The Diagnosis: Subcutaneous Granuloma Annulare 

Subcutaneous granuloma annulare (SGA), also known as deep GA, is a rare variant of GA that usually occurs in children and young adults. It presents as single or multiple, nontender, deep dermal and/or subcutaneous nodules with normal-appearing skin usually on the anterior lower legs, dorsal aspects of the hands and fingers, scalp, or buttocks.^1-3 The pathogenesis of SGA as well as GA is not fully understood, and proposed inciting factors include trauma, insect bite reactions, tuberculin skin testing, vaccines, UV exposure, medications, and viral infections.^3-6 A cell-mediated, delayed-type hypersensitivity reaction to an unknown antigen also has been postulated as a possible mechanism.⁷ Treatment usually is not necessary, as the nature of the condition is benign and the course often is self-limited. Spontaneous resolution occurs within 2 years in 50% of patients with localized GA.^4,8 Surgery usually is not recommended due to the high recurrence rate (40%-75%).^4,9  

Absence of epidermal change in this entity obfuscates clinical recognition, and accurate diagnosis often depends on punch or excisional biopsies revealing characteristic histopathology. The histology of SGA consists of palisaded granulomas with central areas of necrobiosis composed of degenerated collagen, mucin deposition, and nuclear dust from neutrophils that extend into the deep dermis and subcutis.² The periphery of the granulomas is lined by palisading epithelioid histiocytes with occasional multinucleated giant cells.^10,11 Eosinophils often are present.¹² Colloidal iron and Alcian blue stains can be used to highlight the abundant connective tissue mucin of the granulomas.⁴  

The histologic differential diagnosis of SGA includes rheumatoid nodule, necrobiosis lipoidica, epithelioid sarcoma, and tophaceous gout.² Rheumatoid nodules are the most common dermatologic presentation of rheumatoid arthritis and are found in up to 30% to 40% of patients with the disease.^13-15 They present as firm, painless, subcutaneous papulonodules on the extensor surfaces and at sites of trauma or pressure. Histologically, rheumatoid nodules exhibit a homogenous and eosinophilic central area of necrobiosis with fibrin deposition and absent mucin deep within the dermis and subcutaneous tissue (Figure 1). In contrast, granulomas in SGA usually are pale and basophilic with abundant mucin.²  

Necrobiosis lipoidica is a rare chronic granulomatous disease of the skin that most commonly occurs in young to middle-aged adults and is strongly associated with diabetes mellitus.¹⁶ It clinically presents as yellow to red-brown papules and plaques with a peripheral erythematous to violaceous rim usually on the pretibial area. Over time, lesions become yellowish atrophic patches and plaques that sometimes can ulcerate. Histopathology reveals areas of horizontally arranged, palisaded, and interstitial granulomatous dermatitis intermixed with areas of degenerated collagen and widespread fibrosis extending from the superficial dermis into the subcutis (Figure 2).² These areas lack mucin and have an increased number of plasma cells. Eosinophils and/or lymphoid nodules occasionally can be seen.^17,18 

Epithelioid sarcoma is a rare malignant soft tissue sarcoma that tends to occur on the distal extremities in younger patients, typically aged 20 to 40 years, often with preceding trauma to the area. It usually presents as a solitary, poorly defined, hard, subcutaneous nodule. Histologic analysis shows central areas of necrosis and degenerated collagen surrounded by epithelioid and spindle cells with hyperchromatic and pleomorphic nuclei and mitoses (Figure 3).² These tumor cells express positivity for keratins, vimentin, epithelial membrane antigen, and CD34, while they usually are negative for desmin, S-100, and FLI-1 nuclear transcription factor.^2,4,19  

Tophaceous gout results from the accumulation of monosodium urate crystals in the skin. It clinically presents as firm, white-yellow, dermal and subcutaneous papulonodules on the helix of the ear and the skin overlying joints. Histopathology reveals palisaded granulomas surrounding an amorphous feathery material that corresponds to the urate crystals that were destroyed with formalin fixation (Figure 4). When the tissue is fixed with ethanol or is incompletely fixed in formalin, birefringent urate crystals are evident with polarization.²⁰

The Diagnosis: Subcutaneous Granuloma Annulare 

Subcutaneous granuloma annulare (SGA), also known as deep GA, is a rare variant of GA that usually occurs in children and young adults. It presents as single or multiple, nontender, deep dermal and/or subcutaneous nodules with normal-appearing skin usually on the anterior lower legs, dorsal aspects of the hands and fingers, scalp, or buttocks.^1-3 The pathogenesis of SGA as well as GA is not fully understood, and proposed inciting factors include trauma, insect bite reactions, tuberculin skin testing, vaccines, UV exposure, medications, and viral infections.^3-6 A cell-mediated, delayed-type hypersensitivity reaction to an unknown antigen also has been postulated as a possible mechanism.⁷ Treatment usually is not necessary, as the nature of the condition is benign and the course often is self-limited. Spontaneous resolution occurs within 2 years in 50% of patients with localized GA.^4,8 Surgery usually is not recommended due to the high recurrence rate (40%-75%).^4,9  

Absence of epidermal change in this entity obfuscates clinical recognition, and accurate diagnosis often depends on punch or excisional biopsies revealing characteristic histopathology. The histology of SGA consists of palisaded granulomas with central areas of necrobiosis composed of degenerated collagen, mucin deposition, and nuclear dust from neutrophils that extend into the deep dermis and subcutis.² The periphery of the granulomas is lined by palisading epithelioid histiocytes with occasional multinucleated giant cells.^10,11 Eosinophils often are present.¹² Colloidal iron and Alcian blue stains can be used to highlight the abundant connective tissue mucin of the granulomas.⁴  

The histologic differential diagnosis of SGA includes rheumatoid nodule, necrobiosis lipoidica, epithelioid sarcoma, and tophaceous gout.² Rheumatoid nodules are the most common dermatologic presentation of rheumatoid arthritis and are found in up to 30% to 40% of patients with the disease.^13-15 They present as firm, painless, subcutaneous papulonodules on the extensor surfaces and at sites of trauma or pressure. Histologically, rheumatoid nodules exhibit a homogenous and eosinophilic central area of necrobiosis with fibrin deposition and absent mucin deep within the dermis and subcutaneous tissue (Figure 1). In contrast, granulomas in SGA usually are pale and basophilic with abundant mucin.²  

Necrobiosis lipoidica is a rare chronic granulomatous disease of the skin that most commonly occurs in young to middle-aged adults and is strongly associated with diabetes mellitus.¹⁶ It clinically presents as yellow to red-brown papules and plaques with a peripheral erythematous to violaceous rim usually on the pretibial area. Over time, lesions become yellowish atrophic patches and plaques that sometimes can ulcerate. Histopathology reveals areas of horizontally arranged, palisaded, and interstitial granulomatous dermatitis intermixed with areas of degenerated collagen and widespread fibrosis extending from the superficial dermis into the subcutis (Figure 2).² These areas lack mucin and have an increased number of plasma cells. Eosinophils and/or lymphoid nodules occasionally can be seen.^17,18 

Epithelioid sarcoma is a rare malignant soft tissue sarcoma that tends to occur on the distal extremities in younger patients, typically aged 20 to 40 years, often with preceding trauma to the area. It usually presents as a solitary, poorly defined, hard, subcutaneous nodule. Histologic analysis shows central areas of necrosis and degenerated collagen surrounded by epithelioid and spindle cells with hyperchromatic and pleomorphic nuclei and mitoses (Figure 3).² These tumor cells express positivity for keratins, vimentin, epithelial membrane antigen, and CD34, while they usually are negative for desmin, S-100, and FLI-1 nuclear transcription factor.^2,4,19  

Tophaceous gout results from the accumulation of monosodium urate crystals in the skin. It clinically presents as firm, white-yellow, dermal and subcutaneous papulonodules on the helix of the ear and the skin overlying joints. Histopathology reveals palisaded granulomas surrounding an amorphous feathery material that corresponds to the urate crystals that were destroyed with formalin fixation (Figure 4). When the tissue is fixed with ethanol or is incompletely fixed in formalin, birefringent urate crystals are evident with polarization.²⁰

The Diagnosis: Subcutaneous Granuloma Annulare 

Subcutaneous granuloma annulare (SGA), also known as deep GA, is a rare variant of GA that usually occurs in children and young adults. It presents as single or multiple, nontender, deep dermal and/or subcutaneous nodules with normal-appearing skin usually on the anterior lower legs, dorsal aspects of the hands and fingers, scalp, or buttocks.^1-3 The pathogenesis of SGA as well as GA is not fully understood, and proposed inciting factors include trauma, insect bite reactions, tuberculin skin testing, vaccines, UV exposure, medications, and viral infections.^3-6 A cell-mediated, delayed-type hypersensitivity reaction to an unknown antigen also has been postulated as a possible mechanism.⁷ Treatment usually is not necessary, as the nature of the condition is benign and the course often is self-limited. Spontaneous resolution occurs within 2 years in 50% of patients with localized GA.^4,8 Surgery usually is not recommended due to the high recurrence rate (40%-75%).^4,9  

Absence of epidermal change in this entity obfuscates clinical recognition, and accurate diagnosis often depends on punch or excisional biopsies revealing characteristic histopathology. The histology of SGA consists of palisaded granulomas with central areas of necrobiosis composed of degenerated collagen, mucin deposition, and nuclear dust from neutrophils that extend into the deep dermis and subcutis.² The periphery of the granulomas is lined by palisading epithelioid histiocytes with occasional multinucleated giant cells.^10,11 Eosinophils often are present.¹² Colloidal iron and Alcian blue stains can be used to highlight the abundant connective tissue mucin of the granulomas.⁴  

The histologic differential diagnosis of SGA includes rheumatoid nodule, necrobiosis lipoidica, epithelioid sarcoma, and tophaceous gout.² Rheumatoid nodules are the most common dermatologic presentation of rheumatoid arthritis and are found in up to 30% to 40% of patients with the disease.^13-15 They present as firm, painless, subcutaneous papulonodules on the extensor surfaces and at sites of trauma or pressure. Histologically, rheumatoid nodules exhibit a homogenous and eosinophilic central area of necrobiosis with fibrin deposition and absent mucin deep within the dermis and subcutaneous tissue (Figure 1). In contrast, granulomas in SGA usually are pale and basophilic with abundant mucin.²  

Necrobiosis lipoidica is a rare chronic granulomatous disease of the skin that most commonly occurs in young to middle-aged adults and is strongly associated with diabetes mellitus.¹⁶ It clinically presents as yellow to red-brown papules and plaques with a peripheral erythematous to violaceous rim usually on the pretibial area. Over time, lesions become yellowish atrophic patches and plaques that sometimes can ulcerate. Histopathology reveals areas of horizontally arranged, palisaded, and interstitial granulomatous dermatitis intermixed with areas of degenerated collagen and widespread fibrosis extending from the superficial dermis into the subcutis (Figure 2).² These areas lack mucin and have an increased number of plasma cells. Eosinophils and/or lymphoid nodules occasionally can be seen.^17,18 

Epithelioid sarcoma is a rare malignant soft tissue sarcoma that tends to occur on the distal extremities in younger patients, typically aged 20 to 40 years, often with preceding trauma to the area. It usually presents as a solitary, poorly defined, hard, subcutaneous nodule. Histologic analysis shows central areas of necrosis and degenerated collagen surrounded by epithelioid and spindle cells with hyperchromatic and pleomorphic nuclei and mitoses (Figure 3).² These tumor cells express positivity for keratins, vimentin, epithelial membrane antigen, and CD34, while they usually are negative for desmin, S-100, and FLI-1 nuclear transcription factor.^2,4,19  

Tophaceous gout results from the accumulation of monosodium urate crystals in the skin. It clinically presents as firm, white-yellow, dermal and subcutaneous papulonodules on the helix of the ear and the skin overlying joints. Histopathology reveals palisaded granulomas surrounding an amorphous feathery material that corresponds to the urate crystals that were destroyed with formalin fixation (Figure 4). When the tissue is fixed with ethanol or is incompletely fixed in formalin, birefringent urate crystals are evident with polarization.²⁰

Hospitalists and health care teams struggle with issues related to text messaging in the workplace. “It’s happening whether an institution has a secure text messaging platform or not,” said Philip Hagedorn, MD, MBI, associate chief medical information officer at Cincinnati Children’s Hospital Medical Center.

“Many places reacted to this reality by procuring a solution – take your pick of secure text messaging platforms – and implementing it, but bypassed an opportunity to think about how we tailor the use of this culturally ubiquitous medium to the health care setting,” he said.It doesn’t work to just drop a secure text messaging platform into clinical systems and expect that health care practitioners will know how to use them appropriately, Dr. Hagedorn says. “The way we use text messaging in our lives outside health care inevitably bleeds into how we use the medium at work, but it shouldn’t. The needs are different and the stakes are higher for communication in the health care setting.”

In a paper looking at the issue, Dr. Hagedorn and co-authors laid out critical areas of concern, such as text messaging becoming a form of alarm fatigue and also increasing the likelihood of communication error.

“It’s my hope that fellow hospitalists can use this as an opportunity to think deeply about how we communicate in health care,” he said. “If we don’t think critically about how and where something like text messaging should be used in medicine, we risk facing unintended consequences for our patients.”The article discusses several steps for mitigating the risks laid out, including proactive surveillance and targeted training. “These are starting points, and I’m sure there are plenty of other creative solutions out there. We wanted to get the conversation going. We’d love to hear from others who face similar issues or have come up with interesting solutions.”
 

Reference

1. Hagedorn PA, et al. Secure Text Messaging in Healthcare: Latent Threats and Opportunities to Improve Patient Safety. J Hosp Med. 2020 June;15(6):378-380. Published Online First 2019 Sept 18. doi: 10.12788/jhm.3305

Hospitalists and health care teams struggle with issues related to text messaging in the workplace. “It’s happening whether an institution has a secure text messaging platform or not,” said Philip Hagedorn, MD, MBI, associate chief medical information officer at Cincinnati Children’s Hospital Medical Center.

“Many places reacted to this reality by procuring a solution – take your pick of secure text messaging platforms – and implementing it, but bypassed an opportunity to think about how we tailor the use of this culturally ubiquitous medium to the health care setting,” he said.It doesn’t work to just drop a secure text messaging platform into clinical systems and expect that health care practitioners will know how to use them appropriately, Dr. Hagedorn says. “The way we use text messaging in our lives outside health care inevitably bleeds into how we use the medium at work, but it shouldn’t. The needs are different and the stakes are higher for communication in the health care setting.”

In a paper looking at the issue, Dr. Hagedorn and co-authors laid out critical areas of concern, such as text messaging becoming a form of alarm fatigue and also increasing the likelihood of communication error.

“It’s my hope that fellow hospitalists can use this as an opportunity to think deeply about how we communicate in health care,” he said. “If we don’t think critically about how and where something like text messaging should be used in medicine, we risk facing unintended consequences for our patients.”The article discusses several steps for mitigating the risks laid out, including proactive surveillance and targeted training. “These are starting points, and I’m sure there are plenty of other creative solutions out there. We wanted to get the conversation going. We’d love to hear from others who face similar issues or have come up with interesting solutions.”
 

Reference

1. Hagedorn PA, et al. Secure Text Messaging in Healthcare: Latent Threats and Opportunities to Improve Patient Safety. J Hosp Med. 2020 June;15(6):378-380. Published Online First 2019 Sept 18. doi: 10.12788/jhm.3305

Hospitalists and health care teams struggle with issues related to text messaging in the workplace. “It’s happening whether an institution has a secure text messaging platform or not,” said Philip Hagedorn, MD, MBI, associate chief medical information officer at Cincinnati Children’s Hospital Medical Center.

“Many places reacted to this reality by procuring a solution – take your pick of secure text messaging platforms – and implementing it, but bypassed an opportunity to think about how we tailor the use of this culturally ubiquitous medium to the health care setting,” he said.It doesn’t work to just drop a secure text messaging platform into clinical systems and expect that health care practitioners will know how to use them appropriately, Dr. Hagedorn says. “The way we use text messaging in our lives outside health care inevitably bleeds into how we use the medium at work, but it shouldn’t. The needs are different and the stakes are higher for communication in the health care setting.”

In a paper looking at the issue, Dr. Hagedorn and co-authors laid out critical areas of concern, such as text messaging becoming a form of alarm fatigue and also increasing the likelihood of communication error.

“It’s my hope that fellow hospitalists can use this as an opportunity to think deeply about how we communicate in health care,” he said. “If we don’t think critically about how and where something like text messaging should be used in medicine, we risk facing unintended consequences for our patients.”The article discusses several steps for mitigating the risks laid out, including proactive surveillance and targeted training. “These are starting points, and I’m sure there are plenty of other creative solutions out there. We wanted to get the conversation going. We’d love to hear from others who face similar issues or have come up with interesting solutions.”
 

Reference

1. Hagedorn PA, et al. Secure Text Messaging in Healthcare: Latent Threats and Opportunities to Improve Patient Safety. J Hosp Med. 2020 June;15(6):378-380. Published Online First 2019 Sept 18. doi: 10.12788/jhm.3305

The federal government says it will distribute only enough doses of Pfizer’s COVID-19 vaccine to immunize 2.9 million Americans in the first week after the US Food and Drug Administration (FDA) authorizes it, far less than the initially discussed 6.4 million doses.

Theoretically, states have already formulated plans for distribution based on the revised lower amount. But in a briefing with reporters on December 9, officials from Operation Warp Speed and the Department of Health and Human Services (HHS) didn’t make clear exactly what the states were expecting.

Vaccine will be shipped to and allocated by 64 jurisdictions and five federal agencies — the Bureau of Prisons, the Department of Defense, the Department of State, the Indian Health Service, and the Veterans Health Administration — according to the Centers for Disease Control and Prevention’s COVID-19 Vaccination Program Interim Playbook.

It will be up to states — which will receive a supply prorated to population — and these agencies to determine how to prioritize distribution of the 2.9 million doses. Each state and agency has its own plan. Gen. Gustave Perna, the chief operating officer for Operation Warp Speed, said in the briefing that 30 states have told the federal government they will prioritize initial doses for residents and staff of long-term care facilities.

The distribution is contingent on FDA authorization, which could happen soon. The FDA’s Vaccines and Related Biologics Advisory Committee weighed the effectiveness data for the Pfizer vaccine on December 10 and recommended that the agency grant emergency authorization. The FDA could issue a decision at any time.
 

Fewer doses out of the gate

Perna said the federal government will begin shipping the Pfizer vaccine within 24 hours of an FDA authorization.

He said those shipments will include a total of 2.9 million doses — not the 6.4 million that will be available. The government is holding 500,000 doses in reserve and another 2.9 million to guarantee that the first few million people who are vaccinated will be able to receive a second dose 21 days later, said Perna.

In part, that is because the FDA labeling will require that a first dose be followed by a second exactly 21 days later, said HHS Secretary Alex Azar in the briefing.

Federal officials have calculated how much to hold back on the basis of Pfizer’s production, said Azar. At least initially, “we will not distribute a vaccine knowing that the booster will not be available either from reserve supply by us or ongoing expected predicted production,” he said.

Even with Pfizer having reduced its estimates of how much vaccine it can deliver in December, Azar said, “There will be enough vaccine available for 20 million first vaccinations in the month of December.”

That estimate is predicated, however, on the idea that a vaccine under development by Moderna will receive clearance shortly after the FDA assesses that vaccine’s safety and effectiveness on December 17.

This article first appeared on Medscape.com.

The federal government says it will distribute only enough doses of Pfizer’s COVID-19 vaccine to immunize 2.9 million Americans in the first week after the US Food and Drug Administration (FDA) authorizes it, far less than the initially discussed 6.4 million doses.

Theoretically, states have already formulated plans for distribution based on the revised lower amount. But in a briefing with reporters on December 9, officials from Operation Warp Speed and the Department of Health and Human Services (HHS) didn’t make clear exactly what the states were expecting.

Vaccine will be shipped to and allocated by 64 jurisdictions and five federal agencies — the Bureau of Prisons, the Department of Defense, the Department of State, the Indian Health Service, and the Veterans Health Administration — according to the Centers for Disease Control and Prevention’s COVID-19 Vaccination Program Interim Playbook.

It will be up to states — which will receive a supply prorated to population — and these agencies to determine how to prioritize distribution of the 2.9 million doses. Each state and agency has its own plan. Gen. Gustave Perna, the chief operating officer for Operation Warp Speed, said in the briefing that 30 states have told the federal government they will prioritize initial doses for residents and staff of long-term care facilities.

The distribution is contingent on FDA authorization, which could happen soon. The FDA’s Vaccines and Related Biologics Advisory Committee weighed the effectiveness data for the Pfizer vaccine on December 10 and recommended that the agency grant emergency authorization. The FDA could issue a decision at any time.
 

Fewer doses out of the gate

Perna said the federal government will begin shipping the Pfizer vaccine within 24 hours of an FDA authorization.

He said those shipments will include a total of 2.9 million doses — not the 6.4 million that will be available. The government is holding 500,000 doses in reserve and another 2.9 million to guarantee that the first few million people who are vaccinated will be able to receive a second dose 21 days later, said Perna.

In part, that is because the FDA labeling will require that a first dose be followed by a second exactly 21 days later, said HHS Secretary Alex Azar in the briefing.

Federal officials have calculated how much to hold back on the basis of Pfizer’s production, said Azar. At least initially, “we will not distribute a vaccine knowing that the booster will not be available either from reserve supply by us or ongoing expected predicted production,” he said.

Even with Pfizer having reduced its estimates of how much vaccine it can deliver in December, Azar said, “There will be enough vaccine available for 20 million first vaccinations in the month of December.”

That estimate is predicated, however, on the idea that a vaccine under development by Moderna will receive clearance shortly after the FDA assesses that vaccine’s safety and effectiveness on December 17.

This article first appeared on Medscape.com.

The federal government says it will distribute only enough doses of Pfizer’s COVID-19 vaccine to immunize 2.9 million Americans in the first week after the US Food and Drug Administration (FDA) authorizes it, far less than the initially discussed 6.4 million doses.

Theoretically, states have already formulated plans for distribution based on the revised lower amount. But in a briefing with reporters on December 9, officials from Operation Warp Speed and the Department of Health and Human Services (HHS) didn’t make clear exactly what the states were expecting.

Vaccine will be shipped to and allocated by 64 jurisdictions and five federal agencies — the Bureau of Prisons, the Department of Defense, the Department of State, the Indian Health Service, and the Veterans Health Administration — according to the Centers for Disease Control and Prevention’s COVID-19 Vaccination Program Interim Playbook.

It will be up to states — which will receive a supply prorated to population — and these agencies to determine how to prioritize distribution of the 2.9 million doses. Each state and agency has its own plan. Gen. Gustave Perna, the chief operating officer for Operation Warp Speed, said in the briefing that 30 states have told the federal government they will prioritize initial doses for residents and staff of long-term care facilities.

The distribution is contingent on FDA authorization, which could happen soon. The FDA’s Vaccines and Related Biologics Advisory Committee weighed the effectiveness data for the Pfizer vaccine on December 10 and recommended that the agency grant emergency authorization. The FDA could issue a decision at any time.
 

Fewer doses out of the gate

Perna said the federal government will begin shipping the Pfizer vaccine within 24 hours of an FDA authorization.

He said those shipments will include a total of 2.9 million doses — not the 6.4 million that will be available. The government is holding 500,000 doses in reserve and another 2.9 million to guarantee that the first few million people who are vaccinated will be able to receive a second dose 21 days later, said Perna.

In part, that is because the FDA labeling will require that a first dose be followed by a second exactly 21 days later, said HHS Secretary Alex Azar in the briefing.

Federal officials have calculated how much to hold back on the basis of Pfizer’s production, said Azar. At least initially, “we will not distribute a vaccine knowing that the booster will not be available either from reserve supply by us or ongoing expected predicted production,” he said.

Even with Pfizer having reduced its estimates of how much vaccine it can deliver in December, Azar said, “There will be enough vaccine available for 20 million first vaccinations in the month of December.”

That estimate is predicated, however, on the idea that a vaccine under development by Moderna will receive clearance shortly after the FDA assesses that vaccine’s safety and effectiveness on December 17.

This article first appeared on Medscape.com.

The Diagnosis: Kaposi Sarcoma 

On initial presentation, the differential diagnosis included secondary syphilis, Kaposi sarcoma (KS), lichen planus pigmentosus, sarcoidosis, and psoriasis. A laboratory workup was ordered, which included complete blood cell count, comprehensive metabolic panel, antinuclear antibodies, anti-Ro/Sjögren syndrome antigen A and anti-La/Sjögren syndrome antigen B autoantibodies, angiotensin-converting enzyme, rapid plasma reagin, and human immunodeficiency virus (HIV) antibodies. A 4-mm punch biopsy of the rash also was performed from the right upper back. Histology revealed a vascular proliferation that was diffusely positive for human herpesvirus 8 (HHV-8)(Figure 1). The patient was informed of the diagnosis, at which time he revealed he had a history of homosexual relationships, with his last sexual contact being more than 1 year prior to presentation. The laboratory workup confirmed a diagnosis of HIV, and the remainder of the tests were unremarkable. 

He was referred to our university's HIV clinic where he was started on highly active antiretroviral therapy (HAART). His facial swelling worsened, leading to hospital admission. Computed tomography (CT) of the chest, abdomen, and pelvis showed diffuse lymphadenopathy and lung nodules concerning for visceral involvement of KS. Hematology and oncology was consulted for further evaluation, and he was treated with 6 cycles of doxorubicin 20 mg/m², which led to resolution of the lung nodules on CT and improvement of the rash burden. He was then started on alitretinoin gel 0.1% twice daily, which led to continued slow improvement (Figure 2). 

Kaposi sarcoma is a vascular neoplasm that occurs from infection with HHV-8. It typically presents as painless, reddish to violaceous macules or patches involving the skin and mucosa that often progress to plaques or nodules with possible visceral involvement. Kaposi sarcoma is classified into 4 subtypes based on epidemiology and clinical presentation: classic, endemic, iatrogenic, and AIDS associated.^1,2  

Classic KS primarily affects elderly males of Mediterranean or Eastern European descent, with a mean age of 64.¹ years and a male to female ratio of 3 to 1. It has an indolent course and a strong predilection for the skin of the lower extremities. The endemic form occurs mainly in Africa and has a more aggressive course, especially the lymphadenopathic type that affects children younger than 10 years.³ Iatrogenic KS develops in immunosuppressed patients, such as transplant recipients, and may regress if the immunosuppressive agent is stopped.¹ Kaposi sarcoma is an AIDS-defining illness and is the most common malignancy in AIDS patients. It is strongly associated with a low CD4 count, which accounts for the notable decline in its incidence after the widespread introduction of HAART.¹ Among HIV patients, KS has the highest incidence in men who have sex with men. This population has a higher seroprevalence of HHV-8, which suggests possible sexual transmission of HHV-8. AIDS-associated KS most commonly involves the lower extremities, face, and oral mucosa. It may have visceral involvement, particularly of the gastrointestinal and respiratory systems, which carries a poor prognosis.^4,5 

Approximately 40% of patients presenting with KS have gastrointestinal tract involvement.⁶ Of these patients, up to 80% are asymptomatic, with diagnosis usually being made on endoscopy.⁷ In contrast, pulmonary KS is less common and typically is symptomatic. It can involve the lung parenchyma, airways, or pleura and is diagnosed by chest radiography or CT scans. Glucocorticoid therapy is a known trigger for pulmonary KS exacerbation.⁸  

All 4 subtypes share the same histopathologic findings consisting of spindled endothelial cell proliferation, inflammation, and angiogenesis. Immunohistochemistry reveals tumor cells that are CD34 and CD31 positive but are factor VIII negative. Staining for HHV-8 antigen is used to confirm the diagnosis. The inflammatory infiltrate predominantly is lymphocytic with scattered plasma cells.⁹  

The laboratory results and histopathologic findings clearly indicated a diagnosis of KS in our patient. Other entities in the clinical differential would have shown notably different histopathologic findings and laboratory results. Lichen planus pigmentosus displays a lichenoid infiltrate and pigment dropout on histology. Histologic findings of psoriasis include psoriasiform acanthosis, dilated vessels in the dermal papillae, thinning of suprapapillary plates, and neutrophilic microabscesses. Sarcoidosis would demonstrate naked granulomas on histopathology. Syphilis displays variable but often psoriasiform or lichenoid findings on histology, and a positive rapid plasma reagin also would be noted.  

First-line treatment of AIDS-related KS is HAART. For patients with severe and rapidly progressive KS or with visceral involvement, cytotoxic chemotherapy with doxorubicin or taxanes often is required. Additional therapies include radiotherapy, topical alitretinoin, and cryotherapy.^1,10 

The Diagnosis: Kaposi Sarcoma 

On initial presentation, the differential diagnosis included secondary syphilis, Kaposi sarcoma (KS), lichen planus pigmentosus, sarcoidosis, and psoriasis. A laboratory workup was ordered, which included complete blood cell count, comprehensive metabolic panel, antinuclear antibodies, anti-Ro/Sjögren syndrome antigen A and anti-La/Sjögren syndrome antigen B autoantibodies, angiotensin-converting enzyme, rapid plasma reagin, and human immunodeficiency virus (HIV) antibodies. A 4-mm punch biopsy of the rash also was performed from the right upper back. Histology revealed a vascular proliferation that was diffusely positive for human herpesvirus 8 (HHV-8)(Figure 1). The patient was informed of the diagnosis, at which time he revealed he had a history of homosexual relationships, with his last sexual contact being more than 1 year prior to presentation. The laboratory workup confirmed a diagnosis of HIV, and the remainder of the tests were unremarkable. 

He was referred to our university's HIV clinic where he was started on highly active antiretroviral therapy (HAART). His facial swelling worsened, leading to hospital admission. Computed tomography (CT) of the chest, abdomen, and pelvis showed diffuse lymphadenopathy and lung nodules concerning for visceral involvement of KS. Hematology and oncology was consulted for further evaluation, and he was treated with 6 cycles of doxorubicin 20 mg/m², which led to resolution of the lung nodules on CT and improvement of the rash burden. He was then started on alitretinoin gel 0.1% twice daily, which led to continued slow improvement (Figure 2). 

Kaposi sarcoma is a vascular neoplasm that occurs from infection with HHV-8. It typically presents as painless, reddish to violaceous macules or patches involving the skin and mucosa that often progress to plaques or nodules with possible visceral involvement. Kaposi sarcoma is classified into 4 subtypes based on epidemiology and clinical presentation: classic, endemic, iatrogenic, and AIDS associated.^1,2  

Classic KS primarily affects elderly males of Mediterranean or Eastern European descent, with a mean age of 64.¹ years and a male to female ratio of 3 to 1. It has an indolent course and a strong predilection for the skin of the lower extremities. The endemic form occurs mainly in Africa and has a more aggressive course, especially the lymphadenopathic type that affects children younger than 10 years.³ Iatrogenic KS develops in immunosuppressed patients, such as transplant recipients, and may regress if the immunosuppressive agent is stopped.¹ Kaposi sarcoma is an AIDS-defining illness and is the most common malignancy in AIDS patients. It is strongly associated with a low CD4 count, which accounts for the notable decline in its incidence after the widespread introduction of HAART.¹ Among HIV patients, KS has the highest incidence in men who have sex with men. This population has a higher seroprevalence of HHV-8, which suggests possible sexual transmission of HHV-8. AIDS-associated KS most commonly involves the lower extremities, face, and oral mucosa. It may have visceral involvement, particularly of the gastrointestinal and respiratory systems, which carries a poor prognosis.^4,5 

Approximately 40% of patients presenting with KS have gastrointestinal tract involvement.⁶ Of these patients, up to 80% are asymptomatic, with diagnosis usually being made on endoscopy.⁷ In contrast, pulmonary KS is less common and typically is symptomatic. It can involve the lung parenchyma, airways, or pleura and is diagnosed by chest radiography or CT scans. Glucocorticoid therapy is a known trigger for pulmonary KS exacerbation.⁸  

All 4 subtypes share the same histopathologic findings consisting of spindled endothelial cell proliferation, inflammation, and angiogenesis. Immunohistochemistry reveals tumor cells that are CD34 and CD31 positive but are factor VIII negative. Staining for HHV-8 antigen is used to confirm the diagnosis. The inflammatory infiltrate predominantly is lymphocytic with scattered plasma cells.⁹  

The laboratory results and histopathologic findings clearly indicated a diagnosis of KS in our patient. Other entities in the clinical differential would have shown notably different histopathologic findings and laboratory results. Lichen planus pigmentosus displays a lichenoid infiltrate and pigment dropout on histology. Histologic findings of psoriasis include psoriasiform acanthosis, dilated vessels in the dermal papillae, thinning of suprapapillary plates, and neutrophilic microabscesses. Sarcoidosis would demonstrate naked granulomas on histopathology. Syphilis displays variable but often psoriasiform or lichenoid findings on histology, and a positive rapid plasma reagin also would be noted.  

First-line treatment of AIDS-related KS is HAART. For patients with severe and rapidly progressive KS or with visceral involvement, cytotoxic chemotherapy with doxorubicin or taxanes often is required. Additional therapies include radiotherapy, topical alitretinoin, and cryotherapy.^1,10 

The Diagnosis: Kaposi Sarcoma 

On initial presentation, the differential diagnosis included secondary syphilis, Kaposi sarcoma (KS), lichen planus pigmentosus, sarcoidosis, and psoriasis. A laboratory workup was ordered, which included complete blood cell count, comprehensive metabolic panel, antinuclear antibodies, anti-Ro/Sjögren syndrome antigen A and anti-La/Sjögren syndrome antigen B autoantibodies, angiotensin-converting enzyme, rapid plasma reagin, and human immunodeficiency virus (HIV) antibodies. A 4-mm punch biopsy of the rash also was performed from the right upper back. Histology revealed a vascular proliferation that was diffusely positive for human herpesvirus 8 (HHV-8)(Figure 1). The patient was informed of the diagnosis, at which time he revealed he had a history of homosexual relationships, with his last sexual contact being more than 1 year prior to presentation. The laboratory workup confirmed a diagnosis of HIV, and the remainder of the tests were unremarkable. 

He was referred to our university's HIV clinic where he was started on highly active antiretroviral therapy (HAART). His facial swelling worsened, leading to hospital admission. Computed tomography (CT) of the chest, abdomen, and pelvis showed diffuse lymphadenopathy and lung nodules concerning for visceral involvement of KS. Hematology and oncology was consulted for further evaluation, and he was treated with 6 cycles of doxorubicin 20 mg/m², which led to resolution of the lung nodules on CT and improvement of the rash burden. He was then started on alitretinoin gel 0.1% twice daily, which led to continued slow improvement (Figure 2). 

Kaposi sarcoma is a vascular neoplasm that occurs from infection with HHV-8. It typically presents as painless, reddish to violaceous macules or patches involving the skin and mucosa that often progress to plaques or nodules with possible visceral involvement. Kaposi sarcoma is classified into 4 subtypes based on epidemiology and clinical presentation: classic, endemic, iatrogenic, and AIDS associated.^1,2  

Classic KS primarily affects elderly males of Mediterranean or Eastern European descent, with a mean age of 64.¹ years and a male to female ratio of 3 to 1. It has an indolent course and a strong predilection for the skin of the lower extremities. The endemic form occurs mainly in Africa and has a more aggressive course, especially the lymphadenopathic type that affects children younger than 10 years.³ Iatrogenic KS develops in immunosuppressed patients, such as transplant recipients, and may regress if the immunosuppressive agent is stopped.¹ Kaposi sarcoma is an AIDS-defining illness and is the most common malignancy in AIDS patients. It is strongly associated with a low CD4 count, which accounts for the notable decline in its incidence after the widespread introduction of HAART.¹ Among HIV patients, KS has the highest incidence in men who have sex with men. This population has a higher seroprevalence of HHV-8, which suggests possible sexual transmission of HHV-8. AIDS-associated KS most commonly involves the lower extremities, face, and oral mucosa. It may have visceral involvement, particularly of the gastrointestinal and respiratory systems, which carries a poor prognosis.^4,5 

Approximately 40% of patients presenting with KS have gastrointestinal tract involvement.⁶ Of these patients, up to 80% are asymptomatic, with diagnosis usually being made on endoscopy.⁷ In contrast, pulmonary KS is less common and typically is symptomatic. It can involve the lung parenchyma, airways, or pleura and is diagnosed by chest radiography or CT scans. Glucocorticoid therapy is a known trigger for pulmonary KS exacerbation.⁸  

All 4 subtypes share the same histopathologic findings consisting of spindled endothelial cell proliferation, inflammation, and angiogenesis. Immunohistochemistry reveals tumor cells that are CD34 and CD31 positive but are factor VIII negative. Staining for HHV-8 antigen is used to confirm the diagnosis. The inflammatory infiltrate predominantly is lymphocytic with scattered plasma cells.⁹  

The laboratory results and histopathologic findings clearly indicated a diagnosis of KS in our patient. Other entities in the clinical differential would have shown notably different histopathologic findings and laboratory results. Lichen planus pigmentosus displays a lichenoid infiltrate and pigment dropout on histology. Histologic findings of psoriasis include psoriasiform acanthosis, dilated vessels in the dermal papillae, thinning of suprapapillary plates, and neutrophilic microabscesses. Sarcoidosis would demonstrate naked granulomas on histopathology. Syphilis displays variable but often psoriasiform or lichenoid findings on histology, and a positive rapid plasma reagin also would be noted.  

First-line treatment of AIDS-related KS is HAART. For patients with severe and rapidly progressive KS or with visceral involvement, cytotoxic chemotherapy with doxorubicin or taxanes often is required. Additional therapies include radiotherapy, topical alitretinoin, and cryotherapy.^1,10 

The poorer survival rates in Black women compared with White women with breast cancer could be explained to some extent by the finding of much higher rates of  obesity, obesity-related comorbidities, and overall comorbidities in Black women, say researchers reporting a retrospective chart review from their clinic.

Kirsten A. Nyrop, PhD, deputy director for research for the Geriatric Oncology Program at the University of North Carolina, Chapel Hill, and colleagues analyzed medical charts for 144 Black women and 404 White women with early breast cancer.

Obesity rates were nearly double among Black women, at 62% vs 32%.

In addition, significantly more Black women had two or more total comorbidities (62% vs 47%), two or more obesity-related comorbidities (33% vs 10%), hypertension (60% vs 32%), type 2 diabetes (23% vs 6%), and hypercholesterolemia or hyperlipidemia (28% vs 18%).

These racial disparities persisted after adjustment for age and body mass index, both independent predictors of chronic diseases.

The difference in obesity and comorbidity did not translate to differences in treatment decisions such as surgery type, chemotherapy regimen, radiation, or endocrine treatment, the researchers note.

The findings were published online December 7 in the journal Cancer.

They underscore the likely role of obesity and related complications in the racial disparities seen in breast cancer survival outcomes, the authors conclude.

Experts writing in an accompanying editorial agree, while emphasizing the well documented differences in survival.

Compared with White women with breast cancer, Black women with breast cancer have a 42% higher mortality rate and a greater likelihood of dying from breast cancer regardless of their age at diagnosis, note Caitlin E. Taylor, MD, and Jane Lowe Meisel, MD, of Emory University, Atlanta, Georgia.

“Although it is clear that the causes of such disparities are complex and multifactorial, questions remain regarding to what extent patient comorbidities, and specifically obesity, may be playing a role,” they write.

The obesity- and comorbidity-related disparities identified by Nyrop et al “undoubtedly contribute to the overall disparities noted in breast cancer outcomes among Black women,” they add.
 

Takeaway messages

Nyrop and colleagues say their findings have two important takeaway messages:

1) It is important to manage comorbidities in women with newly diagnosed early breast cancer to reduce the risk of mortality from competing causes, and

2) Excess weight at diagnosis and weight gain after primary treatment increase the risk of obesity-related disease that can affect survival, and patients should be educated about the association.

Such conversations should be “patient-centered and culturally appropriate,” they note.

In their editorial, Taylor and Meisel agree with the authors’ conclusions. “Given the higher prevalence of obesity and related comorbidities among Black patients, addressing these issues must become an integral part of early breast cancer management to prolong overall survival and continue improving outcomes for these women.”

In fact, addressing comorbidities early in breast cancer management is important for patients of all racial and ethnic backgrounds, the editorialists add, concluding that the role of obesity as “a critical player underlying breast cancer mortality” is increasingly clear, and that its management is crucial for improved outcomes and quality of life.

This study was supported by the Breast Cancer Research Foundation, the National Cancer Institute’s Breast Cancer Specialized Program of Research Excellence, and the University of North Carolina Lineberger Comprehensive Cancer Center/University Cancer Research Fund. The study authors have disclosed no relevant financial relationships. Meisel has received research support from Pfizer, Eli Lilly, and Seattle Genetics and has served as a paid advisor for Pfizer, PUMA, Novartis, and Clovis Oncology. Taylor has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The poorer survival rates in Black women compared with White women with breast cancer could be explained to some extent by the finding of much higher rates of  obesity, obesity-related comorbidities, and overall comorbidities in Black women, say researchers reporting a retrospective chart review from their clinic.

Kirsten A. Nyrop, PhD, deputy director for research for the Geriatric Oncology Program at the University of North Carolina, Chapel Hill, and colleagues analyzed medical charts for 144 Black women and 404 White women with early breast cancer.

Obesity rates were nearly double among Black women, at 62% vs 32%.

In addition, significantly more Black women had two or more total comorbidities (62% vs 47%), two or more obesity-related comorbidities (33% vs 10%), hypertension (60% vs 32%), type 2 diabetes (23% vs 6%), and hypercholesterolemia or hyperlipidemia (28% vs 18%).

These racial disparities persisted after adjustment for age and body mass index, both independent predictors of chronic diseases.

The difference in obesity and comorbidity did not translate to differences in treatment decisions such as surgery type, chemotherapy regimen, radiation, or endocrine treatment, the researchers note.

The findings were published online December 7 in the journal Cancer.

They underscore the likely role of obesity and related complications in the racial disparities seen in breast cancer survival outcomes, the authors conclude.

Experts writing in an accompanying editorial agree, while emphasizing the well documented differences in survival.

Compared with White women with breast cancer, Black women with breast cancer have a 42% higher mortality rate and a greater likelihood of dying from breast cancer regardless of their age at diagnosis, note Caitlin E. Taylor, MD, and Jane Lowe Meisel, MD, of Emory University, Atlanta, Georgia.

“Although it is clear that the causes of such disparities are complex and multifactorial, questions remain regarding to what extent patient comorbidities, and specifically obesity, may be playing a role,” they write.

The obesity- and comorbidity-related disparities identified by Nyrop et al “undoubtedly contribute to the overall disparities noted in breast cancer outcomes among Black women,” they add.
 

Takeaway messages

Nyrop and colleagues say their findings have two important takeaway messages:

1) It is important to manage comorbidities in women with newly diagnosed early breast cancer to reduce the risk of mortality from competing causes, and

2) Excess weight at diagnosis and weight gain after primary treatment increase the risk of obesity-related disease that can affect survival, and patients should be educated about the association.

Such conversations should be “patient-centered and culturally appropriate,” they note.

In their editorial, Taylor and Meisel agree with the authors’ conclusions. “Given the higher prevalence of obesity and related comorbidities among Black patients, addressing these issues must become an integral part of early breast cancer management to prolong overall survival and continue improving outcomes for these women.”

In fact, addressing comorbidities early in breast cancer management is important for patients of all racial and ethnic backgrounds, the editorialists add, concluding that the role of obesity as “a critical player underlying breast cancer mortality” is increasingly clear, and that its management is crucial for improved outcomes and quality of life.

This study was supported by the Breast Cancer Research Foundation, the National Cancer Institute’s Breast Cancer Specialized Program of Research Excellence, and the University of North Carolina Lineberger Comprehensive Cancer Center/University Cancer Research Fund. The study authors have disclosed no relevant financial relationships. Meisel has received research support from Pfizer, Eli Lilly, and Seattle Genetics and has served as a paid advisor for Pfizer, PUMA, Novartis, and Clovis Oncology. Taylor has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The poorer survival rates in Black women compared with White women with breast cancer could be explained to some extent by the finding of much higher rates of  obesity, obesity-related comorbidities, and overall comorbidities in Black women, say researchers reporting a retrospective chart review from their clinic.

Kirsten A. Nyrop, PhD, deputy director for research for the Geriatric Oncology Program at the University of North Carolina, Chapel Hill, and colleagues analyzed medical charts for 144 Black women and 404 White women with early breast cancer.

Obesity rates were nearly double among Black women, at 62% vs 32%.

In addition, significantly more Black women had two or more total comorbidities (62% vs 47%), two or more obesity-related comorbidities (33% vs 10%), hypertension (60% vs 32%), type 2 diabetes (23% vs 6%), and hypercholesterolemia or hyperlipidemia (28% vs 18%).

These racial disparities persisted after adjustment for age and body mass index, both independent predictors of chronic diseases.

The difference in obesity and comorbidity did not translate to differences in treatment decisions such as surgery type, chemotherapy regimen, radiation, or endocrine treatment, the researchers note.

The findings were published online December 7 in the journal Cancer.

They underscore the likely role of obesity and related complications in the racial disparities seen in breast cancer survival outcomes, the authors conclude.

Experts writing in an accompanying editorial agree, while emphasizing the well documented differences in survival.

Compared with White women with breast cancer, Black women with breast cancer have a 42% higher mortality rate and a greater likelihood of dying from breast cancer regardless of their age at diagnosis, note Caitlin E. Taylor, MD, and Jane Lowe Meisel, MD, of Emory University, Atlanta, Georgia.

“Although it is clear that the causes of such disparities are complex and multifactorial, questions remain regarding to what extent patient comorbidities, and specifically obesity, may be playing a role,” they write.

The obesity- and comorbidity-related disparities identified by Nyrop et al “undoubtedly contribute to the overall disparities noted in breast cancer outcomes among Black women,” they add.
 

Takeaway messages

Nyrop and colleagues say their findings have two important takeaway messages:

1) It is important to manage comorbidities in women with newly diagnosed early breast cancer to reduce the risk of mortality from competing causes, and

2) Excess weight at diagnosis and weight gain after primary treatment increase the risk of obesity-related disease that can affect survival, and patients should be educated about the association.

Such conversations should be “patient-centered and culturally appropriate,” they note.

In their editorial, Taylor and Meisel agree with the authors’ conclusions. “Given the higher prevalence of obesity and related comorbidities among Black patients, addressing these issues must become an integral part of early breast cancer management to prolong overall survival and continue improving outcomes for these women.”

In fact, addressing comorbidities early in breast cancer management is important for patients of all racial and ethnic backgrounds, the editorialists add, concluding that the role of obesity as “a critical player underlying breast cancer mortality” is increasingly clear, and that its management is crucial for improved outcomes and quality of life.

This study was supported by the Breast Cancer Research Foundation, the National Cancer Institute’s Breast Cancer Specialized Program of Research Excellence, and the University of North Carolina Lineberger Comprehensive Cancer Center/University Cancer Research Fund. The study authors have disclosed no relevant financial relationships. Meisel has received research support from Pfizer, Eli Lilly, and Seattle Genetics and has served as a paid advisor for Pfizer, PUMA, Novartis, and Clovis Oncology. Taylor has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Dermatologists are more likely than are nondermatologists to follow practice guidelines when prescribing antihistamines to treat pruritus associated with atopic dermatitis (AD), according to an analysis of a national database.

[email protected]

SOURCE: Garg S et al. Pediatr Dermatol. 2020 Nov 27. doi: 10.1111/pde.14445.

Dermatologists are more likely than are nondermatologists to follow practice guidelines when prescribing antihistamines to treat pruritus associated with atopic dermatitis (AD), according to an analysis of a national database.

[email protected]

SOURCE: Garg S et al. Pediatr Dermatol. 2020 Nov 27. doi: 10.1111/pde.14445.

Dermatologists are more likely than are nondermatologists to follow practice guidelines when prescribing antihistamines to treat pruritus associated with atopic dermatitis (AD), according to an analysis of a national database.

[email protected]

SOURCE: Garg S et al. Pediatr Dermatol. 2020 Nov 27. doi: 10.1111/pde.14445.

In January in many states, the start of a new year also means the start of a new legislative session. For LGBTQ youth and their families, these sessions can create a significant amount of anxiety, as legislators in several states introduce legislation to curtail the rights of this population. In some cases, legislators have attempted to criminalize the provision of gender-affirming medical care to the trans and gender-diverse adolescents that many of us provide care to on a daily basis. As pediatricians, we have an important role in advocating for legislation at the local, state, and federal level that improves the lives of the LGBTQ patients we serve.

2020 started on a positive note for LGBTQ children and adolescents, with Virginia becoming the 20th state to ban conversion therapy for minors. Legislation was introduced in several other states to prohibit this practice, including Kentucky, Missouri, and Ohio, and but they ultimately died in committee or were never referred. While there is not yet a nationwide ban on conversion therapy, legislation was introduced in the last three U.S. Congress sessions to ban this harmful practice. In June 2020, the Supreme Court decision in Bostock vs. Clayton County stated that employers could not fire an employee solely because of that person’s sexual orientation and/or gender identity.

However, 19 separate bills were introduced in 2020 alone in states across the United States that would prohibit gender-affirming care for adolescents under age 18.¹ Many of these bills also would make the provision of gender-affirming medical care codified as felony child abuse, with loss of licensure, fines and/or jail time a possibility for physicians who prescribe hormones or puberty blockers for gender-affirming care to minors. Fortunately, these bills either died in committee or never had a hearing. However, legislation has been prefiled in several states for their 2021 session to again attempt to prohibit minors from obtaining gender-affirming medical care and/or criminalizing the provision of this care by physicians. Other bills were filed or have been prefiled again to allow various medical and mental health providers to refuse to treat LGBTQ patients because of their personal religious beliefs and/or forcing these same providers to tell a parent if a minor reveals to that provider that they are LGBTQ.

Even if this legislation does not pass or get a hearing, the fact that the bills were introduced can have a profound impact on LGBTQ patients and their families. After a bill was introduced in Texas in their 2017 legislative session that would require trans and gender-diverse (TGD) people to use the bathroom based on their sex assigned at birth, the Trevor Project reported that it had an increase of 34% in crisis calls from trans youth who were in distress.² This was similar, but slightly less, than was reported by the Trevor Project in September 2015 when in the run-up to a vote on Houston’s Equal Rights Ordinance, advertising was run equating trans women as predators who could be lying in wait in bathrooms. On the converse, when LGBTQ youth feel supported in the media, courts, and legislatures, this can have a positive impact on their mental health. A 2017 study found that, in states who enacted same-sex marriage laws prior to the 2015 Supreme Court decision in Obergefell, compared with those who did not, there was a 7% relative reduction in the proportion of high school students who attempted suicide.³

The American Academy of Pediatrics published its policy statement in September 2018 outlining suggestions for pediatricians to provide support to TGD youth.⁴ In this position statement, recommendation No. 7 states “that pediatricians have a role in advocating for policies and laws that protect youth who identify as TGD from discrimination and violence.” Therefore, it is incumbent upon us to use our voices to support our LGBTQ youth. In 2020, several pediatricians from the South Dakota chapter of the AAP provided testimony – and organized public rallies – against legislation in that state which would have made gender-affirming care to minors under age 16 punishable by a fine and/or up to 10 years in prison.⁵

So what can you do? First, get to know your local and state legislators. While it was difficult to meet them in person for much of 2020, you can always call their district and/or Capitol offices, email them, or fill out their constituent contact form typically found on their website. Let them know that you oppose bills which introduce discrimination against your LGBTQ patients or threaten to criminalize the care that you provide to these patients.

Second, work with your state medical association or state AAP chapter to encourage them to oppose these harmful laws and support laws that improve the lives of LGBTQ patients. Third, you can write op-eds to your local newspaper, expressing your support for your patients and outlining the detrimental effects that anti-LGBTQ laws have on your patients. Lastly, you can be active on Twitter, Facebook, or other social media platforms sharing stories of how harmful or helpful certain pieces of legislation can be for your patients.

Dr. Cooper is assistant professor of pediatrics at the University of Texas, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas. He has no relevant financial disclosures. Email Dr. Cooper at [email protected].

References

1. “Leglislation affecting LGBT rights across country.” www.aclu.org.

2. “Bathroom Bills Fuel Spike In Calls From Trans Youth To Suicide Hotline.” www.outsmartmagazine.com. 2017 Aug.

3. JAMA Pediatr. 2017 Apr 1. doi: 10.1001/jamapediatrics.2016.4529.

4. Pediatrics. 2018 Oct. doi: 10.1542/peds.2018-2162.

5. Wyckoff AS. “State bills seek to place limits on transgender care, ‘punish’ physicians.” AAP News. 2020 Feb 18.

In January in many states, the start of a new year also means the start of a new legislative session. For LGBTQ youth and their families, these sessions can create a significant amount of anxiety, as legislators in several states introduce legislation to curtail the rights of this population. In some cases, legislators have attempted to criminalize the provision of gender-affirming medical care to the trans and gender-diverse adolescents that many of us provide care to on a daily basis. As pediatricians, we have an important role in advocating for legislation at the local, state, and federal level that improves the lives of the LGBTQ patients we serve.

2020 started on a positive note for LGBTQ children and adolescents, with Virginia becoming the 20th state to ban conversion therapy for minors. Legislation was introduced in several other states to prohibit this practice, including Kentucky, Missouri, and Ohio, and but they ultimately died in committee or were never referred. While there is not yet a nationwide ban on conversion therapy, legislation was introduced in the last three U.S. Congress sessions to ban this harmful practice. In June 2020, the Supreme Court decision in Bostock vs. Clayton County stated that employers could not fire an employee solely because of that person’s sexual orientation and/or gender identity.

However, 19 separate bills were introduced in 2020 alone in states across the United States that would prohibit gender-affirming care for adolescents under age 18.¹ Many of these bills also would make the provision of gender-affirming medical care codified as felony child abuse, with loss of licensure, fines and/or jail time a possibility for physicians who prescribe hormones or puberty blockers for gender-affirming care to minors. Fortunately, these bills either died in committee or never had a hearing. However, legislation has been prefiled in several states for their 2021 session to again attempt to prohibit minors from obtaining gender-affirming medical care and/or criminalizing the provision of this care by physicians. Other bills were filed or have been prefiled again to allow various medical and mental health providers to refuse to treat LGBTQ patients because of their personal religious beliefs and/or forcing these same providers to tell a parent if a minor reveals to that provider that they are LGBTQ.

Even if this legislation does not pass or get a hearing, the fact that the bills were introduced can have a profound impact on LGBTQ patients and their families. After a bill was introduced in Texas in their 2017 legislative session that would require trans and gender-diverse (TGD) people to use the bathroom based on their sex assigned at birth, the Trevor Project reported that it had an increase of 34% in crisis calls from trans youth who were in distress.² This was similar, but slightly less, than was reported by the Trevor Project in September 2015 when in the run-up to a vote on Houston’s Equal Rights Ordinance, advertising was run equating trans women as predators who could be lying in wait in bathrooms. On the converse, when LGBTQ youth feel supported in the media, courts, and legislatures, this can have a positive impact on their mental health. A 2017 study found that, in states who enacted same-sex marriage laws prior to the 2015 Supreme Court decision in Obergefell, compared with those who did not, there was a 7% relative reduction in the proportion of high school students who attempted suicide.³

The American Academy of Pediatrics published its policy statement in September 2018 outlining suggestions for pediatricians to provide support to TGD youth.⁴ In this position statement, recommendation No. 7 states “that pediatricians have a role in advocating for policies and laws that protect youth who identify as TGD from discrimination and violence.” Therefore, it is incumbent upon us to use our voices to support our LGBTQ youth. In 2020, several pediatricians from the South Dakota chapter of the AAP provided testimony – and organized public rallies – against legislation in that state which would have made gender-affirming care to minors under age 16 punishable by a fine and/or up to 10 years in prison.⁵

So what can you do? First, get to know your local and state legislators. While it was difficult to meet them in person for much of 2020, you can always call their district and/or Capitol offices, email them, or fill out their constituent contact form typically found on their website. Let them know that you oppose bills which introduce discrimination against your LGBTQ patients or threaten to criminalize the care that you provide to these patients.

Second, work with your state medical association or state AAP chapter to encourage them to oppose these harmful laws and support laws that improve the lives of LGBTQ patients. Third, you can write op-eds to your local newspaper, expressing your support for your patients and outlining the detrimental effects that anti-LGBTQ laws have on your patients. Lastly, you can be active on Twitter, Facebook, or other social media platforms sharing stories of how harmful or helpful certain pieces of legislation can be for your patients.

Dr. Cooper is assistant professor of pediatrics at the University of Texas, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas. He has no relevant financial disclosures. Email Dr. Cooper at [email protected].

References

1. “Leglislation affecting LGBT rights across country.” www.aclu.org.

2. “Bathroom Bills Fuel Spike In Calls From Trans Youth To Suicide Hotline.” www.outsmartmagazine.com. 2017 Aug.

3. JAMA Pediatr. 2017 Apr 1. doi: 10.1001/jamapediatrics.2016.4529.

4. Pediatrics. 2018 Oct. doi: 10.1542/peds.2018-2162.

5. Wyckoff AS. “State bills seek to place limits on transgender care, ‘punish’ physicians.” AAP News. 2020 Feb 18.

In January in many states, the start of a new year also means the start of a new legislative session. For LGBTQ youth and their families, these sessions can create a significant amount of anxiety, as legislators in several states introduce legislation to curtail the rights of this population. In some cases, legislators have attempted to criminalize the provision of gender-affirming medical care to the trans and gender-diverse adolescents that many of us provide care to on a daily basis. As pediatricians, we have an important role in advocating for legislation at the local, state, and federal level that improves the lives of the LGBTQ patients we serve.

2020 started on a positive note for LGBTQ children and adolescents, with Virginia becoming the 20th state to ban conversion therapy for minors. Legislation was introduced in several other states to prohibit this practice, including Kentucky, Missouri, and Ohio, and but they ultimately died in committee or were never referred. While there is not yet a nationwide ban on conversion therapy, legislation was introduced in the last three U.S. Congress sessions to ban this harmful practice. In June 2020, the Supreme Court decision in Bostock vs. Clayton County stated that employers could not fire an employee solely because of that person’s sexual orientation and/or gender identity.

However, 19 separate bills were introduced in 2020 alone in states across the United States that would prohibit gender-affirming care for adolescents under age 18.¹ Many of these bills also would make the provision of gender-affirming medical care codified as felony child abuse, with loss of licensure, fines and/or jail time a possibility for physicians who prescribe hormones or puberty blockers for gender-affirming care to minors. Fortunately, these bills either died in committee or never had a hearing. However, legislation has been prefiled in several states for their 2021 session to again attempt to prohibit minors from obtaining gender-affirming medical care and/or criminalizing the provision of this care by physicians. Other bills were filed or have been prefiled again to allow various medical and mental health providers to refuse to treat LGBTQ patients because of their personal religious beliefs and/or forcing these same providers to tell a parent if a minor reveals to that provider that they are LGBTQ.

Even if this legislation does not pass or get a hearing, the fact that the bills were introduced can have a profound impact on LGBTQ patients and their families. After a bill was introduced in Texas in their 2017 legislative session that would require trans and gender-diverse (TGD) people to use the bathroom based on their sex assigned at birth, the Trevor Project reported that it had an increase of 34% in crisis calls from trans youth who were in distress.² This was similar, but slightly less, than was reported by the Trevor Project in September 2015 when in the run-up to a vote on Houston’s Equal Rights Ordinance, advertising was run equating trans women as predators who could be lying in wait in bathrooms. On the converse, when LGBTQ youth feel supported in the media, courts, and legislatures, this can have a positive impact on their mental health. A 2017 study found that, in states who enacted same-sex marriage laws prior to the 2015 Supreme Court decision in Obergefell, compared with those who did not, there was a 7% relative reduction in the proportion of high school students who attempted suicide.³

The American Academy of Pediatrics published its policy statement in September 2018 outlining suggestions for pediatricians to provide support to TGD youth.⁴ In this position statement, recommendation No. 7 states “that pediatricians have a role in advocating for policies and laws that protect youth who identify as TGD from discrimination and violence.” Therefore, it is incumbent upon us to use our voices to support our LGBTQ youth. In 2020, several pediatricians from the South Dakota chapter of the AAP provided testimony – and organized public rallies – against legislation in that state which would have made gender-affirming care to minors under age 16 punishable by a fine and/or up to 10 years in prison.⁵

So what can you do? First, get to know your local and state legislators. While it was difficult to meet them in person for much of 2020, you can always call their district and/or Capitol offices, email them, or fill out their constituent contact form typically found on their website. Let them know that you oppose bills which introduce discrimination against your LGBTQ patients or threaten to criminalize the care that you provide to these patients.

Second, work with your state medical association or state AAP chapter to encourage them to oppose these harmful laws and support laws that improve the lives of LGBTQ patients. Third, you can write op-eds to your local newspaper, expressing your support for your patients and outlining the detrimental effects that anti-LGBTQ laws have on your patients. Lastly, you can be active on Twitter, Facebook, or other social media platforms sharing stories of how harmful or helpful certain pieces of legislation can be for your patients.

Dr. Cooper is assistant professor of pediatrics at the University of Texas, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas. He has no relevant financial disclosures. Email Dr. Cooper at [email protected].

References

1. “Leglislation affecting LGBT rights across country.” www.aclu.org.

2. “Bathroom Bills Fuel Spike In Calls From Trans Youth To Suicide Hotline.” www.outsmartmagazine.com. 2017 Aug.

3. JAMA Pediatr. 2017 Apr 1. doi: 10.1001/jamapediatrics.2016.4529.

4. Pediatrics. 2018 Oct. doi: 10.1542/peds.2018-2162.

5. Wyckoff AS. “State bills seek to place limits on transgender care, ‘punish’ physicians.” AAP News. 2020 Feb 18.

A small group of patients with systemic lupus erythematosus (SLE) who have high costs and needs and frequent hospitalizations can be identified through a shared set of sociodemographic characteristics and risk factors that distinguish them from other patients, according to a retrospective analysis of hospitalization data from a tertiary care center.

“The identification of the HNHC [high-need, high-cost] cohort and the risk factors for hospitalizations for this cohort will help pave the way to develop programs that improve the quality of care for high-risk lupus patients and [at the same time] lower the cost of care for all lupus patients,” first author Allen Anandarajah, MBBS, and colleagues at the University of Rochester (N.Y.) wrote in Arthritis Care & Research.

Hospitalizations and readmissions are known to be common in patients with SLE, the authors said, and they “account for a large proportion of the direct costs associated with the care of this disease.”

“While HNHC cohorts have been described with other chronic diseases, this report is the first to describe the existence of such a cohort in the SLE population,” the researchers said.

To see if a small group of SLE patients would constitute the majority of hospitalizations and consequently the costs of such care, Dr. Anandarajah and associates analyzed data from 202 SLE patients and their 467 hospitalizations at the University of Rochester–affiliated Strong Memorial Hospital during July 1, 2013, to June 30, 2016. The patients had a mean age of 46 years and included 183 females. A total of 46.5% were White, 43.1% were African American, 6.9% were Hispanic, and 3.5% were of Asian descent. These patients had median lengths of stay of 7 days per SLE patient and 4 days per admission, with median costs of $19,271 per patient and $14,375 per admission.

The researchers identified 44 patients (22%) who accounted for 275 admissions (59%) during the 3-year period. This group’s median of 4 admissions per patient was significantly higher than the median of 1 recorded in all the other hospitalized SLE patients, as was its number of readmissions within 30 days (105 total and median of 1 vs. 11 total and median of 0). The high-risk SLE patients spent a significantly greater amount of time in the hospital than did other patients (median of 30 days vs. 5 days), and their median cost was more than six times as great ($95,262 vs. $14,360). High-risk patients’ median cost per admission also was significantly greater ($19,376 vs. $12,833).

Infections were the most common cause of hospitalization among both high-risk patients and others (28% vs. 23%, respectively) and the rate of involvement of different organ systems as a cause for hospitalization were similar between the groups, except that patients at lower risk significantly more often had gynecologic/obstetric concerns (10% vs. 2%) or nervous system involvement (16% vs. 5%), and high-risk patients were significantly more likely to have gastrointestinal complaints (20% vs. 8%).

Clinically, high-risk patients had significantly higher median scores on the Systemic Lupus International Collaborating Clinics Damage Index and the Comorbidity Index, as well as a significantly higher median level of double-stranded DNA. However, they had no differences in complement factor levels or body mass index.

The high-risk patients also were younger (mean of 42 vs. 46 years) and were diagnosed at a younger mean age (26 vs. 31 years). More high-risk patients were African American (55% vs. 40%) and were more likely to live in areas identified with poverty (50% vs. 29%).

A multivariate analysis that controlled for relevant confounders showed that high-risk patients had a 10 percentage point lower medication possession ratio, which is an indicator of whether a patient had adequate medication supply in a given time frame. High-risk patients overall had a higher average number of medications to treat lupus.

“Our findings underscore the importance of identifying HNHC SLE patients when designing and implementing interventions to lower hospitalizations and improve the quality of care for lupus patients. Furthermore, it is imperative that we develop programs to address the modifiable social and behavioral factors in addition to providing high-quality clinical care targeted for this group,” the researchers wrote.

Some of the limitations in the generalizability of the results include the use of data from a large tertiary medical center serving a large catchment area, with a consequently sicker group of patients, and the potential to miss readmissions to other nearby hospitals. However, “as one of the few centers [in the region] that provides in-patient rheumatology care ... it is less likely that patients would have sought care elsewhere,” they noted.

The study involved no outside source of funding, and the authors had no relevant conflicts of interest.

[email protected]

SOURCE: Anandarajah A et al. Arthritis Care Res. 2020 Nov 17. doi: 10.1002/acr.24510.

A small group of patients with systemic lupus erythematosus (SLE) who have high costs and needs and frequent hospitalizations can be identified through a shared set of sociodemographic characteristics and risk factors that distinguish them from other patients, according to a retrospective analysis of hospitalization data from a tertiary care center.

“The identification of the HNHC [high-need, high-cost] cohort and the risk factors for hospitalizations for this cohort will help pave the way to develop programs that improve the quality of care for high-risk lupus patients and [at the same time] lower the cost of care for all lupus patients,” first author Allen Anandarajah, MBBS, and colleagues at the University of Rochester (N.Y.) wrote in Arthritis Care & Research.

Hospitalizations and readmissions are known to be common in patients with SLE, the authors said, and they “account for a large proportion of the direct costs associated with the care of this disease.”

“While HNHC cohorts have been described with other chronic diseases, this report is the first to describe the existence of such a cohort in the SLE population,” the researchers said.

To see if a small group of SLE patients would constitute the majority of hospitalizations and consequently the costs of such care, Dr. Anandarajah and associates analyzed data from 202 SLE patients and their 467 hospitalizations at the University of Rochester–affiliated Strong Memorial Hospital during July 1, 2013, to June 30, 2016. The patients had a mean age of 46 years and included 183 females. A total of 46.5% were White, 43.1% were African American, 6.9% were Hispanic, and 3.5% were of Asian descent. These patients had median lengths of stay of 7 days per SLE patient and 4 days per admission, with median costs of $19,271 per patient and $14,375 per admission.

The researchers identified 44 patients (22%) who accounted for 275 admissions (59%) during the 3-year period. This group’s median of 4 admissions per patient was significantly higher than the median of 1 recorded in all the other hospitalized SLE patients, as was its number of readmissions within 30 days (105 total and median of 1 vs. 11 total and median of 0). The high-risk SLE patients spent a significantly greater amount of time in the hospital than did other patients (median of 30 days vs. 5 days), and their median cost was more than six times as great ($95,262 vs. $14,360). High-risk patients’ median cost per admission also was significantly greater ($19,376 vs. $12,833).

Infections were the most common cause of hospitalization among both high-risk patients and others (28% vs. 23%, respectively) and the rate of involvement of different organ systems as a cause for hospitalization were similar between the groups, except that patients at lower risk significantly more often had gynecologic/obstetric concerns (10% vs. 2%) or nervous system involvement (16% vs. 5%), and high-risk patients were significantly more likely to have gastrointestinal complaints (20% vs. 8%).

Clinically, high-risk patients had significantly higher median scores on the Systemic Lupus International Collaborating Clinics Damage Index and the Comorbidity Index, as well as a significantly higher median level of double-stranded DNA. However, they had no differences in complement factor levels or body mass index.

The high-risk patients also were younger (mean of 42 vs. 46 years) and were diagnosed at a younger mean age (26 vs. 31 years). More high-risk patients were African American (55% vs. 40%) and were more likely to live in areas identified with poverty (50% vs. 29%).

A multivariate analysis that controlled for relevant confounders showed that high-risk patients had a 10 percentage point lower medication possession ratio, which is an indicator of whether a patient had adequate medication supply in a given time frame. High-risk patients overall had a higher average number of medications to treat lupus.

“Our findings underscore the importance of identifying HNHC SLE patients when designing and implementing interventions to lower hospitalizations and improve the quality of care for lupus patients. Furthermore, it is imperative that we develop programs to address the modifiable social and behavioral factors in addition to providing high-quality clinical care targeted for this group,” the researchers wrote.

Some of the limitations in the generalizability of the results include the use of data from a large tertiary medical center serving a large catchment area, with a consequently sicker group of patients, and the potential to miss readmissions to other nearby hospitals. However, “as one of the few centers [in the region] that provides in-patient rheumatology care ... it is less likely that patients would have sought care elsewhere,” they noted.

The study involved no outside source of funding, and the authors had no relevant conflicts of interest.

[email protected]

SOURCE: Anandarajah A et al. Arthritis Care Res. 2020 Nov 17. doi: 10.1002/acr.24510.

A small group of patients with systemic lupus erythematosus (SLE) who have high costs and needs and frequent hospitalizations can be identified through a shared set of sociodemographic characteristics and risk factors that distinguish them from other patients, according to a retrospective analysis of hospitalization data from a tertiary care center.

“The identification of the HNHC [high-need, high-cost] cohort and the risk factors for hospitalizations for this cohort will help pave the way to develop programs that improve the quality of care for high-risk lupus patients and [at the same time] lower the cost of care for all lupus patients,” first author Allen Anandarajah, MBBS, and colleagues at the University of Rochester (N.Y.) wrote in Arthritis Care & Research.

Hospitalizations and readmissions are known to be common in patients with SLE, the authors said, and they “account for a large proportion of the direct costs associated with the care of this disease.”

“While HNHC cohorts have been described with other chronic diseases, this report is the first to describe the existence of such a cohort in the SLE population,” the researchers said.

To see if a small group of SLE patients would constitute the majority of hospitalizations and consequently the costs of such care, Dr. Anandarajah and associates analyzed data from 202 SLE patients and their 467 hospitalizations at the University of Rochester–affiliated Strong Memorial Hospital during July 1, 2013, to June 30, 2016. The patients had a mean age of 46 years and included 183 females. A total of 46.5% were White, 43.1% were African American, 6.9% were Hispanic, and 3.5% were of Asian descent. These patients had median lengths of stay of 7 days per SLE patient and 4 days per admission, with median costs of $19,271 per patient and $14,375 per admission.

The researchers identified 44 patients (22%) who accounted for 275 admissions (59%) during the 3-year period. This group’s median of 4 admissions per patient was significantly higher than the median of 1 recorded in all the other hospitalized SLE patients, as was its number of readmissions within 30 days (105 total and median of 1 vs. 11 total and median of 0). The high-risk SLE patients spent a significantly greater amount of time in the hospital than did other patients (median of 30 days vs. 5 days), and their median cost was more than six times as great ($95,262 vs. $14,360). High-risk patients’ median cost per admission also was significantly greater ($19,376 vs. $12,833).

Infections were the most common cause of hospitalization among both high-risk patients and others (28% vs. 23%, respectively) and the rate of involvement of different organ systems as a cause for hospitalization were similar between the groups, except that patients at lower risk significantly more often had gynecologic/obstetric concerns (10% vs. 2%) or nervous system involvement (16% vs. 5%), and high-risk patients were significantly more likely to have gastrointestinal complaints (20% vs. 8%).

Clinically, high-risk patients had significantly higher median scores on the Systemic Lupus International Collaborating Clinics Damage Index and the Comorbidity Index, as well as a significantly higher median level of double-stranded DNA. However, they had no differences in complement factor levels or body mass index.

The high-risk patients also were younger (mean of 42 vs. 46 years) and were diagnosed at a younger mean age (26 vs. 31 years). More high-risk patients were African American (55% vs. 40%) and were more likely to live in areas identified with poverty (50% vs. 29%).

A multivariate analysis that controlled for relevant confounders showed that high-risk patients had a 10 percentage point lower medication possession ratio, which is an indicator of whether a patient had adequate medication supply in a given time frame. High-risk patients overall had a higher average number of medications to treat lupus.

“Our findings underscore the importance of identifying HNHC SLE patients when designing and implementing interventions to lower hospitalizations and improve the quality of care for lupus patients. Furthermore, it is imperative that we develop programs to address the modifiable social and behavioral factors in addition to providing high-quality clinical care targeted for this group,” the researchers wrote.

Some of the limitations in the generalizability of the results include the use of data from a large tertiary medical center serving a large catchment area, with a consequently sicker group of patients, and the potential to miss readmissions to other nearby hospitals. However, “as one of the few centers [in the region] that provides in-patient rheumatology care ... it is less likely that patients would have sought care elsewhere,” they noted.

The study involved no outside source of funding, and the authors had no relevant conflicts of interest.

[email protected]

SOURCE: Anandarajah A et al. Arthritis Care Res. 2020 Nov 17. doi: 10.1002/acr.24510.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

When a COVID-19 vaccine becomes available, who will be first in line? According to an “Interim Playbook for Jurisdiction Operations” published by the Centers for Disease Control and Prevention (CDC) in October, the Departments of Defense (DoD) and State, the Veterans Health Administration (VHA), Indian Health Services, and Bureau of Prisons will all receive a direct allocation, but the distribution of those allocations will depend on the outcomes of an elaborately branched decision tree.

Although the DoD will distribute the vaccine directly to all of its personnel, including retirees and dependents, the plan for members of the Reserve and National Guard is not yet clear. Employees at VHA facilities will receive the vaccine from their departments. The US Department of Veterans Affairs (VA) has announced a “limited-supply phase” for distribution followed by a “general implementation phase.”

The CDC will provide the vaccine to tribal nations that have selected the IHS for distribution (as opposed to the state). According to Government Executive, a separate internal IHS plan suggests the agency would distribute immunizations to tens of thousands of health care and other essential workers, but it isn’t known whether that number includes all of the agency’s workers. 

The VA is likely to receive the largest distribution of vaccine doses, according to internal documents obtained by Government Executive. The agency has said it will only finalize its vaccine strategy after a candidate is approved for use. In a Nov. 17 press release, the VA said, “The plan will be a phased approach based on scientific and historical evidence, lessons learned from past pandemic vaccine plans and input from scientific experts both within and outside VA.”

However, the VA has been criticized for not publicizing a detailed vaccine distribution plan. Several Democrats on the Senate Committee on Veterans’ Affairs, for instance, sent a cautionary letter to VA leaders on Nov. 23, saying, “For COVID-19 vaccine distribution to succeed there must be a well-organized plan to meet the needs of all veterans and their providers…. If the states and other federal agencies have already publicly released their plans, why is VA lagging behind?”

As with most federal and non-federal entities, the VA’s allotment of vaccine will be distributed in phases, based on availability and the number of those in the highest-risk populations, such as frontline health care workers and the elderly, within the organization. But the distribution strategy resembles a set of matryoshka dolls, with priorities nested within priorities.

Staff will be 4 of the first 5 populations to receive the vaccine. Employees at VA nursing homes and the 25 Spinal Cord Injuries and Disorders Centers also are due to receive the first batch, followed by veterans at those facilities. Next would come staff in emergency departments, COVID-19 ICUs, and COVID-19 non-ICUs. After that, employees in “other congregate living settings” and veterans aged > 85 years  would be vaccinated. Other employees critical in the COVID-19 response, such as police, would be next, followed by inpatient staff in other units and staff performing high-risk procedures. Finally, the priorities will be other groups of patients, veterans in other descending-age groups, and homeless veterans and homeless outreach workers.

The general thinking is that it makes more sense to vaccinate the health care workers first. However, even within that calculation there are further decisions to make. The VA has said it’s focusing on the highest-risk individuals for the first inoculations, but it has emphasized that it considers the risk of transmitting the virus to others above the personal risk of severe illness to the employees themselves.

The VA will not require employees to receive an inoculation, although it plans to encourage staff to do so to protect themselves and veterans they serve.

When a COVID-19 vaccine becomes available, who will be first in line? According to an “Interim Playbook for Jurisdiction Operations” published by the Centers for Disease Control and Prevention (CDC) in October, the Departments of Defense (DoD) and State, the Veterans Health Administration (VHA), Indian Health Services, and Bureau of Prisons will all receive a direct allocation, but the distribution of those allocations will depend on the outcomes of an elaborately branched decision tree.

Although the DoD will distribute the vaccine directly to all of its personnel, including retirees and dependents, the plan for members of the Reserve and National Guard is not yet clear. Employees at VHA facilities will receive the vaccine from their departments. The US Department of Veterans Affairs (VA) has announced a “limited-supply phase” for distribution followed by a “general implementation phase.”

The CDC will provide the vaccine to tribal nations that have selected the IHS for distribution (as opposed to the state). According to Government Executive, a separate internal IHS plan suggests the agency would distribute immunizations to tens of thousands of health care and other essential workers, but it isn’t known whether that number includes all of the agency’s workers. 

The VA is likely to receive the largest distribution of vaccine doses, according to internal documents obtained by Government Executive. The agency has said it will only finalize its vaccine strategy after a candidate is approved for use. In a Nov. 17 press release, the VA said, “The plan will be a phased approach based on scientific and historical evidence, lessons learned from past pandemic vaccine plans and input from scientific experts both within and outside VA.”

However, the VA has been criticized for not publicizing a detailed vaccine distribution plan. Several Democrats on the Senate Committee on Veterans’ Affairs, for instance, sent a cautionary letter to VA leaders on Nov. 23, saying, “For COVID-19 vaccine distribution to succeed there must be a well-organized plan to meet the needs of all veterans and their providers…. If the states and other federal agencies have already publicly released their plans, why is VA lagging behind?”

As with most federal and non-federal entities, the VA’s allotment of vaccine will be distributed in phases, based on availability and the number of those in the highest-risk populations, such as frontline health care workers and the elderly, within the organization. But the distribution strategy resembles a set of matryoshka dolls, with priorities nested within priorities.

Staff will be 4 of the first 5 populations to receive the vaccine. Employees at VA nursing homes and the 25 Spinal Cord Injuries and Disorders Centers also are due to receive the first batch, followed by veterans at those facilities. Next would come staff in emergency departments, COVID-19 ICUs, and COVID-19 non-ICUs. After that, employees in “other congregate living settings” and veterans aged > 85 years  would be vaccinated. Other employees critical in the COVID-19 response, such as police, would be next, followed by inpatient staff in other units and staff performing high-risk procedures. Finally, the priorities will be other groups of patients, veterans in other descending-age groups, and homeless veterans and homeless outreach workers.

The general thinking is that it makes more sense to vaccinate the health care workers first. However, even within that calculation there are further decisions to make. The VA has said it’s focusing on the highest-risk individuals for the first inoculations, but it has emphasized that it considers the risk of transmitting the virus to others above the personal risk of severe illness to the employees themselves.

The VA will not require employees to receive an inoculation, although it plans to encourage staff to do so to protect themselves and veterans they serve.

When a COVID-19 vaccine becomes available, who will be first in line? According to an “Interim Playbook for Jurisdiction Operations” published by the Centers for Disease Control and Prevention (CDC) in October, the Departments of Defense (DoD) and State, the Veterans Health Administration (VHA), Indian Health Services, and Bureau of Prisons will all receive a direct allocation, but the distribution of those allocations will depend on the outcomes of an elaborately branched decision tree.

Although the DoD will distribute the vaccine directly to all of its personnel, including retirees and dependents, the plan for members of the Reserve and National Guard is not yet clear. Employees at VHA facilities will receive the vaccine from their departments. The US Department of Veterans Affairs (VA) has announced a “limited-supply phase” for distribution followed by a “general implementation phase.”

The CDC will provide the vaccine to tribal nations that have selected the IHS for distribution (as opposed to the state). According to Government Executive, a separate internal IHS plan suggests the agency would distribute immunizations to tens of thousands of health care and other essential workers, but it isn’t known whether that number includes all of the agency’s workers. 

The VA is likely to receive the largest distribution of vaccine doses, according to internal documents obtained by Government Executive. The agency has said it will only finalize its vaccine strategy after a candidate is approved for use. In a Nov. 17 press release, the VA said, “The plan will be a phased approach based on scientific and historical evidence, lessons learned from past pandemic vaccine plans and input from scientific experts both within and outside VA.”

However, the VA has been criticized for not publicizing a detailed vaccine distribution plan. Several Democrats on the Senate Committee on Veterans’ Affairs, for instance, sent a cautionary letter to VA leaders on Nov. 23, saying, “For COVID-19 vaccine distribution to succeed there must be a well-organized plan to meet the needs of all veterans and their providers…. If the states and other federal agencies have already publicly released their plans, why is VA lagging behind?”

As with most federal and non-federal entities, the VA’s allotment of vaccine will be distributed in phases, based on availability and the number of those in the highest-risk populations, such as frontline health care workers and the elderly, within the organization. But the distribution strategy resembles a set of matryoshka dolls, with priorities nested within priorities.

Staff will be 4 of the first 5 populations to receive the vaccine. Employees at VA nursing homes and the 25 Spinal Cord Injuries and Disorders Centers also are due to receive the first batch, followed by veterans at those facilities. Next would come staff in emergency departments, COVID-19 ICUs, and COVID-19 non-ICUs. After that, employees in “other congregate living settings” and veterans aged > 85 years  would be vaccinated. Other employees critical in the COVID-19 response, such as police, would be next, followed by inpatient staff in other units and staff performing high-risk procedures. Finally, the priorities will be other groups of patients, veterans in other descending-age groups, and homeless veterans and homeless outreach workers.

The general thinking is that it makes more sense to vaccinate the health care workers first. However, even within that calculation there are further decisions to make. The VA has said it’s focusing on the highest-risk individuals for the first inoculations, but it has emphasized that it considers the risk of transmitting the virus to others above the personal risk of severe illness to the employees themselves.

The VA will not require employees to receive an inoculation, although it plans to encourage staff to do so to protect themselves and veterans they serve.