection. Posttreatment Lyme disease syndrome, or chronic Lyme disease, occurs in about 1 in 10 people who are infected.
Mr. Ahrens says he was struck with Lyme 10 years ago and had brain fog, joint pain, and brain lesions detectable on scans for several years after infection.
According to Mr. Ahrens, neuroplasticity-based therapies help combat what researchers have found may be a lingering memory of past infections that lead to a heightened immune response, causing lingering symptoms.
“Essentially, what we believe is happening here, is the brain has learned that these symptoms are life-threatening – because, in fact, they can be,” Mr. Ahrens said. “The brain’s one job is to protect the body, and once it’s learned to associate these symptoms with that potentially very dangerous pathogen, even after it’s gone, things like a normal headache can trigger an immune cascade.”
Studies are underway at the University of Alabama at Birmingham to examine whether constraint-induced therapy – an approach rooted in neuroplasticity and historically used for loss of limb and speech function – is also effective for cognitive impairments like brain fog.
One technique they use is called shaping, which requires a person to repeatedly carry out their personal best function of impaired use – for example, remembering household tasks they have previously forgotten. That is done multiple times over several weeks in the clinic, and patients are given ways to transfer those skills to real-life use.
So far, the results are promising, said Edward Taub, PhD, researcher and professor of psychology at the University of Alabama at Birmingham.
When used in the past for physical impairments, researchers have noted not just clinical improvements, but structural changes. It led to an increase in the brain’s gray matter – which allows individuals to control movement, memory, and emotions – and improved white matter, which helps communication between gray matter areas.
Though results of the cognitive studies have not been published, Dr. Taub said patients with brain fog have shown improvement after just 35 hours of therapy and are nearly 100% improved after 6 months.
“The idea behind this is that the brain is responsive to use,” Dr. Taub said. “The amount of brain territory that’s dedicated to supporting or mediating a given behavioral function depends on the demands placed on the brain.”
A version of this article first appeared on WebMD.com.