Jason Black, MD, trained in family medicine, worked for Kaiser Permanente, and subsequently completed a fellowship in geriatrics. Today, he treats frail elderly patients, mostly residents of nursing homes and assisted living facilities or living in their own homes, for Gilchrist, a hospice and palliative care organization serving Baltimore and central Maryland.

“I’m practicing family medicine to the extent that I’m treating the family unit, including the anxieties of the adult children, and finding solutions for the parents,” said Dr. Black, one of Gilchrist’s 62 employed providers, one third of whom are physicians. One of his most important roles is medication reconciliation and deprescribing.

Palliative care, a medical specialty that focuses on clarifying the treatment goals of seriously ill patients, helping with end-of-life planning, and emphasizing pain and symptom management, has been growing in recent years. Already well-established in most US hospitals, it is expanding in community settings, often as an extension of hospice programs.

Now, by adding primary care physicians and practices to their service mix, palliative care groups are better meeting the needs of a neglected — and costly — population of frail elders. In doing so, they also are better able to find a niche in the rapidly evolving alphabet soup of value-based care and its varieties of shared savings for providers who post positive outcomes.

Most patients Dr. Black sees find it difficult to visit their doctors in a clinic setting, although they face a variety of medical needs and chronic conditions of aging. They may have a prognosis of several years to live and, thus, do not qualify for hospice care. To him, a palliative approach offers the satisfaction of focusing on what is most important to patients at this difficult time in their lives, rather than predetermined clinical metrics like blood pressure or blood glucose. “It takes a lot of work, but it feels important and rewarding,” he said.

A recent survey of community-dwelling older adults in Ontario, Canada, found most patients fail to receive this treatment homes in the final 3 months of life.
 

Continuums of Patients and Models

Gilchrist started as a nonprofit, hospital-affiliated hospice program in 1994 and in 2000 took on the management of a geriatric medicine practice for its parent, Greater Baltimore Medical Center. Today, its physicians and nurse practitioners see a range of patients in geriatric primary care, palliative medicine, and hospice, according to its chief medical officer, Mark J. Gloth, DO.

“As people progress in their disease, their location — where they call home — may change as well,” Dr. Gloth said. “We offer a continuum of care in order to not lose people through those transitions. That’s the core of our mission — making sure we are there to escort people through the difficult moments in their lives.”

Models for value-based care encompass accountable care organizations (ACOs), including the ACO REACH (Realizing Equity, Access, and Community Health) high-needs model for traditional Medicare patients, and Medicare Shared Savings Programs for fee-for-service beneficiaries. These value-based models offer a variety of opportunities for the palliative care organization to share in savings resulting from keeping the patient out of the hospital or emergency room and other quality and cost benchmarks.
 

Coming Together to Meet Needs

Gilchrist is one of nine hospice and palliative organizations that have joined to form their own multistate ACO, Responsive Care Solutions, focused on the clinical needs of frail elderly Medicare beneficiaries. Hospice of the Valley in Phoenix has Geriatric Solutions, a frail elder physician practice. And Capital Caring Health, a hospice and palliative care agency serving metro Washington, DC, has deployed several physicians and nurse practitioners on the road doing primary care at home, said Heidi Young, MD, its Primary Care at Home Lead Physician.

“Five years ago, we started our primary care practice under the umbrella of a 40-year-old hospice organization because we thought we needed to prepare for the changes that are coming to the hospice model,” Dr. Young said. “The thought was that we’re not just a hospice organization; we’re an advanced illness organization. We will come to your home, whatever that is, and provide your primary care.”

The greatest potential gains for a hospice organization are from assuming 100% risk for a large population of patients, keeping them out of the hospital to lower the costs of their care, then reaping those gains under a value-based profit-sharing model, Dr. Young said.

“Our program is still new and working toward getting more patients aligned into value-based models,” she said. “It’s a work in progress.”
 

A Foot in Each World

Agencies like Capital Caring and Gilchrist derive the largest share of their physician income from billing Medicare Part B and other insurers per visit. But that billing is not enough to break even on physician services.

With hopes for a value-based future, Gilchrist also gets grants from elder-facing charitable foundations to cover up to 40% of the costs of its home-based primary care, according to its president, Catherine Hamel. Hospice care continues to be paid on a per-diem basis by Medicare for eligible terminally ill patients, including Medicare Advantage patients, although the Centers for Medicare & Medicaid Services is reportedly considering new models for the hospice benefit.

The National Partnership for Healthcare and Hospice Innovation (NPHI) is a trade group representing more than 100 nonprofit, hospice-based organizations participating in palliative care and value-based care.

For a hospice to be successful in the evolving post–acute care/end-of-life care landscape, it can no longer rely solely on its hospice line of business, no matter how high-quality, said Ethan McChesney, policy director for the Washington, DC-based nonprofit.

NPHI members have developed their own palliative care programs, and perhaps, a quarter have primary care at home practices, Mr. McChesney said. Some of them acquired existing primary care practices in their service area with which they already had relationships; others created their own.

For hospice organizations building a continuum of services for the seriously ill, adding a primary care at home practice is a natural fit, he said. “You can provide all the services you would as a traditional primary care practice while you have the opportunity to establish long-term relationships with patients and their caregivers that lend themselves to palliative care referrals and then hospice referrals downstream [when the patient becomes eligible for hospice care].” Often, this primary medical care is a mix of in-person and telehealth.

Cameron Muir, MD, NPHI’s chief innovation officer, noted that the hamster wheel for primary care doctors has been spinning faster and faster, with reimbursement going down and costs going up.

But with home-based primary care for frail elders under value-based models, Dr. Muir said, the clinician is paid not for making more visits but for taking great care of the patient: “And I’m actually saving Medicare money and getting credit for the hospitalizations that were avoided.”
 

A version of this article appeared on Medscape.com.

Jason Black, MD, trained in family medicine, worked for Kaiser Permanente, and subsequently completed a fellowship in geriatrics. Today, he treats frail elderly patients, mostly residents of nursing homes and assisted living facilities or living in their own homes, for Gilchrist, a hospice and palliative care organization serving Baltimore and central Maryland.

“I’m practicing family medicine to the extent that I’m treating the family unit, including the anxieties of the adult children, and finding solutions for the parents,” said Dr. Black, one of Gilchrist’s 62 employed providers, one third of whom are physicians. One of his most important roles is medication reconciliation and deprescribing.

Palliative care, a medical specialty that focuses on clarifying the treatment goals of seriously ill patients, helping with end-of-life planning, and emphasizing pain and symptom management, has been growing in recent years. Already well-established in most US hospitals, it is expanding in community settings, often as an extension of hospice programs.

Now, by adding primary care physicians and practices to their service mix, palliative care groups are better meeting the needs of a neglected — and costly — population of frail elders. In doing so, they also are better able to find a niche in the rapidly evolving alphabet soup of value-based care and its varieties of shared savings for providers who post positive outcomes.

Most patients Dr. Black sees find it difficult to visit their doctors in a clinic setting, although they face a variety of medical needs and chronic conditions of aging. They may have a prognosis of several years to live and, thus, do not qualify for hospice care. To him, a palliative approach offers the satisfaction of focusing on what is most important to patients at this difficult time in their lives, rather than predetermined clinical metrics like blood pressure or blood glucose. “It takes a lot of work, but it feels important and rewarding,” he said.

A recent survey of community-dwelling older adults in Ontario, Canada, found most patients fail to receive this treatment homes in the final 3 months of life.
 

Continuums of Patients and Models

Gilchrist started as a nonprofit, hospital-affiliated hospice program in 1994 and in 2000 took on the management of a geriatric medicine practice for its parent, Greater Baltimore Medical Center. Today, its physicians and nurse practitioners see a range of patients in geriatric primary care, palliative medicine, and hospice, according to its chief medical officer, Mark J. Gloth, DO.

“As people progress in their disease, their location — where they call home — may change as well,” Dr. Gloth said. “We offer a continuum of care in order to not lose people through those transitions. That’s the core of our mission — making sure we are there to escort people through the difficult moments in their lives.”

Models for value-based care encompass accountable care organizations (ACOs), including the ACO REACH (Realizing Equity, Access, and Community Health) high-needs model for traditional Medicare patients, and Medicare Shared Savings Programs for fee-for-service beneficiaries. These value-based models offer a variety of opportunities for the palliative care organization to share in savings resulting from keeping the patient out of the hospital or emergency room and other quality and cost benchmarks.
 

Coming Together to Meet Needs

Gilchrist is one of nine hospice and palliative organizations that have joined to form their own multistate ACO, Responsive Care Solutions, focused on the clinical needs of frail elderly Medicare beneficiaries. Hospice of the Valley in Phoenix has Geriatric Solutions, a frail elder physician practice. And Capital Caring Health, a hospice and palliative care agency serving metro Washington, DC, has deployed several physicians and nurse practitioners on the road doing primary care at home, said Heidi Young, MD, its Primary Care at Home Lead Physician.

“Five years ago, we started our primary care practice under the umbrella of a 40-year-old hospice organization because we thought we needed to prepare for the changes that are coming to the hospice model,” Dr. Young said. “The thought was that we’re not just a hospice organization; we’re an advanced illness organization. We will come to your home, whatever that is, and provide your primary care.”

The greatest potential gains for a hospice organization are from assuming 100% risk for a large population of patients, keeping them out of the hospital to lower the costs of their care, then reaping those gains under a value-based profit-sharing model, Dr. Young said.

“Our program is still new and working toward getting more patients aligned into value-based models,” she said. “It’s a work in progress.”
 

A Foot in Each World

Agencies like Capital Caring and Gilchrist derive the largest share of their physician income from billing Medicare Part B and other insurers per visit. But that billing is not enough to break even on physician services.

With hopes for a value-based future, Gilchrist also gets grants from elder-facing charitable foundations to cover up to 40% of the costs of its home-based primary care, according to its president, Catherine Hamel. Hospice care continues to be paid on a per-diem basis by Medicare for eligible terminally ill patients, including Medicare Advantage patients, although the Centers for Medicare & Medicaid Services is reportedly considering new models for the hospice benefit.

The National Partnership for Healthcare and Hospice Innovation (NPHI) is a trade group representing more than 100 nonprofit, hospice-based organizations participating in palliative care and value-based care.

For a hospice to be successful in the evolving post–acute care/end-of-life care landscape, it can no longer rely solely on its hospice line of business, no matter how high-quality, said Ethan McChesney, policy director for the Washington, DC-based nonprofit.

NPHI members have developed their own palliative care programs, and perhaps, a quarter have primary care at home practices, Mr. McChesney said. Some of them acquired existing primary care practices in their service area with which they already had relationships; others created their own.

For hospice organizations building a continuum of services for the seriously ill, adding a primary care at home practice is a natural fit, he said. “You can provide all the services you would as a traditional primary care practice while you have the opportunity to establish long-term relationships with patients and their caregivers that lend themselves to palliative care referrals and then hospice referrals downstream [when the patient becomes eligible for hospice care].” Often, this primary medical care is a mix of in-person and telehealth.

Cameron Muir, MD, NPHI’s chief innovation officer, noted that the hamster wheel for primary care doctors has been spinning faster and faster, with reimbursement going down and costs going up.

But with home-based primary care for frail elders under value-based models, Dr. Muir said, the clinician is paid not for making more visits but for taking great care of the patient: “And I’m actually saving Medicare money and getting credit for the hospitalizations that were avoided.”
 

A version of this article appeared on Medscape.com.

Jason Black, MD, trained in family medicine, worked for Kaiser Permanente, and subsequently completed a fellowship in geriatrics. Today, he treats frail elderly patients, mostly residents of nursing homes and assisted living facilities or living in their own homes, for Gilchrist, a hospice and palliative care organization serving Baltimore and central Maryland.

“I’m practicing family medicine to the extent that I’m treating the family unit, including the anxieties of the adult children, and finding solutions for the parents,” said Dr. Black, one of Gilchrist’s 62 employed providers, one third of whom are physicians. One of his most important roles is medication reconciliation and deprescribing.

Palliative care, a medical specialty that focuses on clarifying the treatment goals of seriously ill patients, helping with end-of-life planning, and emphasizing pain and symptom management, has been growing in recent years. Already well-established in most US hospitals, it is expanding in community settings, often as an extension of hospice programs.

Now, by adding primary care physicians and practices to their service mix, palliative care groups are better meeting the needs of a neglected — and costly — population of frail elders. In doing so, they also are better able to find a niche in the rapidly evolving alphabet soup of value-based care and its varieties of shared savings for providers who post positive outcomes.

Most patients Dr. Black sees find it difficult to visit their doctors in a clinic setting, although they face a variety of medical needs and chronic conditions of aging. They may have a prognosis of several years to live and, thus, do not qualify for hospice care. To him, a palliative approach offers the satisfaction of focusing on what is most important to patients at this difficult time in their lives, rather than predetermined clinical metrics like blood pressure or blood glucose. “It takes a lot of work, but it feels important and rewarding,” he said.

A recent survey of community-dwelling older adults in Ontario, Canada, found most patients fail to receive this treatment homes in the final 3 months of life.
 

Continuums of Patients and Models

Gilchrist started as a nonprofit, hospital-affiliated hospice program in 1994 and in 2000 took on the management of a geriatric medicine practice for its parent, Greater Baltimore Medical Center. Today, its physicians and nurse practitioners see a range of patients in geriatric primary care, palliative medicine, and hospice, according to its chief medical officer, Mark J. Gloth, DO.

“As people progress in their disease, their location — where they call home — may change as well,” Dr. Gloth said. “We offer a continuum of care in order to not lose people through those transitions. That’s the core of our mission — making sure we are there to escort people through the difficult moments in their lives.”

Models for value-based care encompass accountable care organizations (ACOs), including the ACO REACH (Realizing Equity, Access, and Community Health) high-needs model for traditional Medicare patients, and Medicare Shared Savings Programs for fee-for-service beneficiaries. These value-based models offer a variety of opportunities for the palliative care organization to share in savings resulting from keeping the patient out of the hospital or emergency room and other quality and cost benchmarks.
 

Coming Together to Meet Needs

Gilchrist is one of nine hospice and palliative organizations that have joined to form their own multistate ACO, Responsive Care Solutions, focused on the clinical needs of frail elderly Medicare beneficiaries. Hospice of the Valley in Phoenix has Geriatric Solutions, a frail elder physician practice. And Capital Caring Health, a hospice and palliative care agency serving metro Washington, DC, has deployed several physicians and nurse practitioners on the road doing primary care at home, said Heidi Young, MD, its Primary Care at Home Lead Physician.

“Five years ago, we started our primary care practice under the umbrella of a 40-year-old hospice organization because we thought we needed to prepare for the changes that are coming to the hospice model,” Dr. Young said. “The thought was that we’re not just a hospice organization; we’re an advanced illness organization. We will come to your home, whatever that is, and provide your primary care.”

The greatest potential gains for a hospice organization are from assuming 100% risk for a large population of patients, keeping them out of the hospital to lower the costs of their care, then reaping those gains under a value-based profit-sharing model, Dr. Young said.

“Our program is still new and working toward getting more patients aligned into value-based models,” she said. “It’s a work in progress.”
 

A Foot in Each World

Agencies like Capital Caring and Gilchrist derive the largest share of their physician income from billing Medicare Part B and other insurers per visit. But that billing is not enough to break even on physician services.

With hopes for a value-based future, Gilchrist also gets grants from elder-facing charitable foundations to cover up to 40% of the costs of its home-based primary care, according to its president, Catherine Hamel. Hospice care continues to be paid on a per-diem basis by Medicare for eligible terminally ill patients, including Medicare Advantage patients, although the Centers for Medicare & Medicaid Services is reportedly considering new models for the hospice benefit.

The National Partnership for Healthcare and Hospice Innovation (NPHI) is a trade group representing more than 100 nonprofit, hospice-based organizations participating in palliative care and value-based care.

For a hospice to be successful in the evolving post–acute care/end-of-life care landscape, it can no longer rely solely on its hospice line of business, no matter how high-quality, said Ethan McChesney, policy director for the Washington, DC-based nonprofit.

NPHI members have developed their own palliative care programs, and perhaps, a quarter have primary care at home practices, Mr. McChesney said. Some of them acquired existing primary care practices in their service area with which they already had relationships; others created their own.

For hospice organizations building a continuum of services for the seriously ill, adding a primary care at home practice is a natural fit, he said. “You can provide all the services you would as a traditional primary care practice while you have the opportunity to establish long-term relationships with patients and their caregivers that lend themselves to palliative care referrals and then hospice referrals downstream [when the patient becomes eligible for hospice care].” Often, this primary medical care is a mix of in-person and telehealth.

Cameron Muir, MD, NPHI’s chief innovation officer, noted that the hamster wheel for primary care doctors has been spinning faster and faster, with reimbursement going down and costs going up.

But with home-based primary care for frail elders under value-based models, Dr. Muir said, the clinician is paid not for making more visits but for taking great care of the patient: “And I’m actually saving Medicare money and getting credit for the hospitalizations that were avoided.”
 

A version of this article appeared on Medscape.com.

To the Editor:

We read with interest the September 2023 Cutis article by Swink et al,¹ “Cat Scratch Disease Presenting With Concurrent Pityriasis Rosea in a 10-Year-Old Girl.” The authors documented the possibility of Bartonella henselae infection as another causative agent for pityriasis rosea (PR) even though the association of PR with human herpesvirus (HHV) 6 and HHV-7 infection is based on several consistent observations and not on occasional findings. The association of PR with endogenous systemic reactivation of HHV-6 and HHV-7 has been identified with different investigations and laboratory techniques. Using polymerase chain reaction, real-time calibrated quantitative polymerase chain reaction, in situ hybridization, immunohistochemistry, and electron microscopy, HHV-6 and HHV-7 have been detected in plasma (a marker of active viral replication), peripheral blood mononuclear cells, and skin lesions from patients with PR.² In addition, HHV-6 and HHV-7 messenger RNA expression and their specific antigens have been detected in PR skin lesions and herpesvirus virions in various stages of morphogenesis as well as in the supernatant of co-cultured peripheral blood mononuclear cells of patients with PR.^2,3 Lastly, the increased levels of several particular cytokines and chemokinesin the sera of patients with PR support a viral role in its pathogenesis.⁴

Bartonella henselae is a gram-negative intracellular facultative bacterium that is commonly implicated in causing zoonotic infections worldwide. The incidence of cat-scratch disease (CSD) was reported to be 6.4 cases per 100,000 population in adults and 9.4 cases per 100,000 population in children aged 5 to 9 years globally.⁵ Approximately 24,000 cases of CSD are reported in the United States every year.⁶ Therefore, considering these data, if B henselae was a causative agent for PR, the eruption would be observed frequently in many patients with CSD, which is not the case. On the contrary, it is possible that B henselae infection may have reactivated HHV-6 and/or HHV-7 infection. It is well established that B henselae causes a robust cell-mediated immune response by activating natural killer and helper T cells (T_H1) and enhancement of cytotoxic T lymphocytes.⁷ It could be assumed that by strongly stimulating the immune response and polarizing it to a specific antigen cell response, B henselae infection may temporarily distract the T cell-mediated control of the latent infections, such as HHV-6 and HHV-7, which may reactivate and cause PR.

It is important to point out that a case of concomitant B henselae and Epstein-Barr virus infection has been described.⁸ Even in that case, the B henselae infection may have reactivated Epstein-Barr virus as well as HHV-6 and HHV-7 in the case described by Swink et al.¹ Epstein-Barr virus reactivation has been detected in one case⁸ through serologic testing—IgM, IgG, Epstein-Barr virus nuclear antigen IgG, and heterophile antibodies—as there were no dermatologic manifestations that may be related to Epstein-Barr virus reactivation from latency.⁹

In conclusion, a viral or bacterial infection such as Epstein-Barr virus or B henselae may have a transactivating function allowing another (latent) virus such as HHV-6 or HHV-7 to reactivate. Indeed, it has been described that SARS-CoV-2 may act as a transactivator agent triggering HHV-6/HHV-7 reactivation, thereby indirectly causing PR clinical manifestation.¹⁰

To the Editor:

We read with interest the September 2023 Cutis article by Swink et al,¹ “Cat Scratch Disease Presenting With Concurrent Pityriasis Rosea in a 10-Year-Old Girl.” The authors documented the possibility of Bartonella henselae infection as another causative agent for pityriasis rosea (PR) even though the association of PR with human herpesvirus (HHV) 6 and HHV-7 infection is based on several consistent observations and not on occasional findings. The association of PR with endogenous systemic reactivation of HHV-6 and HHV-7 has been identified with different investigations and laboratory techniques. Using polymerase chain reaction, real-time calibrated quantitative polymerase chain reaction, in situ hybridization, immunohistochemistry, and electron microscopy, HHV-6 and HHV-7 have been detected in plasma (a marker of active viral replication), peripheral blood mononuclear cells, and skin lesions from patients with PR.² In addition, HHV-6 and HHV-7 messenger RNA expression and their specific antigens have been detected in PR skin lesions and herpesvirus virions in various stages of morphogenesis as well as in the supernatant of co-cultured peripheral blood mononuclear cells of patients with PR.^2,3 Lastly, the increased levels of several particular cytokines and chemokinesin the sera of patients with PR support a viral role in its pathogenesis.⁴

Bartonella henselae is a gram-negative intracellular facultative bacterium that is commonly implicated in causing zoonotic infections worldwide. The incidence of cat-scratch disease (CSD) was reported to be 6.4 cases per 100,000 population in adults and 9.4 cases per 100,000 population in children aged 5 to 9 years globally.⁵ Approximately 24,000 cases of CSD are reported in the United States every year.⁶ Therefore, considering these data, if B henselae was a causative agent for PR, the eruption would be observed frequently in many patients with CSD, which is not the case. On the contrary, it is possible that B henselae infection may have reactivated HHV-6 and/or HHV-7 infection. It is well established that B henselae causes a robust cell-mediated immune response by activating natural killer and helper T cells (T_H1) and enhancement of cytotoxic T lymphocytes.⁷ It could be assumed that by strongly stimulating the immune response and polarizing it to a specific antigen cell response, B henselae infection may temporarily distract the T cell-mediated control of the latent infections, such as HHV-6 and HHV-7, which may reactivate and cause PR.

It is important to point out that a case of concomitant B henselae and Epstein-Barr virus infection has been described.⁸ Even in that case, the B henselae infection may have reactivated Epstein-Barr virus as well as HHV-6 and HHV-7 in the case described by Swink et al.¹ Epstein-Barr virus reactivation has been detected in one case⁸ through serologic testing—IgM, IgG, Epstein-Barr virus nuclear antigen IgG, and heterophile antibodies—as there were no dermatologic manifestations that may be related to Epstein-Barr virus reactivation from latency.⁹

In conclusion, a viral or bacterial infection such as Epstein-Barr virus or B henselae may have a transactivating function allowing another (latent) virus such as HHV-6 or HHV-7 to reactivate. Indeed, it has been described that SARS-CoV-2 may act as a transactivator agent triggering HHV-6/HHV-7 reactivation, thereby indirectly causing PR clinical manifestation.¹⁰

To the Editor:

We read with interest the September 2023 Cutis article by Swink et al,¹ “Cat Scratch Disease Presenting With Concurrent Pityriasis Rosea in a 10-Year-Old Girl.” The authors documented the possibility of Bartonella henselae infection as another causative agent for pityriasis rosea (PR) even though the association of PR with human herpesvirus (HHV) 6 and HHV-7 infection is based on several consistent observations and not on occasional findings. The association of PR with endogenous systemic reactivation of HHV-6 and HHV-7 has been identified with different investigations and laboratory techniques. Using polymerase chain reaction, real-time calibrated quantitative polymerase chain reaction, in situ hybridization, immunohistochemistry, and electron microscopy, HHV-6 and HHV-7 have been detected in plasma (a marker of active viral replication), peripheral blood mononuclear cells, and skin lesions from patients with PR.² In addition, HHV-6 and HHV-7 messenger RNA expression and their specific antigens have been detected in PR skin lesions and herpesvirus virions in various stages of morphogenesis as well as in the supernatant of co-cultured peripheral blood mononuclear cells of patients with PR.^2,3 Lastly, the increased levels of several particular cytokines and chemokinesin the sera of patients with PR support a viral role in its pathogenesis.⁴

Bartonella henselae is a gram-negative intracellular facultative bacterium that is commonly implicated in causing zoonotic infections worldwide. The incidence of cat-scratch disease (CSD) was reported to be 6.4 cases per 100,000 population in adults and 9.4 cases per 100,000 population in children aged 5 to 9 years globally.⁵ Approximately 24,000 cases of CSD are reported in the United States every year.⁶ Therefore, considering these data, if B henselae was a causative agent for PR, the eruption would be observed frequently in many patients with CSD, which is not the case. On the contrary, it is possible that B henselae infection may have reactivated HHV-6 and/or HHV-7 infection. It is well established that B henselae causes a robust cell-mediated immune response by activating natural killer and helper T cells (T_H1) and enhancement of cytotoxic T lymphocytes.⁷ It could be assumed that by strongly stimulating the immune response and polarizing it to a specific antigen cell response, B henselae infection may temporarily distract the T cell-mediated control of the latent infections, such as HHV-6 and HHV-7, which may reactivate and cause PR.

It is important to point out that a case of concomitant B henselae and Epstein-Barr virus infection has been described.⁸ Even in that case, the B henselae infection may have reactivated Epstein-Barr virus as well as HHV-6 and HHV-7 in the case described by Swink et al.¹ Epstein-Barr virus reactivation has been detected in one case⁸ through serologic testing—IgM, IgG, Epstein-Barr virus nuclear antigen IgG, and heterophile antibodies—as there were no dermatologic manifestations that may be related to Epstein-Barr virus reactivation from latency.⁹

In conclusion, a viral or bacterial infection such as Epstein-Barr virus or B henselae may have a transactivating function allowing another (latent) virus such as HHV-6 or HHV-7 to reactivate. Indeed, it has been described that SARS-CoV-2 may act as a transactivator agent triggering HHV-6/HHV-7 reactivation, thereby indirectly causing PR clinical manifestation.¹⁰

To the Editor:

Cellulitis is the most common reason for skin-related hospital admissions.¹ Despite its frequency, it is suspected that many cases of cellulitis are misdiagnosed as other etiologies presenting with similar symptoms such as a ruptured Baker cyst. These cysts are located behind the knee and can present with calf pain, peripheral edema, and erythema when ruptured. Symptoms of a ruptured Baker cyst can be indistinguishable from cellulitis as well as deep vein thrombosis (DVT), both manifesting with lower extremity pain, swelling, and erythema, making diagnosis challenging.² The hemorrhagic crescent sign—a crescent of ecchymosis distal to the medial malleolus and on the foot that results from synovial injury or rupture—can be a useful diagnostic tool to differentiate between the causes of acute swelling and pain of the leg.² When observed, the hemorrhagic crescent sign supports testing for synovial pathology at the knee.

A 63-year-old man presented to an outside hospital for evaluation of a fever (temperature, 101 °F [38.3 °C]), as well as pain, edema, and erythema of the right lower leg of 2 days’ duration. He had a history of leg cellulitis, gout, diabetes mellitus, lymphedema, and peripheral neuropathy. On admission, he was found to have elevated C-reactive protein (45 mg/L [reference range, <8 mg/L]) and mild leukocytosis (13,500 cells/μL [reference range, 4500–11,000 cells/μL]). A venous duplex scan did not demonstrate signs of thrombosis. Antibiotic therapy was started for suspected cellulitis including levofloxacin, piperacillin-tazobactam, and linezolid. Despite broad-spectrum antibiotic coverage, the patient continued to be febrile and experienced progressive erythema and swelling of the right lower leg, at which point he was transferred to our institution. A new antibiotic regimen of vancomycin, cefepime, and clindamycin was started and showed no improvement, after which dermatology was consulted.

Physical examination revealed unilateral edema and calor of the right lower leg with a demarcated erythematous rash extending to the level of the knee. Furthermore, a hemorrhagic crescent sign was present below the right medial malleolus (Figure). The popliteal fossa was supple, though the patient was adamant that he had a Baker cyst. Punch biopsies demonstrated epidermal spongiosis and extensive edema with perivascular inflammation. No organisms were found by stain and culture. Ultrasound records confirmed a Baker cyst present at least 4 months prior; however, a repeat ultrasound showed resolution. A diagnosis of pseudocellulitis secondary to Baker cyst rupture was made, and corticosteroids were started, resulting in marked reduction in erythema and edema of the lower leg and hospital discharge.

This case highlights the importance of early involvement of dermatology when cellulitis is suspected. A study of 635 patients in the United Kingdom referred to dermatology for lower limb cellulitis found that 210 (33%) patients did not have cellulitis and only 18 (3%) required hospital admission.³ Dermatology consultations have been shown to benefit patients with inflammatory skin disease by decreasing length of stay and reducing readmissions.⁴

Our patient had several risk factors for cellulitis, including obesity, lymphedema, and chronic kidney disease, in addition to having fevers and unilateral involvement. However, failure of symptoms to improve with broad-spectrum antibiotics made a diagnosis of cellulitis less likely. In this case, a severe immune response to the ruptured Baker cyst mimicked the presentation of cellulitis.

Ruptured Baker cysts have been reported to cause acute leg swelling, mimicking the symptoms of cellulitis or DVT.^2,5 The presence of a hemorrhagic crescent sign can be a useful diagnostic tool, as in our patient, because it has been reported as an indication of synovial injury or rupture, supporting the exclusion of cellulitis or DVT when it is observed.⁶ Prior reports have observed ecchymosis on the foot in as little as 1 day after the onset of calf swelling and at the lateral malleolus 3 days after the onset of calf swelling.⁵

Following suspicion of a ruptured Baker cyst causing pseudocellulitis, an ultrasound can be used to confirm the diagnosis. Ultrasonography shows a large hypoechoic space behind the calf muscles, which is pathognomonic of a ruptured Baker cyst.⁷

In conclusion, when a hemorrhagic crescent sign is observed, one should be suspicious for a ruptured Baker cyst or other synovial pathology as an etiology of pseudocellulitis. Early recognition of the hemorrhagic crescent sign can help rule out cellulitis and DVT, thereby reducing the amount of intravenous antibiotic prescribed, decreasing the length of hospital stay, and reducing readmission.

To the Editor:

Cellulitis is the most common reason for skin-related hospital admissions.¹ Despite its frequency, it is suspected that many cases of cellulitis are misdiagnosed as other etiologies presenting with similar symptoms such as a ruptured Baker cyst. These cysts are located behind the knee and can present with calf pain, peripheral edema, and erythema when ruptured. Symptoms of a ruptured Baker cyst can be indistinguishable from cellulitis as well as deep vein thrombosis (DVT), both manifesting with lower extremity pain, swelling, and erythema, making diagnosis challenging.² The hemorrhagic crescent sign—a crescent of ecchymosis distal to the medial malleolus and on the foot that results from synovial injury or rupture—can be a useful diagnostic tool to differentiate between the causes of acute swelling and pain of the leg.² When observed, the hemorrhagic crescent sign supports testing for synovial pathology at the knee.

A 63-year-old man presented to an outside hospital for evaluation of a fever (temperature, 101 °F [38.3 °C]), as well as pain, edema, and erythema of the right lower leg of 2 days’ duration. He had a history of leg cellulitis, gout, diabetes mellitus, lymphedema, and peripheral neuropathy. On admission, he was found to have elevated C-reactive protein (45 mg/L [reference range, <8 mg/L]) and mild leukocytosis (13,500 cells/μL [reference range, 4500–11,000 cells/μL]). A venous duplex scan did not demonstrate signs of thrombosis. Antibiotic therapy was started for suspected cellulitis including levofloxacin, piperacillin-tazobactam, and linezolid. Despite broad-spectrum antibiotic coverage, the patient continued to be febrile and experienced progressive erythema and swelling of the right lower leg, at which point he was transferred to our institution. A new antibiotic regimen of vancomycin, cefepime, and clindamycin was started and showed no improvement, after which dermatology was consulted.

Physical examination revealed unilateral edema and calor of the right lower leg with a demarcated erythematous rash extending to the level of the knee. Furthermore, a hemorrhagic crescent sign was present below the right medial malleolus (Figure). The popliteal fossa was supple, though the patient was adamant that he had a Baker cyst. Punch biopsies demonstrated epidermal spongiosis and extensive edema with perivascular inflammation. No organisms were found by stain and culture. Ultrasound records confirmed a Baker cyst present at least 4 months prior; however, a repeat ultrasound showed resolution. A diagnosis of pseudocellulitis secondary to Baker cyst rupture was made, and corticosteroids were started, resulting in marked reduction in erythema and edema of the lower leg and hospital discharge.

This case highlights the importance of early involvement of dermatology when cellulitis is suspected. A study of 635 patients in the United Kingdom referred to dermatology for lower limb cellulitis found that 210 (33%) patients did not have cellulitis and only 18 (3%) required hospital admission.³ Dermatology consultations have been shown to benefit patients with inflammatory skin disease by decreasing length of stay and reducing readmissions.⁴

Our patient had several risk factors for cellulitis, including obesity, lymphedema, and chronic kidney disease, in addition to having fevers and unilateral involvement. However, failure of symptoms to improve with broad-spectrum antibiotics made a diagnosis of cellulitis less likely. In this case, a severe immune response to the ruptured Baker cyst mimicked the presentation of cellulitis.

Ruptured Baker cysts have been reported to cause acute leg swelling, mimicking the symptoms of cellulitis or DVT.^2,5 The presence of a hemorrhagic crescent sign can be a useful diagnostic tool, as in our patient, because it has been reported as an indication of synovial injury or rupture, supporting the exclusion of cellulitis or DVT when it is observed.⁶ Prior reports have observed ecchymosis on the foot in as little as 1 day after the onset of calf swelling and at the lateral malleolus 3 days after the onset of calf swelling.⁵

Following suspicion of a ruptured Baker cyst causing pseudocellulitis, an ultrasound can be used to confirm the diagnosis. Ultrasonography shows a large hypoechoic space behind the calf muscles, which is pathognomonic of a ruptured Baker cyst.⁷

In conclusion, when a hemorrhagic crescent sign is observed, one should be suspicious for a ruptured Baker cyst or other synovial pathology as an etiology of pseudocellulitis. Early recognition of the hemorrhagic crescent sign can help rule out cellulitis and DVT, thereby reducing the amount of intravenous antibiotic prescribed, decreasing the length of hospital stay, and reducing readmission.

To the Editor:

Cellulitis is the most common reason for skin-related hospital admissions.¹ Despite its frequency, it is suspected that many cases of cellulitis are misdiagnosed as other etiologies presenting with similar symptoms such as a ruptured Baker cyst. These cysts are located behind the knee and can present with calf pain, peripheral edema, and erythema when ruptured. Symptoms of a ruptured Baker cyst can be indistinguishable from cellulitis as well as deep vein thrombosis (DVT), both manifesting with lower extremity pain, swelling, and erythema, making diagnosis challenging.² The hemorrhagic crescent sign—a crescent of ecchymosis distal to the medial malleolus and on the foot that results from synovial injury or rupture—can be a useful diagnostic tool to differentiate between the causes of acute swelling and pain of the leg.² When observed, the hemorrhagic crescent sign supports testing for synovial pathology at the knee.

A 63-year-old man presented to an outside hospital for evaluation of a fever (temperature, 101 °F [38.3 °C]), as well as pain, edema, and erythema of the right lower leg of 2 days’ duration. He had a history of leg cellulitis, gout, diabetes mellitus, lymphedema, and peripheral neuropathy. On admission, he was found to have elevated C-reactive protein (45 mg/L [reference range, <8 mg/L]) and mild leukocytosis (13,500 cells/μL [reference range, 4500–11,000 cells/μL]). A venous duplex scan did not demonstrate signs of thrombosis. Antibiotic therapy was started for suspected cellulitis including levofloxacin, piperacillin-tazobactam, and linezolid. Despite broad-spectrum antibiotic coverage, the patient continued to be febrile and experienced progressive erythema and swelling of the right lower leg, at which point he was transferred to our institution. A new antibiotic regimen of vancomycin, cefepime, and clindamycin was started and showed no improvement, after which dermatology was consulted.

Physical examination revealed unilateral edema and calor of the right lower leg with a demarcated erythematous rash extending to the level of the knee. Furthermore, a hemorrhagic crescent sign was present below the right medial malleolus (Figure). The popliteal fossa was supple, though the patient was adamant that he had a Baker cyst. Punch biopsies demonstrated epidermal spongiosis and extensive edema with perivascular inflammation. No organisms were found by stain and culture. Ultrasound records confirmed a Baker cyst present at least 4 months prior; however, a repeat ultrasound showed resolution. A diagnosis of pseudocellulitis secondary to Baker cyst rupture was made, and corticosteroids were started, resulting in marked reduction in erythema and edema of the lower leg and hospital discharge.

This case highlights the importance of early involvement of dermatology when cellulitis is suspected. A study of 635 patients in the United Kingdom referred to dermatology for lower limb cellulitis found that 210 (33%) patients did not have cellulitis and only 18 (3%) required hospital admission.³ Dermatology consultations have been shown to benefit patients with inflammatory skin disease by decreasing length of stay and reducing readmissions.⁴

Our patient had several risk factors for cellulitis, including obesity, lymphedema, and chronic kidney disease, in addition to having fevers and unilateral involvement. However, failure of symptoms to improve with broad-spectrum antibiotics made a diagnosis of cellulitis less likely. In this case, a severe immune response to the ruptured Baker cyst mimicked the presentation of cellulitis.

Ruptured Baker cysts have been reported to cause acute leg swelling, mimicking the symptoms of cellulitis or DVT.^2,5 The presence of a hemorrhagic crescent sign can be a useful diagnostic tool, as in our patient, because it has been reported as an indication of synovial injury or rupture, supporting the exclusion of cellulitis or DVT when it is observed.⁶ Prior reports have observed ecchymosis on the foot in as little as 1 day after the onset of calf swelling and at the lateral malleolus 3 days after the onset of calf swelling.⁵

Following suspicion of a ruptured Baker cyst causing pseudocellulitis, an ultrasound can be used to confirm the diagnosis. Ultrasonography shows a large hypoechoic space behind the calf muscles, which is pathognomonic of a ruptured Baker cyst.⁷

In conclusion, when a hemorrhagic crescent sign is observed, one should be suspicious for a ruptured Baker cyst or other synovial pathology as an etiology of pseudocellulitis. Early recognition of the hemorrhagic crescent sign can help rule out cellulitis and DVT, thereby reducing the amount of intravenous antibiotic prescribed, decreasing the length of hospital stay, and reducing readmission.

Asthma is not well controlled in about half of patients with the disease in the UK and Europe, increasing the risk of hospital admission and severe illness, and increasing healthcare costs. 

Now, the authors of a new study have reported that poorly controlled asthma is also associated with a higher carbon footprint, eight times higher than that of well-controlled asthma and equivalent to the greenhouse gas emissions produced by more than 124,000 homes each year in the UK.

The study was published in the journal Thorax and is part of the Healthcare-Based Environmental Cost of Treatment (CARBON) programme, which aims to provide a broader understanding of the carbon footprint associated with respiratory care. 

John Bell, BMBCh, medical director of BioPharmaceuticals Medical, AstraZeneca, and co-author of the study, said that he was surprised by the scale to which poorly controlled asthma contributed to the overall carbon footprint of asthma care. “This suggests that suboptimal asthma care is not just a public health issue, but also one which has environmental consequences,” he said.

Improving the care of asthma patients could help the NHS meet its net zero target, the authors suggested.
 

SABA – Largest Contributor to Asthma-Related Greenhouse Gases

Healthcare is a major contributor to greenhouse gas emissions. In 2020, the NHS set an ambitious target of reducing its carbon footprint by 80% over the next 15 years, with the aim of reaching net zero by 2045.

To estimate the environmental footprint of asthma care in the UK, the researchers retrospectively analyzed anonymized data of 236,506 people with asthma submitted to the Clinical Practice Research Datalink between 2008 and 2019. 

Greenhouse gas (GHG) emissions, measured as carbon dioxide equivalent (CO2e), were then estimated for asthma-related medication use, healthcare resource utilization, and severe exacerbations.

Well-controlled asthma was considered as having no episodes of severe worsening symptoms and fewer than three prescriptions of short-acting beta-agonists (SABAs) reliever inhalers in a year. Poorly controlled asthma included three or more SABA canister prescriptions or one or more episodes of severe worsening symptoms in a year.

Almost one in two patients with asthma (47.3%) were categorized as being poorly controlled. 

The researchers estimated the overall carbon footprint attributed to asthma care when scaled to the entire UK asthma population was 750,540 tonnes CO2e/year, with poorly controlled asthma contributing to excess GHG emissions of 303,874 tonnes CO2e/year. 

“Poorly controlled asthma generated three-fold higher greenhouse gas emissions per capita compared with well-controlled asthma, when taking into account GHG emissions related to all aspects of asthma care, including routine prescribing and management,” Dr. Bell explained. It also generated eight-fold higher excess per capita carbon footprint compared to well-controlled asthma.

SABA relievers represented the largest contributors to per capita asthma-related GHG emissions, accounting for more than 60% of overall GHG emissions and more than 90% of excess GHG emissions. The remainder was mostly due to healthcare resource utilization, such as GP and hospital visits, required to treat severe worsening symptoms.

The researchers acknowledged various limitations to their findings, including that the study results were largely descriptive in nature. And factors other than the level of asthma symptom control, such as prescribing patterns, may also have contributed to high SABA use.
 

Couple Optimized Patient Outcomes With Environmental Targets

With inappropriate SABA use having emerged as the single largest contributor to asthma care-related GHG emissions, improving this care could achieve substantial carbon emissions savings and help the NHS meet its net zero target, the authors explained. 

This improvement could include the adoption of the Global Initiative for Asthma (GINA) treatment strategies that, since 2019, no longer recommends that SABAs are used alone as the preferred reliever for acute asthma symptoms, the authors wrote. 

However, the National Institute for Health and Care Excellence (NICE) asthma guidelines still recommend SABA alone as a reliever therapy.

On the other hand, the Primary Care Respiratory Society (PCRS) highlights on its website that the Medicines and Healthcare Products Regulatory Agency (MHRA) had approved the use of a dual (inhaled corticosteroid/formoterol) combination treatment to be used as a reliever therapy for people aged 12 and over.

“In the UK, this new therapy option does not yet sit within an approved national guideline as NICE last updated its treatment pathway in 2020. We await a new national asthma guideline but do not anticipate this new joint approach between NICE, BTS [British Thoracic Society], and SIGN [Scottish Intercollegiate Guidelines Network] to publish until 2024,” the society wrote.

Dr. Bell explained that the carbon footprint of asthma care increased with higher socio-economic deprivation. “Thus, targeting suboptimal care to areas of higher deprivation could help improve patient outcomes and address health inequities, with the additional benefit of reducing the overall carbon footprint of asthma care,” he said.

This coupling of optimized patient outcomes with environmental targets to decrease GHG emissions could be extended to other chronic progressive diseases, particularly those associated with multi-morbidities, the authors wrote.

Dr. Andy Whittamore, MBBS, clinical lead at Asthma + Lung UK, who was not involved in the research, said: “This study highlights that high levels of uncontrolled asthma not only put thousands of people at risk of life-threatening asthma attacks, but also have a detrimental effect on the environment. It’s important to point out that people shouldn’t stop taking their inhalers because they are worried about the environment. The best thing for the environment is to keep your asthma under control,” he emphasized.

Please refer to the study for full study author disclosures.Dr. Hicks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape UK.

Asthma is not well controlled in about half of patients with the disease in the UK and Europe, increasing the risk of hospital admission and severe illness, and increasing healthcare costs. 

Now, the authors of a new study have reported that poorly controlled asthma is also associated with a higher carbon footprint, eight times higher than that of well-controlled asthma and equivalent to the greenhouse gas emissions produced by more than 124,000 homes each year in the UK.

The study was published in the journal Thorax and is part of the Healthcare-Based Environmental Cost of Treatment (CARBON) programme, which aims to provide a broader understanding of the carbon footprint associated with respiratory care. 

John Bell, BMBCh, medical director of BioPharmaceuticals Medical, AstraZeneca, and co-author of the study, said that he was surprised by the scale to which poorly controlled asthma contributed to the overall carbon footprint of asthma care. “This suggests that suboptimal asthma care is not just a public health issue, but also one which has environmental consequences,” he said.

Improving the care of asthma patients could help the NHS meet its net zero target, the authors suggested.
 

SABA – Largest Contributor to Asthma-Related Greenhouse Gases

Healthcare is a major contributor to greenhouse gas emissions. In 2020, the NHS set an ambitious target of reducing its carbon footprint by 80% over the next 15 years, with the aim of reaching net zero by 2045.

To estimate the environmental footprint of asthma care in the UK, the researchers retrospectively analyzed anonymized data of 236,506 people with asthma submitted to the Clinical Practice Research Datalink between 2008 and 2019. 

Greenhouse gas (GHG) emissions, measured as carbon dioxide equivalent (CO2e), were then estimated for asthma-related medication use, healthcare resource utilization, and severe exacerbations.

Well-controlled asthma was considered as having no episodes of severe worsening symptoms and fewer than three prescriptions of short-acting beta-agonists (SABAs) reliever inhalers in a year. Poorly controlled asthma included three or more SABA canister prescriptions or one or more episodes of severe worsening symptoms in a year.

Almost one in two patients with asthma (47.3%) were categorized as being poorly controlled. 

The researchers estimated the overall carbon footprint attributed to asthma care when scaled to the entire UK asthma population was 750,540 tonnes CO2e/year, with poorly controlled asthma contributing to excess GHG emissions of 303,874 tonnes CO2e/year. 

“Poorly controlled asthma generated three-fold higher greenhouse gas emissions per capita compared with well-controlled asthma, when taking into account GHG emissions related to all aspects of asthma care, including routine prescribing and management,” Dr. Bell explained. It also generated eight-fold higher excess per capita carbon footprint compared to well-controlled asthma.

SABA relievers represented the largest contributors to per capita asthma-related GHG emissions, accounting for more than 60% of overall GHG emissions and more than 90% of excess GHG emissions. The remainder was mostly due to healthcare resource utilization, such as GP and hospital visits, required to treat severe worsening symptoms.

The researchers acknowledged various limitations to their findings, including that the study results were largely descriptive in nature. And factors other than the level of asthma symptom control, such as prescribing patterns, may also have contributed to high SABA use.
 

Couple Optimized Patient Outcomes With Environmental Targets

With inappropriate SABA use having emerged as the single largest contributor to asthma care-related GHG emissions, improving this care could achieve substantial carbon emissions savings and help the NHS meet its net zero target, the authors explained. 

This improvement could include the adoption of the Global Initiative for Asthma (GINA) treatment strategies that, since 2019, no longer recommends that SABAs are used alone as the preferred reliever for acute asthma symptoms, the authors wrote. 

However, the National Institute for Health and Care Excellence (NICE) asthma guidelines still recommend SABA alone as a reliever therapy.

On the other hand, the Primary Care Respiratory Society (PCRS) highlights on its website that the Medicines and Healthcare Products Regulatory Agency (MHRA) had approved the use of a dual (inhaled corticosteroid/formoterol) combination treatment to be used as a reliever therapy for people aged 12 and over.

“In the UK, this new therapy option does not yet sit within an approved national guideline as NICE last updated its treatment pathway in 2020. We await a new national asthma guideline but do not anticipate this new joint approach between NICE, BTS [British Thoracic Society], and SIGN [Scottish Intercollegiate Guidelines Network] to publish until 2024,” the society wrote.

Dr. Bell explained that the carbon footprint of asthma care increased with higher socio-economic deprivation. “Thus, targeting suboptimal care to areas of higher deprivation could help improve patient outcomes and address health inequities, with the additional benefit of reducing the overall carbon footprint of asthma care,” he said.

This coupling of optimized patient outcomes with environmental targets to decrease GHG emissions could be extended to other chronic progressive diseases, particularly those associated with multi-morbidities, the authors wrote.

Dr. Andy Whittamore, MBBS, clinical lead at Asthma + Lung UK, who was not involved in the research, said: “This study highlights that high levels of uncontrolled asthma not only put thousands of people at risk of life-threatening asthma attacks, but also have a detrimental effect on the environment. It’s important to point out that people shouldn’t stop taking their inhalers because they are worried about the environment. The best thing for the environment is to keep your asthma under control,” he emphasized.

Please refer to the study for full study author disclosures.Dr. Hicks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape UK.

Asthma is not well controlled in about half of patients with the disease in the UK and Europe, increasing the risk of hospital admission and severe illness, and increasing healthcare costs. 

Now, the authors of a new study have reported that poorly controlled asthma is also associated with a higher carbon footprint, eight times higher than that of well-controlled asthma and equivalent to the greenhouse gas emissions produced by more than 124,000 homes each year in the UK.

The study was published in the journal Thorax and is part of the Healthcare-Based Environmental Cost of Treatment (CARBON) programme, which aims to provide a broader understanding of the carbon footprint associated with respiratory care. 

John Bell, BMBCh, medical director of BioPharmaceuticals Medical, AstraZeneca, and co-author of the study, said that he was surprised by the scale to which poorly controlled asthma contributed to the overall carbon footprint of asthma care. “This suggests that suboptimal asthma care is not just a public health issue, but also one which has environmental consequences,” he said.

Improving the care of asthma patients could help the NHS meet its net zero target, the authors suggested.
 

SABA – Largest Contributor to Asthma-Related Greenhouse Gases

Healthcare is a major contributor to greenhouse gas emissions. In 2020, the NHS set an ambitious target of reducing its carbon footprint by 80% over the next 15 years, with the aim of reaching net zero by 2045.

To estimate the environmental footprint of asthma care in the UK, the researchers retrospectively analyzed anonymized data of 236,506 people with asthma submitted to the Clinical Practice Research Datalink between 2008 and 2019. 

Greenhouse gas (GHG) emissions, measured as carbon dioxide equivalent (CO2e), were then estimated for asthma-related medication use, healthcare resource utilization, and severe exacerbations.

Well-controlled asthma was considered as having no episodes of severe worsening symptoms and fewer than three prescriptions of short-acting beta-agonists (SABAs) reliever inhalers in a year. Poorly controlled asthma included three or more SABA canister prescriptions or one or more episodes of severe worsening symptoms in a year.

Almost one in two patients with asthma (47.3%) were categorized as being poorly controlled. 

The researchers estimated the overall carbon footprint attributed to asthma care when scaled to the entire UK asthma population was 750,540 tonnes CO2e/year, with poorly controlled asthma contributing to excess GHG emissions of 303,874 tonnes CO2e/year. 

“Poorly controlled asthma generated three-fold higher greenhouse gas emissions per capita compared with well-controlled asthma, when taking into account GHG emissions related to all aspects of asthma care, including routine prescribing and management,” Dr. Bell explained. It also generated eight-fold higher excess per capita carbon footprint compared to well-controlled asthma.

SABA relievers represented the largest contributors to per capita asthma-related GHG emissions, accounting for more than 60% of overall GHG emissions and more than 90% of excess GHG emissions. The remainder was mostly due to healthcare resource utilization, such as GP and hospital visits, required to treat severe worsening symptoms.

The researchers acknowledged various limitations to their findings, including that the study results were largely descriptive in nature. And factors other than the level of asthma symptom control, such as prescribing patterns, may also have contributed to high SABA use.
 

Couple Optimized Patient Outcomes With Environmental Targets

With inappropriate SABA use having emerged as the single largest contributor to asthma care-related GHG emissions, improving this care could achieve substantial carbon emissions savings and help the NHS meet its net zero target, the authors explained. 

This improvement could include the adoption of the Global Initiative for Asthma (GINA) treatment strategies that, since 2019, no longer recommends that SABAs are used alone as the preferred reliever for acute asthma symptoms, the authors wrote. 

However, the National Institute for Health and Care Excellence (NICE) asthma guidelines still recommend SABA alone as a reliever therapy.

On the other hand, the Primary Care Respiratory Society (PCRS) highlights on its website that the Medicines and Healthcare Products Regulatory Agency (MHRA) had approved the use of a dual (inhaled corticosteroid/formoterol) combination treatment to be used as a reliever therapy for people aged 12 and over.

“In the UK, this new therapy option does not yet sit within an approved national guideline as NICE last updated its treatment pathway in 2020. We await a new national asthma guideline but do not anticipate this new joint approach between NICE, BTS [British Thoracic Society], and SIGN [Scottish Intercollegiate Guidelines Network] to publish until 2024,” the society wrote.

Dr. Bell explained that the carbon footprint of asthma care increased with higher socio-economic deprivation. “Thus, targeting suboptimal care to areas of higher deprivation could help improve patient outcomes and address health inequities, with the additional benefit of reducing the overall carbon footprint of asthma care,” he said.

This coupling of optimized patient outcomes with environmental targets to decrease GHG emissions could be extended to other chronic progressive diseases, particularly those associated with multi-morbidities, the authors wrote.

Dr. Andy Whittamore, MBBS, clinical lead at Asthma + Lung UK, who was not involved in the research, said: “This study highlights that high levels of uncontrolled asthma not only put thousands of people at risk of life-threatening asthma attacks, but also have a detrimental effect on the environment. It’s important to point out that people shouldn’t stop taking their inhalers because they are worried about the environment. The best thing for the environment is to keep your asthma under control,” he emphasized.

Please refer to the study for full study author disclosures.Dr. Hicks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape UK.

This transcript has been edited for clarity.

Hi. I’m Art Caplan, at the Division of Medical Ethics at New York University’s Grossman School of Medicine.

Very recently, a homeopathic midwife in New York was fined $300,000 for giving out phony injections for kids who were looking to get immunized in order to go to school. She gave pellets, which are sometimes called nosodes, I believe, with homeopathic ingredients, meaning next to nothing in them, and then basically certified that these children — and there were over 1500 of them — were compliant with New York State requirements to be vaccinated to go to school.

However, homeopathy is straight-up bunk. We have seen it again and again discredited as just something that doesn’t work. It has a tradition, but it’s basically nonsense. It certainly doesn’t work as a way to vaccinate anybody.

This midwife basically lied and gave phony certification to the parents of these kids. I’m not talking about the COVID-19 vaccine. I’m talking measles, mumps, rubella, flu, and polio — the childhood immunization schedule. For whatever reason, they put their faith in her and she went along with this fraud.

I think the fine is appropriate, but I think she should be penalized further. Why? When you send 1500 kids to school, mostly in Long Island, New York, but to schools all over the place, you are setting up conditions to bring back epidemic diseases like measles.

We’re already seeing measles outbreaks. At least five states have them. There’s a significant measles outbreak in Philadelphia. Although I can’t say for sure, I believe those outbreaks are directly linked to parents, post–COVID-19, becoming vaccine hesitant and either not vaccinating and lying or going to alternative practitioners like this midwife and claiming that they have been vaccinated.

You’re doing harm not only to the children who you allow to go to school under phony pretenses, but also you’re putting their classmates at risk. We all know that measles is very, very contagious. You’re risking the return of a disease that leads to hospitalization and sometimes even death. That is basically unconscionable.

I think her license should be taken away and she should not be practicing anymore. I believe that anyone who is involved in this kind of phony, dangerous, fraudulent practice ought to be severely punished.

Pre–COVID-19, we had just about gotten rid of measles and mumps. We didn’t see these diseases. Sometimes parents got a bit lazy in childhood vaccination basically because we had used immunization to get rid of the diseases.

Going to alternative healers and allowing people to get away with fraudulent nonsense risks bringing back disabling and deadly killers is not fair to you, me, and other people who are put at risk. It’s not fair to the kids who go to school with other kids who they think are vaccinated but aren’t.

I’m Art Caplan, at the Division of Medical Ethics at the New York University Grossman School of Medicine. Thanks for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan, at the Division of Medical Ethics at New York University’s Grossman School of Medicine.

Very recently, a homeopathic midwife in New York was fined $300,000 for giving out phony injections for kids who were looking to get immunized in order to go to school. She gave pellets, which are sometimes called nosodes, I believe, with homeopathic ingredients, meaning next to nothing in them, and then basically certified that these children — and there were over 1500 of them — were compliant with New York State requirements to be vaccinated to go to school.

However, homeopathy is straight-up bunk. We have seen it again and again discredited as just something that doesn’t work. It has a tradition, but it’s basically nonsense. It certainly doesn’t work as a way to vaccinate anybody.

This midwife basically lied and gave phony certification to the parents of these kids. I’m not talking about the COVID-19 vaccine. I’m talking measles, mumps, rubella, flu, and polio — the childhood immunization schedule. For whatever reason, they put their faith in her and she went along with this fraud.

I think the fine is appropriate, but I think she should be penalized further. Why? When you send 1500 kids to school, mostly in Long Island, New York, but to schools all over the place, you are setting up conditions to bring back epidemic diseases like measles.

We’re already seeing measles outbreaks. At least five states have them. There’s a significant measles outbreak in Philadelphia. Although I can’t say for sure, I believe those outbreaks are directly linked to parents, post–COVID-19, becoming vaccine hesitant and either not vaccinating and lying or going to alternative practitioners like this midwife and claiming that they have been vaccinated.

You’re doing harm not only to the children who you allow to go to school under phony pretenses, but also you’re putting their classmates at risk. We all know that measles is very, very contagious. You’re risking the return of a disease that leads to hospitalization and sometimes even death. That is basically unconscionable.

I think her license should be taken away and she should not be practicing anymore. I believe that anyone who is involved in this kind of phony, dangerous, fraudulent practice ought to be severely punished.

Pre–COVID-19, we had just about gotten rid of measles and mumps. We didn’t see these diseases. Sometimes parents got a bit lazy in childhood vaccination basically because we had used immunization to get rid of the diseases.

Going to alternative healers and allowing people to get away with fraudulent nonsense risks bringing back disabling and deadly killers is not fair to you, me, and other people who are put at risk. It’s not fair to the kids who go to school with other kids who they think are vaccinated but aren’t.

I’m Art Caplan, at the Division of Medical Ethics at the New York University Grossman School of Medicine. Thanks for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan, at the Division of Medical Ethics at New York University’s Grossman School of Medicine.

Very recently, a homeopathic midwife in New York was fined $300,000 for giving out phony injections for kids who were looking to get immunized in order to go to school. She gave pellets, which are sometimes called nosodes, I believe, with homeopathic ingredients, meaning next to nothing in them, and then basically certified that these children — and there were over 1500 of them — were compliant with New York State requirements to be vaccinated to go to school.

However, homeopathy is straight-up bunk. We have seen it again and again discredited as just something that doesn’t work. It has a tradition, but it’s basically nonsense. It certainly doesn’t work as a way to vaccinate anybody.

This midwife basically lied and gave phony certification to the parents of these kids. I’m not talking about the COVID-19 vaccine. I’m talking measles, mumps, rubella, flu, and polio — the childhood immunization schedule. For whatever reason, they put their faith in her and she went along with this fraud.

I think the fine is appropriate, but I think she should be penalized further. Why? When you send 1500 kids to school, mostly in Long Island, New York, but to schools all over the place, you are setting up conditions to bring back epidemic diseases like measles.

We’re already seeing measles outbreaks. At least five states have them. There’s a significant measles outbreak in Philadelphia. Although I can’t say for sure, I believe those outbreaks are directly linked to parents, post–COVID-19, becoming vaccine hesitant and either not vaccinating and lying or going to alternative practitioners like this midwife and claiming that they have been vaccinated.

You’re doing harm not only to the children who you allow to go to school under phony pretenses, but also you’re putting their classmates at risk. We all know that measles is very, very contagious. You’re risking the return of a disease that leads to hospitalization and sometimes even death. That is basically unconscionable.

I think her license should be taken away and she should not be practicing anymore. I believe that anyone who is involved in this kind of phony, dangerous, fraudulent practice ought to be severely punished.

Pre–COVID-19, we had just about gotten rid of measles and mumps. We didn’t see these diseases. Sometimes parents got a bit lazy in childhood vaccination basically because we had used immunization to get rid of the diseases.

Going to alternative healers and allowing people to get away with fraudulent nonsense risks bringing back disabling and deadly killers is not fair to you, me, and other people who are put at risk. It’s not fair to the kids who go to school with other kids who they think are vaccinated but aren’t.

I’m Art Caplan, at the Division of Medical Ethics at the New York University Grossman School of Medicine. Thanks for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved letibotulinumtoxinA-wlbg, an injectable neurotoxin long used in South Korea for the treatment of moderate to severe glabellar (frown) lines in adults. Developed by Hugel, the product is being marketed under the brand name Letybo.

The FDA’s approval was based on positive results from three phase 3 trials of letibotulinumtoxinA-wlbg that enrolled more than 1000 individuals in the United States and Europe. According to information in the package insert, the most common adverse reaction reported in the trials was headache, which occurred in 2% of trial participants. Other adverse events reported by fewer than 1% of trial participants included brow ptosis, eyelid ptosis, and blepharospasm, while the most frequently reported injection site reactions included administrative site swelling, facial pain, folliculitis, and periorbital hematoma.

According to a press release from the company, letibotulinumtoxinA-wlbg has been the leading neurotoxin brand in South Korea for 7 consecutive years, and the product has been sold in more than 50 different countries. Hugel plans to launch Letybo for US-based aesthetic clinicians in the latter half of 2024.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved letibotulinumtoxinA-wlbg, an injectable neurotoxin long used in South Korea for the treatment of moderate to severe glabellar (frown) lines in adults. Developed by Hugel, the product is being marketed under the brand name Letybo.

The FDA’s approval was based on positive results from three phase 3 trials of letibotulinumtoxinA-wlbg that enrolled more than 1000 individuals in the United States and Europe. According to information in the package insert, the most common adverse reaction reported in the trials was headache, which occurred in 2% of trial participants. Other adverse events reported by fewer than 1% of trial participants included brow ptosis, eyelid ptosis, and blepharospasm, while the most frequently reported injection site reactions included administrative site swelling, facial pain, folliculitis, and periorbital hematoma.

According to a press release from the company, letibotulinumtoxinA-wlbg has been the leading neurotoxin brand in South Korea for 7 consecutive years, and the product has been sold in more than 50 different countries. Hugel plans to launch Letybo for US-based aesthetic clinicians in the latter half of 2024.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved letibotulinumtoxinA-wlbg, an injectable neurotoxin long used in South Korea for the treatment of moderate to severe glabellar (frown) lines in adults. Developed by Hugel, the product is being marketed under the brand name Letybo.

The FDA’s approval was based on positive results from three phase 3 trials of letibotulinumtoxinA-wlbg that enrolled more than 1000 individuals in the United States and Europe. According to information in the package insert, the most common adverse reaction reported in the trials was headache, which occurred in 2% of trial participants. Other adverse events reported by fewer than 1% of trial participants included brow ptosis, eyelid ptosis, and blepharospasm, while the most frequently reported injection site reactions included administrative site swelling, facial pain, folliculitis, and periorbital hematoma.

According to a press release from the company, letibotulinumtoxinA-wlbg has been the leading neurotoxin brand in South Korea for 7 consecutive years, and the product has been sold in more than 50 different countries. Hugel plans to launch Letybo for US-based aesthetic clinicians in the latter half of 2024.

A version of this article appeared on Medscape.com.

TOPLINE:

Treatment modifications, such as dose reductions, schedule changes, or use of less toxic regimens, can improve how well older patients with advanced cancer and aging-related conditions tolerate chemotherapy regimens.

METHODOLOGY:

• Older patients are underrepresented in clinical trials, which means the reported risks associated with standard-of-care regimens typically reflect outcomes in younger, healthier patients. This underrepresentation in clinical trials has also led to uncertainties about the safety of standard chemotherapy regimens in older patients who often have other health conditions to manage, alongside cancer.
• In this secondary analysis, researchers evaluated the association between primary treatment modifications to standard-of-care chemotherapy regimens and treatment tolerability.
• The trial included 609 patients aged ≥ 70 years who had advanced cancer alongside at least one age-related condition, such as impaired cognition, and planned to start a new palliative chemotherapy regimen in the community oncology setting. The most common cancer types were gastrointestinal cancer (37.4%) and lung cancer (28.6%).
• The primary outcome was grade 3-5 adverse events within 3 months of chemotherapy initiation.
• Secondary outcomes included patient-reported functional decline and combined adverse outcomes, which incorporated clinician-rated toxic effects, patient-reported functional decline, and 6-month overall survival.

TAKEAWAY: 

• Overall, 281 patients (46.1%) received a primary treatment modification, most often a dose reduction (71.9%) or a scheduling change (11.7%).
• Patients who received primary treatment modifications had a 15% lower risk for grades 3-5 adverse effects (relative risk [RR], 0.85) and a 20% lower risk for patient-reported functional decline (RR, 0.80) than those who received standard treatment.
• Patients receiving treatment modifications had 32% lower risk for a worse combined adverse outcome (odds ratio, 0.68).
• Cancer type may matter as well. When looking at outcomes by cancer type, patients with gastrointestinal cancers who received a primary treatment modification had a lower risk for toxic effects (RR, 0.82), whereas patients with lung cancer did not (RR, 1.03; 95% CI, 0.88-1.20).

IN PRACTICE:

These findings “can help oncologists to choose the optimal drug regimen, select a safe and effective initial dose, and undertake appropriate monitoring strategies to manage the clinical care of older people with advanced cancer,” the authors said. 

SOURCE:

This study, led by Mostafa R. Mohamed from University of Rochester, New York, was published February 15 in JAMA Network Open.

LIMITATIONS: 

Residual confounding may be present. Extremely healthy older patients may have been excluded due to study criteria, limiting generalizability. There may be variation in toxicities due to inclusion of patients with multiple heterogeneous cancer.

DISCLOSURES:

This work was supported by the National Cancer Institute and the University of Rochester, New York. The authors disclosed financial relationships outside this work.

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

TOPLINE:

Treatment modifications, such as dose reductions, schedule changes, or use of less toxic regimens, can improve how well older patients with advanced cancer and aging-related conditions tolerate chemotherapy regimens.

METHODOLOGY:

• Older patients are underrepresented in clinical trials, which means the reported risks associated with standard-of-care regimens typically reflect outcomes in younger, healthier patients. This underrepresentation in clinical trials has also led to uncertainties about the safety of standard chemotherapy regimens in older patients who often have other health conditions to manage, alongside cancer.
• In this secondary analysis, researchers evaluated the association between primary treatment modifications to standard-of-care chemotherapy regimens and treatment tolerability.
• The trial included 609 patients aged ≥ 70 years who had advanced cancer alongside at least one age-related condition, such as impaired cognition, and planned to start a new palliative chemotherapy regimen in the community oncology setting. The most common cancer types were gastrointestinal cancer (37.4%) and lung cancer (28.6%).
• The primary outcome was grade 3-5 adverse events within 3 months of chemotherapy initiation.
• Secondary outcomes included patient-reported functional decline and combined adverse outcomes, which incorporated clinician-rated toxic effects, patient-reported functional decline, and 6-month overall survival.

TAKEAWAY: 

• Overall, 281 patients (46.1%) received a primary treatment modification, most often a dose reduction (71.9%) or a scheduling change (11.7%).
• Patients who received primary treatment modifications had a 15% lower risk for grades 3-5 adverse effects (relative risk [RR], 0.85) and a 20% lower risk for patient-reported functional decline (RR, 0.80) than those who received standard treatment.
• Patients receiving treatment modifications had 32% lower risk for a worse combined adverse outcome (odds ratio, 0.68).
• Cancer type may matter as well. When looking at outcomes by cancer type, patients with gastrointestinal cancers who received a primary treatment modification had a lower risk for toxic effects (RR, 0.82), whereas patients with lung cancer did not (RR, 1.03; 95% CI, 0.88-1.20).

IN PRACTICE:

These findings “can help oncologists to choose the optimal drug regimen, select a safe and effective initial dose, and undertake appropriate monitoring strategies to manage the clinical care of older people with advanced cancer,” the authors said. 

SOURCE:

This study, led by Mostafa R. Mohamed from University of Rochester, New York, was published February 15 in JAMA Network Open.

LIMITATIONS: 

Residual confounding may be present. Extremely healthy older patients may have been excluded due to study criteria, limiting generalizability. There may be variation in toxicities due to inclusion of patients with multiple heterogeneous cancer.

DISCLOSURES:

This work was supported by the National Cancer Institute and the University of Rochester, New York. The authors disclosed financial relationships outside this work.

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

TOPLINE:

Treatment modifications, such as dose reductions, schedule changes, or use of less toxic regimens, can improve how well older patients with advanced cancer and aging-related conditions tolerate chemotherapy regimens.

METHODOLOGY:

• Older patients are underrepresented in clinical trials, which means the reported risks associated with standard-of-care regimens typically reflect outcomes in younger, healthier patients. This underrepresentation in clinical trials has also led to uncertainties about the safety of standard chemotherapy regimens in older patients who often have other health conditions to manage, alongside cancer.
• In this secondary analysis, researchers evaluated the association between primary treatment modifications to standard-of-care chemotherapy regimens and treatment tolerability.
• The trial included 609 patients aged ≥ 70 years who had advanced cancer alongside at least one age-related condition, such as impaired cognition, and planned to start a new palliative chemotherapy regimen in the community oncology setting. The most common cancer types were gastrointestinal cancer (37.4%) and lung cancer (28.6%).
• The primary outcome was grade 3-5 adverse events within 3 months of chemotherapy initiation.
• Secondary outcomes included patient-reported functional decline and combined adverse outcomes, which incorporated clinician-rated toxic effects, patient-reported functional decline, and 6-month overall survival.

TAKEAWAY: 

• Overall, 281 patients (46.1%) received a primary treatment modification, most often a dose reduction (71.9%) or a scheduling change (11.7%).
• Patients who received primary treatment modifications had a 15% lower risk for grades 3-5 adverse effects (relative risk [RR], 0.85) and a 20% lower risk for patient-reported functional decline (RR, 0.80) than those who received standard treatment.
• Patients receiving treatment modifications had 32% lower risk for a worse combined adverse outcome (odds ratio, 0.68).
• Cancer type may matter as well. When looking at outcomes by cancer type, patients with gastrointestinal cancers who received a primary treatment modification had a lower risk for toxic effects (RR, 0.82), whereas patients with lung cancer did not (RR, 1.03; 95% CI, 0.88-1.20).

IN PRACTICE:

These findings “can help oncologists to choose the optimal drug regimen, select a safe and effective initial dose, and undertake appropriate monitoring strategies to manage the clinical care of older people with advanced cancer,” the authors said. 

SOURCE:

This study, led by Mostafa R. Mohamed from University of Rochester, New York, was published February 15 in JAMA Network Open.

LIMITATIONS: 

Residual confounding may be present. Extremely healthy older patients may have been excluded due to study criteria, limiting generalizability. There may be variation in toxicities due to inclusion of patients with multiple heterogeneous cancer.

DISCLOSURES:

This work was supported by the National Cancer Institute and the University of Rochester, New York. The authors disclosed financial relationships outside this work.

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

TOPLINE:

Metformin cuts the risk for diabetic nephropathy (DN) and major kidney and cardiovascular events in patients with newly diagnosed type 2 diabetes (T2D) across various renal function states.

METHODOLOGY:

Metformin is a first-line treatment in US and South Korean T2D management guidelines, except for patients with advanced chronic kidney disease (CKD) (stage, ≥ 4; estimated glomerular filtration rate [eGFR], < 30).

The study used data from the databases of three tertiary hospitals in South Korea to assess the effect of metformin on long-term renal and cardiovascular outcomes across various renal function states in patients with newly diagnosed T2D.

Four groups of treatment-control comparative cohorts were identified at each hospital: Patients who had not yet developed DN at T2D diagnosis (mean age in treatment and control cohorts, 61-65 years) and those with reduced renal function (CKD stages 3A, 3B, and 4).

Patients who continuously received metformin after T2D diagnosis and beyond the observation period were 1:1 propensity score matched with controls who were prescribed oral hypoglycemic agents other than metformin.

Primary outcomes were net major adverse cardiovascular events including strokes (MACEs) or in-hospital death and a composite of major adverse kidney events (MAKEs) or in-hospital death.

TAKEAWAY:

Among patients without DN at T2D diagnosis, the continuous use of metformin vs other oral hypoglycemic agents was associated with a lower risk for:

Overt DN (incidence rate ratio [IRR], 0.82; 95% CI, 0.71-0.95),

MACEs (IRR, 0.76; 95% CI, 0.64-0.92), and

MAKEs (IRR, 0.45; 95% CI, 0.33-0.62).

Compared with non-metformin or discontinued metformin use, the continuous use of metformin was associated with a lower risk for MACE across CKD stages 3A (IRR, 0.70; 95% CI, 0.57-0.87), 3B (IRR, 0.83; 95% CI, 0.74-0.93), and 4 (IRR, 0.71; 95% CI, 0.60-0.85).

Similarly, the risk for MAKE was lower among continuous metformin users than in nonusers or discontinuous metformin users across CKD stage 3A (IRR, 0.39; 95% CI, 0.35-0.43), 3B (IRR, 0.44; 95% CI, 0.40-0.48), and 4 (IRR, 0.45; 95% CI, 0.39-0.51).

IN PRACTICE:

“The significance of the current study is highlighted by its integration of real-world clinical data, which encompasses patients diagnosed with CDK4 [eGRF, 15-29 mL/min/1.73 m2], a group currently considered contraindicated,” the authors wrote.

SOURCE:

The study, led by Yongjin Yi, MD, PhD, Department of Internal Medicine, Dankook University College of Medicine, Cheonan-si, Republic of Korea, was published in Scientific Reports.

LIMITATIONS:

There may be a possibility of selection bias because of the retrospective and observational nature of this study. Despite achieving a 1:1 propensity score matching to address the confounding factors, some variables, such as serum albumin and A1c levels, remained unbalanced after matching. The paper did not include observation length or patient numbers, but in response to an email query from Medscape, Yi notes that in one hospital, the mean duration of observation for the control and treatment groups was about 6.5 years, and the total number in the treatment groups across data from three hospitals was 11,675, with the same number of matched controls.

DISCLOSURES:

This study was supported by a Young Investigator Research Grant from the Korean Society of Nephrology, a grant from the Seoul National University Bundang Hospital Research Fund, and the Bio&Medical Technology Development Program of the National Research Foundation funded by the Korean government. The authors disclosed no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Metformin cuts the risk for diabetic nephropathy (DN) and major kidney and cardiovascular events in patients with newly diagnosed type 2 diabetes (T2D) across various renal function states.

METHODOLOGY:

Metformin is a first-line treatment in US and South Korean T2D management guidelines, except for patients with advanced chronic kidney disease (CKD) (stage, ≥ 4; estimated glomerular filtration rate [eGFR], < 30).

The study used data from the databases of three tertiary hospitals in South Korea to assess the effect of metformin on long-term renal and cardiovascular outcomes across various renal function states in patients with newly diagnosed T2D.

Four groups of treatment-control comparative cohorts were identified at each hospital: Patients who had not yet developed DN at T2D diagnosis (mean age in treatment and control cohorts, 61-65 years) and those with reduced renal function (CKD stages 3A, 3B, and 4).

Patients who continuously received metformin after T2D diagnosis and beyond the observation period were 1:1 propensity score matched with controls who were prescribed oral hypoglycemic agents other than metformin.

Primary outcomes were net major adverse cardiovascular events including strokes (MACEs) or in-hospital death and a composite of major adverse kidney events (MAKEs) or in-hospital death.

TAKEAWAY:

Among patients without DN at T2D diagnosis, the continuous use of metformin vs other oral hypoglycemic agents was associated with a lower risk for:

Overt DN (incidence rate ratio [IRR], 0.82; 95% CI, 0.71-0.95),

MACEs (IRR, 0.76; 95% CI, 0.64-0.92), and

MAKEs (IRR, 0.45; 95% CI, 0.33-0.62).

Compared with non-metformin or discontinued metformin use, the continuous use of metformin was associated with a lower risk for MACE across CKD stages 3A (IRR, 0.70; 95% CI, 0.57-0.87), 3B (IRR, 0.83; 95% CI, 0.74-0.93), and 4 (IRR, 0.71; 95% CI, 0.60-0.85).

Similarly, the risk for MAKE was lower among continuous metformin users than in nonusers or discontinuous metformin users across CKD stage 3A (IRR, 0.39; 95% CI, 0.35-0.43), 3B (IRR, 0.44; 95% CI, 0.40-0.48), and 4 (IRR, 0.45; 95% CI, 0.39-0.51).

IN PRACTICE:

“The significance of the current study is highlighted by its integration of real-world clinical data, which encompasses patients diagnosed with CDK4 [eGRF, 15-29 mL/min/1.73 m2], a group currently considered contraindicated,” the authors wrote.

SOURCE:

The study, led by Yongjin Yi, MD, PhD, Department of Internal Medicine, Dankook University College of Medicine, Cheonan-si, Republic of Korea, was published in Scientific Reports.

LIMITATIONS:

There may be a possibility of selection bias because of the retrospective and observational nature of this study. Despite achieving a 1:1 propensity score matching to address the confounding factors, some variables, such as serum albumin and A1c levels, remained unbalanced after matching. The paper did not include observation length or patient numbers, but in response to an email query from Medscape, Yi notes that in one hospital, the mean duration of observation for the control and treatment groups was about 6.5 years, and the total number in the treatment groups across data from three hospitals was 11,675, with the same number of matched controls.

DISCLOSURES:

This study was supported by a Young Investigator Research Grant from the Korean Society of Nephrology, a grant from the Seoul National University Bundang Hospital Research Fund, and the Bio&Medical Technology Development Program of the National Research Foundation funded by the Korean government. The authors disclosed no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Metformin cuts the risk for diabetic nephropathy (DN) and major kidney and cardiovascular events in patients with newly diagnosed type 2 diabetes (T2D) across various renal function states.

METHODOLOGY:

Metformin is a first-line treatment in US and South Korean T2D management guidelines, except for patients with advanced chronic kidney disease (CKD) (stage, ≥ 4; estimated glomerular filtration rate [eGFR], < 30).

The study used data from the databases of three tertiary hospitals in South Korea to assess the effect of metformin on long-term renal and cardiovascular outcomes across various renal function states in patients with newly diagnosed T2D.

Four groups of treatment-control comparative cohorts were identified at each hospital: Patients who had not yet developed DN at T2D diagnosis (mean age in treatment and control cohorts, 61-65 years) and those with reduced renal function (CKD stages 3A, 3B, and 4).

Patients who continuously received metformin after T2D diagnosis and beyond the observation period were 1:1 propensity score matched with controls who were prescribed oral hypoglycemic agents other than metformin.

Primary outcomes were net major adverse cardiovascular events including strokes (MACEs) or in-hospital death and a composite of major adverse kidney events (MAKEs) or in-hospital death.

TAKEAWAY:

Among patients without DN at T2D diagnosis, the continuous use of metformin vs other oral hypoglycemic agents was associated with a lower risk for:

Overt DN (incidence rate ratio [IRR], 0.82; 95% CI, 0.71-0.95),

MACEs (IRR, 0.76; 95% CI, 0.64-0.92), and

MAKEs (IRR, 0.45; 95% CI, 0.33-0.62).

Compared with non-metformin or discontinued metformin use, the continuous use of metformin was associated with a lower risk for MACE across CKD stages 3A (IRR, 0.70; 95% CI, 0.57-0.87), 3B (IRR, 0.83; 95% CI, 0.74-0.93), and 4 (IRR, 0.71; 95% CI, 0.60-0.85).

Similarly, the risk for MAKE was lower among continuous metformin users than in nonusers or discontinuous metformin users across CKD stage 3A (IRR, 0.39; 95% CI, 0.35-0.43), 3B (IRR, 0.44; 95% CI, 0.40-0.48), and 4 (IRR, 0.45; 95% CI, 0.39-0.51).

IN PRACTICE:

“The significance of the current study is highlighted by its integration of real-world clinical data, which encompasses patients diagnosed with CDK4 [eGRF, 15-29 mL/min/1.73 m2], a group currently considered contraindicated,” the authors wrote.

SOURCE:

The study, led by Yongjin Yi, MD, PhD, Department of Internal Medicine, Dankook University College of Medicine, Cheonan-si, Republic of Korea, was published in Scientific Reports.

LIMITATIONS:

There may be a possibility of selection bias because of the retrospective and observational nature of this study. Despite achieving a 1:1 propensity score matching to address the confounding factors, some variables, such as serum albumin and A1c levels, remained unbalanced after matching. The paper did not include observation length or patient numbers, but in response to an email query from Medscape, Yi notes that in one hospital, the mean duration of observation for the control and treatment groups was about 6.5 years, and the total number in the treatment groups across data from three hospitals was 11,675, with the same number of matched controls.

DISCLOSURES:

This study was supported by a Young Investigator Research Grant from the Korean Society of Nephrology, a grant from the Seoul National University Bundang Hospital Research Fund, and the Bio&Medical Technology Development Program of the National Research Foundation funded by the Korean government. The authors disclosed no competing interests.

A version of this article appeared on Medscape.com.

The risk of developing a new autoimmune inflammatory rheumatic disease (AIRD) is greater following a COVID-19 infection than after an influenza infection or in the general population, according to a study published March 5 in Annals of Internal Medicine. More severe COVID-19 infections were linked to a greater risk of incident rheumatic disease, but vaccination appeared protective against development of a new AIRD.

“Importantly, this study shows the value of vaccination to prevent severe disease and these types of sequelae,” Anne Davidson, MBBS, a professor in the Institute of Molecular Medicine at The Feinstein Institutes for Medical Research in Manhasset, New York, who was not involved in the study, said in an interview.

More Robust and Rigorous Research

Past cohort studies finding an increased risk of rheumatic disease after COVID-19 “based their findings solely on comparisons between infected and uninfected groups, which could be influenced by ascertainment bias due to disparities in care, differences in health-seeking tendencies, and inherent risks among the groups,” Min Seo Kim, MD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and his colleagues reported. Their study, however, required at least two claims with codes for rheumatic disease and compared patients with COVID-19 to those with flu “to adjust for the potentially heightened detection of AIRD in SARS-CoV-2–infected persons owing to their interactions with the health care system.”

Dr. Alfred Kim said the fact that they used at least two claims codes “gives a little more credence that the patients were actually experiencing some sort of autoimmune inflammatory condition as opposed to a very transient issue post COVID that just went away on its own.”

He acknowledged that the previous research was reasonably strong, “especially in light of the fact that there has been so much work done on a molecular level demonstrating that COVID-19 is associated with a substantial increase in autoantibodies in a significant proportion of patients, so this always opened up the possibility that this could associate with some sort of autoimmune disease downstream.”

While the study is well done with a large population, “it still has limitations that might overestimate the effect,” Kevin W. Byram, MD, associate professor of medicine in rheumatology and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in the study, said in an interview. “We certainly have seen individual cases of new rheumatic disease where COVID-19 infection is likely the trigger,” but the phenomenon is not new, he added.

“Many autoimmune diseases are spurred by a loss of tolerance that might be induced by a pathogen of some sort,” Dr. Byram said. “The study is right to point out different forms of bias that might be at play. One in particular that is important to consider in a study like this is the lack of case-level adjudication regarding the diagnosis of rheumatic disease” since the study relied on available ICD-10 codes and medication prescriptions.

Risk Varied With Disease Severity and Vaccination Status

Among the Korean patients, 3.9% had a COVID-19 infection and 0.98% had an influenza infection. After matching, the comparison populations included 94,504 patients with COVID-19 versus 94,504 patients with flu, and 177,083 patients with COVID-19 versus 675,750 uninfected controls.

The risk of developing an AIRD at least 1 month after infection in South Korean patients with COVID-19 was 25% higher than in uninfected control participants (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.18–1.31; P < .05) and 30% higher than in influenza patients (aHR, 1.3; 95% CI, 1.02–1.59; P < .05). Specifically, risk in South Korean patients with COVID-19 was significantly increased for connective tissue disease and both treated and untreated AIRD but not for inflammatory arthritis.

Among the Japanese patients, 8.2% had COVID-19 and 0.99% had flu, resulting in matched populations of 115,003 with COVID-19 versus 110,310 with flu, and 960,849 with COVID-19 versus 1,606,873 uninfected patients. The effect size was larger in Japanese patients, with a 79% increased risk for AIRD in patients with COVID-19, compared with the general population (aHR, 1.79; 95% CI, 1.77–1.82; P < .05) and a 14% increased risk, compared with patients with influenza infection (aHR, 1.14; 95% CI, 1.10–1.17; P < .05). In Japanese patients, risk was increased across all four categories, including a doubled risk for inflammatory arthritis (aHR, 2.02; 95% CI, 1.96–2.07; P < .05), compared with the general population.

The researchers had data only from the South Korean cohort to calculate risk based on vaccination status, SARS-CoV-2 variant (wild type versus Delta), and COVID-19 severity. Researchers determined a COVID-19 infection to be moderate-to-severe based on billing codes for ICU admission or requiring oxygen therapy, extracorporeal membrane oxygenation, renal replacement, or CPR.

Infection with both the original strain and the Delta variant were linked to similar increased risks for AIRD, but moderate to severe COVID-19 infections had greater risk of subsequent AIRD (aHR, 1.42; P < .05) than mild infections (aHR, 1.22; P < .05). Vaccination was linked to a lower risk of AIRD within the COVID-19 patient population: One dose was linked to a 41% reduced risk (HR, 0.59; P < .05) and two doses were linked to a 58% reduced risk (HR, 0.42; P < .05), regardless of the vaccine type, compared with unvaccinated patients with COVID-19. The apparent protective effect of vaccination was true only for patients with mild COVID-19, not those with moderate to severe infection.

“One has to wonder whether or not these people were at much higher risk of developing autoimmune disease that just got exposed because they got COVID, so that a fraction of these would have gotten an autoimmune disease downstream,” Dr. Alfred Kim said. Regardless, one clinical implication of the findings is the reduced risk in vaccinated patients, regardless of the vaccine type, given the fact that “mRNA vaccination in particular has not been associated with any autoantibody development,” he said.

Though the correlations in the study cannot translate to causation, several mechanisms might be at play in a viral infection contributing to autoimmune risk, Dr. Davidson said. Given that viral nucleic acids also recognize self-nucleic acids, “a large load of viral nucleic acid may break tolerance,” or “viral proteins could also mimic self-proteins,” she said. “In addition, tolerance may be broken by a highly inflammatory environment associated with the release of cytokines and other inflammatory mediators.”

The association between new-onset autoimmune disease and severe COVID-19 infection suggests multiple mechanisms may be involved in excess immune stimulation, Dr. Davidson said. But she added that it’s unclear how these findings, involving the original strain and Delta variant of SARS-CoV-2, might relate to currently circulating variants.

The research was funded by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of Food and Drug Safety of the Republic of Korea. The authors reported no relevant financial relationships with industry. Dr. Alfred Kim has sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, and Novartis; receives royalties from a patent with Kypha Inc.; and has done consulting or speaking for Amgen, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, GlaxoSmithKline, Kypha, Miltenyi Biotech, Pfizer, Rheumatology & Arthritis Learning Network, Synthekine, Techtonic Therapeutics, and UpToDate. Dr. Byram reported consulting for TenSixteen Bio. Dr. Davidson had no disclosures.

The risk of developing a new autoimmune inflammatory rheumatic disease (AIRD) is greater following a COVID-19 infection than after an influenza infection or in the general population, according to a study published March 5 in Annals of Internal Medicine. More severe COVID-19 infections were linked to a greater risk of incident rheumatic disease, but vaccination appeared protective against development of a new AIRD.

“Importantly, this study shows the value of vaccination to prevent severe disease and these types of sequelae,” Anne Davidson, MBBS, a professor in the Institute of Molecular Medicine at The Feinstein Institutes for Medical Research in Manhasset, New York, who was not involved in the study, said in an interview.

More Robust and Rigorous Research

Past cohort studies finding an increased risk of rheumatic disease after COVID-19 “based their findings solely on comparisons between infected and uninfected groups, which could be influenced by ascertainment bias due to disparities in care, differences in health-seeking tendencies, and inherent risks among the groups,” Min Seo Kim, MD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and his colleagues reported. Their study, however, required at least two claims with codes for rheumatic disease and compared patients with COVID-19 to those with flu “to adjust for the potentially heightened detection of AIRD in SARS-CoV-2–infected persons owing to their interactions with the health care system.”

Dr. Alfred Kim said the fact that they used at least two claims codes “gives a little more credence that the patients were actually experiencing some sort of autoimmune inflammatory condition as opposed to a very transient issue post COVID that just went away on its own.”

He acknowledged that the previous research was reasonably strong, “especially in light of the fact that there has been so much work done on a molecular level demonstrating that COVID-19 is associated with a substantial increase in autoantibodies in a significant proportion of patients, so this always opened up the possibility that this could associate with some sort of autoimmune disease downstream.”

While the study is well done with a large population, “it still has limitations that might overestimate the effect,” Kevin W. Byram, MD, associate professor of medicine in rheumatology and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in the study, said in an interview. “We certainly have seen individual cases of new rheumatic disease where COVID-19 infection is likely the trigger,” but the phenomenon is not new, he added.

“Many autoimmune diseases are spurred by a loss of tolerance that might be induced by a pathogen of some sort,” Dr. Byram said. “The study is right to point out different forms of bias that might be at play. One in particular that is important to consider in a study like this is the lack of case-level adjudication regarding the diagnosis of rheumatic disease” since the study relied on available ICD-10 codes and medication prescriptions.

Risk Varied With Disease Severity and Vaccination Status

Among the Korean patients, 3.9% had a COVID-19 infection and 0.98% had an influenza infection. After matching, the comparison populations included 94,504 patients with COVID-19 versus 94,504 patients with flu, and 177,083 patients with COVID-19 versus 675,750 uninfected controls.

The risk of developing an AIRD at least 1 month after infection in South Korean patients with COVID-19 was 25% higher than in uninfected control participants (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.18–1.31; P < .05) and 30% higher than in influenza patients (aHR, 1.3; 95% CI, 1.02–1.59; P < .05). Specifically, risk in South Korean patients with COVID-19 was significantly increased for connective tissue disease and both treated and untreated AIRD but not for inflammatory arthritis.

Among the Japanese patients, 8.2% had COVID-19 and 0.99% had flu, resulting in matched populations of 115,003 with COVID-19 versus 110,310 with flu, and 960,849 with COVID-19 versus 1,606,873 uninfected patients. The effect size was larger in Japanese patients, with a 79% increased risk for AIRD in patients with COVID-19, compared with the general population (aHR, 1.79; 95% CI, 1.77–1.82; P < .05) and a 14% increased risk, compared with patients with influenza infection (aHR, 1.14; 95% CI, 1.10–1.17; P < .05). In Japanese patients, risk was increased across all four categories, including a doubled risk for inflammatory arthritis (aHR, 2.02; 95% CI, 1.96–2.07; P < .05), compared with the general population.

The researchers had data only from the South Korean cohort to calculate risk based on vaccination status, SARS-CoV-2 variant (wild type versus Delta), and COVID-19 severity. Researchers determined a COVID-19 infection to be moderate-to-severe based on billing codes for ICU admission or requiring oxygen therapy, extracorporeal membrane oxygenation, renal replacement, or CPR.

Infection with both the original strain and the Delta variant were linked to similar increased risks for AIRD, but moderate to severe COVID-19 infections had greater risk of subsequent AIRD (aHR, 1.42; P < .05) than mild infections (aHR, 1.22; P < .05). Vaccination was linked to a lower risk of AIRD within the COVID-19 patient population: One dose was linked to a 41% reduced risk (HR, 0.59; P < .05) and two doses were linked to a 58% reduced risk (HR, 0.42; P < .05), regardless of the vaccine type, compared with unvaccinated patients with COVID-19. The apparent protective effect of vaccination was true only for patients with mild COVID-19, not those with moderate to severe infection.

“One has to wonder whether or not these people were at much higher risk of developing autoimmune disease that just got exposed because they got COVID, so that a fraction of these would have gotten an autoimmune disease downstream,” Dr. Alfred Kim said. Regardless, one clinical implication of the findings is the reduced risk in vaccinated patients, regardless of the vaccine type, given the fact that “mRNA vaccination in particular has not been associated with any autoantibody development,” he said.

Though the correlations in the study cannot translate to causation, several mechanisms might be at play in a viral infection contributing to autoimmune risk, Dr. Davidson said. Given that viral nucleic acids also recognize self-nucleic acids, “a large load of viral nucleic acid may break tolerance,” or “viral proteins could also mimic self-proteins,” she said. “In addition, tolerance may be broken by a highly inflammatory environment associated with the release of cytokines and other inflammatory mediators.”

The association between new-onset autoimmune disease and severe COVID-19 infection suggests multiple mechanisms may be involved in excess immune stimulation, Dr. Davidson said. But she added that it’s unclear how these findings, involving the original strain and Delta variant of SARS-CoV-2, might relate to currently circulating variants.

The research was funded by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of Food and Drug Safety of the Republic of Korea. The authors reported no relevant financial relationships with industry. Dr. Alfred Kim has sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, and Novartis; receives royalties from a patent with Kypha Inc.; and has done consulting or speaking for Amgen, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, GlaxoSmithKline, Kypha, Miltenyi Biotech, Pfizer, Rheumatology & Arthritis Learning Network, Synthekine, Techtonic Therapeutics, and UpToDate. Dr. Byram reported consulting for TenSixteen Bio. Dr. Davidson had no disclosures.

The risk of developing a new autoimmune inflammatory rheumatic disease (AIRD) is greater following a COVID-19 infection than after an influenza infection or in the general population, according to a study published March 5 in Annals of Internal Medicine. More severe COVID-19 infections were linked to a greater risk of incident rheumatic disease, but vaccination appeared protective against development of a new AIRD.

“Importantly, this study shows the value of vaccination to prevent severe disease and these types of sequelae,” Anne Davidson, MBBS, a professor in the Institute of Molecular Medicine at The Feinstein Institutes for Medical Research in Manhasset, New York, who was not involved in the study, said in an interview.

More Robust and Rigorous Research

Past cohort studies finding an increased risk of rheumatic disease after COVID-19 “based their findings solely on comparisons between infected and uninfected groups, which could be influenced by ascertainment bias due to disparities in care, differences in health-seeking tendencies, and inherent risks among the groups,” Min Seo Kim, MD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and his colleagues reported. Their study, however, required at least two claims with codes for rheumatic disease and compared patients with COVID-19 to those with flu “to adjust for the potentially heightened detection of AIRD in SARS-CoV-2–infected persons owing to their interactions with the health care system.”

Dr. Alfred Kim said the fact that they used at least two claims codes “gives a little more credence that the patients were actually experiencing some sort of autoimmune inflammatory condition as opposed to a very transient issue post COVID that just went away on its own.”

He acknowledged that the previous research was reasonably strong, “especially in light of the fact that there has been so much work done on a molecular level demonstrating that COVID-19 is associated with a substantial increase in autoantibodies in a significant proportion of patients, so this always opened up the possibility that this could associate with some sort of autoimmune disease downstream.”

While the study is well done with a large population, “it still has limitations that might overestimate the effect,” Kevin W. Byram, MD, associate professor of medicine in rheumatology and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in the study, said in an interview. “We certainly have seen individual cases of new rheumatic disease where COVID-19 infection is likely the trigger,” but the phenomenon is not new, he added.

“Many autoimmune diseases are spurred by a loss of tolerance that might be induced by a pathogen of some sort,” Dr. Byram said. “The study is right to point out different forms of bias that might be at play. One in particular that is important to consider in a study like this is the lack of case-level adjudication regarding the diagnosis of rheumatic disease” since the study relied on available ICD-10 codes and medication prescriptions.

Risk Varied With Disease Severity and Vaccination Status

Among the Korean patients, 3.9% had a COVID-19 infection and 0.98% had an influenza infection. After matching, the comparison populations included 94,504 patients with COVID-19 versus 94,504 patients with flu, and 177,083 patients with COVID-19 versus 675,750 uninfected controls.

The risk of developing an AIRD at least 1 month after infection in South Korean patients with COVID-19 was 25% higher than in uninfected control participants (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.18–1.31; P < .05) and 30% higher than in influenza patients (aHR, 1.3; 95% CI, 1.02–1.59; P < .05). Specifically, risk in South Korean patients with COVID-19 was significantly increased for connective tissue disease and both treated and untreated AIRD but not for inflammatory arthritis.

Among the Japanese patients, 8.2% had COVID-19 and 0.99% had flu, resulting in matched populations of 115,003 with COVID-19 versus 110,310 with flu, and 960,849 with COVID-19 versus 1,606,873 uninfected patients. The effect size was larger in Japanese patients, with a 79% increased risk for AIRD in patients with COVID-19, compared with the general population (aHR, 1.79; 95% CI, 1.77–1.82; P < .05) and a 14% increased risk, compared with patients with influenza infection (aHR, 1.14; 95% CI, 1.10–1.17; P < .05). In Japanese patients, risk was increased across all four categories, including a doubled risk for inflammatory arthritis (aHR, 2.02; 95% CI, 1.96–2.07; P < .05), compared with the general population.

The researchers had data only from the South Korean cohort to calculate risk based on vaccination status, SARS-CoV-2 variant (wild type versus Delta), and COVID-19 severity. Researchers determined a COVID-19 infection to be moderate-to-severe based on billing codes for ICU admission or requiring oxygen therapy, extracorporeal membrane oxygenation, renal replacement, or CPR.

Infection with both the original strain and the Delta variant were linked to similar increased risks for AIRD, but moderate to severe COVID-19 infections had greater risk of subsequent AIRD (aHR, 1.42; P < .05) than mild infections (aHR, 1.22; P < .05). Vaccination was linked to a lower risk of AIRD within the COVID-19 patient population: One dose was linked to a 41% reduced risk (HR, 0.59; P < .05) and two doses were linked to a 58% reduced risk (HR, 0.42; P < .05), regardless of the vaccine type, compared with unvaccinated patients with COVID-19. The apparent protective effect of vaccination was true only for patients with mild COVID-19, not those with moderate to severe infection.

“One has to wonder whether or not these people were at much higher risk of developing autoimmune disease that just got exposed because they got COVID, so that a fraction of these would have gotten an autoimmune disease downstream,” Dr. Alfred Kim said. Regardless, one clinical implication of the findings is the reduced risk in vaccinated patients, regardless of the vaccine type, given the fact that “mRNA vaccination in particular has not been associated with any autoantibody development,” he said.

Though the correlations in the study cannot translate to causation, several mechanisms might be at play in a viral infection contributing to autoimmune risk, Dr. Davidson said. Given that viral nucleic acids also recognize self-nucleic acids, “a large load of viral nucleic acid may break tolerance,” or “viral proteins could also mimic self-proteins,” she said. “In addition, tolerance may be broken by a highly inflammatory environment associated with the release of cytokines and other inflammatory mediators.”

The association between new-onset autoimmune disease and severe COVID-19 infection suggests multiple mechanisms may be involved in excess immune stimulation, Dr. Davidson said. But she added that it’s unclear how these findings, involving the original strain and Delta variant of SARS-CoV-2, might relate to currently circulating variants.

The research was funded by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of Food and Drug Safety of the Republic of Korea. The authors reported no relevant financial relationships with industry. Dr. Alfred Kim has sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, and Novartis; receives royalties from a patent with Kypha Inc.; and has done consulting or speaking for Amgen, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, GlaxoSmithKline, Kypha, Miltenyi Biotech, Pfizer, Rheumatology & Arthritis Learning Network, Synthekine, Techtonic Therapeutics, and UpToDate. Dr. Byram reported consulting for TenSixteen Bio. Dr. Davidson had no disclosures.

The Diagnosis: Gastric Acid Dermatitis

After further discussion, the patient indicated that he had vomited during the night of alcohol consumption, and the vomitus remained on the affected areas until the next morning, indicating that excessive alcohol ingestion stimulated abundant secretion of gastric acid, which caused the symptoms. Additionally, the presence of clothing acted as a buffer in the unaffected areas, which helped make the final diagnosis of gastric acid dermatitis. The patient was treated with external application of recombinant bovine basic fibroblast growth factor gel (21,000 IU/5 g) once daily, and the lesions greatly improved within 7 days. The burning pain of the throat, stomach, and esophagus resolved after consultation with an otolaryngologist and a gastroenterologist.

Gastric acid dermatitis is a new term used to describe an acute skin burn caused by the patient's own gastric acid. Generally, the pH of human gastric acid is between 0.9 and 1.8 but will be diluted after eating and will gradually increase to approximately 3.5, which is not enough to induce burns on the skin.¹ In addition, the skin barrier is capable of preventing transient gastric acid corrosion.^2,3 However, the release of a large amount of gastric acid after excessive alcohol ingestion coupled with 1 night of lethargy left enough acid and time to induce skin burns in our patient.

Dermatitis caused by other allergic or chemical factors, such as Paederus dermatitis, was excluded, as the patient’s manifestation occurred during the inactive period of Paederus fuscipes. Furthermore, the patient denied any history of contact with chemicals in the last month. Food eruptions primarily manifest as systemic anaphylaxis with eruptive and pruritic rashes after consumption of seafood, eggs, milk, or other proteins, while alcoholic contact dermatitis is a form of irritating dermatitis that could be easily induced again by direct skin contact with alcohol.

Management of gastric acid dermatitis is similar to that for other chemical burns. Because scarring seldom occurs, the central issue is to restore the skin barrier as quickly as possible and to avoid or alleviate postinflammatory hyperpigmentation. Treatments to restore the skin barrier include recombinant bovine or human-derived basic fibroblast growth factor gel, moist exposed burn ointment, and medical sodium hyaluronate gelatin. To treat postinflammatory hyperpigmentation, some whitening agents such as compound superoxide dismutase arbutin cream and hydroquinone cream as well as the Q-switched Nd:YAG laser are effective to ameliorate the skin condition. If skin burns are on sun-exposed areas, photoprotection is necessary to prevent hyperpigmentation.

Acknowledgment—We thank the patient for granting permission to publish this information.

The Diagnosis: Gastric Acid Dermatitis

After further discussion, the patient indicated that he had vomited during the night of alcohol consumption, and the vomitus remained on the affected areas until the next morning, indicating that excessive alcohol ingestion stimulated abundant secretion of gastric acid, which caused the symptoms. Additionally, the presence of clothing acted as a buffer in the unaffected areas, which helped make the final diagnosis of gastric acid dermatitis. The patient was treated with external application of recombinant bovine basic fibroblast growth factor gel (21,000 IU/5 g) once daily, and the lesions greatly improved within 7 days. The burning pain of the throat, stomach, and esophagus resolved after consultation with an otolaryngologist and a gastroenterologist.

Gastric acid dermatitis is a new term used to describe an acute skin burn caused by the patient's own gastric acid. Generally, the pH of human gastric acid is between 0.9 and 1.8 but will be diluted after eating and will gradually increase to approximately 3.5, which is not enough to induce burns on the skin.¹ In addition, the skin barrier is capable of preventing transient gastric acid corrosion.^2,3 However, the release of a large amount of gastric acid after excessive alcohol ingestion coupled with 1 night of lethargy left enough acid and time to induce skin burns in our patient.

Dermatitis caused by other allergic or chemical factors, such as Paederus dermatitis, was excluded, as the patient’s manifestation occurred during the inactive period of Paederus fuscipes. Furthermore, the patient denied any history of contact with chemicals in the last month. Food eruptions primarily manifest as systemic anaphylaxis with eruptive and pruritic rashes after consumption of seafood, eggs, milk, or other proteins, while alcoholic contact dermatitis is a form of irritating dermatitis that could be easily induced again by direct skin contact with alcohol.

Management of gastric acid dermatitis is similar to that for other chemical burns. Because scarring seldom occurs, the central issue is to restore the skin barrier as quickly as possible and to avoid or alleviate postinflammatory hyperpigmentation. Treatments to restore the skin barrier include recombinant bovine or human-derived basic fibroblast growth factor gel, moist exposed burn ointment, and medical sodium hyaluronate gelatin. To treat postinflammatory hyperpigmentation, some whitening agents such as compound superoxide dismutase arbutin cream and hydroquinone cream as well as the Q-switched Nd:YAG laser are effective to ameliorate the skin condition. If skin burns are on sun-exposed areas, photoprotection is necessary to prevent hyperpigmentation.

Acknowledgment—We thank the patient for granting permission to publish this information.

The Diagnosis: Gastric Acid Dermatitis

After further discussion, the patient indicated that he had vomited during the night of alcohol consumption, and the vomitus remained on the affected areas until the next morning, indicating that excessive alcohol ingestion stimulated abundant secretion of gastric acid, which caused the symptoms. Additionally, the presence of clothing acted as a buffer in the unaffected areas, which helped make the final diagnosis of gastric acid dermatitis. The patient was treated with external application of recombinant bovine basic fibroblast growth factor gel (21,000 IU/5 g) once daily, and the lesions greatly improved within 7 days. The burning pain of the throat, stomach, and esophagus resolved after consultation with an otolaryngologist and a gastroenterologist.

Gastric acid dermatitis is a new term used to describe an acute skin burn caused by the patient's own gastric acid. Generally, the pH of human gastric acid is between 0.9 and 1.8 but will be diluted after eating and will gradually increase to approximately 3.5, which is not enough to induce burns on the skin.¹ In addition, the skin barrier is capable of preventing transient gastric acid corrosion.^2,3 However, the release of a large amount of gastric acid after excessive alcohol ingestion coupled with 1 night of lethargy left enough acid and time to induce skin burns in our patient.

Dermatitis caused by other allergic or chemical factors, such as Paederus dermatitis, was excluded, as the patient’s manifestation occurred during the inactive period of Paederus fuscipes. Furthermore, the patient denied any history of contact with chemicals in the last month. Food eruptions primarily manifest as systemic anaphylaxis with eruptive and pruritic rashes after consumption of seafood, eggs, milk, or other proteins, while alcoholic contact dermatitis is a form of irritating dermatitis that could be easily induced again by direct skin contact with alcohol.

Management of gastric acid dermatitis is similar to that for other chemical burns. Because scarring seldom occurs, the central issue is to restore the skin barrier as quickly as possible and to avoid or alleviate postinflammatory hyperpigmentation. Treatments to restore the skin barrier include recombinant bovine or human-derived basic fibroblast growth factor gel, moist exposed burn ointment, and medical sodium hyaluronate gelatin. To treat postinflammatory hyperpigmentation, some whitening agents such as compound superoxide dismutase arbutin cream and hydroquinone cream as well as the Q-switched Nd:YAG laser are effective to ameliorate the skin condition. If skin burns are on sun-exposed areas, photoprotection is necessary to prevent hyperpigmentation.

Acknowledgment—We thank the patient for granting permission to publish this information.