Federal Practitioner

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

Nearly half of older adults with dementia experience falls, suggests new research that also identifies multiple risk factors for these falls.

In a study of more than 5,500 participants, 45.5% of those with dementia experienced one or more falls, compared with 30.9% of their peers without dementia.

Vision impairment and living with a spouse were among the strongest predictors of future fall risk among participants living with dementia. Interestingly, high neighborhood social deprivation, which is reflected by such things as income and education, was associated with lower odds of falling.

Overall, the results highlight the need for a multidisciplinary approach to preventing falls among elderly individuals with dementia, said lead author Safiyyah M. Okoye, PhD, assistant professor, College of Nursing and Health Professions, Drexel University, Philadelphia.

“We need to consider different dimensions and figure out how we can try to go beyond the clinic in our interactions,” she said.

Dr. Okoye noted that in addition to reviewing medications that may contribute to falls and screening for vision problems, clinicians might also consider resources to improve the home environment and ensure that families have appropriate caregiving.

The findings were published online  in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
 

No ‘silver bullet’

Every year, falls cause millions of injuries in older adults, and those with dementia are especially vulnerable. This population has twice the risk of falling and up to three times the risk of incurring serious fall-related injuries, such as fractures, the researchers noted.

Falls are a leading cause of hospitalization among those with dementia. Previous evidence has shown that persons with dementia are more likely to experience negative health consequences, such as delirium, while in hospital, compared with those without dementia. Even minor fall-related injuries are associated with the patient’s being discharged to a nursing home rather than returning home.

Dr. Okoye stressed that many factors contribute to falls, including health status; function, such as the ability to walk and balance; medications; home environment; and activity level.

“There are multidimensional aspects, and we can’t just find one silver bullet to address falls. It should be addressed comprehensively,” she said.

Existing studies “overwhelmingly” focus on factors related to health and function that could be addressed in the doctor’s office or with a referral, rather than on environmental and social factors, Dr. Okoye noted.

And even though the risk of falling is high among community-dwelling seniors with dementia, very few studies have addressed the risk of falls among these adults, she added.

The new analysis included a nationally representative sample of 5,581 community-dwelling adults who participated in both the 2015 and 2016 National Health and Aging Trends Study (NHATS). The NHATS is a population-based survey of health and disability trends and trajectories among Americans aged 65 years and older.

During interviews, participants were asked, personally or by proxy, about falls during the previous 12 months. Having fallen at baseline was evaluated as a possible predictor of falls in the subsequent 12 months.

To determine probable dementia, researchers asked whether a doctor had ever told the participants that they had dementia or Alzheimer’s disease. They also used a dementia screening questionnaire and neuropsychological tests of memory, orientation, and executive function.

Of the total sample, most (n = 5,093) did not have dementia.

Physical environmental factors that were assessed included conditions at home, such as clutter, tripping hazards, and structural issues, as well as neighborhood social and economic deprivation – such as income, education levels, and employment status.
 

Fall rates and counterintuitive findings

Results showed that significantly more of those with dementia than without experienced one or more falls (45.5% vs. 30.9%; P < .001).

In addition, a history of falling was significantly associated with subsequent falls among those with dementia (odds ratio, 6.20; 95% confidence interval, 3.81-10.09), as was vision impairment (OR, 2.22; 95% CI, 1.12-4.40) and living with a spouse versus alone (OR, 2.43; 95% CI, 1.09-5.43).

A possible explanation for higher fall risk among those living with a partner is that those living alone usually have better functioning, the investigators noted. Also, live-in partners tend to be of a similar age as the person with dementia and may have challenges of their own.

Interestingly, high neighborhood social deprivation was associated with lower odds of falling (OR, 0.55 for the highest deprivation scores; 95% CI, 0.31-0.98), a finding Dr. Okoye said was “counterintuitive.”

This result could be related to the social environment, she noted. “Maybe there are more people around in the house, more people with eyes on the person, or more people in the community who know the person. Despite the low economic resources, there could be social resources there,” she said.

The new findings underscore the idea that falling is a multidimensional phenomenon among older adults with dementia as well as those without dementia, Dr. Okoye noted.

Doctors can play a role in reducing falls among patients with dementia by asking about falls, possibly eliminating medications that are associated with risk of falling, and screening for and correcting vision and hearing impairments, she suggested.

They may also help determine household hazards for a patient, such as clutter and poor lighting, and ensure that these are addressed, Dr. Okoye added.
 

No surprise

Commenting on the study, David S. Knopman, MD, a clinical neurologist at Mayo Clinic, Rochester, Minn., said the finding that visual impairment and a prior history of falling are predictive of subsequent falls “comes as no surprise.”

Dr. Knopman, whose research focuses on late-life cognitive disorders, was not involved with the current study.

Risk reduction is “of course” a key management goal, he said. “Vigilance and optimizing the patient’s living space to reduce fall risks are the major strategies,” he added.

Dr. Knopman reiterated that falls among those with dementia are associated with higher mortality and often lead to loss of the capacity to live outside of an institution.

The study was supported by the National Institute on Aging. The investigators and Dr. Knopman report no relevant financial relationships.

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

Nearly half of older adults with dementia experience falls, suggests new research that also identifies multiple risk factors for these falls.

In a study of more than 5,500 participants, 45.5% of those with dementia experienced one or more falls, compared with 30.9% of their peers without dementia.

Vision impairment and living with a spouse were among the strongest predictors of future fall risk among participants living with dementia. Interestingly, high neighborhood social deprivation, which is reflected by such things as income and education, was associated with lower odds of falling.

Overall, the results highlight the need for a multidisciplinary approach to preventing falls among elderly individuals with dementia, said lead author Safiyyah M. Okoye, PhD, assistant professor, College of Nursing and Health Professions, Drexel University, Philadelphia.

“We need to consider different dimensions and figure out how we can try to go beyond the clinic in our interactions,” she said.

Dr. Okoye noted that in addition to reviewing medications that may contribute to falls and screening for vision problems, clinicians might also consider resources to improve the home environment and ensure that families have appropriate caregiving.

The findings were published online  in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
 

No ‘silver bullet’

Every year, falls cause millions of injuries in older adults, and those with dementia are especially vulnerable. This population has twice the risk of falling and up to three times the risk of incurring serious fall-related injuries, such as fractures, the researchers noted.

Falls are a leading cause of hospitalization among those with dementia. Previous evidence has shown that persons with dementia are more likely to experience negative health consequences, such as delirium, while in hospital, compared with those without dementia. Even minor fall-related injuries are associated with the patient’s being discharged to a nursing home rather than returning home.

Dr. Okoye stressed that many factors contribute to falls, including health status; function, such as the ability to walk and balance; medications; home environment; and activity level.

“There are multidimensional aspects, and we can’t just find one silver bullet to address falls. It should be addressed comprehensively,” she said.

Existing studies “overwhelmingly” focus on factors related to health and function that could be addressed in the doctor’s office or with a referral, rather than on environmental and social factors, Dr. Okoye noted.

And even though the risk of falling is high among community-dwelling seniors with dementia, very few studies have addressed the risk of falls among these adults, she added.

The new analysis included a nationally representative sample of 5,581 community-dwelling adults who participated in both the 2015 and 2016 National Health and Aging Trends Study (NHATS). The NHATS is a population-based survey of health and disability trends and trajectories among Americans aged 65 years and older.

During interviews, participants were asked, personally or by proxy, about falls during the previous 12 months. Having fallen at baseline was evaluated as a possible predictor of falls in the subsequent 12 months.

To determine probable dementia, researchers asked whether a doctor had ever told the participants that they had dementia or Alzheimer’s disease. They also used a dementia screening questionnaire and neuropsychological tests of memory, orientation, and executive function.

Of the total sample, most (n = 5,093) did not have dementia.

Physical environmental factors that were assessed included conditions at home, such as clutter, tripping hazards, and structural issues, as well as neighborhood social and economic deprivation – such as income, education levels, and employment status.
 

Fall rates and counterintuitive findings

Results showed that significantly more of those with dementia than without experienced one or more falls (45.5% vs. 30.9%; P < .001).

In addition, a history of falling was significantly associated with subsequent falls among those with dementia (odds ratio, 6.20; 95% confidence interval, 3.81-10.09), as was vision impairment (OR, 2.22; 95% CI, 1.12-4.40) and living with a spouse versus alone (OR, 2.43; 95% CI, 1.09-5.43).

A possible explanation for higher fall risk among those living with a partner is that those living alone usually have better functioning, the investigators noted. Also, live-in partners tend to be of a similar age as the person with dementia and may have challenges of their own.

Interestingly, high neighborhood social deprivation was associated with lower odds of falling (OR, 0.55 for the highest deprivation scores; 95% CI, 0.31-0.98), a finding Dr. Okoye said was “counterintuitive.”

This result could be related to the social environment, she noted. “Maybe there are more people around in the house, more people with eyes on the person, or more people in the community who know the person. Despite the low economic resources, there could be social resources there,” she said.

The new findings underscore the idea that falling is a multidimensional phenomenon among older adults with dementia as well as those without dementia, Dr. Okoye noted.

Doctors can play a role in reducing falls among patients with dementia by asking about falls, possibly eliminating medications that are associated with risk of falling, and screening for and correcting vision and hearing impairments, she suggested.

They may also help determine household hazards for a patient, such as clutter and poor lighting, and ensure that these are addressed, Dr. Okoye added.
 

No surprise

Commenting on the study, David S. Knopman, MD, a clinical neurologist at Mayo Clinic, Rochester, Minn., said the finding that visual impairment and a prior history of falling are predictive of subsequent falls “comes as no surprise.”

Dr. Knopman, whose research focuses on late-life cognitive disorders, was not involved with the current study.

Risk reduction is “of course” a key management goal, he said. “Vigilance and optimizing the patient’s living space to reduce fall risks are the major strategies,” he added.

Dr. Knopman reiterated that falls among those with dementia are associated with higher mortality and often lead to loss of the capacity to live outside of an institution.

The study was supported by the National Institute on Aging. The investigators and Dr. Knopman report no relevant financial relationships.

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

Nearly half of older adults with dementia experience falls, suggests new research that also identifies multiple risk factors for these falls.

In a study of more than 5,500 participants, 45.5% of those with dementia experienced one or more falls, compared with 30.9% of their peers without dementia.

Vision impairment and living with a spouse were among the strongest predictors of future fall risk among participants living with dementia. Interestingly, high neighborhood social deprivation, which is reflected by such things as income and education, was associated with lower odds of falling.

Overall, the results highlight the need for a multidisciplinary approach to preventing falls among elderly individuals with dementia, said lead author Safiyyah M. Okoye, PhD, assistant professor, College of Nursing and Health Professions, Drexel University, Philadelphia.

“We need to consider different dimensions and figure out how we can try to go beyond the clinic in our interactions,” she said.

Dr. Okoye noted that in addition to reviewing medications that may contribute to falls and screening for vision problems, clinicians might also consider resources to improve the home environment and ensure that families have appropriate caregiving.

The findings were published online  in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
 

No ‘silver bullet’

Every year, falls cause millions of injuries in older adults, and those with dementia are especially vulnerable. This population has twice the risk of falling and up to three times the risk of incurring serious fall-related injuries, such as fractures, the researchers noted.

Falls are a leading cause of hospitalization among those with dementia. Previous evidence has shown that persons with dementia are more likely to experience negative health consequences, such as delirium, while in hospital, compared with those without dementia. Even minor fall-related injuries are associated with the patient’s being discharged to a nursing home rather than returning home.

Dr. Okoye stressed that many factors contribute to falls, including health status; function, such as the ability to walk and balance; medications; home environment; and activity level.

“There are multidimensional aspects, and we can’t just find one silver bullet to address falls. It should be addressed comprehensively,” she said.

Existing studies “overwhelmingly” focus on factors related to health and function that could be addressed in the doctor’s office or with a referral, rather than on environmental and social factors, Dr. Okoye noted.

And even though the risk of falling is high among community-dwelling seniors with dementia, very few studies have addressed the risk of falls among these adults, she added.

The new analysis included a nationally representative sample of 5,581 community-dwelling adults who participated in both the 2015 and 2016 National Health and Aging Trends Study (NHATS). The NHATS is a population-based survey of health and disability trends and trajectories among Americans aged 65 years and older.

During interviews, participants were asked, personally or by proxy, about falls during the previous 12 months. Having fallen at baseline was evaluated as a possible predictor of falls in the subsequent 12 months.

To determine probable dementia, researchers asked whether a doctor had ever told the participants that they had dementia or Alzheimer’s disease. They also used a dementia screening questionnaire and neuropsychological tests of memory, orientation, and executive function.

Of the total sample, most (n = 5,093) did not have dementia.

Physical environmental factors that were assessed included conditions at home, such as clutter, tripping hazards, and structural issues, as well as neighborhood social and economic deprivation – such as income, education levels, and employment status.
 

Fall rates and counterintuitive findings

Results showed that significantly more of those with dementia than without experienced one or more falls (45.5% vs. 30.9%; P < .001).

In addition, a history of falling was significantly associated with subsequent falls among those with dementia (odds ratio, 6.20; 95% confidence interval, 3.81-10.09), as was vision impairment (OR, 2.22; 95% CI, 1.12-4.40) and living with a spouse versus alone (OR, 2.43; 95% CI, 1.09-5.43).

A possible explanation for higher fall risk among those living with a partner is that those living alone usually have better functioning, the investigators noted. Also, live-in partners tend to be of a similar age as the person with dementia and may have challenges of their own.

Interestingly, high neighborhood social deprivation was associated with lower odds of falling (OR, 0.55 for the highest deprivation scores; 95% CI, 0.31-0.98), a finding Dr. Okoye said was “counterintuitive.”

This result could be related to the social environment, she noted. “Maybe there are more people around in the house, more people with eyes on the person, or more people in the community who know the person. Despite the low economic resources, there could be social resources there,” she said.

The new findings underscore the idea that falling is a multidimensional phenomenon among older adults with dementia as well as those without dementia, Dr. Okoye noted.

Doctors can play a role in reducing falls among patients with dementia by asking about falls, possibly eliminating medications that are associated with risk of falling, and screening for and correcting vision and hearing impairments, she suggested.

They may also help determine household hazards for a patient, such as clutter and poor lighting, and ensure that these are addressed, Dr. Okoye added.
 

No surprise

Commenting on the study, David S. Knopman, MD, a clinical neurologist at Mayo Clinic, Rochester, Minn., said the finding that visual impairment and a prior history of falling are predictive of subsequent falls “comes as no surprise.”

Dr. Knopman, whose research focuses on late-life cognitive disorders, was not involved with the current study.

Risk reduction is “of course” a key management goal, he said. “Vigilance and optimizing the patient’s living space to reduce fall risks are the major strategies,” he added.

Dr. Knopman reiterated that falls among those with dementia are associated with higher mortality and often lead to loss of the capacity to live outside of an institution.

The study was supported by the National Institute on Aging. The investigators and Dr. Knopman report no relevant financial relationships.

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

Vaccinations have substantially reduced morbidity and mortality from many infectious diseases. Despite the clear value of vaccinations in public health, efforts to better understand adverse events (AEs) following immunization are important to sustain public trust and vaccine confidence. Noninfectious inflammation of the heart may manifest as myocarditis or pericarditis, or occasionally, with shared signs and symptoms of each, as myopericarditis. This is a rare AE following some immunizations. Vaccine-associated myocarditis, pericarditis, or myopericarditis (VAMP) has been most clearly associated with smallpox vaccines and mRNA COVID-19 vaccines.^1-6 Although extremely rare, VAMP also has been associated with other vaccines.^7,8 Limited information exists to guide shared clinical decision making on COVID-19 vaccination in persons with a history of VAMP. It is unknown whether individuals with a history of VAMP are at higher risk for developing a recurrence or experiencing a more severe outcome following COVID-19 vaccination.

Methods

As part of the collaborative public health mission with the Centers for Disease Control and Prevention (CDC) for enhanced vaccine AE surveillance, the Defense Health Agency Immunization Healthcare Division (IHD) maintains a clinical database of service members and beneficiaries referred for suspected AEs following immunizations. A review of all AEs following immunization cases in this database from January 1, 2003, through February 28, 2022, identified individuals meeting the following criteria: (a) VAMP prior to receipt of COVID-19 vaccine; (b) receipt of COVID-19 vaccine in 2021; and (c) medical documentation in available electronic health records sufficient to describe health status at least 30 days following COVID-19 vaccination.⁹ If medical entries suggested cardiac symptoms following a COVID-19 vaccine, additional information was sought to verify VAMP based on current published criteria.^10,11 Both the initial VAMP cases and the suspected COVID-19 VAMP cases were adjudicated by a team of vaccine experts and specialists in immunology, cardiology, and preventive medicine.

This retrospective review was approved and conducted in accordance with the Walter Reed National Military Medical Center Institutional Review Board protocol #20664. All individuals with recurrent VAMP consented to share their health records and clinical details.

Results

Among 9260 cases in the IHD database, 431 met the case definition for VAMP.

Among the 179 patients included in this analysis, 171 (96%) were male. Their median age was 39 years at the time of COVID-19 vaccination.

Within 1 month of receipt of any COVID-19 vaccine, 11 individuals had documented symptoms suggesting cardiac involvement, specifically, chest pain, palpitations, or dyspnea. After cardiac evaluation, 4 patients met the criteria for VAMP after COVID-19 vaccination.^10,11 Seven patients either did not meet the criteria for VAMP or had alternative causes for their symptoms.

Two men aged 49 and 50 years with a history of vaccine-associated myocarditis following smallpox vaccination (Dryvax and ACAM2000) developed myocarditis 3 days after their second dose of the Moderna vaccine. One of these patients received a Pfizer-BioNTech booster 10 months later with no recurrence of symptoms. A 55-year-old man with a history of vaccine-associated myocarditis following Dryvax vaccination developed myocarditis 2 days after his Pfizer-BioNTech booster. None of the patients who developed post-COVID-19 VAMP reported residual symptoms from their initial VAMP episode, which occurred 12 to 18 years earlier. All were hospitalized briefly for observation and had complete symptom resolution within 6 weeks.

A 25-year-old man developed pericarditis 4 days after his second Pfizer-BioNTech vaccination. His previous ACAM2000 vaccine-associated myocarditis occurred 3 years earlier, with no residual symptoms. Of note, he had a mild COVID-19 infection 78 days before the onset of his pericarditis. After the onset of his COVID-19 vaccine-associated pericarditis, he continued to experience transient bouts of chest pressure and exertional dyspnea that resolved within 7 months of onset.

The median interval between COVID-19 vaccine doses in those who developed post-COVID-19 VAMP was within the recommended mRNA vaccine dosing intervals of 3 to 4 weeks and was consistent with the median mRNA vaccine dosing intervals among the entire cohort.

Due to the small cohort size and other limitations of this study, the suggested rate of cardiac injury in this review (4 cases in 179 persons, or 2.2%) is an imprecise estimate of risk in a small population (95% CI, 0.1%-4.4%). While this rate may seem higher than expected within the general population after COVID-19 vaccination, it is lower than the estimated lifetime risk of recurrent myocarditis from any cause.^6,12

Discussion

To our knowledge, this is the first report describing cardiac outcomes after COVID-19 vaccination among a cohort of individuals with prior history of VAMP. Four cases of COVID-19 VAMP were identified among 179 patients with previous VAMP. All cases had experienced VAMP after the smallpox vaccine several years earlier, with complete resolution of symptoms. Three cases presented with recurrent VAMP after their second dose of an mRNA COVID-19 vaccine, and one after an mRNA booster dose. All fully recovered over the course of several months.

Myocarditis is a heterogeneous inflammatory injury with diverse, sometimes idiopathic, etiologies.¹³ In contrast to infection-related cardiac injury, prior reports of vaccine-associated myocarditis have suggested a hypersensitivity reaction characterized by patchy eosinophilic infiltrates, a benign clinical course, and good prognosis.^2,3

There are several common features between VAMP after smallpox and COVID-19 vaccination. Cases occur predominantly in young men. The onset of symptoms after smallpox vaccine (mean, 10 days) and after mRNA COVID-19 vaccine (mean, 3 days) appears to correspond to the timing of peak postvaccination pro-inflammatory cytokine elevation.¹⁴ While all VAMP cases are serious events, the majority of patients appear to have a relatively benign clinical course with rapid and full recovery.¹³

Patients who have experienced an inflammatory cardiac injury may be at higher risk for recurrence, but quantifying risk of this rare phenomenon is challenging. Cases of VAMP after the COVID-19 vaccine have occasionally been reported in patients with previous cardiac injury unrelated to vaccination.^15-17 The cases presented here represent the first report of recurrent VAMP following prior non-COVID-19 vaccinations.

Most patients with prior VAMP in this cohort did not experience cardiac-suggestive symptoms following COVID-19 vaccination. Among 11 patients who developed symptoms, 3 had confirmed myocarditis and 1 had confirmed pericarditis. The clinical course for these patients with recurrent VAMP was observed to be no different in severity or duration from those who experience new-onset VAMP.⁴ All other patients not meeting criteria for VAMP or having alternative explanations for their symptoms also had a benign clinical course. Nonetheless, of the study cohort of 179, recurrent VAMP was diagnosed in 4 of the 11 who developed cardiac-suggestive symptoms following COVID-19 vaccination. The importance of cardiac evaluation should be emphasized for any patient presenting with chest pain, dyspnea, or other cardiac-suggestive symptoms following vaccination.

Strengths and Limitations

The strength of this review of VAMP recurrence associated with COVID-19 vaccination derives from our large and unique longitudinal database of VAMP among current and prior service members. Additionally, the IHD’s ongoing enhanced vaccine AEs surveillance provides the opportunity to contact patients and review their electronic health records over an extended interval of time.

When interpreting this report’s implications, limitations inherent to any retrospective case review should be considered. The cohort of cases of prior VAMP included primarily healthy, fit, young service members; this population is not representative of the general population. The cohort included prior VAMP cases that generally occurred after smallpox vaccination. Experiences after smallpox vaccine may not apply to cardiac injury from other vaccines or etiologies. By the nature of this review, the population studied at the time of COVID-19 vaccination was somewhat older than those most likely to develop an initial bout of VAMP.² This review was limited by information available in the electronic health records of a small number of patients. Subclinical cases of VAMP and cases without adequate clinical evaluation also could not be included.

Conclusions

Noninfectious inflammation of the heart (myocarditis, pericarditis, or myopericarditis) is a rare AE following certain vaccines, especially live replicating smallpox vaccine and mRNA COVID-19 vaccines. In this observational analysis, the majority of patients with previous VAMP successfully received a COVID-19 vaccine without recurrence. The 4 patients who were identified with recurrent VAMP following COVID-19 vaccination all recovered with supportive care. While the CDC endorses that individuals with a history of infectious myocarditis may receive COVID-19 vaccine after symptoms have resolved, there is currently insufficient safety data regarding COVID-19 vaccination of those with prior non-COVID-19 VAMP or following subsequent COVID-19 vaccination in those with prior VAMP related to COVID-19.¹⁰ For these individuals, COVID-19 vaccination is a precaution.¹⁰ Although insufficient to determine a precise level of risk, this report does provide data on which to base the CDC-recommended shared decision-making counseling of these patients. More research is needed to better define factors that increase risk for, or protection from, immune-mediated AEs following immunization, including VAMP. While benefits of vaccination have clearly outweighed risks during the COVID-19 pandemic, such research may optimize future vaccine recommendations.¹⁸

Vaccinations have substantially reduced morbidity and mortality from many infectious diseases. Despite the clear value of vaccinations in public health, efforts to better understand adverse events (AEs) following immunization are important to sustain public trust and vaccine confidence. Noninfectious inflammation of the heart may manifest as myocarditis or pericarditis, or occasionally, with shared signs and symptoms of each, as myopericarditis. This is a rare AE following some immunizations. Vaccine-associated myocarditis, pericarditis, or myopericarditis (VAMP) has been most clearly associated with smallpox vaccines and mRNA COVID-19 vaccines.^1-6 Although extremely rare, VAMP also has been associated with other vaccines.^7,8 Limited information exists to guide shared clinical decision making on COVID-19 vaccination in persons with a history of VAMP. It is unknown whether individuals with a history of VAMP are at higher risk for developing a recurrence or experiencing a more severe outcome following COVID-19 vaccination.

Methods

As part of the collaborative public health mission with the Centers for Disease Control and Prevention (CDC) for enhanced vaccine AE surveillance, the Defense Health Agency Immunization Healthcare Division (IHD) maintains a clinical database of service members and beneficiaries referred for suspected AEs following immunizations. A review of all AEs following immunization cases in this database from January 1, 2003, through February 28, 2022, identified individuals meeting the following criteria: (a) VAMP prior to receipt of COVID-19 vaccine; (b) receipt of COVID-19 vaccine in 2021; and (c) medical documentation in available electronic health records sufficient to describe health status at least 30 days following COVID-19 vaccination.⁹ If medical entries suggested cardiac symptoms following a COVID-19 vaccine, additional information was sought to verify VAMP based on current published criteria.^10,11 Both the initial VAMP cases and the suspected COVID-19 VAMP cases were adjudicated by a team of vaccine experts and specialists in immunology, cardiology, and preventive medicine.

This retrospective review was approved and conducted in accordance with the Walter Reed National Military Medical Center Institutional Review Board protocol #20664. All individuals with recurrent VAMP consented to share their health records and clinical details.

Results

Among 9260 cases in the IHD database, 431 met the case definition for VAMP.

Among the 179 patients included in this analysis, 171 (96%) were male. Their median age was 39 years at the time of COVID-19 vaccination.

Within 1 month of receipt of any COVID-19 vaccine, 11 individuals had documented symptoms suggesting cardiac involvement, specifically, chest pain, palpitations, or dyspnea. After cardiac evaluation, 4 patients met the criteria for VAMP after COVID-19 vaccination.^10,11 Seven patients either did not meet the criteria for VAMP or had alternative causes for their symptoms.

Two men aged 49 and 50 years with a history of vaccine-associated myocarditis following smallpox vaccination (Dryvax and ACAM2000) developed myocarditis 3 days after their second dose of the Moderna vaccine. One of these patients received a Pfizer-BioNTech booster 10 months later with no recurrence of symptoms. A 55-year-old man with a history of vaccine-associated myocarditis following Dryvax vaccination developed myocarditis 2 days after his Pfizer-BioNTech booster. None of the patients who developed post-COVID-19 VAMP reported residual symptoms from their initial VAMP episode, which occurred 12 to 18 years earlier. All were hospitalized briefly for observation and had complete symptom resolution within 6 weeks.

A 25-year-old man developed pericarditis 4 days after his second Pfizer-BioNTech vaccination. His previous ACAM2000 vaccine-associated myocarditis occurred 3 years earlier, with no residual symptoms. Of note, he had a mild COVID-19 infection 78 days before the onset of his pericarditis. After the onset of his COVID-19 vaccine-associated pericarditis, he continued to experience transient bouts of chest pressure and exertional dyspnea that resolved within 7 months of onset.

The median interval between COVID-19 vaccine doses in those who developed post-COVID-19 VAMP was within the recommended mRNA vaccine dosing intervals of 3 to 4 weeks and was consistent with the median mRNA vaccine dosing intervals among the entire cohort.

Due to the small cohort size and other limitations of this study, the suggested rate of cardiac injury in this review (4 cases in 179 persons, or 2.2%) is an imprecise estimate of risk in a small population (95% CI, 0.1%-4.4%). While this rate may seem higher than expected within the general population after COVID-19 vaccination, it is lower than the estimated lifetime risk of recurrent myocarditis from any cause.^6,12

Discussion

To our knowledge, this is the first report describing cardiac outcomes after COVID-19 vaccination among a cohort of individuals with prior history of VAMP. Four cases of COVID-19 VAMP were identified among 179 patients with previous VAMP. All cases had experienced VAMP after the smallpox vaccine several years earlier, with complete resolution of symptoms. Three cases presented with recurrent VAMP after their second dose of an mRNA COVID-19 vaccine, and one after an mRNA booster dose. All fully recovered over the course of several months.

Myocarditis is a heterogeneous inflammatory injury with diverse, sometimes idiopathic, etiologies.¹³ In contrast to infection-related cardiac injury, prior reports of vaccine-associated myocarditis have suggested a hypersensitivity reaction characterized by patchy eosinophilic infiltrates, a benign clinical course, and good prognosis.^2,3

There are several common features between VAMP after smallpox and COVID-19 vaccination. Cases occur predominantly in young men. The onset of symptoms after smallpox vaccine (mean, 10 days) and after mRNA COVID-19 vaccine (mean, 3 days) appears to correspond to the timing of peak postvaccination pro-inflammatory cytokine elevation.¹⁴ While all VAMP cases are serious events, the majority of patients appear to have a relatively benign clinical course with rapid and full recovery.¹³

Patients who have experienced an inflammatory cardiac injury may be at higher risk for recurrence, but quantifying risk of this rare phenomenon is challenging. Cases of VAMP after the COVID-19 vaccine have occasionally been reported in patients with previous cardiac injury unrelated to vaccination.^15-17 The cases presented here represent the first report of recurrent VAMP following prior non-COVID-19 vaccinations.

Most patients with prior VAMP in this cohort did not experience cardiac-suggestive symptoms following COVID-19 vaccination. Among 11 patients who developed symptoms, 3 had confirmed myocarditis and 1 had confirmed pericarditis. The clinical course for these patients with recurrent VAMP was observed to be no different in severity or duration from those who experience new-onset VAMP.⁴ All other patients not meeting criteria for VAMP or having alternative explanations for their symptoms also had a benign clinical course. Nonetheless, of the study cohort of 179, recurrent VAMP was diagnosed in 4 of the 11 who developed cardiac-suggestive symptoms following COVID-19 vaccination. The importance of cardiac evaluation should be emphasized for any patient presenting with chest pain, dyspnea, or other cardiac-suggestive symptoms following vaccination.

Strengths and Limitations

The strength of this review of VAMP recurrence associated with COVID-19 vaccination derives from our large and unique longitudinal database of VAMP among current and prior service members. Additionally, the IHD’s ongoing enhanced vaccine AEs surveillance provides the opportunity to contact patients and review their electronic health records over an extended interval of time.

When interpreting this report’s implications, limitations inherent to any retrospective case review should be considered. The cohort of cases of prior VAMP included primarily healthy, fit, young service members; this population is not representative of the general population. The cohort included prior VAMP cases that generally occurred after smallpox vaccination. Experiences after smallpox vaccine may not apply to cardiac injury from other vaccines or etiologies. By the nature of this review, the population studied at the time of COVID-19 vaccination was somewhat older than those most likely to develop an initial bout of VAMP.² This review was limited by information available in the electronic health records of a small number of patients. Subclinical cases of VAMP and cases without adequate clinical evaluation also could not be included.

Conclusions

Noninfectious inflammation of the heart (myocarditis, pericarditis, or myopericarditis) is a rare AE following certain vaccines, especially live replicating smallpox vaccine and mRNA COVID-19 vaccines. In this observational analysis, the majority of patients with previous VAMP successfully received a COVID-19 vaccine without recurrence. The 4 patients who were identified with recurrent VAMP following COVID-19 vaccination all recovered with supportive care. While the CDC endorses that individuals with a history of infectious myocarditis may receive COVID-19 vaccine after symptoms have resolved, there is currently insufficient safety data regarding COVID-19 vaccination of those with prior non-COVID-19 VAMP or following subsequent COVID-19 vaccination in those with prior VAMP related to COVID-19.¹⁰ For these individuals, COVID-19 vaccination is a precaution.¹⁰ Although insufficient to determine a precise level of risk, this report does provide data on which to base the CDC-recommended shared decision-making counseling of these patients. More research is needed to better define factors that increase risk for, or protection from, immune-mediated AEs following immunization, including VAMP. While benefits of vaccination have clearly outweighed risks during the COVID-19 pandemic, such research may optimize future vaccine recommendations.¹⁸

Vaccinations have substantially reduced morbidity and mortality from many infectious diseases. Despite the clear value of vaccinations in public health, efforts to better understand adverse events (AEs) following immunization are important to sustain public trust and vaccine confidence. Noninfectious inflammation of the heart may manifest as myocarditis or pericarditis, or occasionally, with shared signs and symptoms of each, as myopericarditis. This is a rare AE following some immunizations. Vaccine-associated myocarditis, pericarditis, or myopericarditis (VAMP) has been most clearly associated with smallpox vaccines and mRNA COVID-19 vaccines.^1-6 Although extremely rare, VAMP also has been associated with other vaccines.^7,8 Limited information exists to guide shared clinical decision making on COVID-19 vaccination in persons with a history of VAMP. It is unknown whether individuals with a history of VAMP are at higher risk for developing a recurrence or experiencing a more severe outcome following COVID-19 vaccination.

Methods

As part of the collaborative public health mission with the Centers for Disease Control and Prevention (CDC) for enhanced vaccine AE surveillance, the Defense Health Agency Immunization Healthcare Division (IHD) maintains a clinical database of service members and beneficiaries referred for suspected AEs following immunizations. A review of all AEs following immunization cases in this database from January 1, 2003, through February 28, 2022, identified individuals meeting the following criteria: (a) VAMP prior to receipt of COVID-19 vaccine; (b) receipt of COVID-19 vaccine in 2021; and (c) medical documentation in available electronic health records sufficient to describe health status at least 30 days following COVID-19 vaccination.⁹ If medical entries suggested cardiac symptoms following a COVID-19 vaccine, additional information was sought to verify VAMP based on current published criteria.^10,11 Both the initial VAMP cases and the suspected COVID-19 VAMP cases were adjudicated by a team of vaccine experts and specialists in immunology, cardiology, and preventive medicine.

This retrospective review was approved and conducted in accordance with the Walter Reed National Military Medical Center Institutional Review Board protocol #20664. All individuals with recurrent VAMP consented to share their health records and clinical details.

Results

Among 9260 cases in the IHD database, 431 met the case definition for VAMP.

Among the 179 patients included in this analysis, 171 (96%) were male. Their median age was 39 years at the time of COVID-19 vaccination.

Within 1 month of receipt of any COVID-19 vaccine, 11 individuals had documented symptoms suggesting cardiac involvement, specifically, chest pain, palpitations, or dyspnea. After cardiac evaluation, 4 patients met the criteria for VAMP after COVID-19 vaccination.^10,11 Seven patients either did not meet the criteria for VAMP or had alternative causes for their symptoms.

Two men aged 49 and 50 years with a history of vaccine-associated myocarditis following smallpox vaccination (Dryvax and ACAM2000) developed myocarditis 3 days after their second dose of the Moderna vaccine. One of these patients received a Pfizer-BioNTech booster 10 months later with no recurrence of symptoms. A 55-year-old man with a history of vaccine-associated myocarditis following Dryvax vaccination developed myocarditis 2 days after his Pfizer-BioNTech booster. None of the patients who developed post-COVID-19 VAMP reported residual symptoms from their initial VAMP episode, which occurred 12 to 18 years earlier. All were hospitalized briefly for observation and had complete symptom resolution within 6 weeks.

A 25-year-old man developed pericarditis 4 days after his second Pfizer-BioNTech vaccination. His previous ACAM2000 vaccine-associated myocarditis occurred 3 years earlier, with no residual symptoms. Of note, he had a mild COVID-19 infection 78 days before the onset of his pericarditis. After the onset of his COVID-19 vaccine-associated pericarditis, he continued to experience transient bouts of chest pressure and exertional dyspnea that resolved within 7 months of onset.

The median interval between COVID-19 vaccine doses in those who developed post-COVID-19 VAMP was within the recommended mRNA vaccine dosing intervals of 3 to 4 weeks and was consistent with the median mRNA vaccine dosing intervals among the entire cohort.

Due to the small cohort size and other limitations of this study, the suggested rate of cardiac injury in this review (4 cases in 179 persons, or 2.2%) is an imprecise estimate of risk in a small population (95% CI, 0.1%-4.4%). While this rate may seem higher than expected within the general population after COVID-19 vaccination, it is lower than the estimated lifetime risk of recurrent myocarditis from any cause.^6,12

Discussion

To our knowledge, this is the first report describing cardiac outcomes after COVID-19 vaccination among a cohort of individuals with prior history of VAMP. Four cases of COVID-19 VAMP were identified among 179 patients with previous VAMP. All cases had experienced VAMP after the smallpox vaccine several years earlier, with complete resolution of symptoms. Three cases presented with recurrent VAMP after their second dose of an mRNA COVID-19 vaccine, and one after an mRNA booster dose. All fully recovered over the course of several months.

Myocarditis is a heterogeneous inflammatory injury with diverse, sometimes idiopathic, etiologies.¹³ In contrast to infection-related cardiac injury, prior reports of vaccine-associated myocarditis have suggested a hypersensitivity reaction characterized by patchy eosinophilic infiltrates, a benign clinical course, and good prognosis.^2,3

There are several common features between VAMP after smallpox and COVID-19 vaccination. Cases occur predominantly in young men. The onset of symptoms after smallpox vaccine (mean, 10 days) and after mRNA COVID-19 vaccine (mean, 3 days) appears to correspond to the timing of peak postvaccination pro-inflammatory cytokine elevation.¹⁴ While all VAMP cases are serious events, the majority of patients appear to have a relatively benign clinical course with rapid and full recovery.¹³

Patients who have experienced an inflammatory cardiac injury may be at higher risk for recurrence, but quantifying risk of this rare phenomenon is challenging. Cases of VAMP after the COVID-19 vaccine have occasionally been reported in patients with previous cardiac injury unrelated to vaccination.^15-17 The cases presented here represent the first report of recurrent VAMP following prior non-COVID-19 vaccinations.

Most patients with prior VAMP in this cohort did not experience cardiac-suggestive symptoms following COVID-19 vaccination. Among 11 patients who developed symptoms, 3 had confirmed myocarditis and 1 had confirmed pericarditis. The clinical course for these patients with recurrent VAMP was observed to be no different in severity or duration from those who experience new-onset VAMP.⁴ All other patients not meeting criteria for VAMP or having alternative explanations for their symptoms also had a benign clinical course. Nonetheless, of the study cohort of 179, recurrent VAMP was diagnosed in 4 of the 11 who developed cardiac-suggestive symptoms following COVID-19 vaccination. The importance of cardiac evaluation should be emphasized for any patient presenting with chest pain, dyspnea, or other cardiac-suggestive symptoms following vaccination.

Strengths and Limitations

The strength of this review of VAMP recurrence associated with COVID-19 vaccination derives from our large and unique longitudinal database of VAMP among current and prior service members. Additionally, the IHD’s ongoing enhanced vaccine AEs surveillance provides the opportunity to contact patients and review their electronic health records over an extended interval of time.

When interpreting this report’s implications, limitations inherent to any retrospective case review should be considered. The cohort of cases of prior VAMP included primarily healthy, fit, young service members; this population is not representative of the general population. The cohort included prior VAMP cases that generally occurred after smallpox vaccination. Experiences after smallpox vaccine may not apply to cardiac injury from other vaccines or etiologies. By the nature of this review, the population studied at the time of COVID-19 vaccination was somewhat older than those most likely to develop an initial bout of VAMP.² This review was limited by information available in the electronic health records of a small number of patients. Subclinical cases of VAMP and cases without adequate clinical evaluation also could not be included.

Conclusions

Noninfectious inflammation of the heart (myocarditis, pericarditis, or myopericarditis) is a rare AE following certain vaccines, especially live replicating smallpox vaccine and mRNA COVID-19 vaccines. In this observational analysis, the majority of patients with previous VAMP successfully received a COVID-19 vaccine without recurrence. The 4 patients who were identified with recurrent VAMP following COVID-19 vaccination all recovered with supportive care. While the CDC endorses that individuals with a history of infectious myocarditis may receive COVID-19 vaccine after symptoms have resolved, there is currently insufficient safety data regarding COVID-19 vaccination of those with prior non-COVID-19 VAMP or following subsequent COVID-19 vaccination in those with prior VAMP related to COVID-19.¹⁰ For these individuals, COVID-19 vaccination is a precaution.¹⁰ Although insufficient to determine a precise level of risk, this report does provide data on which to base the CDC-recommended shared decision-making counseling of these patients. More research is needed to better define factors that increase risk for, or protection from, immune-mediated AEs following immunization, including VAMP. While benefits of vaccination have clearly outweighed risks during the COVID-19 pandemic, such research may optimize future vaccine recommendations.¹⁸

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show. Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” said lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore.

The findings were published online in JAMA.
 

Dose dependent effect

For their study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study was collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than were those with normal hearing (prevalence ratio, 1.61; 95% confidence interval [CI], 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: Normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate to severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assisted devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). Similar data were published in JAMA Neurology, suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships. Full disclosures for study authors are included in the original article.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show. Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” said lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore.

The findings were published online in JAMA.
 

Dose dependent effect

For their study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study was collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than were those with normal hearing (prevalence ratio, 1.61; 95% confidence interval [CI], 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: Normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate to severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assisted devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). Similar data were published in JAMA Neurology, suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships. Full disclosures for study authors are included in the original article.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show. Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” said lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore.

The findings were published online in JAMA.
 

Dose dependent effect

For their study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study was collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than were those with normal hearing (prevalence ratio, 1.61; 95% confidence interval [CI], 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: Normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate to severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assisted devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). Similar data were published in JAMA Neurology, suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships. Full disclosures for study authors are included in the original article.

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

PARIS – How can the problem of poor treatment compliance in patients with hypertension be resolved? A new therapeutic approach could be a game-changer.

Many approaches have been explored in recent years to make life easier for patients living with chronic conditions that require them to take daily medication: subcutaneous implantable devices, nanogels, and, more specifically in the case of hypertension, renal denervation or small interfering RNA (siRNA) with a long half-life.

It’s siRNA that Michel Azizi, MD, PhD, head of the blood pressure clinic at Georges Pompidou European Hospital (HEGP) in Paris, discussed at the International Meeting of the French Society of Hypertension.

These small molecules have already shown their worth in treating rare diseases such as transthyretin amyloidosis. More recently, treating hypercholesterolemia with the PCSK9 inhibitor inclisiran has proven effective. “One subcutaneous injection of inclisiran reduces LDL cholesterol by 50% for a period of 210 days,” said Dr. Azizi.

The benefit of a new therapeutic siRNA – zilebesiran, administered subcutaneously – in treating hypertension is currently the subject of a phase II clinical trial.

This is a double-stranded RNA. One of the strands is linked to a sugar, N-acetylgalactosamine (GalNAc), which protects these highly fragile siRNA and binds with a very strong affinity in the liver. The second strand binds to a specific area of the RNA to prevent synthesis of the precursor peptide of angiotensin, angiotensinogen. The resulting effect is suppression of the production of angiotensin I and II, which leads to a long-lasting lowering of blood pressure.
 

Lasting efficacy

Phase I studies with zilebesiran have demonstrated a long-term effect, with a reduction of greater than 90% in circulating angiotensinogen over 6 months after a single subcutaneous dose (800 mg). The peak in reduction of circulating angiotensinogen occurs after approximately 3 weeks.

“It’s extremely powerful,” said Dr. Azizi.

Lasting reductions in blood pressure have also been observed, with 24-hour ambulatory blood pressure monitoring showing a reduction in systolic BP of greater than 15 mm Hg 8 weeks after administration of a single dose of zilebesiran (800 mg).

Zilebesiran was also well tolerated, with only mild to moderate reactions at the site of the injection (n = 5/56) and no serious treatment-related adverse events, hypotension, or significant changes in kidney or liver function.

“In terms of benefits, the effect is ongoing. Zilebesiran leads to reduced medication use and causes less variability in blood pressure response. Nevertheless, interfering RNA acts slowly, meaning that zilebesiran would not be suitable for people presenting with a hypertensive crisis. The fact that it blocks the renin-angiotensin system [RAS] for a very long period of time also poses the question of how to reverse its hypotensive effects,” said Dr. Azizi.
 

Unanswered questions

The lasting RAS antagonist and blood pressure–lowering effects pose a potential safety problem in circumstances involving patients in a state of hypovolemia and hypotension who require rapid blood pressure–raising interventions to prevent morbidity and mortality.

In recent studies, Estrellita Uijl et al. have thus examined strategies to counteract the blood pressure–lowering effect of siRNA in spontaneously hypertensive rats.

Fludrocortisone and a high-salt diet were both successful in gradually increasing blood pressure, which returned to its baseline levels on days 5 and 7, respectively. Yet this rate of response would be wholly inadequate in an urgent clinical situation.

However, midodrine could not reduce blood pressure to normal levels, whether administered subcutaneously or orally.

A rapid and short-lasting increase in blood pressure was observed with bolus doses of vasopressors, but clinically, these would need to be administered intravenously to achieve a lasting effect. Such administration would require hospitalization, close monitoring, and the use of human resources and additional health care provisions.

Encouragingly, the laboratory that created this molecule, Alnylam Pharmaceuticals, has come up with an antidote: Reversir. It is a GalNAc-conjugated, single-stranded, high-affinity oligonucleotide complementary to the zilebesiran strand that achieves effective reversal of siRNA activity in 24 hours.

In the future, after the phase 2 trials have been completed, whether or not zilebesiran reduces the incidence of cardiovascular events and mortality remains to be seen. But as for Dr. Azizi, the director of HEGP’s blood pressure clinic in Paris, he has no doubt that “this approach is about to shake up how we treat patients in the cardiovascular field.”
 

On the horizon

Zilebesiran is being studied in phase 2 trials in patients with mild to moderate hypertension not taking antihypertensive drugs (KARDIA-1: 375 patients; double-blind, placebo-controlled, five-arm trial; zilebesiran at 150, 300, and 600 mg twice per year and 300 mg once every 3 months) and in patients whose blood pressure is not controlled (KARDIA-2: 800 patients; initial open-label start-up period of 4 weeks with indapamide/amlodipine/olmesartan, followed by a double-blind, placebo-controlled study over 6 months, then an open-label extension study for up to 12 additional months; zilebesiran at 600 mg on the first day of the initial double-blind period, then every 6 months during the open-label extension period).

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

PARIS – How can the problem of poor treatment compliance in patients with hypertension be resolved? A new therapeutic approach could be a game-changer.

Many approaches have been explored in recent years to make life easier for patients living with chronic conditions that require them to take daily medication: subcutaneous implantable devices, nanogels, and, more specifically in the case of hypertension, renal denervation or small interfering RNA (siRNA) with a long half-life.

It’s siRNA that Michel Azizi, MD, PhD, head of the blood pressure clinic at Georges Pompidou European Hospital (HEGP) in Paris, discussed at the International Meeting of the French Society of Hypertension.

These small molecules have already shown their worth in treating rare diseases such as transthyretin amyloidosis. More recently, treating hypercholesterolemia with the PCSK9 inhibitor inclisiran has proven effective. “One subcutaneous injection of inclisiran reduces LDL cholesterol by 50% for a period of 210 days,” said Dr. Azizi.

The benefit of a new therapeutic siRNA – zilebesiran, administered subcutaneously – in treating hypertension is currently the subject of a phase II clinical trial.

This is a double-stranded RNA. One of the strands is linked to a sugar, N-acetylgalactosamine (GalNAc), which protects these highly fragile siRNA and binds with a very strong affinity in the liver. The second strand binds to a specific area of the RNA to prevent synthesis of the precursor peptide of angiotensin, angiotensinogen. The resulting effect is suppression of the production of angiotensin I and II, which leads to a long-lasting lowering of blood pressure.
 

Lasting efficacy

Phase I studies with zilebesiran have demonstrated a long-term effect, with a reduction of greater than 90% in circulating angiotensinogen over 6 months after a single subcutaneous dose (800 mg). The peak in reduction of circulating angiotensinogen occurs after approximately 3 weeks.

“It’s extremely powerful,” said Dr. Azizi.

Lasting reductions in blood pressure have also been observed, with 24-hour ambulatory blood pressure monitoring showing a reduction in systolic BP of greater than 15 mm Hg 8 weeks after administration of a single dose of zilebesiran (800 mg).

Zilebesiran was also well tolerated, with only mild to moderate reactions at the site of the injection (n = 5/56) and no serious treatment-related adverse events, hypotension, or significant changes in kidney or liver function.

“In terms of benefits, the effect is ongoing. Zilebesiran leads to reduced medication use and causes less variability in blood pressure response. Nevertheless, interfering RNA acts slowly, meaning that zilebesiran would not be suitable for people presenting with a hypertensive crisis. The fact that it blocks the renin-angiotensin system [RAS] for a very long period of time also poses the question of how to reverse its hypotensive effects,” said Dr. Azizi.
 

Unanswered questions

The lasting RAS antagonist and blood pressure–lowering effects pose a potential safety problem in circumstances involving patients in a state of hypovolemia and hypotension who require rapid blood pressure–raising interventions to prevent morbidity and mortality.

In recent studies, Estrellita Uijl et al. have thus examined strategies to counteract the blood pressure–lowering effect of siRNA in spontaneously hypertensive rats.

Fludrocortisone and a high-salt diet were both successful in gradually increasing blood pressure, which returned to its baseline levels on days 5 and 7, respectively. Yet this rate of response would be wholly inadequate in an urgent clinical situation.

However, midodrine could not reduce blood pressure to normal levels, whether administered subcutaneously or orally.

A rapid and short-lasting increase in blood pressure was observed with bolus doses of vasopressors, but clinically, these would need to be administered intravenously to achieve a lasting effect. Such administration would require hospitalization, close monitoring, and the use of human resources and additional health care provisions.

Encouragingly, the laboratory that created this molecule, Alnylam Pharmaceuticals, has come up with an antidote: Reversir. It is a GalNAc-conjugated, single-stranded, high-affinity oligonucleotide complementary to the zilebesiran strand that achieves effective reversal of siRNA activity in 24 hours.

In the future, after the phase 2 trials have been completed, whether or not zilebesiran reduces the incidence of cardiovascular events and mortality remains to be seen. But as for Dr. Azizi, the director of HEGP’s blood pressure clinic in Paris, he has no doubt that “this approach is about to shake up how we treat patients in the cardiovascular field.”
 

On the horizon

Zilebesiran is being studied in phase 2 trials in patients with mild to moderate hypertension not taking antihypertensive drugs (KARDIA-1: 375 patients; double-blind, placebo-controlled, five-arm trial; zilebesiran at 150, 300, and 600 mg twice per year and 300 mg once every 3 months) and in patients whose blood pressure is not controlled (KARDIA-2: 800 patients; initial open-label start-up period of 4 weeks with indapamide/amlodipine/olmesartan, followed by a double-blind, placebo-controlled study over 6 months, then an open-label extension study for up to 12 additional months; zilebesiran at 600 mg on the first day of the initial double-blind period, then every 6 months during the open-label extension period).

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

PARIS – How can the problem of poor treatment compliance in patients with hypertension be resolved? A new therapeutic approach could be a game-changer.

Many approaches have been explored in recent years to make life easier for patients living with chronic conditions that require them to take daily medication: subcutaneous implantable devices, nanogels, and, more specifically in the case of hypertension, renal denervation or small interfering RNA (siRNA) with a long half-life.

It’s siRNA that Michel Azizi, MD, PhD, head of the blood pressure clinic at Georges Pompidou European Hospital (HEGP) in Paris, discussed at the International Meeting of the French Society of Hypertension.

These small molecules have already shown their worth in treating rare diseases such as transthyretin amyloidosis. More recently, treating hypercholesterolemia with the PCSK9 inhibitor inclisiran has proven effective. “One subcutaneous injection of inclisiran reduces LDL cholesterol by 50% for a period of 210 days,” said Dr. Azizi.

The benefit of a new therapeutic siRNA – zilebesiran, administered subcutaneously – in treating hypertension is currently the subject of a phase II clinical trial.

This is a double-stranded RNA. One of the strands is linked to a sugar, N-acetylgalactosamine (GalNAc), which protects these highly fragile siRNA and binds with a very strong affinity in the liver. The second strand binds to a specific area of the RNA to prevent synthesis of the precursor peptide of angiotensin, angiotensinogen. The resulting effect is suppression of the production of angiotensin I and II, which leads to a long-lasting lowering of blood pressure.
 

Lasting efficacy

Phase I studies with zilebesiran have demonstrated a long-term effect, with a reduction of greater than 90% in circulating angiotensinogen over 6 months after a single subcutaneous dose (800 mg). The peak in reduction of circulating angiotensinogen occurs after approximately 3 weeks.

“It’s extremely powerful,” said Dr. Azizi.

Lasting reductions in blood pressure have also been observed, with 24-hour ambulatory blood pressure monitoring showing a reduction in systolic BP of greater than 15 mm Hg 8 weeks after administration of a single dose of zilebesiran (800 mg).

Zilebesiran was also well tolerated, with only mild to moderate reactions at the site of the injection (n = 5/56) and no serious treatment-related adverse events, hypotension, or significant changes in kidney or liver function.

“In terms of benefits, the effect is ongoing. Zilebesiran leads to reduced medication use and causes less variability in blood pressure response. Nevertheless, interfering RNA acts slowly, meaning that zilebesiran would not be suitable for people presenting with a hypertensive crisis. The fact that it blocks the renin-angiotensin system [RAS] for a very long period of time also poses the question of how to reverse its hypotensive effects,” said Dr. Azizi.
 

Unanswered questions

The lasting RAS antagonist and blood pressure–lowering effects pose a potential safety problem in circumstances involving patients in a state of hypovolemia and hypotension who require rapid blood pressure–raising interventions to prevent morbidity and mortality.

In recent studies, Estrellita Uijl et al. have thus examined strategies to counteract the blood pressure–lowering effect of siRNA in spontaneously hypertensive rats.

Fludrocortisone and a high-salt diet were both successful in gradually increasing blood pressure, which returned to its baseline levels on days 5 and 7, respectively. Yet this rate of response would be wholly inadequate in an urgent clinical situation.

However, midodrine could not reduce blood pressure to normal levels, whether administered subcutaneously or orally.

A rapid and short-lasting increase in blood pressure was observed with bolus doses of vasopressors, but clinically, these would need to be administered intravenously to achieve a lasting effect. Such administration would require hospitalization, close monitoring, and the use of human resources and additional health care provisions.

Encouragingly, the laboratory that created this molecule, Alnylam Pharmaceuticals, has come up with an antidote: Reversir. It is a GalNAc-conjugated, single-stranded, high-affinity oligonucleotide complementary to the zilebesiran strand that achieves effective reversal of siRNA activity in 24 hours.

In the future, after the phase 2 trials have been completed, whether or not zilebesiran reduces the incidence of cardiovascular events and mortality remains to be seen. But as for Dr. Azizi, the director of HEGP’s blood pressure clinic in Paris, he has no doubt that “this approach is about to shake up how we treat patients in the cardiovascular field.”
 

On the horizon

Zilebesiran is being studied in phase 2 trials in patients with mild to moderate hypertension not taking antihypertensive drugs (KARDIA-1: 375 patients; double-blind, placebo-controlled, five-arm trial; zilebesiran at 150, 300, and 600 mg twice per year and 300 mg once every 3 months) and in patients whose blood pressure is not controlled (KARDIA-2: 800 patients; initial open-label start-up period of 4 weeks with indapamide/amlodipine/olmesartan, followed by a double-blind, placebo-controlled study over 6 months, then an open-label extension study for up to 12 additional months; zilebesiran at 600 mg on the first day of the initial double-blind period, then every 6 months during the open-label extension period).

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

How effective are the COVID-19 vaccines, third time around? Researchers compared 2 large groups of veterans to find out how well a third dose protected against documented infection, symptomatic COVID-19, and COVID-19–related hospitalization, intensive care unit (ICU) admission, and death.

The research, published in Nature, used electronic health records of 65,196 veterans who received BNT162b2 (Pfizer-BioNTech) and 65,196 who received mRNA-1273 (Moderna). They chose to study the 16 weeks between October 20, 2021 and February 8, 2022, which included both Delta- and Omicron-variant waves.

During the follow-up (median, 77 days), 2994 COVID-19 infections were documented, of which 200 were detected as symptomatic, 194 required hospitalization, and 52 required ICU admission. Twenty-two patients died.

In a previous head-to-head trial comparing breakthrough COVID-19 outcomes after the first doses of the 2 vaccines (given when the Alpha and Delta variants were predominant), the researchers had found a low risk of documented infection and severe outcomes, but lower for the Moderna vaccine. They note that few head-to-head comparisons have been made of third-dose effectiveness.

As expected, in this trial, the researchers found a “nearly identical” pattern for the risk of the 2 vaccine groups. Although the risks for all of the measured outcomes over 16 weeks were low for both vaccines ≤ 4% for documented infection and < 0.03% for death in each group—those veterans who received the Pfizer-BioNTech vaccine had an excess of 45 documented infections and 11 hospitalizations per 10,000 persons, compared with the Moderna group.  The Pfizer-BioNTech group also had a higher risk of documented infection over 9 weeks of follow-up, during which an Omicron-variant predominated.

Given the high effectiveness of a third dose of both vaccines, either vaccine is strongly recommended, the researchers conclude. They point to “evidence of clear and comparable benefits” for the most severe outcomes: The difference in estimated 16-week risk of death between the 2 groups was two-thousandths of 1 %.

They add that, while the differences in estimated risk for less severe outcomes between the 2 groups were small on the absolute scale, they may be meaningful when considering the population scale at which these vaccines are deployed.

How effective are the COVID-19 vaccines, third time around? Researchers compared 2 large groups of veterans to find out how well a third dose protected against documented infection, symptomatic COVID-19, and COVID-19–related hospitalization, intensive care unit (ICU) admission, and death.

The research, published in Nature, used electronic health records of 65,196 veterans who received BNT162b2 (Pfizer-BioNTech) and 65,196 who received mRNA-1273 (Moderna). They chose to study the 16 weeks between October 20, 2021 and February 8, 2022, which included both Delta- and Omicron-variant waves.

During the follow-up (median, 77 days), 2994 COVID-19 infections were documented, of which 200 were detected as symptomatic, 194 required hospitalization, and 52 required ICU admission. Twenty-two patients died.

In a previous head-to-head trial comparing breakthrough COVID-19 outcomes after the first doses of the 2 vaccines (given when the Alpha and Delta variants were predominant), the researchers had found a low risk of documented infection and severe outcomes, but lower for the Moderna vaccine. They note that few head-to-head comparisons have been made of third-dose effectiveness.

As expected, in this trial, the researchers found a “nearly identical” pattern for the risk of the 2 vaccine groups. Although the risks for all of the measured outcomes over 16 weeks were low for both vaccines ≤ 4% for documented infection and < 0.03% for death in each group—those veterans who received the Pfizer-BioNTech vaccine had an excess of 45 documented infections and 11 hospitalizations per 10,000 persons, compared with the Moderna group.  The Pfizer-BioNTech group also had a higher risk of documented infection over 9 weeks of follow-up, during which an Omicron-variant predominated.

Given the high effectiveness of a third dose of both vaccines, either vaccine is strongly recommended, the researchers conclude. They point to “evidence of clear and comparable benefits” for the most severe outcomes: The difference in estimated 16-week risk of death between the 2 groups was two-thousandths of 1 %.

They add that, while the differences in estimated risk for less severe outcomes between the 2 groups were small on the absolute scale, they may be meaningful when considering the population scale at which these vaccines are deployed.

How effective are the COVID-19 vaccines, third time around? Researchers compared 2 large groups of veterans to find out how well a third dose protected against documented infection, symptomatic COVID-19, and COVID-19–related hospitalization, intensive care unit (ICU) admission, and death.

The research, published in Nature, used electronic health records of 65,196 veterans who received BNT162b2 (Pfizer-BioNTech) and 65,196 who received mRNA-1273 (Moderna). They chose to study the 16 weeks between October 20, 2021 and February 8, 2022, which included both Delta- and Omicron-variant waves.

During the follow-up (median, 77 days), 2994 COVID-19 infections were documented, of which 200 were detected as symptomatic, 194 required hospitalization, and 52 required ICU admission. Twenty-two patients died.

In a previous head-to-head trial comparing breakthrough COVID-19 outcomes after the first doses of the 2 vaccines (given when the Alpha and Delta variants were predominant), the researchers had found a low risk of documented infection and severe outcomes, but lower for the Moderna vaccine. They note that few head-to-head comparisons have been made of third-dose effectiveness.

As expected, in this trial, the researchers found a “nearly identical” pattern for the risk of the 2 vaccine groups. Although the risks for all of the measured outcomes over 16 weeks were low for both vaccines ≤ 4% for documented infection and < 0.03% for death in each group—those veterans who received the Pfizer-BioNTech vaccine had an excess of 45 documented infections and 11 hospitalizations per 10,000 persons, compared with the Moderna group.  The Pfizer-BioNTech group also had a higher risk of documented infection over 9 weeks of follow-up, during which an Omicron-variant predominated.

Given the high effectiveness of a third dose of both vaccines, either vaccine is strongly recommended, the researchers conclude. They point to “evidence of clear and comparable benefits” for the most severe outcomes: The difference in estimated 16-week risk of death between the 2 groups was two-thousandths of 1 %.

They add that, while the differences in estimated risk for less severe outcomes between the 2 groups were small on the absolute scale, they may be meaningful when considering the population scale at which these vaccines are deployed.

Black veterans are less likely to have their benefits claims processed and paid than are their White peers because of systemic problems within the US Department of Veterans Affairs, according to a lawsuit filed against the agency.

“A Black veteran who served honorably can walk into the VA, file a disability claim, and be at a significantly higher likelihood of having that claim denied,” said Adam Henderson, a student working with the Yale Law School Veterans Legal Services Clinic, one of several groups connected to the lawsuit.

“The VA has denied countless meritorious applications of Black veterans and thus deprived them and their families of the support that they are entitled to.”

The suit, filed in federal court by the clinic on behalf of Vietnam War veteran Conley Monk Jr., asks for “redress for the harms caused by the failure of VA staff and leaders to administer these benefits programs in a manner free from racial discrimination against Black veterans.”

In a press conference announcing the lawsuit, the effort received backing from Sen. Richard Blumenthal (D, Connecticut) who called it an “unacceptable” situation.

“Black veterans are denied benefits at a very significantly disproportionate rate,” he said. “We know the results. We want to know the reason why.”

The suit stems from an analysis of VA claims records released by the department following an earlier legal action. Between 2001 and 2020, the average denial rate for disability claims filed for Black veterans was 29.5%, significantly above the 24.2% for White veterans.

Attorneys allege the problems date back even further and that VA officials should have known about the racial disparities in the system from previous complaints.

“The negligence of VA leadership, and their failure to train, supervise, monitor and instruct agency officials to take steps to identify and correct racial disparities, led to systematic benefits obstruction for Black veterans,” the suit states.

Monk is a Black disabled Marine Corps veteran who previously sued the military to overturn his less-than-honorable military discharge due to complications from undiagnosed posttraumatic stress disorder.

He was subsequently granted access to a host of veterans benefits but not to retroactive payouts for claims he was denied in the 1970s.

“They didn’t fully compensate me or my family,” he said. “I wasn’t able to give my kids my educational benefits. We should have been receiving checks while they were growing up.”

Along with potential past benefits for Monk, individuals involved with the lawsuit said the move could force the VA to reassess thousands of other unfairly dismissed cases. “For decades [the US government] has allowed racially discriminatory practices to obstruct Black veterans from easily accessing veterans housing, education, and health care benefits with wide-reaching economic consequences for Black veterans and their families,” said Richard Brookshire, executive director of the Black Veterans Project.

“This lawsuit reckons with the shameful history of racism by the Department of Veteran Affairs and seeks to redress long-standing improprieties reverberating across generations of Black military service.”

In a statement, VA press secretary Terrence Hayes did not directly respond to the lawsuit but noted that “throughout history, there have been unacceptable disparities in both VA benefits decisions and military discharge status due to racism, which have wrongly left Black veterans without access to VA care and benefits.”

“We are actively working to right these wrongs, and we will stop at nothing to ensure that all Black veterans get the VA services they have earned and deserve,” he said. “We are currently studying racial disparities in benefits claims decisions, and we will publish the results of that study as soon as they are available.”

Hayes said the department has already begun targeted outreach to Black veterans to help them with claims and is “taking steps to ensure that our claims process combats institutional racism, rather than perpetuating it.”

Black veterans are less likely to have their benefits claims processed and paid than are their White peers because of systemic problems within the US Department of Veterans Affairs, according to a lawsuit filed against the agency.

“A Black veteran who served honorably can walk into the VA, file a disability claim, and be at a significantly higher likelihood of having that claim denied,” said Adam Henderson, a student working with the Yale Law School Veterans Legal Services Clinic, one of several groups connected to the lawsuit.

“The VA has denied countless meritorious applications of Black veterans and thus deprived them and their families of the support that they are entitled to.”

The suit, filed in federal court by the clinic on behalf of Vietnam War veteran Conley Monk Jr., asks for “redress for the harms caused by the failure of VA staff and leaders to administer these benefits programs in a manner free from racial discrimination against Black veterans.”

In a press conference announcing the lawsuit, the effort received backing from Sen. Richard Blumenthal (D, Connecticut) who called it an “unacceptable” situation.

“Black veterans are denied benefits at a very significantly disproportionate rate,” he said. “We know the results. We want to know the reason why.”

The suit stems from an analysis of VA claims records released by the department following an earlier legal action. Between 2001 and 2020, the average denial rate for disability claims filed for Black veterans was 29.5%, significantly above the 24.2% for White veterans.

Attorneys allege the problems date back even further and that VA officials should have known about the racial disparities in the system from previous complaints.

“The negligence of VA leadership, and their failure to train, supervise, monitor and instruct agency officials to take steps to identify and correct racial disparities, led to systematic benefits obstruction for Black veterans,” the suit states.

Monk is a Black disabled Marine Corps veteran who previously sued the military to overturn his less-than-honorable military discharge due to complications from undiagnosed posttraumatic stress disorder.

He was subsequently granted access to a host of veterans benefits but not to retroactive payouts for claims he was denied in the 1970s.

“They didn’t fully compensate me or my family,” he said. “I wasn’t able to give my kids my educational benefits. We should have been receiving checks while they were growing up.”

Along with potential past benefits for Monk, individuals involved with the lawsuit said the move could force the VA to reassess thousands of other unfairly dismissed cases. “For decades [the US government] has allowed racially discriminatory practices to obstruct Black veterans from easily accessing veterans housing, education, and health care benefits with wide-reaching economic consequences for Black veterans and their families,” said Richard Brookshire, executive director of the Black Veterans Project.

“This lawsuit reckons with the shameful history of racism by the Department of Veteran Affairs and seeks to redress long-standing improprieties reverberating across generations of Black military service.”

In a statement, VA press secretary Terrence Hayes did not directly respond to the lawsuit but noted that “throughout history, there have been unacceptable disparities in both VA benefits decisions and military discharge status due to racism, which have wrongly left Black veterans without access to VA care and benefits.”

“We are actively working to right these wrongs, and we will stop at nothing to ensure that all Black veterans get the VA services they have earned and deserve,” he said. “We are currently studying racial disparities in benefits claims decisions, and we will publish the results of that study as soon as they are available.”

Hayes said the department has already begun targeted outreach to Black veterans to help them with claims and is “taking steps to ensure that our claims process combats institutional racism, rather than perpetuating it.”

Black veterans are less likely to have their benefits claims processed and paid than are their White peers because of systemic problems within the US Department of Veterans Affairs, according to a lawsuit filed against the agency.

“A Black veteran who served honorably can walk into the VA, file a disability claim, and be at a significantly higher likelihood of having that claim denied,” said Adam Henderson, a student working with the Yale Law School Veterans Legal Services Clinic, one of several groups connected to the lawsuit.

“The VA has denied countless meritorious applications of Black veterans and thus deprived them and their families of the support that they are entitled to.”

The suit, filed in federal court by the clinic on behalf of Vietnam War veteran Conley Monk Jr., asks for “redress for the harms caused by the failure of VA staff and leaders to administer these benefits programs in a manner free from racial discrimination against Black veterans.”

In a press conference announcing the lawsuit, the effort received backing from Sen. Richard Blumenthal (D, Connecticut) who called it an “unacceptable” situation.

“Black veterans are denied benefits at a very significantly disproportionate rate,” he said. “We know the results. We want to know the reason why.”

The suit stems from an analysis of VA claims records released by the department following an earlier legal action. Between 2001 and 2020, the average denial rate for disability claims filed for Black veterans was 29.5%, significantly above the 24.2% for White veterans.

Attorneys allege the problems date back even further and that VA officials should have known about the racial disparities in the system from previous complaints.

“The negligence of VA leadership, and their failure to train, supervise, monitor and instruct agency officials to take steps to identify and correct racial disparities, led to systematic benefits obstruction for Black veterans,” the suit states.

Monk is a Black disabled Marine Corps veteran who previously sued the military to overturn his less-than-honorable military discharge due to complications from undiagnosed posttraumatic stress disorder.

He was subsequently granted access to a host of veterans benefits but not to retroactive payouts for claims he was denied in the 1970s.

“They didn’t fully compensate me or my family,” he said. “I wasn’t able to give my kids my educational benefits. We should have been receiving checks while they were growing up.”

Along with potential past benefits for Monk, individuals involved with the lawsuit said the move could force the VA to reassess thousands of other unfairly dismissed cases. “For decades [the US government] has allowed racially discriminatory practices to obstruct Black veterans from easily accessing veterans housing, education, and health care benefits with wide-reaching economic consequences for Black veterans and their families,” said Richard Brookshire, executive director of the Black Veterans Project.

“This lawsuit reckons with the shameful history of racism by the Department of Veteran Affairs and seeks to redress long-standing improprieties reverberating across generations of Black military service.”

In a statement, VA press secretary Terrence Hayes did not directly respond to the lawsuit but noted that “throughout history, there have been unacceptable disparities in both VA benefits decisions and military discharge status due to racism, which have wrongly left Black veterans without access to VA care and benefits.”

“We are actively working to right these wrongs, and we will stop at nothing to ensure that all Black veterans get the VA services they have earned and deserve,” he said. “We are currently studying racial disparities in benefits claims decisions, and we will publish the results of that study as soon as they are available.”

Hayes said the department has already begun targeted outreach to Black veterans to help them with claims and is “taking steps to ensure that our claims process combats institutional racism, rather than perpetuating it.”

Asthma affects more than 300 million people worldwide.¹ While many of these cases can achieve control with standard therapy, 5% to 10% of these cases are classified as severe asthma, remaining poorly controlled despite treatment with inhaled corticosteroids (ICS) and long-acting β agonists (LABA).² These patients also account for the majority of morbidity and mortality associated with the disease, with increased hospitalizations, intensive care unit (ICU) stays, detrimental adverse effects of oral corticosteroids (OCS), and lower quality of life.^3-6 Additionally, the financial repercussions of severe asthma are notable; in the United States, the estimated cost of asthma management is $82 billion annually, with $3 billion accounting for asthma-related work/school absences.⁷

In the past several years, the use of anti-immunoglobulin E (IgE), anti-interleukin-4 (IL-4), and anti-IL-5 biologic agents for severe asthma has been shown to decrease asthma exacerbations, improve lung function, reduce corticosteroid use, and decrease hospitalizations, especially for type 2 helper T cell (TH2-high) asthma.^8-10 However, clinicians have observed significant barriers to the implementation and widespread use of biologics, including insurance coverage, long wait times, follow-up, and limited access for lower income groups.^11,12

This article describes a unique model for a severe asthma clinic located at the Washington DC Veterans Affairs Medical Center (WDCVAMC) that is dually staffed by an allergist and pulmonologist. This clinic uses biologic agents for patients with difficult-to-treat asthma, many of whom require repeated or prolonged steroid use, in addition to prolonged and recurrent hospitalizations for exacerbations. The objective of this clinic is to provide a standardized approach to the management of severe asthma with the perspective of both an allergist and pulmonologist, thereby reducing the need to schedule appointments with multiple specialties and reducing delays in initiating biologics. This article presents the preliminary findings of 30 months of severe asthma management with various biologic agents, examining the impact of these therapies on hospitalizations, asthma exacerbations, ICU stays, and OCS use. The findings of this study support the benefits of biologics and suggest that the use of these agents within a dually staffed clinic may be a particularly effective model through which to manage severe asthma.

Background

Asthma affects approximately 20 million adults in the United States.¹³ Veterans are a population particularly impacted by asthma. Between 2015 and 2018, 10.9% of all veterans reported being diagnosed with asthma and 5.1% stated that they currently have asthma, compared with 13.4% and 8.0% of nonveterans, respectively.¹⁴ Veterans are susceptible to many of the factors that can trigger exacerbations while engaging in military service, such as chemical and environmental exposures both abroad and domestically.^15,16 Additionally, medication adherence is often challenging among the veteran population, particularly with more involved therapy, such as inhaler use.¹⁷ Such factors contribute to asthma exacerbations, with 2.9% of veterans reporting at least 1 asthma exacerbation in the past 12 months.¹⁴

Over the past several years, the development and use of biologic agents have transformed the management of severe asthma.⁸ Before the development of biologic agents for severe asthma, treatment options for patients were limited. While OCS are frequently used for asthma exacerbations, they are associated with a multiplicity of undesirable adverse effects, including weight gain, mood lability, gastrointestinal upset, hyperglycemia, risk of bone fractures, and hypertension.^18-20 The regular use of OCS are particularly problematic among other medical comorbidities commonly affecting the veteran population, such as diabetes and hypertension.^21-22

The WDCVAMC severe allergy clinic used 3 biologic agents: omalizumab (anti-IgE), benralizumab (anti-IL-5), and agent dupilumab (anti-IL-4). These medications have shown significant improvements in quality of life, reduction in asthma exacerbations and hospitalizations, and decreased use of OCS.^8,9 While research has firmly established the medical benefits of the use of biologic agents in severe asthma, several barriers exist in implementing widespread use.^11,12

In Gelhorn and colleagues’ study examining both physician and patient challenges in the use of biologics for severe asthma, scheduling, administrative time, and insurance costs were found to be major barriers to the use of these medications.¹² Patients expressed a preference for the administration of these medications in a specialist’s office but cited long wait times and scheduling difficulties as barriers. One of the most notable challenges from the physician perspective was the difficulty in obtaining reimbursement from insurance companies, requiring them to devote significant portions of time to prior authorizations and documentation.¹²

This article examines a dual specialty clinic that focuses on the treatment of severe asthma with biologic agents. This model is unique for several reasons. First, given the US Department of Veterans Affairs (VA) health care model, the health care practitioners (HCPs) in this clinic can avoid much of the administrative burden of obtaining reimbursement or working with insurance companies. Additionally, by dedicating specific days to the severe asthma clinic, patients do not experience long wait times to see both an allergist and pulmonologist. By seeing both clinicians, concurrent allergic and pulmonary issues can be addressed in the same visit, rather than delaying treatment by waiting on 2 specialist appointments.

Severe Asthma Clinic

The severe asthma clinic was started in September 2017 by a pulmonologist and an allergist at WDCVAMC. After experiencing substantial delays with the initiation of biologics for their patients and multiple referrals between their clinics, these physicians wanted to start a dually staffed asthma clinic to specifically focus on evaluating and treating severe asthma. A dedicated severe asthma clinic allowed the allergist and pulmonologist to streamline resources and collaborate to advocate for patients with the pharmacy section. Additionally, patients can benefit from the perspective of both specialists, as both the pulmonologist and allergist evaluate each patient and discuss the next steps of management.

This clinic is composed of 4 registered nurses, an allergist, and a pulmonologist. Clinic is held twice monthly through both telemedicine and in-office visits. The VA has strict guidelines for the use of certain biologics, including blood eosinophil count > 150 cells/µL, failure of traditional therapy, and frequent use of OCS. Additionally, to ensure these biologic agents are prescribed to patients that will benefit from them, the patients enrolled in this clinic are already on maximum therapy for their asthma, meaning all other therapeutic options (inhalers and oral medications) are being used. The clinic services all patients with severe asthma, not just patients who are on biologic therapy. Often, patients are referred to the severe allergy clinic late in their disease course given a lack of familiarity with biologic agents from prescribers and both institutional and insurance barriers.

Before the COVID-19 pandemic, spirometry and fractional exhaled nitric oxide (FENO) tests were recorded at each visit. Initially during the pandemic, the clinic transitioned to primarily telemedicine visits due to patients’ hesitance to seek in-person care. More recently, the clinic has transitioned back to primarily office visits; patients are seen in clinic on average every 3 months. At each visit, the patient is seen by both the pulmonologist and allergist. Additionally, the nursing staff reviews inhaler adherence with patients, spacer use, documents, Asthma Control Test (ACT) scores, and schedules follow-up visits.

Every 4 to 8 weeks, patients receive biologics agent at the WDCVAMC infusion center depending on the agent. The infusion center also instructs patients how to handle self-administered medications, like benralizumab, if the patient expresses a preference for taking it at home. Omalizumab has a boxed warning for anaphylaxis, although the other biologics in this study have a low risk of anaphylaxis. All patients receiving omalizumab, benralizumab, and dupilumab were provided with epinephrine injection devices in case of an allergic reaction and were taught how to use them in the clinic.^23,24

If patients continued to experience asthma exacerbations after the initiation of a biologic, a change in agent was considered after 4 to 6 months. Additionally, a complete blood count, respiratory allergy panel, and pulmonary function tests (PFTs) were completed.

Clinic Patients

Preliminary data were obtained from a retrospective chart review of 15 patients enrolled in the severe asthma clinic over 30 months. The inclusion criteria for chart review consisted of patients aged > 18 years receiving a biologic agent for > 3 months for the treatment of severe asthma. The outcomes examined included steroid use, emergency department (ED) visits, hospitalizations, FEV₁, and ICU stays.

Seven patients used benralizumab, 6 used dupilumab, and 2 used omalizumab (Table).

There was a notable clinical improvement in these patients. Before starting a biologic agent, all the patients in this study were prescribed steroids at least once a year for an asthma exacerbation, with a mean of 4.2 steroid tapers per year.

Discussion

The 15 patients in this initial data were referred to the severe asthma clinic by pulmonology, ear, nose, and throat (ENT), primary care, and a hospitalist during an in-patient stay. As the enrollment in our clinic grows, an increasing number of patients are referred from the allergy clinic as well. Patients in the severe asthma clinic also are referred by regional centers as news of the clinic is spread by word of mouth to surrounding VA facilities. As our clinic gains the capacity to serve more patients, we hope to contact WDCVAMC primary care, pulmonology, allergy, and ENT departments to raise awareness of the clinic.

Benralizumab and dupilumab were the most used agents in this preliminary data. This finding was largely due to the ability of patients to self-administer benralizumab, which was particularly beneficial during the COVID-19 pandemic. Of note, 5 patients in this study switched from another biologic agent to benralizumab due to the ability to self-administer. Three of 5 patients that required steroids after initiating benralizumab used fewer steroids than they had previously. This finding suggests benralizumab may be the preferred agent when travel time to health care is a challenge, reducing the need for frequent clinic visits and transportation.

This preliminary data supports previous studies that have demonstrated that biologic agents improve clinical outcomes by reducing asthma exacerbations, OCS use, hospitalizations, and ICU stays for patients on all 4 biologic agents. In addition to improving patient health through avoiding complications of prolonged OCS use and hospital stays, the decrease in ED visits and hospitalizations provides a substantial cost reduction to the health care system.  

These findings highlight the strength of a unique model of a combined allergy/pulmonary clinic. Before this combined clinic model, both pulmonology and allergy clinics noted delays in the initiation of biologics for patients who were potential candidates. Impediments include referrals between each specialty for evaluation of concurrent pulmonary conditions or allergy testing, overlap in asthma management, and a delay in coordination with the pharmacy department to start biologic agents. A dedicated severe asthma clinic staffed by both an allergist and pulmonologist provides a convenient option for patients to be seen by both specialists, reducing the need for separate appointments with each specialty, transportation to those appointments, and clinical time. This is particularly beneficial in a clinic such as this model, as this clinic serves patients from 4 states and Washington, DC. An additional benefit of this model is trained staff who directly communicate with the pharmacy in the initiation of these agents, allocate time to educating patients in biologic use, and coordinate follow-up.

Limitations

There were several limitations to this report. First, the number of patients examined in this preliminary data set is small. Due to the COVID-19 pandemic, there was a limited ability to see patients in person, and patients were seen exclusively over telemedicine for several months. For this reason, collecting data such as patient surveys and laboratory work following the initiation of a biologic was a challenge. Additionally, during the height of COVID-19, WDCVAMC did not perform aerosolizing procedures, such as PFTs and FENOs; thus, peak flows were obtained instead. Examining metrics, such as FENOs and IgE levels, and expanding PFT data would provide additional insight into the impact of biologic agents on clinical outcomes. Patient survey data in the form of ACTs or satisfaction surveys would also yield important data examining the impact of this clinic design and biologic use on patient experience. As of December 2022, 114 patients are enrolled in the clinic. We are working to collect the above laboratory results and spirometry for these patients so that these results can be published with a more robust data set. Another limitation of the information presented is that it is a retrospective data analysis; the data collected was contingent upon documentation and the assumption that these patients were exclusively receiving care through the VA. For example, steroid use before and after initiation of biologic was taken from asthma clinic notes and the patient’s medication list. Therefore, there is a possibility that not all instances were accounted for if that patient sought care outside the VA or whether it was not documented in a follow-up note.

Conclusions

The model of a combined allergy/pulmonology clinic can be particularly efficacious in the treatment of severe asthma, as it reduces the need for multiple appointments with different specialties, reduces wait time before starting a biologic agent, and offers the perspective of 2 specialists. This kind of model could be an example to many clinics in the VA. With a rapid increase in telemedicine due to the COVID-19 pandemic, multiple physicians consulting simultaneously is becoming a more feasible possibility across multiple specialties. As the use of biologics becomes more widespread, a combined clinic design is an efficient and promising method to improve severe asthma management.

This preliminary data continue to support previous research that shows biologic agents have led to better clinical outcomes through the reduction of asthma exacerbations, hospitalizations, and improved PFTs. While this initial data set highlights the results for 15 patients, there are 86 patients currently enrolled in this clinic. We are collecting additional data to publish more comprehensive results.