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Rare hematologic malignancy may first present to a dermatologist

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Dermatologists may be the first clinicians to diagnose blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare, aggressive hematologic malignancy that involves the skin in about 80% of cases.

Courtesy Dr. Brittney K. DeClerck
Imaging from a case of BPDCN revealed infiltrate of immature, blastoid cells showing cytologic atypia present throughout the dermis.

“You won’t see blastic plasmacytoid dendritic cell neoplasm listed on our primary cutaneous lymphoma classifications because it’s not technically a primary cutaneous disease,” Brittney K. DeClerck, MD, said during the annual meeting of the Pacific Dermatologic Association. “It’s a systemic disease that has secondary cutaneous manifestations. That’s a very important distinction to make, in terms of not missing the underlying disease associated with what might be commonly first seen on the skin.”

Dr. Brittney K. DeClerck

BPDCN is a malignancy of plasmacytoid dendritic cells, which capture, process, and present antigen, and allow the remainder of the immune system to be activated. “They are mainly derived from the myeloid cell lineage, and possibly from the lymphoid line in a subset of cases,” said Dr. DeClerck, associate professor of clinical pathology and dermatology at the University of Southern California, Los Angeles. “They secrete high levels of type I interferons, which is important for antiviral immunity, but they can also be implicated in severe systemic inflammatory diseases, such as systemic lupus erythematosus and systemic sclerosis.”

BPDCN involves the skin in about 80% of cases, she added, “but invariably at some point it involves the bone marrow and has an acute leukemic presentation, whether or not it happens concurrently with what we see on the skin as dermatologists. We also see variable involvement of the peripheral blood, lymph nodes, and the central nervous system.”

The classification of BPDCN has changed over time based on evolving immunohistochemical markers and technologies. For example, in 1995 it was called agranular CD4+ NK cell leukemia, in 2001 it was called blastic NK-cell lymphoma, in 2005 it was called CD4+/CD56+ hematodermic neoplasm, and in 2008 it was called BPDCN (AML subset). In 2016 it became classified as its own entity: BPDCN.

Because of changing nomenclature, the true incidence of the disease is unknown, but according to the best available literature, 75% of cases occur in men and the median age is between 60 and 70 years, “but all ages can be affected,” Dr. DeClerck said. “Cases seem to come in clusters. Our most recent cluster has been in our pediatric population. At Children’s Hospital Los Angeles, we’ve had three cases in the last couple of years. To me, that was a bit unusual.”

She added that 10%-20% of patients will have either a history of, or will develop another, hematologic malignancy, such as myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML).

The general prognosis of BPDCN is poor, and the mean time from onset of lesions to an actual diagnosis is about 6.2 months, which underscores the importance of early diagnosis, Dr. DeClerck said. “There can be some nondescript solitary lesions that patients can present with, so don’t hesitate to biopsy.” The median overall survival is less than 20 months, but patients under 60 years of age have a slightly better prognosis.
 

 

 

Clinical presentation

Clinically, the malignancy presents with variable involvement of the skin, bone marrow, lymph nodes, peripheral blood, and central nervous system. “Patients may have one or all of these,” she said. Because 80% of patients have skin lesions, “dermatologists should be aware of this entity in order to communicate with our pathologists to understand that maybe one biopsy isn’t enough. Several biopsies may be required.”

The most common dermatologic presentation of BPDCN is erythematous to deeply violaceous nodules. Other patients may present with infiltrated ecchymotic plaques or petechial to hyperpigmented macules, patches, and plaques. Biopsy reveals a diffusely infiltrated dermis of markedly atypical large cells, but occasionally can be more subtle. “Early lesions may only be perivascular in nature, so going on high power on anything that looks atypical on low power is important in these cases,” Dr. DeClerck said.

The recommended histochemical stains for suspected BPDCN include CD123, CD4, and CD56. “We need to have other stains to rule out other things, such as negative stains that are going to exclude other T cell and B cell processes, and Merkel cell carcinoma, which can express CD56. We also want to have another confirmatory stain because other things can express CD123, CD4, and CD56. Commonly we use TCL1 or TCF4.”

The differential diagnosis of cutaneous findings includes leukemia cutis, mycosis fungoides, NK/T-cell lymphoma, and cutaneous gamma-delta T-cell lymphoma, while the differential diagnosis of biopsy findings includes AML, acute lymphoblastic leukemia, and NK/T-cell lymphoma.

Treatment of BPDCN

Historically, BPDCN was treated with multiagent high-dose chemotherapy. “Patients would frequently respond early but would relapse quickly, progress, and have a poor outcome,” Dr. DeClerck said. Now, first-line therapy is tagraxofusp-erzs (Elzonris) or multiagent chemotherapy based on where the patient is in the course of disease. Tagraxofusp-erzs is an IL-3 conjugated diphtheria toxic fusion protein which binds to CD123, which was approved by the Food and Drug Administration in 2018 for treating BPDCN. After that initial therapy, it is determined whether the patient has a complete response or failed response, she said. “If they have a complete response, they frequently go on to bone marrow transplantation, which is the only curative therapy at this point for these patients.”

According to Dr. DeClerck, an anti-BCL-2 therapy, venetoclax, can be used for patients with BPDCN as well. National Comprehensive Cancer Network (NCCN) guidelines for the treatment of BPDCN can be found on the NCCN website.

Dr. DeClerck emphasized the importance of reviewing biopsy results with a hematopathologist, “because there are complex leukemias that are beyond what dermatopathologists have been trained in.” Once a patient is diagnosed with BPDCN, she recommends rapid referral to a large center for treatment and possible bone marrow transplantation.

Dr. DeClerck disclosed that she is an adviser for tagraxofusp-erzs manufacturer Stemline Therapeutics.

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Dermatologists may be the first clinicians to diagnose blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare, aggressive hematologic malignancy that involves the skin in about 80% of cases.

Courtesy Dr. Brittney K. DeClerck
Imaging from a case of BPDCN revealed infiltrate of immature, blastoid cells showing cytologic atypia present throughout the dermis.

“You won’t see blastic plasmacytoid dendritic cell neoplasm listed on our primary cutaneous lymphoma classifications because it’s not technically a primary cutaneous disease,” Brittney K. DeClerck, MD, said during the annual meeting of the Pacific Dermatologic Association. “It’s a systemic disease that has secondary cutaneous manifestations. That’s a very important distinction to make, in terms of not missing the underlying disease associated with what might be commonly first seen on the skin.”

Dr. Brittney K. DeClerck

BPDCN is a malignancy of plasmacytoid dendritic cells, which capture, process, and present antigen, and allow the remainder of the immune system to be activated. “They are mainly derived from the myeloid cell lineage, and possibly from the lymphoid line in a subset of cases,” said Dr. DeClerck, associate professor of clinical pathology and dermatology at the University of Southern California, Los Angeles. “They secrete high levels of type I interferons, which is important for antiviral immunity, but they can also be implicated in severe systemic inflammatory diseases, such as systemic lupus erythematosus and systemic sclerosis.”

BPDCN involves the skin in about 80% of cases, she added, “but invariably at some point it involves the bone marrow and has an acute leukemic presentation, whether or not it happens concurrently with what we see on the skin as dermatologists. We also see variable involvement of the peripheral blood, lymph nodes, and the central nervous system.”

The classification of BPDCN has changed over time based on evolving immunohistochemical markers and technologies. For example, in 1995 it was called agranular CD4+ NK cell leukemia, in 2001 it was called blastic NK-cell lymphoma, in 2005 it was called CD4+/CD56+ hematodermic neoplasm, and in 2008 it was called BPDCN (AML subset). In 2016 it became classified as its own entity: BPDCN.

Because of changing nomenclature, the true incidence of the disease is unknown, but according to the best available literature, 75% of cases occur in men and the median age is between 60 and 70 years, “but all ages can be affected,” Dr. DeClerck said. “Cases seem to come in clusters. Our most recent cluster has been in our pediatric population. At Children’s Hospital Los Angeles, we’ve had three cases in the last couple of years. To me, that was a bit unusual.”

She added that 10%-20% of patients will have either a history of, or will develop another, hematologic malignancy, such as myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML).

The general prognosis of BPDCN is poor, and the mean time from onset of lesions to an actual diagnosis is about 6.2 months, which underscores the importance of early diagnosis, Dr. DeClerck said. “There can be some nondescript solitary lesions that patients can present with, so don’t hesitate to biopsy.” The median overall survival is less than 20 months, but patients under 60 years of age have a slightly better prognosis.
 

 

 

Clinical presentation

Clinically, the malignancy presents with variable involvement of the skin, bone marrow, lymph nodes, peripheral blood, and central nervous system. “Patients may have one or all of these,” she said. Because 80% of patients have skin lesions, “dermatologists should be aware of this entity in order to communicate with our pathologists to understand that maybe one biopsy isn’t enough. Several biopsies may be required.”

The most common dermatologic presentation of BPDCN is erythematous to deeply violaceous nodules. Other patients may present with infiltrated ecchymotic plaques or petechial to hyperpigmented macules, patches, and plaques. Biopsy reveals a diffusely infiltrated dermis of markedly atypical large cells, but occasionally can be more subtle. “Early lesions may only be perivascular in nature, so going on high power on anything that looks atypical on low power is important in these cases,” Dr. DeClerck said.

The recommended histochemical stains for suspected BPDCN include CD123, CD4, and CD56. “We need to have other stains to rule out other things, such as negative stains that are going to exclude other T cell and B cell processes, and Merkel cell carcinoma, which can express CD56. We also want to have another confirmatory stain because other things can express CD123, CD4, and CD56. Commonly we use TCL1 or TCF4.”

The differential diagnosis of cutaneous findings includes leukemia cutis, mycosis fungoides, NK/T-cell lymphoma, and cutaneous gamma-delta T-cell lymphoma, while the differential diagnosis of biopsy findings includes AML, acute lymphoblastic leukemia, and NK/T-cell lymphoma.

Treatment of BPDCN

Historically, BPDCN was treated with multiagent high-dose chemotherapy. “Patients would frequently respond early but would relapse quickly, progress, and have a poor outcome,” Dr. DeClerck said. Now, first-line therapy is tagraxofusp-erzs (Elzonris) or multiagent chemotherapy based on where the patient is in the course of disease. Tagraxofusp-erzs is an IL-3 conjugated diphtheria toxic fusion protein which binds to CD123, which was approved by the Food and Drug Administration in 2018 for treating BPDCN. After that initial therapy, it is determined whether the patient has a complete response or failed response, she said. “If they have a complete response, they frequently go on to bone marrow transplantation, which is the only curative therapy at this point for these patients.”

According to Dr. DeClerck, an anti-BCL-2 therapy, venetoclax, can be used for patients with BPDCN as well. National Comprehensive Cancer Network (NCCN) guidelines for the treatment of BPDCN can be found on the NCCN website.

Dr. DeClerck emphasized the importance of reviewing biopsy results with a hematopathologist, “because there are complex leukemias that are beyond what dermatopathologists have been trained in.” Once a patient is diagnosed with BPDCN, she recommends rapid referral to a large center for treatment and possible bone marrow transplantation.

Dr. DeClerck disclosed that she is an adviser for tagraxofusp-erzs manufacturer Stemline Therapeutics.

Dermatologists may be the first clinicians to diagnose blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare, aggressive hematologic malignancy that involves the skin in about 80% of cases.

Courtesy Dr. Brittney K. DeClerck
Imaging from a case of BPDCN revealed infiltrate of immature, blastoid cells showing cytologic atypia present throughout the dermis.

“You won’t see blastic plasmacytoid dendritic cell neoplasm listed on our primary cutaneous lymphoma classifications because it’s not technically a primary cutaneous disease,” Brittney K. DeClerck, MD, said during the annual meeting of the Pacific Dermatologic Association. “It’s a systemic disease that has secondary cutaneous manifestations. That’s a very important distinction to make, in terms of not missing the underlying disease associated with what might be commonly first seen on the skin.”

Dr. Brittney K. DeClerck

BPDCN is a malignancy of plasmacytoid dendritic cells, which capture, process, and present antigen, and allow the remainder of the immune system to be activated. “They are mainly derived from the myeloid cell lineage, and possibly from the lymphoid line in a subset of cases,” said Dr. DeClerck, associate professor of clinical pathology and dermatology at the University of Southern California, Los Angeles. “They secrete high levels of type I interferons, which is important for antiviral immunity, but they can also be implicated in severe systemic inflammatory diseases, such as systemic lupus erythematosus and systemic sclerosis.”

BPDCN involves the skin in about 80% of cases, she added, “but invariably at some point it involves the bone marrow and has an acute leukemic presentation, whether or not it happens concurrently with what we see on the skin as dermatologists. We also see variable involvement of the peripheral blood, lymph nodes, and the central nervous system.”

The classification of BPDCN has changed over time based on evolving immunohistochemical markers and technologies. For example, in 1995 it was called agranular CD4+ NK cell leukemia, in 2001 it was called blastic NK-cell lymphoma, in 2005 it was called CD4+/CD56+ hematodermic neoplasm, and in 2008 it was called BPDCN (AML subset). In 2016 it became classified as its own entity: BPDCN.

Because of changing nomenclature, the true incidence of the disease is unknown, but according to the best available literature, 75% of cases occur in men and the median age is between 60 and 70 years, “but all ages can be affected,” Dr. DeClerck said. “Cases seem to come in clusters. Our most recent cluster has been in our pediatric population. At Children’s Hospital Los Angeles, we’ve had three cases in the last couple of years. To me, that was a bit unusual.”

She added that 10%-20% of patients will have either a history of, or will develop another, hematologic malignancy, such as myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML).

The general prognosis of BPDCN is poor, and the mean time from onset of lesions to an actual diagnosis is about 6.2 months, which underscores the importance of early diagnosis, Dr. DeClerck said. “There can be some nondescript solitary lesions that patients can present with, so don’t hesitate to biopsy.” The median overall survival is less than 20 months, but patients under 60 years of age have a slightly better prognosis.
 

 

 

Clinical presentation

Clinically, the malignancy presents with variable involvement of the skin, bone marrow, lymph nodes, peripheral blood, and central nervous system. “Patients may have one or all of these,” she said. Because 80% of patients have skin lesions, “dermatologists should be aware of this entity in order to communicate with our pathologists to understand that maybe one biopsy isn’t enough. Several biopsies may be required.”

The most common dermatologic presentation of BPDCN is erythematous to deeply violaceous nodules. Other patients may present with infiltrated ecchymotic plaques or petechial to hyperpigmented macules, patches, and plaques. Biopsy reveals a diffusely infiltrated dermis of markedly atypical large cells, but occasionally can be more subtle. “Early lesions may only be perivascular in nature, so going on high power on anything that looks atypical on low power is important in these cases,” Dr. DeClerck said.

The recommended histochemical stains for suspected BPDCN include CD123, CD4, and CD56. “We need to have other stains to rule out other things, such as negative stains that are going to exclude other T cell and B cell processes, and Merkel cell carcinoma, which can express CD56. We also want to have another confirmatory stain because other things can express CD123, CD4, and CD56. Commonly we use TCL1 or TCF4.”

The differential diagnosis of cutaneous findings includes leukemia cutis, mycosis fungoides, NK/T-cell lymphoma, and cutaneous gamma-delta T-cell lymphoma, while the differential diagnosis of biopsy findings includes AML, acute lymphoblastic leukemia, and NK/T-cell lymphoma.

Treatment of BPDCN

Historically, BPDCN was treated with multiagent high-dose chemotherapy. “Patients would frequently respond early but would relapse quickly, progress, and have a poor outcome,” Dr. DeClerck said. Now, first-line therapy is tagraxofusp-erzs (Elzonris) or multiagent chemotherapy based on where the patient is in the course of disease. Tagraxofusp-erzs is an IL-3 conjugated diphtheria toxic fusion protein which binds to CD123, which was approved by the Food and Drug Administration in 2018 for treating BPDCN. After that initial therapy, it is determined whether the patient has a complete response or failed response, she said. “If they have a complete response, they frequently go on to bone marrow transplantation, which is the only curative therapy at this point for these patients.”

According to Dr. DeClerck, an anti-BCL-2 therapy, venetoclax, can be used for patients with BPDCN as well. National Comprehensive Cancer Network (NCCN) guidelines for the treatment of BPDCN can be found on the NCCN website.

Dr. DeClerck emphasized the importance of reviewing biopsy results with a hematopathologist, “because there are complex leukemias that are beyond what dermatopathologists have been trained in.” Once a patient is diagnosed with BPDCN, she recommends rapid referral to a large center for treatment and possible bone marrow transplantation.

Dr. DeClerck disclosed that she is an adviser for tagraxofusp-erzs manufacturer Stemline Therapeutics.

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New COVID-19 strain has reached the U.S.

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Thu, 09/23/2021 - 13:11

A strain of COVID-19 first reported in Japan surfaced at a Kentucky nursing home in the spring.

Deadline, citing a Centers for Disease Control and Prevention report, said 26 residents and 20 workers tested positive for COVID-19 at a skilled care nursing home. The facility has 83 residents and 116 employees.

On March 1, 28 specimens that had been subjected to whole genome sequencing were found to have “mutations aligning with the R.1 lineage,” Deadline said.

About 90% of the facility’s residents and 52% of the staff had received two COVID vaccine doses, the CDC said. Because of the high vaccination rate, the finding raises concerns about “reduced protective immunity” in relation to the R.1 variant, the CDC said.

However, the nursing home case appears to show that the vaccine keeps most people from getting extremely sick, the CDC said. The vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective for employees.

“Compared with unvaccinated persons, vaccinated persons had reduced risk for SARS-CoV-2 infection and symptomatic COVID-19,” the CDC said. The vaccination of nursing home residents and health care workers “is essential to reduce the risk for symptomatic COVID-19, as is continued focus on infection prevention and control practices,” the CDC said.

Since being reported in Kentucky, R.1 has been detected more than 10,000 times in the United States, Forbes reported, basing that number on entries in the GISAID SARS-CoV-2 database.

Overall, more than 42 million cases of COVID have been reported since the start of the pandemic.

Deadline reported that the R.1 strain was first detected in Japan in January among three members of one family. The family members had no history of traveling abroad, Deadline said, citing an National Institutes of Health report.

The CDC has not classified R.1 as a variant of concern yet but noted it has “several mutations of importance” and “demonstrates evidence of increasing virus transmissibility.”

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

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A strain of COVID-19 first reported in Japan surfaced at a Kentucky nursing home in the spring.

Deadline, citing a Centers for Disease Control and Prevention report, said 26 residents and 20 workers tested positive for COVID-19 at a skilled care nursing home. The facility has 83 residents and 116 employees.

On March 1, 28 specimens that had been subjected to whole genome sequencing were found to have “mutations aligning with the R.1 lineage,” Deadline said.

About 90% of the facility’s residents and 52% of the staff had received two COVID vaccine doses, the CDC said. Because of the high vaccination rate, the finding raises concerns about “reduced protective immunity” in relation to the R.1 variant, the CDC said.

However, the nursing home case appears to show that the vaccine keeps most people from getting extremely sick, the CDC said. The vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective for employees.

“Compared with unvaccinated persons, vaccinated persons had reduced risk for SARS-CoV-2 infection and symptomatic COVID-19,” the CDC said. The vaccination of nursing home residents and health care workers “is essential to reduce the risk for symptomatic COVID-19, as is continued focus on infection prevention and control practices,” the CDC said.

Since being reported in Kentucky, R.1 has been detected more than 10,000 times in the United States, Forbes reported, basing that number on entries in the GISAID SARS-CoV-2 database.

Overall, more than 42 million cases of COVID have been reported since the start of the pandemic.

Deadline reported that the R.1 strain was first detected in Japan in January among three members of one family. The family members had no history of traveling abroad, Deadline said, citing an National Institutes of Health report.

The CDC has not classified R.1 as a variant of concern yet but noted it has “several mutations of importance” and “demonstrates evidence of increasing virus transmissibility.”

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

A strain of COVID-19 first reported in Japan surfaced at a Kentucky nursing home in the spring.

Deadline, citing a Centers for Disease Control and Prevention report, said 26 residents and 20 workers tested positive for COVID-19 at a skilled care nursing home. The facility has 83 residents and 116 employees.

On March 1, 28 specimens that had been subjected to whole genome sequencing were found to have “mutations aligning with the R.1 lineage,” Deadline said.

About 90% of the facility’s residents and 52% of the staff had received two COVID vaccine doses, the CDC said. Because of the high vaccination rate, the finding raises concerns about “reduced protective immunity” in relation to the R.1 variant, the CDC said.

However, the nursing home case appears to show that the vaccine keeps most people from getting extremely sick, the CDC said. The vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective for employees.

“Compared with unvaccinated persons, vaccinated persons had reduced risk for SARS-CoV-2 infection and symptomatic COVID-19,” the CDC said. The vaccination of nursing home residents and health care workers “is essential to reduce the risk for symptomatic COVID-19, as is continued focus on infection prevention and control practices,” the CDC said.

Since being reported in Kentucky, R.1 has been detected more than 10,000 times in the United States, Forbes reported, basing that number on entries in the GISAID SARS-CoV-2 database.

Overall, more than 42 million cases of COVID have been reported since the start of the pandemic.

Deadline reported that the R.1 strain was first detected in Japan in January among three members of one family. The family members had no history of traveling abroad, Deadline said, citing an National Institutes of Health report.

The CDC has not classified R.1 as a variant of concern yet but noted it has “several mutations of importance” and “demonstrates evidence of increasing virus transmissibility.”

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

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Your bathroom towel rack has a dirty little secret

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Thu, 09/23/2021 - 10:03

 

Bacteria get the rack ... the towel rack

Obviously, bathrooms have germs. Some people are cleaner about their bathrooms than others, but in general most people just try not to think about the microscopic critters crawling about.

Now you would probably think that the toilet is the dirtiest part of the bathroom because that’s where ... you know, most of the business takes place. Or maybe you’d guess the floor. Truth be told, though, the dirtiest part of the bathroom is where the towels are hung.

pxfuel


According to research conducted by electric heating company Rointe in the United Kingdom, bathroom radiators and towel racks/bars are the most germy and dirty parts of the bathroom.

Company investigators examined five bathrooms using swabs that changed color on contact with bacteria and found that 60% of towel racks and radiators were “really dirty,” compared with 50% of sink drains and just 10% of toilets.

Most people probably pay more attention to the sink, floors, and toilets while cleaning, the company suggested, and dampness is a factor in bacteria growth, so it’s no surprise that towels that stay wet on a rack are prime spots for dust, mildew, and mold.

The toilet may be busier, but you don’t put your face in it.
 

Anti-vaxxers would like to be called ‘purebloods’

COVID-19 anti-vaxxers are an interesting bunch, to be kind. And TikTok is a wacky place. So you can just imagine that anti-vaxxer TikTok is a very strange place. The citizens of anti-vax TikTok have decided that the real reason so many people dislike them is branding. They consider anti-vaccination to be a negative word (duh), so they now want to be referred to as “purebloods.”

peterschreiber_media/iStock/Getty Images

Harry Potter doesn’t quite occupy the zeitgeist as it once did, so let’s give you a reminder: In the books, purebloods came from old wizarding families and claimed not to have any Muggle, or nonmagic, blood. While having pure wizard blood was no guarantee of being a villain, most of them were. In addition, it is made quite clear throughout the novels that having supposedly pure blood had no relevance on one’s wizarding ability. Pureblood was a meaningless title, and only the characters with small, cruel minds concerned themselves over it.

Perhaps the anti-vaxxers have decided that they want to be called the same thing. Maybe they just like the name. It does sound impressive and vaguely regal: Pureblood. Like something the nobles of medieval Europe might have used.

Critical-thinking skills may be in short supply here, or maybe the anti-vaxxers know exactly what they’re doing.
 

Hated broccoli? Blame your DNA

Were you that kid who would rather sit at the table for hours than eat your broccoli? Well, as much as your parents might have pushed you, new research suggests that it might be their fault you didn’t like it to begin with.

Hans Braxmeier/Pixabay

Investigators at Australia’s national science agency, CSIRO, recently reported that distaste for Brassica vegetables – broccoli, Brussels sprouts, cabbage, and cauliflower – can be traced to the oral microbiome.

These vegetables have a compound called S-methyl-L-cysteine sulfoxide that gives off sulfurous odors ... mmm, sulfurous ... when mixed with an enzyme in the plant, and that enzyme is also produced by bacteria in some people’s oral microbiomes. So why do adults tolerate these Brassica veggies more than children? It’s all about levels.

The researchers tested the idea by asking 98 child/parent pairs to rate the odors and by using gas chromatography-olfactometry-mass spectrometry to identify the odor-active compounds in both raw and steamed cauliflower and broccoli. The children whose saliva produced high levels of sulfur volatiles disliked Brassica vegetables the most, they reported, and the children with high levels of sulfur volatiles usually had parents who produced high levels.

Despite that connection, however, the distaste for raw Brassica seen in children wasn’t seen in adults.

Maybe it’s not that taste buds change as we age, maybe we just learn to tolerate the sulfurousness.

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Bacteria get the rack ... the towel rack

Obviously, bathrooms have germs. Some people are cleaner about their bathrooms than others, but in general most people just try not to think about the microscopic critters crawling about.

Now you would probably think that the toilet is the dirtiest part of the bathroom because that’s where ... you know, most of the business takes place. Or maybe you’d guess the floor. Truth be told, though, the dirtiest part of the bathroom is where the towels are hung.

pxfuel


According to research conducted by electric heating company Rointe in the United Kingdom, bathroom radiators and towel racks/bars are the most germy and dirty parts of the bathroom.

Company investigators examined five bathrooms using swabs that changed color on contact with bacteria and found that 60% of towel racks and radiators were “really dirty,” compared with 50% of sink drains and just 10% of toilets.

Most people probably pay more attention to the sink, floors, and toilets while cleaning, the company suggested, and dampness is a factor in bacteria growth, so it’s no surprise that towels that stay wet on a rack are prime spots for dust, mildew, and mold.

The toilet may be busier, but you don’t put your face in it.
 

Anti-vaxxers would like to be called ‘purebloods’

COVID-19 anti-vaxxers are an interesting bunch, to be kind. And TikTok is a wacky place. So you can just imagine that anti-vaxxer TikTok is a very strange place. The citizens of anti-vax TikTok have decided that the real reason so many people dislike them is branding. They consider anti-vaccination to be a negative word (duh), so they now want to be referred to as “purebloods.”

peterschreiber_media/iStock/Getty Images

Harry Potter doesn’t quite occupy the zeitgeist as it once did, so let’s give you a reminder: In the books, purebloods came from old wizarding families and claimed not to have any Muggle, or nonmagic, blood. While having pure wizard blood was no guarantee of being a villain, most of them were. In addition, it is made quite clear throughout the novels that having supposedly pure blood had no relevance on one’s wizarding ability. Pureblood was a meaningless title, and only the characters with small, cruel minds concerned themselves over it.

Perhaps the anti-vaxxers have decided that they want to be called the same thing. Maybe they just like the name. It does sound impressive and vaguely regal: Pureblood. Like something the nobles of medieval Europe might have used.

Critical-thinking skills may be in short supply here, or maybe the anti-vaxxers know exactly what they’re doing.
 

Hated broccoli? Blame your DNA

Were you that kid who would rather sit at the table for hours than eat your broccoli? Well, as much as your parents might have pushed you, new research suggests that it might be their fault you didn’t like it to begin with.

Hans Braxmeier/Pixabay

Investigators at Australia’s national science agency, CSIRO, recently reported that distaste for Brassica vegetables – broccoli, Brussels sprouts, cabbage, and cauliflower – can be traced to the oral microbiome.

These vegetables have a compound called S-methyl-L-cysteine sulfoxide that gives off sulfurous odors ... mmm, sulfurous ... when mixed with an enzyme in the plant, and that enzyme is also produced by bacteria in some people’s oral microbiomes. So why do adults tolerate these Brassica veggies more than children? It’s all about levels.

The researchers tested the idea by asking 98 child/parent pairs to rate the odors and by using gas chromatography-olfactometry-mass spectrometry to identify the odor-active compounds in both raw and steamed cauliflower and broccoli. The children whose saliva produced high levels of sulfur volatiles disliked Brassica vegetables the most, they reported, and the children with high levels of sulfur volatiles usually had parents who produced high levels.

Despite that connection, however, the distaste for raw Brassica seen in children wasn’t seen in adults.

Maybe it’s not that taste buds change as we age, maybe we just learn to tolerate the sulfurousness.

 

Bacteria get the rack ... the towel rack

Obviously, bathrooms have germs. Some people are cleaner about their bathrooms than others, but in general most people just try not to think about the microscopic critters crawling about.

Now you would probably think that the toilet is the dirtiest part of the bathroom because that’s where ... you know, most of the business takes place. Or maybe you’d guess the floor. Truth be told, though, the dirtiest part of the bathroom is where the towels are hung.

pxfuel


According to research conducted by electric heating company Rointe in the United Kingdom, bathroom radiators and towel racks/bars are the most germy and dirty parts of the bathroom.

Company investigators examined five bathrooms using swabs that changed color on contact with bacteria and found that 60% of towel racks and radiators were “really dirty,” compared with 50% of sink drains and just 10% of toilets.

Most people probably pay more attention to the sink, floors, and toilets while cleaning, the company suggested, and dampness is a factor in bacteria growth, so it’s no surprise that towels that stay wet on a rack are prime spots for dust, mildew, and mold.

The toilet may be busier, but you don’t put your face in it.
 

Anti-vaxxers would like to be called ‘purebloods’

COVID-19 anti-vaxxers are an interesting bunch, to be kind. And TikTok is a wacky place. So you can just imagine that anti-vaxxer TikTok is a very strange place. The citizens of anti-vax TikTok have decided that the real reason so many people dislike them is branding. They consider anti-vaccination to be a negative word (duh), so they now want to be referred to as “purebloods.”

peterschreiber_media/iStock/Getty Images

Harry Potter doesn’t quite occupy the zeitgeist as it once did, so let’s give you a reminder: In the books, purebloods came from old wizarding families and claimed not to have any Muggle, or nonmagic, blood. While having pure wizard blood was no guarantee of being a villain, most of them were. In addition, it is made quite clear throughout the novels that having supposedly pure blood had no relevance on one’s wizarding ability. Pureblood was a meaningless title, and only the characters with small, cruel minds concerned themselves over it.

Perhaps the anti-vaxxers have decided that they want to be called the same thing. Maybe they just like the name. It does sound impressive and vaguely regal: Pureblood. Like something the nobles of medieval Europe might have used.

Critical-thinking skills may be in short supply here, or maybe the anti-vaxxers know exactly what they’re doing.
 

Hated broccoli? Blame your DNA

Were you that kid who would rather sit at the table for hours than eat your broccoli? Well, as much as your parents might have pushed you, new research suggests that it might be their fault you didn’t like it to begin with.

Hans Braxmeier/Pixabay

Investigators at Australia’s national science agency, CSIRO, recently reported that distaste for Brassica vegetables – broccoli, Brussels sprouts, cabbage, and cauliflower – can be traced to the oral microbiome.

These vegetables have a compound called S-methyl-L-cysteine sulfoxide that gives off sulfurous odors ... mmm, sulfurous ... when mixed with an enzyme in the plant, and that enzyme is also produced by bacteria in some people’s oral microbiomes. So why do adults tolerate these Brassica veggies more than children? It’s all about levels.

The researchers tested the idea by asking 98 child/parent pairs to rate the odors and by using gas chromatography-olfactometry-mass spectrometry to identify the odor-active compounds in both raw and steamed cauliflower and broccoli. The children whose saliva produced high levels of sulfur volatiles disliked Brassica vegetables the most, they reported, and the children with high levels of sulfur volatiles usually had parents who produced high levels.

Despite that connection, however, the distaste for raw Brassica seen in children wasn’t seen in adults.

Maybe it’s not that taste buds change as we age, maybe we just learn to tolerate the sulfurousness.

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FDA OKs Pfizer COVID booster for 65 and over, those at high risk

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Thu, 09/23/2021 - 10:31

 

The U.S. Food and Drug Administration (FDA) late Sept. 22 granted emergency use authorization (EUA) for a third dose of the Pfizer COVID-19 vaccine for those over the age of 65 and a wide swath of Americans at higher risk for infection.

The agency’s move comes as a Centers for Disease Control and Prevention (CDC) panel ended the first day of a 2-day meeting. That panel, the Advisory Committee on Immunization Practices (ACIP), is expected to vote Sept. 23 to instruct doctors on how to administer the boosters.

The FDA officially authorized the vaccine not only for individuals 65 and older, but also for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers whose jobs increase their risk for infection.

“After considering the totality of the available scientific evidence and the deliberations of our advisory committee of independent, external experts, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for a booster dose in certain populations such as health care workers, teachers and daycare staff, grocery workers and those in homeless shelters or prisons, among others,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release.

The recommendations align with those from an FDA advisory panel Sept. 17.

The agency determined that the benefits of a booster dose outweigh the risks for people now authorized to receive it, according to the news release.
 

Other questions remain

So, how will this work? That was the main question weighing on the minds of the CDC’s ACIP during their first day of a 2-day meeting where they are expected to make recommendations on booster doses for Americans.

The panel discussed situations the FDA will still need to consider, such as what should be done for Americans who were originally vaccinated with a Moderna or Johnson and Johnson vaccine, but are not covered under the revised EUA, which is only for those people who received Pfizer’s two-dose vaccine regimen.

“That’s going to leave half of the people immunized in this age group having received the vaccine and being told that they’re at risk now for waning immunity and hospitalization unable to get a booster dose,” said committee member Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine in Philadelphia. “So that’s a big public health panic that we would like to avoid.”

Johnson and Johnson recently reported that second doses of its vaccine boosted its efficacy to almost 94% against COVID-19. A new study, published ahead of peer review, suggests that the efficacy of the single-dose Johnson and Johnson shot has fallen to about 78% against symptomatic infection during the Delta surge.

Moderna has applied for permission to market third doses of its vaccine in the United States, but the FDA has given no timeline on when it might make a decision. 

Doran Fink, MD, PhD, deputy director of the FDA’s Division of Vaccines and Related Products Applications, a representative advising the committee Sept. 22, said the agency was working as rapidly as possible on Moderna’s submission.

Regarding the question of whether it was OK to mix vaccines, rather than match them, Dr. Fink said there are currently not enough data available to inform that decision.

Those answers are coming, though. John Beigel, MD, associate director of clinical research at the National Institute of Allergy and Infectious Diseases, revealed that the federal government has a study underway to see what happens when the vaccines are mixed with each other. 

He said that data from the study would be available later this fall, and would certainly help physicians and other healthcare providers know whether it’s effective or safe to use them interchangeably.
 

 

 

Correlates of immunity

The ACIP left much of its schedule open Sept. 23 to discuss extra Pfizer doses and vote on how they should be used.

Pfizer had originally applied to the FDA for an amendment to its FDA approval, which would have given doctors a freer hand to prescribe third doses as they saw fit, in patients as young as 16.

But the FDA’s Vaccines and Related Biological Products Advisory Committee voted Sept. 17 against granting the amendment. The committee was particularly concerned about the lack of data in teens ages 16 and 17, who have the highest risk for a rare side effect that causes heart inflammation that requires hospital care.

Instead, they recommended — and the FDA agreed per their decision Sept. 22 — that third doses should be given to people at higher risk for severe breakthrough infections because of advanced age or because they work in an occupation that puts them at high risk for exposure. 

The CDC panel heard important presentations on new science that is helping to identify the correlates of immunity. 

The correlates of immunity are biomarkers that can be measured in blood that help doctors understand how protected a person may be against COVID-19. These markers of immunity are not yet known for the COVID-19 vaccines.

Emerging evidence shows that booster doses of the Pfizer vaccine cause front-line immune defenders — called binding antibodies — to roughly triple soon after a person gets the third shot. 

Neutralizing antibodies also jump soon after two vaccine doses, but they fall over time, which is natural. The body doesn’t need these foot soldiers to be on guard all the time, so they go away. 

The body retains its memory of how to make them, however, so they can quickly be marshaled again, if needed.

Early studies suggest that antibodies account for about two thirds of a person’s protection against COVID, while the longer-lasting T-cells and B-cells account for about one third.

After the antibody levels fall, it may take a few days to recreate this army. In the meantime, the virus can try to break in. This can cause symptoms, which can make a person feel terrible, but for the most part, vaccinated individuals don’t need hospital care and are nearly always protected from dying — even against the Delta variant.

Those most likely to be at risk for a breakthrough infection are older, because immune function wanes with age.
 

Essential workers

Essential workers, such as those who work in healthcare, may also benefit from high antibody levels, which can minimize symptoms and help them get back to work more quickly.

Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, said that in her area staffing levels are critical right now.

“I’m actually sitting in one of the deepest red [states] with high rates of COVID. We don’t have enough health care workers currently to take care of the unvaccinated,” she said. 

“When we have beds, we are often missing staff, and so the idea of vaccinating health care workers is to be a little bit different than our idea of using vaccines in the general population,” Dr. Talbot said.

Oliver Brooks, MD, chief medical officer of the Watts Healthcare Corporation in Los Angeles, said he was in favor of making a public statement about the temporary nature of the potential recommendations Sept. 23, because they probably won’t cover all who might need a third shot.

“We may want to go on record stating what it is that would allow us to broaden our recommendation or restrict our recommendation,” Dr. Brooks said.

The considerations of who should get an extra dose are not always straightforward.

New modeling by the Harvard TH Chan School of Public Health and the CDC to assist the government’s decisions on boosters had a surprise finding: in nursing homes, it’s more effective to vaccinate healthcare workers than it is to give booster doses to these residents. Nursing homes are at the mercy of community transmission. 

In regions with high transmission, it’s easy for a caregiver to bring the virus into a facility — so the models found that the transmission from these workers is a more effective strategy than giving third doses to the already highly vaccinated group of seniors who live in them.

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

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The U.S. Food and Drug Administration (FDA) late Sept. 22 granted emergency use authorization (EUA) for a third dose of the Pfizer COVID-19 vaccine for those over the age of 65 and a wide swath of Americans at higher risk for infection.

The agency’s move comes as a Centers for Disease Control and Prevention (CDC) panel ended the first day of a 2-day meeting. That panel, the Advisory Committee on Immunization Practices (ACIP), is expected to vote Sept. 23 to instruct doctors on how to administer the boosters.

The FDA officially authorized the vaccine not only for individuals 65 and older, but also for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers whose jobs increase their risk for infection.

“After considering the totality of the available scientific evidence and the deliberations of our advisory committee of independent, external experts, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for a booster dose in certain populations such as health care workers, teachers and daycare staff, grocery workers and those in homeless shelters or prisons, among others,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release.

The recommendations align with those from an FDA advisory panel Sept. 17.

The agency determined that the benefits of a booster dose outweigh the risks for people now authorized to receive it, according to the news release.
 

Other questions remain

So, how will this work? That was the main question weighing on the minds of the CDC’s ACIP during their first day of a 2-day meeting where they are expected to make recommendations on booster doses for Americans.

The panel discussed situations the FDA will still need to consider, such as what should be done for Americans who were originally vaccinated with a Moderna or Johnson and Johnson vaccine, but are not covered under the revised EUA, which is only for those people who received Pfizer’s two-dose vaccine regimen.

“That’s going to leave half of the people immunized in this age group having received the vaccine and being told that they’re at risk now for waning immunity and hospitalization unable to get a booster dose,” said committee member Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine in Philadelphia. “So that’s a big public health panic that we would like to avoid.”

Johnson and Johnson recently reported that second doses of its vaccine boosted its efficacy to almost 94% against COVID-19. A new study, published ahead of peer review, suggests that the efficacy of the single-dose Johnson and Johnson shot has fallen to about 78% against symptomatic infection during the Delta surge.

Moderna has applied for permission to market third doses of its vaccine in the United States, but the FDA has given no timeline on when it might make a decision. 

Doran Fink, MD, PhD, deputy director of the FDA’s Division of Vaccines and Related Products Applications, a representative advising the committee Sept. 22, said the agency was working as rapidly as possible on Moderna’s submission.

Regarding the question of whether it was OK to mix vaccines, rather than match them, Dr. Fink said there are currently not enough data available to inform that decision.

Those answers are coming, though. John Beigel, MD, associate director of clinical research at the National Institute of Allergy and Infectious Diseases, revealed that the federal government has a study underway to see what happens when the vaccines are mixed with each other. 

He said that data from the study would be available later this fall, and would certainly help physicians and other healthcare providers know whether it’s effective or safe to use them interchangeably.
 

 

 

Correlates of immunity

The ACIP left much of its schedule open Sept. 23 to discuss extra Pfizer doses and vote on how they should be used.

Pfizer had originally applied to the FDA for an amendment to its FDA approval, which would have given doctors a freer hand to prescribe third doses as they saw fit, in patients as young as 16.

But the FDA’s Vaccines and Related Biological Products Advisory Committee voted Sept. 17 against granting the amendment. The committee was particularly concerned about the lack of data in teens ages 16 and 17, who have the highest risk for a rare side effect that causes heart inflammation that requires hospital care.

Instead, they recommended — and the FDA agreed per their decision Sept. 22 — that third doses should be given to people at higher risk for severe breakthrough infections because of advanced age or because they work in an occupation that puts them at high risk for exposure. 

The CDC panel heard important presentations on new science that is helping to identify the correlates of immunity. 

The correlates of immunity are biomarkers that can be measured in blood that help doctors understand how protected a person may be against COVID-19. These markers of immunity are not yet known for the COVID-19 vaccines.

Emerging evidence shows that booster doses of the Pfizer vaccine cause front-line immune defenders — called binding antibodies — to roughly triple soon after a person gets the third shot. 

Neutralizing antibodies also jump soon after two vaccine doses, but they fall over time, which is natural. The body doesn’t need these foot soldiers to be on guard all the time, so they go away. 

The body retains its memory of how to make them, however, so they can quickly be marshaled again, if needed.

Early studies suggest that antibodies account for about two thirds of a person’s protection against COVID, while the longer-lasting T-cells and B-cells account for about one third.

After the antibody levels fall, it may take a few days to recreate this army. In the meantime, the virus can try to break in. This can cause symptoms, which can make a person feel terrible, but for the most part, vaccinated individuals don’t need hospital care and are nearly always protected from dying — even against the Delta variant.

Those most likely to be at risk for a breakthrough infection are older, because immune function wanes with age.
 

Essential workers

Essential workers, such as those who work in healthcare, may also benefit from high antibody levels, which can minimize symptoms and help them get back to work more quickly.

Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, said that in her area staffing levels are critical right now.

“I’m actually sitting in one of the deepest red [states] with high rates of COVID. We don’t have enough health care workers currently to take care of the unvaccinated,” she said. 

“When we have beds, we are often missing staff, and so the idea of vaccinating health care workers is to be a little bit different than our idea of using vaccines in the general population,” Dr. Talbot said.

Oliver Brooks, MD, chief medical officer of the Watts Healthcare Corporation in Los Angeles, said he was in favor of making a public statement about the temporary nature of the potential recommendations Sept. 23, because they probably won’t cover all who might need a third shot.

“We may want to go on record stating what it is that would allow us to broaden our recommendation or restrict our recommendation,” Dr. Brooks said.

The considerations of who should get an extra dose are not always straightforward.

New modeling by the Harvard TH Chan School of Public Health and the CDC to assist the government’s decisions on boosters had a surprise finding: in nursing homes, it’s more effective to vaccinate healthcare workers than it is to give booster doses to these residents. Nursing homes are at the mercy of community transmission. 

In regions with high transmission, it’s easy for a caregiver to bring the virus into a facility — so the models found that the transmission from these workers is a more effective strategy than giving third doses to the already highly vaccinated group of seniors who live in them.

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

 

The U.S. Food and Drug Administration (FDA) late Sept. 22 granted emergency use authorization (EUA) for a third dose of the Pfizer COVID-19 vaccine for those over the age of 65 and a wide swath of Americans at higher risk for infection.

The agency’s move comes as a Centers for Disease Control and Prevention (CDC) panel ended the first day of a 2-day meeting. That panel, the Advisory Committee on Immunization Practices (ACIP), is expected to vote Sept. 23 to instruct doctors on how to administer the boosters.

The FDA officially authorized the vaccine not only for individuals 65 and older, but also for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers whose jobs increase their risk for infection.

“After considering the totality of the available scientific evidence and the deliberations of our advisory committee of independent, external experts, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for a booster dose in certain populations such as health care workers, teachers and daycare staff, grocery workers and those in homeless shelters or prisons, among others,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release.

The recommendations align with those from an FDA advisory panel Sept. 17.

The agency determined that the benefits of a booster dose outweigh the risks for people now authorized to receive it, according to the news release.
 

Other questions remain

So, how will this work? That was the main question weighing on the minds of the CDC’s ACIP during their first day of a 2-day meeting where they are expected to make recommendations on booster doses for Americans.

The panel discussed situations the FDA will still need to consider, such as what should be done for Americans who were originally vaccinated with a Moderna or Johnson and Johnson vaccine, but are not covered under the revised EUA, which is only for those people who received Pfizer’s two-dose vaccine regimen.

“That’s going to leave half of the people immunized in this age group having received the vaccine and being told that they’re at risk now for waning immunity and hospitalization unable to get a booster dose,” said committee member Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine in Philadelphia. “So that’s a big public health panic that we would like to avoid.”

Johnson and Johnson recently reported that second doses of its vaccine boosted its efficacy to almost 94% against COVID-19. A new study, published ahead of peer review, suggests that the efficacy of the single-dose Johnson and Johnson shot has fallen to about 78% against symptomatic infection during the Delta surge.

Moderna has applied for permission to market third doses of its vaccine in the United States, but the FDA has given no timeline on when it might make a decision. 

Doran Fink, MD, PhD, deputy director of the FDA’s Division of Vaccines and Related Products Applications, a representative advising the committee Sept. 22, said the agency was working as rapidly as possible on Moderna’s submission.

Regarding the question of whether it was OK to mix vaccines, rather than match them, Dr. Fink said there are currently not enough data available to inform that decision.

Those answers are coming, though. John Beigel, MD, associate director of clinical research at the National Institute of Allergy and Infectious Diseases, revealed that the federal government has a study underway to see what happens when the vaccines are mixed with each other. 

He said that data from the study would be available later this fall, and would certainly help physicians and other healthcare providers know whether it’s effective or safe to use them interchangeably.
 

 

 

Correlates of immunity

The ACIP left much of its schedule open Sept. 23 to discuss extra Pfizer doses and vote on how they should be used.

Pfizer had originally applied to the FDA for an amendment to its FDA approval, which would have given doctors a freer hand to prescribe third doses as they saw fit, in patients as young as 16.

But the FDA’s Vaccines and Related Biological Products Advisory Committee voted Sept. 17 against granting the amendment. The committee was particularly concerned about the lack of data in teens ages 16 and 17, who have the highest risk for a rare side effect that causes heart inflammation that requires hospital care.

Instead, they recommended — and the FDA agreed per their decision Sept. 22 — that third doses should be given to people at higher risk for severe breakthrough infections because of advanced age or because they work in an occupation that puts them at high risk for exposure. 

The CDC panel heard important presentations on new science that is helping to identify the correlates of immunity. 

The correlates of immunity are biomarkers that can be measured in blood that help doctors understand how protected a person may be against COVID-19. These markers of immunity are not yet known for the COVID-19 vaccines.

Emerging evidence shows that booster doses of the Pfizer vaccine cause front-line immune defenders — called binding antibodies — to roughly triple soon after a person gets the third shot. 

Neutralizing antibodies also jump soon after two vaccine doses, but they fall over time, which is natural. The body doesn’t need these foot soldiers to be on guard all the time, so they go away. 

The body retains its memory of how to make them, however, so they can quickly be marshaled again, if needed.

Early studies suggest that antibodies account for about two thirds of a person’s protection against COVID, while the longer-lasting T-cells and B-cells account for about one third.

After the antibody levels fall, it may take a few days to recreate this army. In the meantime, the virus can try to break in. This can cause symptoms, which can make a person feel terrible, but for the most part, vaccinated individuals don’t need hospital care and are nearly always protected from dying — even against the Delta variant.

Those most likely to be at risk for a breakthrough infection are older, because immune function wanes with age.
 

Essential workers

Essential workers, such as those who work in healthcare, may also benefit from high antibody levels, which can minimize symptoms and help them get back to work more quickly.

Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, said that in her area staffing levels are critical right now.

“I’m actually sitting in one of the deepest red [states] with high rates of COVID. We don’t have enough health care workers currently to take care of the unvaccinated,” she said. 

“When we have beds, we are often missing staff, and so the idea of vaccinating health care workers is to be a little bit different than our idea of using vaccines in the general population,” Dr. Talbot said.

Oliver Brooks, MD, chief medical officer of the Watts Healthcare Corporation in Los Angeles, said he was in favor of making a public statement about the temporary nature of the potential recommendations Sept. 23, because they probably won’t cover all who might need a third shot.

“We may want to go on record stating what it is that would allow us to broaden our recommendation or restrict our recommendation,” Dr. Brooks said.

The considerations of who should get an extra dose are not always straightforward.

New modeling by the Harvard TH Chan School of Public Health and the CDC to assist the government’s decisions on boosters had a surprise finding: in nursing homes, it’s more effective to vaccinate healthcare workers than it is to give booster doses to these residents. Nursing homes are at the mercy of community transmission. 

In regions with high transmission, it’s easy for a caregiver to bring the virus into a facility — so the models found that the transmission from these workers is a more effective strategy than giving third doses to the already highly vaccinated group of seniors who live in them.

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

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Botulinum Toxin for the Treatment of Intractable Raynaud Phenomenon

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Botulinum Toxin for the Treatment of Intractable Raynaud Phenomenon

To the Editor:

Raynaud phenomenon (RP) is an episodic vasospasm of the digits that can lead to ulceration, gangrene, and autoamputation with prolonged ischemia. OnabotulinumtoxinA has been implemented as a treatment of intractable RP by paralyzing the muscles of the digital arteries. We report a case of a woman with severe RP secondary to systemic lupus erythematosus (SLE) who was treated with onabotulinumtoxinA injections after multiple treatment modalities failed to improve her condition. We describe the dosage and injection technique used to produce clinical improvement in our patient and compare it to prior reports in the literature.

A 33-year-old woman presented to the emergency department for worsening foot pain of 5 days' duration with dusky purple color changes concerning for impending Raynaud crisis related to RP. The patient had a history of antiphospholipid antibody syndrome (APS) and SLE with overlapping symptoms of polymyositis and scleroderma. She had been hospitalized for RP multiple times prior to the current admission. She was medically managed with nifedipine, sildenafil, losartan potassium, aspirin, alprostadil, and prostaglandin infusions, and was surgically managed with a right-hand sympathectomy and right ulnar artery bypass graft that had subsequently thrombosed. At the current presentation, she had painful dusky toes on both feet though more pronounced on the left foot. She endorsed foot pain while walking and tenderness to palpation of the fingers, which were minimally improved with intravenous prostaglandins.

Physical examination revealed blanching of the digits in both hands with pits in the right fourth and left first digits. Dusky patches overlaid all the toes as well as the superior plantar aspects of the feet (Figure 1). Given the history of APS, a punch biopsy was performed on the left medial plantar foot and results showed no histologic evidence of vasculitis or vasculopathy. Necrotic foci were present on the left and right second metatarsal bones, which were not reperfusable (Figure 2). The clinical findings and punch biopsy results favored RP as opposed to vasculopathy from APS.

FIGURE 1. A and B, Dusky patches on the dorsal aspect of the toes as well as the superior plantar aspect of the feet, respectively, at presentation.

Several interventions were attempted, and after 4 days with no response, the patient agreed to receive treatment with onabotulinumtoxinA. OnabotulinumtoxinA (5 U) was injected into the subcutaneous tissue of the medial and lateral aspects of each of the first and second toes near the proximal phalanges (40 U total). However, treatment could not be completed due to severe pain caused by the injections despite preprocedure regional nerve blocks to both lower extremities, preinjection icing, and lorazepam. Two days later, the patient tolerated onabotulinumtoxinA injections of all remaining digits of both feet (60 U total). She noted slight clinical improvement soon thereafter. One week after treatment of all 10 toes, she reported decreased pain and reduced duskiness of both feet (Figure 3).

FIGURE 2. Punch biopsy of the left medial plantar foot at a site of several dusky patches showed no vasculitis or vasculopathy (H&E, original magnification ×20).

One month later, the patient endorsed recurring pain in the hands and feet. Physical examination revealed reticular cyanosis and increased violaceous patches of the hands; the feet were overall unchanged from the prior hospitalization. At 4-month follow-up, there was gangrene on the left second, third, and fifth toe in addition to areas of induration noted on the fingers. She was repeatedly hospitalized over the next 6 months for pain management and gangrene of the toes, and finally underwent an amputation of the left and right second toe at the proximal and middle phalanx, respectively. She currently is continuing extensive medical management for pain and gangrene of the digits; she has not received additional onabotulinumtoxinA injections.

FIGURE 3. A and B, Reduced duskiness of both feet was demonstrated at 1-week posttreatment with onabotulinumtoxinA injections.

Raynaud phenomenon is a vascular disorder characterized by intermittent arteriolar vasospasm of the digits, often due to cold temperature or stress. Approximately 90% of RP cases are primarily idiopathic, with the remaining cases secondary to other diseases, typically systemic sclerosis, SLE, or mixed connective tissue disease.1 Symptoms present with characteristic changing of hands from white (ischemia) to blue (hypoxia) to red (reperfusion). Episodic attacks of vasospasm and ischemia can be painful and lead to digital ulcerations and necrosis of the digits or hands. Other complications including digital tuft pits, pterygium inversum unguis, or torturous nail fold capillaries with capillary dropout also may be seen.2

Although the etiology is multifactorial, the pathophysiology primarily is due to an imbalance of vasodilation and vasoconstriction. Perturbed levels of vasodilatory mediators include nitric oxide, prostacyclin, and calcitonin gene-related peptide.3 Meanwhile, abnormal neural sympathetic control of α-adrenergic receptors located on smooth muscle vasculature and subsequent endothelial hyperproliferation may contribute to inappropriate vasoconstriction.4

 

 

The first-line therapy for mild to moderate disease refractory to conservative management includes monotherapy with dihydropyridine calcium channel blockers. For severe disease, combination therapy involves addition of other classes of medications including phosphodiesterase 5 inhibitors, topical nitrates, angiotensin receptor blockers, or selective serotonin reuptake inhibitors. Intravenous prostacyclin, endothelin receptor blockers, and onabotulinumtoxinA injections may be added as third-line therapy. Finally, surgical management including sympathectomy with continued pharmacologic therapy may be needed for disease recalcitrant to the aforementioned options.2

OnabotulinumtoxinA is a neurotoxin produced by the bacterium Clostridium botulinum. The toxin’s mechanism of action involves inhibition of the release of presynaptic acetylcholine-containing vesicles at the neuromuscular junction through cleavage of sensory nerve action potential receptor proteins. In addition, it inhibits smooth muscle vasoconstriction and pain by blocking α2-adrenergic receptors on blood vessels and chronic pain-transmitting C fibers in nerves, respectively.3,5

Only recently has onabotulinumtoxinA been used for treatment of RP. Botulinum toxin is approved for the treatment of spastic and dystonic diseases such as blepharospasm, headaches in patients with chronic migraines, upper limb spasticity, cervical dystonia, torticollis, ocular strabismus, and hyperhidrosis.3 However, the versatility of its therapeutic effects is evident in its broad off-label clinical applications, including achalasia; carpal tunnel syndrome; and spasticity relating to stroke, paraplegia, and cerebral palsy, among many others.5

Few studies have analyzed the use of onabotulinumtoxinA for the treatment of RP.3,6 There is no consensus yet regarding dose, dilution, or injection sites. One vial of onabotulinumtoxinA contains 100 U and is reconstituted in 20 mL of normal saline to produce 5 U/mL. The simplest technique involves the injection of 5 U into the medial and lateral aspects of each finger at its base, at the level of or just proximal to the A1 pulley, for a total of 50 U per hand.7 In the foot, injection can be made at the base of each toe near the proximal phalanges. A regimen of 50 to 100 U per hand was used by Neumeister et al5 on 19 patients, who subsequently standardized it to 10 U on each neurovascular bundle in a follow-up study,7 giving a total volume of 2 mL per injection. Associated pain or a burning sensation initially may be experienced, which may be mitigated by a lidocaine hydrochloride wrist block prior to injection.7 This technique produced immediate and lasting pain relief, increased tissue perfusion, and resolved digital ulcers in 28 of 33 patients. Most patients reported immediate relief, and a few noted gradual reduction in pain and resolution of chronic ulcers within 2 months. Of the 33 patients, 7 (21.2%) required repeat injections for recurrent pain, but the majority were pain free up to 6 years later with a single injection schedule.7

Injection into the palmar region, wrists, and/or fingers also may be performed. Effects of using different injection sites (eg, neurovascular bundle, distal palm, proximal hand) have been explored and were not notably different between these locations.8 Lastly, the frequency of injections may be attenuated according to the spectrum and severity of the patient’s symptoms. In a report of 11 patients who received a total of 100 U of onabotulinumtoxinA per hand, 5 required repeat injections within 3 to 8 months.9

 

 

Studies have reported onabotulinumtoxinA to be a promising option for the treatment of intractable symptoms. Likewise, our patient had a notable reduction in pain with signs of clinical improvement within 24 to 48 hours after injection. The need for amputation 6 months later likely was because the patient’s toes were already necrosing prior to treatment with onabotulinumtoxinA. Thus, the timing of intervention may play a critical role in response to onabotulinumtoxinA injections, particularly because the severity of our patient’s presentation was comparable to other cases reported in the literature. Even in reports using a smaller dose—2 U injected into each toe as opposed to 10 U per toe, as in our case—follow-up showed favorable results.10 In other reports, response can be perceived within days to a week, with remarkable improvement of numbness, pain, digit color, and wound resolution, in addition to decreased frequency and severity of attacks. Moreover, greater vasodilation and subsequent tissue perfusion have been evidenced by objective measures including digital transcutaneous oxygen saturation and Doppler sonography.7,8 Side effects, which are minimal and temporary, include local pain triggering a vasospastic attack and intrinsic muscle weakness; more rarely, dysesthesia and thenar eminence atrophy have been reported.11

Available studies have shown onabotulinumtoxinA to produce favorable results in the treatment of vasospastic disease. We suspect that an earlier intervention for our patient—before necrosis of the toes developed—would have led to a more positive outcome, consistent with other reports. Treatment with onabotulinumtoxinA is an approach to consider when the standard-of-care treatments for RP have been exhausted, as timely intervention may prevent the need for surgery. The indications and appropriate dosing protocol remain to be defined, in addition to more thorough evaluation of its efficacy relative to other medical and surgical options.

References
  1. Neumeister MW. The role of botulinum toxin in vasospastic disorders of the hand. Hand Clin. 2015;31:23-37. doi:10.1016/j.hcl.2014.09.003
  2. Bakst R, Merola JF, Franks AG, et al. Raynaud’s phenomenon: pathogenesis and management. J Am Acad Dermatol. 2008;59:633-653. doi:10.1016/j.jaad.2008.06.004
  3. Iorio ML, Masden DL, Higgins JP. Botulinum toxin a treatment of Raynaud’s phenomenon: a review. Semin Arthritis Rheum. 2012;41:599-603. doi:10.1016/j.semarthrit.2011.07.006
  4. Wigley FM, Flavahan NA. Raynaud’s phenomenon. N Engl J Med. 2016;375:556-565. doi:10.1056/NEJMra1507638
  5. Neumeister MW, Chambers CB, Herron MS, et al. Botox therapy for ischemic digits. Plast Reconstr Surg. 2009;124:191-200. doi:10.1097/PRS.0b013e3181a80576
  6. Sycha T, Graninger M, Auff E, et al. Botulinum toxin in the treatment of Raynaud’s phenomenon: a pilot study. Eur J Clin Invest. 2004;34:312-313. doi:10.1016/j.jaad.2013.06.029
  7. Neumeister MW. Botulinum toxin type A in the treatment of Raynaud’s phenomenon. J Hand Surg Am. 2010;35:2085-2092. doi:10.1016/j.jhsa.2010.09.019
  8. Fregene A, Ditmars D, Siddiqui A. Botulinum toxin type A: a treatment option for digital ischemia in patients with Raynaud’s phenomenon. J Hand Surg Am. 2009;34:446-452. doi:10.1016/j.jhsa.2008.11.026
  9. Van Beek AL, Lim PK, Gear AJL, et al. Management of vasospastic disorders with botulinum toxin A. Plast Reconstr Surg. 2007;119:217-226. doi:10.1097/01.prs.0000244860.00674.57
  10. Dhaliwal K, Griffin M, Denton CP, et al. The novel use of botulinum toxin A for the treatment of Raynaud’s phenomenon in the toes. BMJ Case Rep. 2018;2018:2017-2019. doi:10.1136/bcr-2017-219348
  11. Eickhoff JC, Smith JK, Landau ME, et al. Iatrogenic thenar eminence atrophy after Botox A injection for secondary Raynaud phenomenon. J Clin Rheumatol. 2016;22:395-396. doi:10.1097/RHU.0000000000000450
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From the Department of Dermatology, University of California, Irvine.

The authors report no conflict of interest.

Correspondence: Nathan W. Rojek, MD, University of California, Department of Dermatology, 118 Med Surg 1, Irvine, CA 92697-2400 ([email protected]).

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From the Department of Dermatology, University of California, Irvine.

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Correspondence: Nathan W. Rojek, MD, University of California, Department of Dermatology, 118 Med Surg 1, Irvine, CA 92697-2400 ([email protected]).

Author and Disclosure Information

From the Department of Dermatology, University of California, Irvine.

The authors report no conflict of interest.

Correspondence: Nathan W. Rojek, MD, University of California, Department of Dermatology, 118 Med Surg 1, Irvine, CA 92697-2400 ([email protected]).

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To the Editor:

Raynaud phenomenon (RP) is an episodic vasospasm of the digits that can lead to ulceration, gangrene, and autoamputation with prolonged ischemia. OnabotulinumtoxinA has been implemented as a treatment of intractable RP by paralyzing the muscles of the digital arteries. We report a case of a woman with severe RP secondary to systemic lupus erythematosus (SLE) who was treated with onabotulinumtoxinA injections after multiple treatment modalities failed to improve her condition. We describe the dosage and injection technique used to produce clinical improvement in our patient and compare it to prior reports in the literature.

A 33-year-old woman presented to the emergency department for worsening foot pain of 5 days' duration with dusky purple color changes concerning for impending Raynaud crisis related to RP. The patient had a history of antiphospholipid antibody syndrome (APS) and SLE with overlapping symptoms of polymyositis and scleroderma. She had been hospitalized for RP multiple times prior to the current admission. She was medically managed with nifedipine, sildenafil, losartan potassium, aspirin, alprostadil, and prostaglandin infusions, and was surgically managed with a right-hand sympathectomy and right ulnar artery bypass graft that had subsequently thrombosed. At the current presentation, she had painful dusky toes on both feet though more pronounced on the left foot. She endorsed foot pain while walking and tenderness to palpation of the fingers, which were minimally improved with intravenous prostaglandins.

Physical examination revealed blanching of the digits in both hands with pits in the right fourth and left first digits. Dusky patches overlaid all the toes as well as the superior plantar aspects of the feet (Figure 1). Given the history of APS, a punch biopsy was performed on the left medial plantar foot and results showed no histologic evidence of vasculitis or vasculopathy. Necrotic foci were present on the left and right second metatarsal bones, which were not reperfusable (Figure 2). The clinical findings and punch biopsy results favored RP as opposed to vasculopathy from APS.

FIGURE 1. A and B, Dusky patches on the dorsal aspect of the toes as well as the superior plantar aspect of the feet, respectively, at presentation.

Several interventions were attempted, and after 4 days with no response, the patient agreed to receive treatment with onabotulinumtoxinA. OnabotulinumtoxinA (5 U) was injected into the subcutaneous tissue of the medial and lateral aspects of each of the first and second toes near the proximal phalanges (40 U total). However, treatment could not be completed due to severe pain caused by the injections despite preprocedure regional nerve blocks to both lower extremities, preinjection icing, and lorazepam. Two days later, the patient tolerated onabotulinumtoxinA injections of all remaining digits of both feet (60 U total). She noted slight clinical improvement soon thereafter. One week after treatment of all 10 toes, she reported decreased pain and reduced duskiness of both feet (Figure 3).

FIGURE 2. Punch biopsy of the left medial plantar foot at a site of several dusky patches showed no vasculitis or vasculopathy (H&E, original magnification ×20).

One month later, the patient endorsed recurring pain in the hands and feet. Physical examination revealed reticular cyanosis and increased violaceous patches of the hands; the feet were overall unchanged from the prior hospitalization. At 4-month follow-up, there was gangrene on the left second, third, and fifth toe in addition to areas of induration noted on the fingers. She was repeatedly hospitalized over the next 6 months for pain management and gangrene of the toes, and finally underwent an amputation of the left and right second toe at the proximal and middle phalanx, respectively. She currently is continuing extensive medical management for pain and gangrene of the digits; she has not received additional onabotulinumtoxinA injections.

FIGURE 3. A and B, Reduced duskiness of both feet was demonstrated at 1-week posttreatment with onabotulinumtoxinA injections.

Raynaud phenomenon is a vascular disorder characterized by intermittent arteriolar vasospasm of the digits, often due to cold temperature or stress. Approximately 90% of RP cases are primarily idiopathic, with the remaining cases secondary to other diseases, typically systemic sclerosis, SLE, or mixed connective tissue disease.1 Symptoms present with characteristic changing of hands from white (ischemia) to blue (hypoxia) to red (reperfusion). Episodic attacks of vasospasm and ischemia can be painful and lead to digital ulcerations and necrosis of the digits or hands. Other complications including digital tuft pits, pterygium inversum unguis, or torturous nail fold capillaries with capillary dropout also may be seen.2

Although the etiology is multifactorial, the pathophysiology primarily is due to an imbalance of vasodilation and vasoconstriction. Perturbed levels of vasodilatory mediators include nitric oxide, prostacyclin, and calcitonin gene-related peptide.3 Meanwhile, abnormal neural sympathetic control of α-adrenergic receptors located on smooth muscle vasculature and subsequent endothelial hyperproliferation may contribute to inappropriate vasoconstriction.4

 

 

The first-line therapy for mild to moderate disease refractory to conservative management includes monotherapy with dihydropyridine calcium channel blockers. For severe disease, combination therapy involves addition of other classes of medications including phosphodiesterase 5 inhibitors, topical nitrates, angiotensin receptor blockers, or selective serotonin reuptake inhibitors. Intravenous prostacyclin, endothelin receptor blockers, and onabotulinumtoxinA injections may be added as third-line therapy. Finally, surgical management including sympathectomy with continued pharmacologic therapy may be needed for disease recalcitrant to the aforementioned options.2

OnabotulinumtoxinA is a neurotoxin produced by the bacterium Clostridium botulinum. The toxin’s mechanism of action involves inhibition of the release of presynaptic acetylcholine-containing vesicles at the neuromuscular junction through cleavage of sensory nerve action potential receptor proteins. In addition, it inhibits smooth muscle vasoconstriction and pain by blocking α2-adrenergic receptors on blood vessels and chronic pain-transmitting C fibers in nerves, respectively.3,5

Only recently has onabotulinumtoxinA been used for treatment of RP. Botulinum toxin is approved for the treatment of spastic and dystonic diseases such as blepharospasm, headaches in patients with chronic migraines, upper limb spasticity, cervical dystonia, torticollis, ocular strabismus, and hyperhidrosis.3 However, the versatility of its therapeutic effects is evident in its broad off-label clinical applications, including achalasia; carpal tunnel syndrome; and spasticity relating to stroke, paraplegia, and cerebral palsy, among many others.5

Few studies have analyzed the use of onabotulinumtoxinA for the treatment of RP.3,6 There is no consensus yet regarding dose, dilution, or injection sites. One vial of onabotulinumtoxinA contains 100 U and is reconstituted in 20 mL of normal saline to produce 5 U/mL. The simplest technique involves the injection of 5 U into the medial and lateral aspects of each finger at its base, at the level of or just proximal to the A1 pulley, for a total of 50 U per hand.7 In the foot, injection can be made at the base of each toe near the proximal phalanges. A regimen of 50 to 100 U per hand was used by Neumeister et al5 on 19 patients, who subsequently standardized it to 10 U on each neurovascular bundle in a follow-up study,7 giving a total volume of 2 mL per injection. Associated pain or a burning sensation initially may be experienced, which may be mitigated by a lidocaine hydrochloride wrist block prior to injection.7 This technique produced immediate and lasting pain relief, increased tissue perfusion, and resolved digital ulcers in 28 of 33 patients. Most patients reported immediate relief, and a few noted gradual reduction in pain and resolution of chronic ulcers within 2 months. Of the 33 patients, 7 (21.2%) required repeat injections for recurrent pain, but the majority were pain free up to 6 years later with a single injection schedule.7

Injection into the palmar region, wrists, and/or fingers also may be performed. Effects of using different injection sites (eg, neurovascular bundle, distal palm, proximal hand) have been explored and were not notably different between these locations.8 Lastly, the frequency of injections may be attenuated according to the spectrum and severity of the patient’s symptoms. In a report of 11 patients who received a total of 100 U of onabotulinumtoxinA per hand, 5 required repeat injections within 3 to 8 months.9

 

 

Studies have reported onabotulinumtoxinA to be a promising option for the treatment of intractable symptoms. Likewise, our patient had a notable reduction in pain with signs of clinical improvement within 24 to 48 hours after injection. The need for amputation 6 months later likely was because the patient’s toes were already necrosing prior to treatment with onabotulinumtoxinA. Thus, the timing of intervention may play a critical role in response to onabotulinumtoxinA injections, particularly because the severity of our patient’s presentation was comparable to other cases reported in the literature. Even in reports using a smaller dose—2 U injected into each toe as opposed to 10 U per toe, as in our case—follow-up showed favorable results.10 In other reports, response can be perceived within days to a week, with remarkable improvement of numbness, pain, digit color, and wound resolution, in addition to decreased frequency and severity of attacks. Moreover, greater vasodilation and subsequent tissue perfusion have been evidenced by objective measures including digital transcutaneous oxygen saturation and Doppler sonography.7,8 Side effects, which are minimal and temporary, include local pain triggering a vasospastic attack and intrinsic muscle weakness; more rarely, dysesthesia and thenar eminence atrophy have been reported.11

Available studies have shown onabotulinumtoxinA to produce favorable results in the treatment of vasospastic disease. We suspect that an earlier intervention for our patient—before necrosis of the toes developed—would have led to a more positive outcome, consistent with other reports. Treatment with onabotulinumtoxinA is an approach to consider when the standard-of-care treatments for RP have been exhausted, as timely intervention may prevent the need for surgery. The indications and appropriate dosing protocol remain to be defined, in addition to more thorough evaluation of its efficacy relative to other medical and surgical options.

To the Editor:

Raynaud phenomenon (RP) is an episodic vasospasm of the digits that can lead to ulceration, gangrene, and autoamputation with prolonged ischemia. OnabotulinumtoxinA has been implemented as a treatment of intractable RP by paralyzing the muscles of the digital arteries. We report a case of a woman with severe RP secondary to systemic lupus erythematosus (SLE) who was treated with onabotulinumtoxinA injections after multiple treatment modalities failed to improve her condition. We describe the dosage and injection technique used to produce clinical improvement in our patient and compare it to prior reports in the literature.

A 33-year-old woman presented to the emergency department for worsening foot pain of 5 days' duration with dusky purple color changes concerning for impending Raynaud crisis related to RP. The patient had a history of antiphospholipid antibody syndrome (APS) and SLE with overlapping symptoms of polymyositis and scleroderma. She had been hospitalized for RP multiple times prior to the current admission. She was medically managed with nifedipine, sildenafil, losartan potassium, aspirin, alprostadil, and prostaglandin infusions, and was surgically managed with a right-hand sympathectomy and right ulnar artery bypass graft that had subsequently thrombosed. At the current presentation, she had painful dusky toes on both feet though more pronounced on the left foot. She endorsed foot pain while walking and tenderness to palpation of the fingers, which were minimally improved with intravenous prostaglandins.

Physical examination revealed blanching of the digits in both hands with pits in the right fourth and left first digits. Dusky patches overlaid all the toes as well as the superior plantar aspects of the feet (Figure 1). Given the history of APS, a punch biopsy was performed on the left medial plantar foot and results showed no histologic evidence of vasculitis or vasculopathy. Necrotic foci were present on the left and right second metatarsal bones, which were not reperfusable (Figure 2). The clinical findings and punch biopsy results favored RP as opposed to vasculopathy from APS.

FIGURE 1. A and B, Dusky patches on the dorsal aspect of the toes as well as the superior plantar aspect of the feet, respectively, at presentation.

Several interventions were attempted, and after 4 days with no response, the patient agreed to receive treatment with onabotulinumtoxinA. OnabotulinumtoxinA (5 U) was injected into the subcutaneous tissue of the medial and lateral aspects of each of the first and second toes near the proximal phalanges (40 U total). However, treatment could not be completed due to severe pain caused by the injections despite preprocedure regional nerve blocks to both lower extremities, preinjection icing, and lorazepam. Two days later, the patient tolerated onabotulinumtoxinA injections of all remaining digits of both feet (60 U total). She noted slight clinical improvement soon thereafter. One week after treatment of all 10 toes, she reported decreased pain and reduced duskiness of both feet (Figure 3).

FIGURE 2. Punch biopsy of the left medial plantar foot at a site of several dusky patches showed no vasculitis or vasculopathy (H&E, original magnification ×20).

One month later, the patient endorsed recurring pain in the hands and feet. Physical examination revealed reticular cyanosis and increased violaceous patches of the hands; the feet were overall unchanged from the prior hospitalization. At 4-month follow-up, there was gangrene on the left second, third, and fifth toe in addition to areas of induration noted on the fingers. She was repeatedly hospitalized over the next 6 months for pain management and gangrene of the toes, and finally underwent an amputation of the left and right second toe at the proximal and middle phalanx, respectively. She currently is continuing extensive medical management for pain and gangrene of the digits; she has not received additional onabotulinumtoxinA injections.

FIGURE 3. A and B, Reduced duskiness of both feet was demonstrated at 1-week posttreatment with onabotulinumtoxinA injections.

Raynaud phenomenon is a vascular disorder characterized by intermittent arteriolar vasospasm of the digits, often due to cold temperature or stress. Approximately 90% of RP cases are primarily idiopathic, with the remaining cases secondary to other diseases, typically systemic sclerosis, SLE, or mixed connective tissue disease.1 Symptoms present with characteristic changing of hands from white (ischemia) to blue (hypoxia) to red (reperfusion). Episodic attacks of vasospasm and ischemia can be painful and lead to digital ulcerations and necrosis of the digits or hands. Other complications including digital tuft pits, pterygium inversum unguis, or torturous nail fold capillaries with capillary dropout also may be seen.2

Although the etiology is multifactorial, the pathophysiology primarily is due to an imbalance of vasodilation and vasoconstriction. Perturbed levels of vasodilatory mediators include nitric oxide, prostacyclin, and calcitonin gene-related peptide.3 Meanwhile, abnormal neural sympathetic control of α-adrenergic receptors located on smooth muscle vasculature and subsequent endothelial hyperproliferation may contribute to inappropriate vasoconstriction.4

 

 

The first-line therapy for mild to moderate disease refractory to conservative management includes monotherapy with dihydropyridine calcium channel blockers. For severe disease, combination therapy involves addition of other classes of medications including phosphodiesterase 5 inhibitors, topical nitrates, angiotensin receptor blockers, or selective serotonin reuptake inhibitors. Intravenous prostacyclin, endothelin receptor blockers, and onabotulinumtoxinA injections may be added as third-line therapy. Finally, surgical management including sympathectomy with continued pharmacologic therapy may be needed for disease recalcitrant to the aforementioned options.2

OnabotulinumtoxinA is a neurotoxin produced by the bacterium Clostridium botulinum. The toxin’s mechanism of action involves inhibition of the release of presynaptic acetylcholine-containing vesicles at the neuromuscular junction through cleavage of sensory nerve action potential receptor proteins. In addition, it inhibits smooth muscle vasoconstriction and pain by blocking α2-adrenergic receptors on blood vessels and chronic pain-transmitting C fibers in nerves, respectively.3,5

Only recently has onabotulinumtoxinA been used for treatment of RP. Botulinum toxin is approved for the treatment of spastic and dystonic diseases such as blepharospasm, headaches in patients with chronic migraines, upper limb spasticity, cervical dystonia, torticollis, ocular strabismus, and hyperhidrosis.3 However, the versatility of its therapeutic effects is evident in its broad off-label clinical applications, including achalasia; carpal tunnel syndrome; and spasticity relating to stroke, paraplegia, and cerebral palsy, among many others.5

Few studies have analyzed the use of onabotulinumtoxinA for the treatment of RP.3,6 There is no consensus yet regarding dose, dilution, or injection sites. One vial of onabotulinumtoxinA contains 100 U and is reconstituted in 20 mL of normal saline to produce 5 U/mL. The simplest technique involves the injection of 5 U into the medial and lateral aspects of each finger at its base, at the level of or just proximal to the A1 pulley, for a total of 50 U per hand.7 In the foot, injection can be made at the base of each toe near the proximal phalanges. A regimen of 50 to 100 U per hand was used by Neumeister et al5 on 19 patients, who subsequently standardized it to 10 U on each neurovascular bundle in a follow-up study,7 giving a total volume of 2 mL per injection. Associated pain or a burning sensation initially may be experienced, which may be mitigated by a lidocaine hydrochloride wrist block prior to injection.7 This technique produced immediate and lasting pain relief, increased tissue perfusion, and resolved digital ulcers in 28 of 33 patients. Most patients reported immediate relief, and a few noted gradual reduction in pain and resolution of chronic ulcers within 2 months. Of the 33 patients, 7 (21.2%) required repeat injections for recurrent pain, but the majority were pain free up to 6 years later with a single injection schedule.7

Injection into the palmar region, wrists, and/or fingers also may be performed. Effects of using different injection sites (eg, neurovascular bundle, distal palm, proximal hand) have been explored and were not notably different between these locations.8 Lastly, the frequency of injections may be attenuated according to the spectrum and severity of the patient’s symptoms. In a report of 11 patients who received a total of 100 U of onabotulinumtoxinA per hand, 5 required repeat injections within 3 to 8 months.9

 

 

Studies have reported onabotulinumtoxinA to be a promising option for the treatment of intractable symptoms. Likewise, our patient had a notable reduction in pain with signs of clinical improvement within 24 to 48 hours after injection. The need for amputation 6 months later likely was because the patient’s toes were already necrosing prior to treatment with onabotulinumtoxinA. Thus, the timing of intervention may play a critical role in response to onabotulinumtoxinA injections, particularly because the severity of our patient’s presentation was comparable to other cases reported in the literature. Even in reports using a smaller dose—2 U injected into each toe as opposed to 10 U per toe, as in our case—follow-up showed favorable results.10 In other reports, response can be perceived within days to a week, with remarkable improvement of numbness, pain, digit color, and wound resolution, in addition to decreased frequency and severity of attacks. Moreover, greater vasodilation and subsequent tissue perfusion have been evidenced by objective measures including digital transcutaneous oxygen saturation and Doppler sonography.7,8 Side effects, which are minimal and temporary, include local pain triggering a vasospastic attack and intrinsic muscle weakness; more rarely, dysesthesia and thenar eminence atrophy have been reported.11

Available studies have shown onabotulinumtoxinA to produce favorable results in the treatment of vasospastic disease. We suspect that an earlier intervention for our patient—before necrosis of the toes developed—would have led to a more positive outcome, consistent with other reports. Treatment with onabotulinumtoxinA is an approach to consider when the standard-of-care treatments for RP have been exhausted, as timely intervention may prevent the need for surgery. The indications and appropriate dosing protocol remain to be defined, in addition to more thorough evaluation of its efficacy relative to other medical and surgical options.

References
  1. Neumeister MW. The role of botulinum toxin in vasospastic disorders of the hand. Hand Clin. 2015;31:23-37. doi:10.1016/j.hcl.2014.09.003
  2. Bakst R, Merola JF, Franks AG, et al. Raynaud’s phenomenon: pathogenesis and management. J Am Acad Dermatol. 2008;59:633-653. doi:10.1016/j.jaad.2008.06.004
  3. Iorio ML, Masden DL, Higgins JP. Botulinum toxin a treatment of Raynaud’s phenomenon: a review. Semin Arthritis Rheum. 2012;41:599-603. doi:10.1016/j.semarthrit.2011.07.006
  4. Wigley FM, Flavahan NA. Raynaud’s phenomenon. N Engl J Med. 2016;375:556-565. doi:10.1056/NEJMra1507638
  5. Neumeister MW, Chambers CB, Herron MS, et al. Botox therapy for ischemic digits. Plast Reconstr Surg. 2009;124:191-200. doi:10.1097/PRS.0b013e3181a80576
  6. Sycha T, Graninger M, Auff E, et al. Botulinum toxin in the treatment of Raynaud’s phenomenon: a pilot study. Eur J Clin Invest. 2004;34:312-313. doi:10.1016/j.jaad.2013.06.029
  7. Neumeister MW. Botulinum toxin type A in the treatment of Raynaud’s phenomenon. J Hand Surg Am. 2010;35:2085-2092. doi:10.1016/j.jhsa.2010.09.019
  8. Fregene A, Ditmars D, Siddiqui A. Botulinum toxin type A: a treatment option for digital ischemia in patients with Raynaud’s phenomenon. J Hand Surg Am. 2009;34:446-452. doi:10.1016/j.jhsa.2008.11.026
  9. Van Beek AL, Lim PK, Gear AJL, et al. Management of vasospastic disorders with botulinum toxin A. Plast Reconstr Surg. 2007;119:217-226. doi:10.1097/01.prs.0000244860.00674.57
  10. Dhaliwal K, Griffin M, Denton CP, et al. The novel use of botulinum toxin A for the treatment of Raynaud’s phenomenon in the toes. BMJ Case Rep. 2018;2018:2017-2019. doi:10.1136/bcr-2017-219348
  11. Eickhoff JC, Smith JK, Landau ME, et al. Iatrogenic thenar eminence atrophy after Botox A injection for secondary Raynaud phenomenon. J Clin Rheumatol. 2016;22:395-396. doi:10.1097/RHU.0000000000000450
References
  1. Neumeister MW. The role of botulinum toxin in vasospastic disorders of the hand. Hand Clin. 2015;31:23-37. doi:10.1016/j.hcl.2014.09.003
  2. Bakst R, Merola JF, Franks AG, et al. Raynaud’s phenomenon: pathogenesis and management. J Am Acad Dermatol. 2008;59:633-653. doi:10.1016/j.jaad.2008.06.004
  3. Iorio ML, Masden DL, Higgins JP. Botulinum toxin a treatment of Raynaud’s phenomenon: a review. Semin Arthritis Rheum. 2012;41:599-603. doi:10.1016/j.semarthrit.2011.07.006
  4. Wigley FM, Flavahan NA. Raynaud’s phenomenon. N Engl J Med. 2016;375:556-565. doi:10.1056/NEJMra1507638
  5. Neumeister MW, Chambers CB, Herron MS, et al. Botox therapy for ischemic digits. Plast Reconstr Surg. 2009;124:191-200. doi:10.1097/PRS.0b013e3181a80576
  6. Sycha T, Graninger M, Auff E, et al. Botulinum toxin in the treatment of Raynaud’s phenomenon: a pilot study. Eur J Clin Invest. 2004;34:312-313. doi:10.1016/j.jaad.2013.06.029
  7. Neumeister MW. Botulinum toxin type A in the treatment of Raynaud’s phenomenon. J Hand Surg Am. 2010;35:2085-2092. doi:10.1016/j.jhsa.2010.09.019
  8. Fregene A, Ditmars D, Siddiqui A. Botulinum toxin type A: a treatment option for digital ischemia in patients with Raynaud’s phenomenon. J Hand Surg Am. 2009;34:446-452. doi:10.1016/j.jhsa.2008.11.026
  9. Van Beek AL, Lim PK, Gear AJL, et al. Management of vasospastic disorders with botulinum toxin A. Plast Reconstr Surg. 2007;119:217-226. doi:10.1097/01.prs.0000244860.00674.57
  10. Dhaliwal K, Griffin M, Denton CP, et al. The novel use of botulinum toxin A for the treatment of Raynaud’s phenomenon in the toes. BMJ Case Rep. 2018;2018:2017-2019. doi:10.1136/bcr-2017-219348
  11. Eickhoff JC, Smith JK, Landau ME, et al. Iatrogenic thenar eminence atrophy after Botox A injection for secondary Raynaud phenomenon. J Clin Rheumatol. 2016;22:395-396. doi:10.1097/RHU.0000000000000450
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  • Raynaud phenomenon (RP) is a vascular disorder characterized by episodic vasospasms of the digits often due to cold temperature or stress.
  • OnabotulinumtoxinA has been implemented as a treatment of intractable RP after failure with traditional treatments, such as calcium channel blockers, angiotensin receptor blockers, prostaglandins, endothelin receptor blockers, and phosphodiesterase 5 inhibitors.
  • A standard technique of delivery of onabotulinumtoxinA involves injection of 5 U/mL into the medial and lateral aspects of each finger at its base (near the metacarpal head) for a total of 50 U per hand or foot.
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New finasteride lawsuit brings renewed attention to psychiatric, ED adverse event reports

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Wed, 09/22/2021 - 16:49

A new lawsuit seeking to force the Food and Drug Administration to act on a request to add stricter warnings to finasteride or remove it from the market may rekindle a debate on whether some of the observed side effects from the hair loss drug merit a closer look and, potentially, better counseling and monitoring from clinicians.

Dr. Robert M. Bernstein

The nonprofit advocacy group Public Citizen filed the suit on behalf of the Post-Finasteride Syndrome Foundation (PFSF) in the U.S. District Court for the District of Columbia. The PFSF had filed a citizen’s petition in 2017 that requested that the FDA either take the 1-mg formulation off the market, or add warnings about the potential for erectile dysfunction, depression, and suicidal ideation, among other adverse reactions.

The PFSF has alleged that long-term use of Propecia (and its generic equivalents) can lead to postfinasteride syndrome (PFS), characterized by sexual dysfunction and psycho-neurocognitive symptoms. The symptoms may continue long after men stop taking the drug, according to PFSF.

Public Citizen said the FDA needs to take action in part because U.S. prescriptions of the hair loss formulation “more than doubled from 2015 to 2020,” and online and telemedicine companies such as Hims, Roman, and Keeps “aggressively market and sell generic finasteride for hair loss.” According to GoodRx, a 1-month supply of generic 1-mg tablets costs as little as $8-$10.

Both Canadian and British regulatory authorities have added warnings about depression and suicide to the Propecia label but the FDA has not changed its labeling. An agency spokesperson told this news organization that the “FDA does not comment on the status of pending citizen petitions or on pending litigation.”

Propecia’s developer, Merck, has not responded to several requests for comment from this news organization.

Why some patients develop PFS and others do not is still not understood, but some clinicians said they counsel all patients on the risks of severe and persistent side effects that have been associated with Propecia.

Robert M. Bernstein, MD, of the department of dermatology at Columbia University, New York, and a fellow of the International Society of Hair Restoration Surgery, said that 2%-4% of his patients have some side effects, similar to the original reported incidence, with sexual dysfunction being the most common.

If a man experiences an adverse effect, the drug should be stopped, Dr. Bernstein said in an interview. He noted that “there seems to be a significant increased risk of persistent side effects in people with certain psychiatric conditions, and those people should be counseled carefully before considering the medication.”

“Everybody should be warned that the risk of persistent side effects is real but in the average person it is quite uncommon,” added Dr. Bernstein, founder of Bernstein Medical, a division of Schweiger Dermatology Group focusing on the diagnosis and treatment of hair loss. “I don’t think it should be withdrawn from the market,” he said.

Dr. Alan R. Jacobs


Alan Jacobs, MD, a Manhattan-based neuroendocrinologist and behavioral neurologist in private practice who said he has treated hundreds of men for PFS, and who is an expert witness for the plaintiff in a suit alleging that finasteride led to a man’s suicide, said that taking the drug off the market would be unfortunate because it helps so many men. “I don’t think you need to get rid of the drug per se,” he said in an interview. “But very rapidly, people need to do clinical research to find out how to predict who’s more at risk,” he added.

Michael S. Irwig, MD, associate professor of medicine at Harvard Medical School, Boston, who has studied the persistent sexual and nonsexual side effects of finasteride, said he believes there should be a boxed warning on the finasteride label to let the men who take it “know that they can have permanent persistent sexual dysfunction, and/or depression and suicide have been noted with this medicine.

“Those who prescribe it should be having a conversation with patients about the potential risks and benefits so that everybody knows about the potential before they get on the medicine,” said Dr. Irwig, who also is an endocrinologist at Beth Israel Deaconess Medical Center in Boston.
 

 

 

Other countries warn of psychiatric effects

The FDA approved the 1-mg form of finasteride for male pattern hair loss in 1997.

In 2012, the label and the patient insert were updated to state that side effects included less desire for sex, erectile dysfunction, and a decrease in the amount of semen produced, but that those adverse events occurred in less than 2% of men and generally went away in most men who stopped taking the drug.

That label change unleashed a flood of more than 1,000 lawsuits against Merck. The company reportedly settled at least half of them for $4.3 million in 2018. The Superior Court of New Jersey closed out the consolidated class action against Merck in May 2021, noting that all of the cases had been settled or dismissed.

The suits generally accused Merck of not giving adequate warning about sexual side effects, according to an investigation by Reuters. That 2019 special report found that Merck had understated the number of men who experienced sexual side effects and the duration of those symptoms. The news organization also reported that from 2009 to 2018, the FDA received 5,000 reports of sexual or mental health side effects – and sometimes both – in men who took finasteride. Some 350 of the men reported suicidal thoughts, and there were 50 reports of suicide.

Public Citizen’s lawsuit alleges that VigiBase, which is managed by the World Health Organization Collaborating Centre for International Drug Monitoring, lists 378 cases of suicidal ideation, 39 cases of suicide attempt, and 88 cases of completed suicide associated with finasteride use. VigiBase collects data from 153 countries on adverse reactions to medications.

In February 2021, more documents from the class action lawsuits were unsealed in response to a Reuters request. According to the news organization, the documents showed that Merck knew of reports of depression, including suicidal thoughts, as early as 2009.



However, according to Reuters, the FDA in 2011 granted Merck’s request to only note depression as a potential side effect, without including the risk of suicidal ideation.

The current FDA label notes a small incidence of sexual dysfunction, including decreased libido (1.8% in trials) and erectile dysfunction (1.3%) and mentions depression as a side effect observed during the postmarketing period.

The Canadian label has the same statistics on sexual side effects but is much stronger on mental adverse effects: “Psychiatric disorders: mood alterations and depression, decreased libido that continued after discontinuation of treatment. Mood alterations including depressed mood and, less frequently, suicidal ideation have been reported in patients treated with finasteride 1 mg. Patients should be monitored for psychiatric symptoms, and if these occur, the patient should be advised to seek medical advice.”

In the United Kingdom, patients prescribed the drug are given a leaflet, which notes that “Mood alterations such as depressed mood, depression and, less frequently, suicidal thoughts have been reported in patients treated with Propecia,” and advises patients to stop taking the drug if they experience any of those symptoms and to discuss it with their physician.

Public Citizen noted in its lawsuit that French and German drug regulators have sent letters to clinicians advising them to inform patients of the risk of suicidal thoughts and anxiety.

 

 

Is there biological plausibility?

To bolster its argument that finasteride has dangerous psychiatric side effects, the advocacy organization cited a study first published in JAMA Dermatology in late 2020 that investigated suicidality and psychological adverse events in patients taking finasteride.

David-Dan Nguyen, MPH, and his colleagues at Brigham and Women’s Hospital in Boston, McGill University, Montreal, and the University of Montreal, examined the VigiBase database and found 356 cases of suicidality and 2,926 psychological adverse events; cases were highest from 2015 to 2019.

They documented what they called a “significant disproportionality signal for suicidality (reporting odds ratio, 1.63; 95% confidence interval, 2.90-4.15) and psychological adverse events (ROR, 4.33; 95% CI, 4.17-4.49) with finasteride, especially in younger men and those with alopecia, but not in older men or those with benign prostatic hyperplasia.

The study authors noted that some studies have suggested that men with depression have low levels of the neurosteroid allopregnanolone, which is produced by the 5-alpha reductase enzyme. Finasteride is a 5-alpha reductase inhibitor.

According to Public Citizen’s lawsuit, “The product labeling does not disclose important information about finasteride’s mechanism of action,” and “the drug inhibits multiple steroid hormone pathways that are responsible for the formation of brain neurosteroids that regulate many critical functions in the central nervous system, like sexual function, mood, sleep, cognitive function, the stress response, and motivation.”

Dr. Jacobs said that “there’s a lot of good solid high-quality research, mostly in animals, but also some on humans, showing a plausible link between blocking 5-alpha reductase in the brain, deficiency of neuroactive steroids, and depression.”

The author of an accompanying editorial, Roger S. Ho, MD, MPH, an associate professor in the department of dermatology, New York University, was skeptical. “Without a plausible biological hypothesis pharmacodynamically linking the drug and the reported adverse event, this kind of analysis may lead to false findings,” Dr. Ho said in the editorial about the Nguyen study.

Dr. Ho also wrote that he believed that the lack of a suicidality signal for dutasteride, a drug with a similar mechanism of action, but without as much media attention, “hints at a potential reporting bias unique to finasteride.”

He recommended that clinicians “conduct a full evaluation and a detailed, personalized risk-benefit assessment for patients before each prescription of finasteride.”
 

Important medicine, important caveats

Dr. Jacobs said that many of the men who come to him with side effects after taking finasteride have “been blown off by most of the doctors they go to see.”

Urologists dismiss them because their sexual dysfunction is not a gonad issue. They are told that it’s in their head, said Dr. Jacobs, adding that, “it is in their head, but it’s biological.”

The drug’s label advises that sexual side effects disappear when the drug is stopped. “That’s only true most of the time, not all of the time,” said Dr. Jacobs, adding that the persistence of any side effects impacts what he calls a “small subset” of men who take the drug.

“We have treated tens of thousands of patients who have benefited from the medicine and had no side effects,” said Dr. Bernstein. “But there is a lot that’s still not known about it.”

Even so, “baldness in young people is not a benign condition,” he said, adding that it can be socially debilitating. “An 18-year-old with a full head of thick hair who’s totally bald in 3 or 4 years – that can totally change his psyche,” Dr. Bernstein said. Finasteride may be the best option for those young men, and it is an important medication, he said. Does it need to be used more carefully? “Certainly you can’t argue with that,” he commented.

Dr. Bernstein and Dr. Irwig reported no conflicts. Dr. Jacobs disclosed that he is an expert witness for the plaintiffs in a suit against Propecia maker Merck.

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A new lawsuit seeking to force the Food and Drug Administration to act on a request to add stricter warnings to finasteride or remove it from the market may rekindle a debate on whether some of the observed side effects from the hair loss drug merit a closer look and, potentially, better counseling and monitoring from clinicians.

Dr. Robert M. Bernstein

The nonprofit advocacy group Public Citizen filed the suit on behalf of the Post-Finasteride Syndrome Foundation (PFSF) in the U.S. District Court for the District of Columbia. The PFSF had filed a citizen’s petition in 2017 that requested that the FDA either take the 1-mg formulation off the market, or add warnings about the potential for erectile dysfunction, depression, and suicidal ideation, among other adverse reactions.

The PFSF has alleged that long-term use of Propecia (and its generic equivalents) can lead to postfinasteride syndrome (PFS), characterized by sexual dysfunction and psycho-neurocognitive symptoms. The symptoms may continue long after men stop taking the drug, according to PFSF.

Public Citizen said the FDA needs to take action in part because U.S. prescriptions of the hair loss formulation “more than doubled from 2015 to 2020,” and online and telemedicine companies such as Hims, Roman, and Keeps “aggressively market and sell generic finasteride for hair loss.” According to GoodRx, a 1-month supply of generic 1-mg tablets costs as little as $8-$10.

Both Canadian and British regulatory authorities have added warnings about depression and suicide to the Propecia label but the FDA has not changed its labeling. An agency spokesperson told this news organization that the “FDA does not comment on the status of pending citizen petitions or on pending litigation.”

Propecia’s developer, Merck, has not responded to several requests for comment from this news organization.

Why some patients develop PFS and others do not is still not understood, but some clinicians said they counsel all patients on the risks of severe and persistent side effects that have been associated with Propecia.

Robert M. Bernstein, MD, of the department of dermatology at Columbia University, New York, and a fellow of the International Society of Hair Restoration Surgery, said that 2%-4% of his patients have some side effects, similar to the original reported incidence, with sexual dysfunction being the most common.

If a man experiences an adverse effect, the drug should be stopped, Dr. Bernstein said in an interview. He noted that “there seems to be a significant increased risk of persistent side effects in people with certain psychiatric conditions, and those people should be counseled carefully before considering the medication.”

“Everybody should be warned that the risk of persistent side effects is real but in the average person it is quite uncommon,” added Dr. Bernstein, founder of Bernstein Medical, a division of Schweiger Dermatology Group focusing on the diagnosis and treatment of hair loss. “I don’t think it should be withdrawn from the market,” he said.

Dr. Alan R. Jacobs


Alan Jacobs, MD, a Manhattan-based neuroendocrinologist and behavioral neurologist in private practice who said he has treated hundreds of men for PFS, and who is an expert witness for the plaintiff in a suit alleging that finasteride led to a man’s suicide, said that taking the drug off the market would be unfortunate because it helps so many men. “I don’t think you need to get rid of the drug per se,” he said in an interview. “But very rapidly, people need to do clinical research to find out how to predict who’s more at risk,” he added.

Michael S. Irwig, MD, associate professor of medicine at Harvard Medical School, Boston, who has studied the persistent sexual and nonsexual side effects of finasteride, said he believes there should be a boxed warning on the finasteride label to let the men who take it “know that they can have permanent persistent sexual dysfunction, and/or depression and suicide have been noted with this medicine.

“Those who prescribe it should be having a conversation with patients about the potential risks and benefits so that everybody knows about the potential before they get on the medicine,” said Dr. Irwig, who also is an endocrinologist at Beth Israel Deaconess Medical Center in Boston.
 

 

 

Other countries warn of psychiatric effects

The FDA approved the 1-mg form of finasteride for male pattern hair loss in 1997.

In 2012, the label and the patient insert were updated to state that side effects included less desire for sex, erectile dysfunction, and a decrease in the amount of semen produced, but that those adverse events occurred in less than 2% of men and generally went away in most men who stopped taking the drug.

That label change unleashed a flood of more than 1,000 lawsuits against Merck. The company reportedly settled at least half of them for $4.3 million in 2018. The Superior Court of New Jersey closed out the consolidated class action against Merck in May 2021, noting that all of the cases had been settled or dismissed.

The suits generally accused Merck of not giving adequate warning about sexual side effects, according to an investigation by Reuters. That 2019 special report found that Merck had understated the number of men who experienced sexual side effects and the duration of those symptoms. The news organization also reported that from 2009 to 2018, the FDA received 5,000 reports of sexual or mental health side effects – and sometimes both – in men who took finasteride. Some 350 of the men reported suicidal thoughts, and there were 50 reports of suicide.

Public Citizen’s lawsuit alleges that VigiBase, which is managed by the World Health Organization Collaborating Centre for International Drug Monitoring, lists 378 cases of suicidal ideation, 39 cases of suicide attempt, and 88 cases of completed suicide associated with finasteride use. VigiBase collects data from 153 countries on adverse reactions to medications.

In February 2021, more documents from the class action lawsuits were unsealed in response to a Reuters request. According to the news organization, the documents showed that Merck knew of reports of depression, including suicidal thoughts, as early as 2009.



However, according to Reuters, the FDA in 2011 granted Merck’s request to only note depression as a potential side effect, without including the risk of suicidal ideation.

The current FDA label notes a small incidence of sexual dysfunction, including decreased libido (1.8% in trials) and erectile dysfunction (1.3%) and mentions depression as a side effect observed during the postmarketing period.

The Canadian label has the same statistics on sexual side effects but is much stronger on mental adverse effects: “Psychiatric disorders: mood alterations and depression, decreased libido that continued after discontinuation of treatment. Mood alterations including depressed mood and, less frequently, suicidal ideation have been reported in patients treated with finasteride 1 mg. Patients should be monitored for psychiatric symptoms, and if these occur, the patient should be advised to seek medical advice.”

In the United Kingdom, patients prescribed the drug are given a leaflet, which notes that “Mood alterations such as depressed mood, depression and, less frequently, suicidal thoughts have been reported in patients treated with Propecia,” and advises patients to stop taking the drug if they experience any of those symptoms and to discuss it with their physician.

Public Citizen noted in its lawsuit that French and German drug regulators have sent letters to clinicians advising them to inform patients of the risk of suicidal thoughts and anxiety.

 

 

Is there biological plausibility?

To bolster its argument that finasteride has dangerous psychiatric side effects, the advocacy organization cited a study first published in JAMA Dermatology in late 2020 that investigated suicidality and psychological adverse events in patients taking finasteride.

David-Dan Nguyen, MPH, and his colleagues at Brigham and Women’s Hospital in Boston, McGill University, Montreal, and the University of Montreal, examined the VigiBase database and found 356 cases of suicidality and 2,926 psychological adverse events; cases were highest from 2015 to 2019.

They documented what they called a “significant disproportionality signal for suicidality (reporting odds ratio, 1.63; 95% confidence interval, 2.90-4.15) and psychological adverse events (ROR, 4.33; 95% CI, 4.17-4.49) with finasteride, especially in younger men and those with alopecia, but not in older men or those with benign prostatic hyperplasia.

The study authors noted that some studies have suggested that men with depression have low levels of the neurosteroid allopregnanolone, which is produced by the 5-alpha reductase enzyme. Finasteride is a 5-alpha reductase inhibitor.

According to Public Citizen’s lawsuit, “The product labeling does not disclose important information about finasteride’s mechanism of action,” and “the drug inhibits multiple steroid hormone pathways that are responsible for the formation of brain neurosteroids that regulate many critical functions in the central nervous system, like sexual function, mood, sleep, cognitive function, the stress response, and motivation.”

Dr. Jacobs said that “there’s a lot of good solid high-quality research, mostly in animals, but also some on humans, showing a plausible link between blocking 5-alpha reductase in the brain, deficiency of neuroactive steroids, and depression.”

The author of an accompanying editorial, Roger S. Ho, MD, MPH, an associate professor in the department of dermatology, New York University, was skeptical. “Without a plausible biological hypothesis pharmacodynamically linking the drug and the reported adverse event, this kind of analysis may lead to false findings,” Dr. Ho said in the editorial about the Nguyen study.

Dr. Ho also wrote that he believed that the lack of a suicidality signal for dutasteride, a drug with a similar mechanism of action, but without as much media attention, “hints at a potential reporting bias unique to finasteride.”

He recommended that clinicians “conduct a full evaluation and a detailed, personalized risk-benefit assessment for patients before each prescription of finasteride.”
 

Important medicine, important caveats

Dr. Jacobs said that many of the men who come to him with side effects after taking finasteride have “been blown off by most of the doctors they go to see.”

Urologists dismiss them because their sexual dysfunction is not a gonad issue. They are told that it’s in their head, said Dr. Jacobs, adding that, “it is in their head, but it’s biological.”

The drug’s label advises that sexual side effects disappear when the drug is stopped. “That’s only true most of the time, not all of the time,” said Dr. Jacobs, adding that the persistence of any side effects impacts what he calls a “small subset” of men who take the drug.

“We have treated tens of thousands of patients who have benefited from the medicine and had no side effects,” said Dr. Bernstein. “But there is a lot that’s still not known about it.”

Even so, “baldness in young people is not a benign condition,” he said, adding that it can be socially debilitating. “An 18-year-old with a full head of thick hair who’s totally bald in 3 or 4 years – that can totally change his psyche,” Dr. Bernstein said. Finasteride may be the best option for those young men, and it is an important medication, he said. Does it need to be used more carefully? “Certainly you can’t argue with that,” he commented.

Dr. Bernstein and Dr. Irwig reported no conflicts. Dr. Jacobs disclosed that he is an expert witness for the plaintiffs in a suit against Propecia maker Merck.

A new lawsuit seeking to force the Food and Drug Administration to act on a request to add stricter warnings to finasteride or remove it from the market may rekindle a debate on whether some of the observed side effects from the hair loss drug merit a closer look and, potentially, better counseling and monitoring from clinicians.

Dr. Robert M. Bernstein

The nonprofit advocacy group Public Citizen filed the suit on behalf of the Post-Finasteride Syndrome Foundation (PFSF) in the U.S. District Court for the District of Columbia. The PFSF had filed a citizen’s petition in 2017 that requested that the FDA either take the 1-mg formulation off the market, or add warnings about the potential for erectile dysfunction, depression, and suicidal ideation, among other adverse reactions.

The PFSF has alleged that long-term use of Propecia (and its generic equivalents) can lead to postfinasteride syndrome (PFS), characterized by sexual dysfunction and psycho-neurocognitive symptoms. The symptoms may continue long after men stop taking the drug, according to PFSF.

Public Citizen said the FDA needs to take action in part because U.S. prescriptions of the hair loss formulation “more than doubled from 2015 to 2020,” and online and telemedicine companies such as Hims, Roman, and Keeps “aggressively market and sell generic finasteride for hair loss.” According to GoodRx, a 1-month supply of generic 1-mg tablets costs as little as $8-$10.

Both Canadian and British regulatory authorities have added warnings about depression and suicide to the Propecia label but the FDA has not changed its labeling. An agency spokesperson told this news organization that the “FDA does not comment on the status of pending citizen petitions or on pending litigation.”

Propecia’s developer, Merck, has not responded to several requests for comment from this news organization.

Why some patients develop PFS and others do not is still not understood, but some clinicians said they counsel all patients on the risks of severe and persistent side effects that have been associated with Propecia.

Robert M. Bernstein, MD, of the department of dermatology at Columbia University, New York, and a fellow of the International Society of Hair Restoration Surgery, said that 2%-4% of his patients have some side effects, similar to the original reported incidence, with sexual dysfunction being the most common.

If a man experiences an adverse effect, the drug should be stopped, Dr. Bernstein said in an interview. He noted that “there seems to be a significant increased risk of persistent side effects in people with certain psychiatric conditions, and those people should be counseled carefully before considering the medication.”

“Everybody should be warned that the risk of persistent side effects is real but in the average person it is quite uncommon,” added Dr. Bernstein, founder of Bernstein Medical, a division of Schweiger Dermatology Group focusing on the diagnosis and treatment of hair loss. “I don’t think it should be withdrawn from the market,” he said.

Dr. Alan R. Jacobs


Alan Jacobs, MD, a Manhattan-based neuroendocrinologist and behavioral neurologist in private practice who said he has treated hundreds of men for PFS, and who is an expert witness for the plaintiff in a suit alleging that finasteride led to a man’s suicide, said that taking the drug off the market would be unfortunate because it helps so many men. “I don’t think you need to get rid of the drug per se,” he said in an interview. “But very rapidly, people need to do clinical research to find out how to predict who’s more at risk,” he added.

Michael S. Irwig, MD, associate professor of medicine at Harvard Medical School, Boston, who has studied the persistent sexual and nonsexual side effects of finasteride, said he believes there should be a boxed warning on the finasteride label to let the men who take it “know that they can have permanent persistent sexual dysfunction, and/or depression and suicide have been noted with this medicine.

“Those who prescribe it should be having a conversation with patients about the potential risks and benefits so that everybody knows about the potential before they get on the medicine,” said Dr. Irwig, who also is an endocrinologist at Beth Israel Deaconess Medical Center in Boston.
 

 

 

Other countries warn of psychiatric effects

The FDA approved the 1-mg form of finasteride for male pattern hair loss in 1997.

In 2012, the label and the patient insert were updated to state that side effects included less desire for sex, erectile dysfunction, and a decrease in the amount of semen produced, but that those adverse events occurred in less than 2% of men and generally went away in most men who stopped taking the drug.

That label change unleashed a flood of more than 1,000 lawsuits against Merck. The company reportedly settled at least half of them for $4.3 million in 2018. The Superior Court of New Jersey closed out the consolidated class action against Merck in May 2021, noting that all of the cases had been settled or dismissed.

The suits generally accused Merck of not giving adequate warning about sexual side effects, according to an investigation by Reuters. That 2019 special report found that Merck had understated the number of men who experienced sexual side effects and the duration of those symptoms. The news organization also reported that from 2009 to 2018, the FDA received 5,000 reports of sexual or mental health side effects – and sometimes both – in men who took finasteride. Some 350 of the men reported suicidal thoughts, and there were 50 reports of suicide.

Public Citizen’s lawsuit alleges that VigiBase, which is managed by the World Health Organization Collaborating Centre for International Drug Monitoring, lists 378 cases of suicidal ideation, 39 cases of suicide attempt, and 88 cases of completed suicide associated with finasteride use. VigiBase collects data from 153 countries on adverse reactions to medications.

In February 2021, more documents from the class action lawsuits were unsealed in response to a Reuters request. According to the news organization, the documents showed that Merck knew of reports of depression, including suicidal thoughts, as early as 2009.



However, according to Reuters, the FDA in 2011 granted Merck’s request to only note depression as a potential side effect, without including the risk of suicidal ideation.

The current FDA label notes a small incidence of sexual dysfunction, including decreased libido (1.8% in trials) and erectile dysfunction (1.3%) and mentions depression as a side effect observed during the postmarketing period.

The Canadian label has the same statistics on sexual side effects but is much stronger on mental adverse effects: “Psychiatric disorders: mood alterations and depression, decreased libido that continued after discontinuation of treatment. Mood alterations including depressed mood and, less frequently, suicidal ideation have been reported in patients treated with finasteride 1 mg. Patients should be monitored for psychiatric symptoms, and if these occur, the patient should be advised to seek medical advice.”

In the United Kingdom, patients prescribed the drug are given a leaflet, which notes that “Mood alterations such as depressed mood, depression and, less frequently, suicidal thoughts have been reported in patients treated with Propecia,” and advises patients to stop taking the drug if they experience any of those symptoms and to discuss it with their physician.

Public Citizen noted in its lawsuit that French and German drug regulators have sent letters to clinicians advising them to inform patients of the risk of suicidal thoughts and anxiety.

 

 

Is there biological plausibility?

To bolster its argument that finasteride has dangerous psychiatric side effects, the advocacy organization cited a study first published in JAMA Dermatology in late 2020 that investigated suicidality and psychological adverse events in patients taking finasteride.

David-Dan Nguyen, MPH, and his colleagues at Brigham and Women’s Hospital in Boston, McGill University, Montreal, and the University of Montreal, examined the VigiBase database and found 356 cases of suicidality and 2,926 psychological adverse events; cases were highest from 2015 to 2019.

They documented what they called a “significant disproportionality signal for suicidality (reporting odds ratio, 1.63; 95% confidence interval, 2.90-4.15) and psychological adverse events (ROR, 4.33; 95% CI, 4.17-4.49) with finasteride, especially in younger men and those with alopecia, but not in older men or those with benign prostatic hyperplasia.

The study authors noted that some studies have suggested that men with depression have low levels of the neurosteroid allopregnanolone, which is produced by the 5-alpha reductase enzyme. Finasteride is a 5-alpha reductase inhibitor.

According to Public Citizen’s lawsuit, “The product labeling does not disclose important information about finasteride’s mechanism of action,” and “the drug inhibits multiple steroid hormone pathways that are responsible for the formation of brain neurosteroids that regulate many critical functions in the central nervous system, like sexual function, mood, sleep, cognitive function, the stress response, and motivation.”

Dr. Jacobs said that “there’s a lot of good solid high-quality research, mostly in animals, but also some on humans, showing a plausible link between blocking 5-alpha reductase in the brain, deficiency of neuroactive steroids, and depression.”

The author of an accompanying editorial, Roger S. Ho, MD, MPH, an associate professor in the department of dermatology, New York University, was skeptical. “Without a plausible biological hypothesis pharmacodynamically linking the drug and the reported adverse event, this kind of analysis may lead to false findings,” Dr. Ho said in the editorial about the Nguyen study.

Dr. Ho also wrote that he believed that the lack of a suicidality signal for dutasteride, a drug with a similar mechanism of action, but without as much media attention, “hints at a potential reporting bias unique to finasteride.”

He recommended that clinicians “conduct a full evaluation and a detailed, personalized risk-benefit assessment for patients before each prescription of finasteride.”
 

Important medicine, important caveats

Dr. Jacobs said that many of the men who come to him with side effects after taking finasteride have “been blown off by most of the doctors they go to see.”

Urologists dismiss them because their sexual dysfunction is not a gonad issue. They are told that it’s in their head, said Dr. Jacobs, adding that, “it is in their head, but it’s biological.”

The drug’s label advises that sexual side effects disappear when the drug is stopped. “That’s only true most of the time, not all of the time,” said Dr. Jacobs, adding that the persistence of any side effects impacts what he calls a “small subset” of men who take the drug.

“We have treated tens of thousands of patients who have benefited from the medicine and had no side effects,” said Dr. Bernstein. “But there is a lot that’s still not known about it.”

Even so, “baldness in young people is not a benign condition,” he said, adding that it can be socially debilitating. “An 18-year-old with a full head of thick hair who’s totally bald in 3 or 4 years – that can totally change his psyche,” Dr. Bernstein said. Finasteride may be the best option for those young men, and it is an important medication, he said. Does it need to be used more carefully? “Certainly you can’t argue with that,” he commented.

Dr. Bernstein and Dr. Irwig reported no conflicts. Dr. Jacobs disclosed that he is an expert witness for the plaintiffs in a suit against Propecia maker Merck.

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Will ‘Dr. Disinformation’ ever face the music?

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Tue, 09/28/2021 - 08:54

On Sept. 5, Rashid Buttar, DO, posted on Twitter that COVID-19 “was a planned operation” and shared an article alleging that most people who got the COVID vaccine would be dead by 2025.

His statement is a recent example in what has been a steady stream of spurious claims surrounding the COVID vaccines and treatments that swirl around the public consciousness. Others include testimony in June by Sherri Jane Tenpenny, DO, before Ohio state legislators that the vaccine could cause people to become magnetized. Clips from the hearing went viral on the Internet. On April 9, 2020, Joseph Mercola, DO, posted a video titled “Could hydrogen peroxide treat coronavirus?” which was shared more than 4,600 times. In the video, Dr. Mercola said inhaling hydrogen peroxide through a nebulizer could prevent or cure COVID.

These physicians are identified as members of the “Disinformation Dozen,” a group of top superspreaders of COVID vaccine misinformation on social media, according to a 2021 report by the nonprofit Center for Countering Digital Hate. The report, based on an analysis of antivaccine content on social media platforms, found that 12 people were responsible for 65% of it. The group is composed of physicians, antivaccine activists, and people known for promoting alternative medicine.

The physician voices are of particular concern because their medical credentials lend credence to their unproven, often dangerous pronouncements. All three continue to hold medical licenses and have not faced consequences for their COVID-related statements.

But leaders of professional medical organizations increasingly are calling for that to change and urging medical oversight boards to take more aggressive action.

In July, the Federation of State Medical Boards, the national umbrella organization for the state-based boards, issued a statement making clear that doctors who generate and spread COVID misinformation could be subject to disciplinary action, including the suspension or revocation of their licenses. The American Board of Family Medicine, American Board of Internal Medicine, and American Board of Pediatrics issued a joint statement Sept. 9 in support of the state boards’ position, warning that “such unethical or unprofessional conduct may prompt their respective board to take action that could put their certification at risk.”

And the superspreaders identified by the center’s report are not alone. KHN identified 20 other doctors who have made false or misleading claims about COVID by combing through published fact checks and other news coverage.

For example, at an Indiana school board meeting in August, Dan Stock, MD, claimed the surge in covid cases this summer was due to “antibody mediated viral enhancement” from people receiving covid vaccines. PolitiFact rated his claim “Pants on Fire” false.

Stella Immanuel, MD, a member of a group America’s Frontline Doctors, which has consistently made false statements about COVID, said in a video that went viral in July 2020 that masks weren’t needed because covid could be cured by hydroxychloroquine. Dr. Immanuel’s website currently promotes a set of vitamins, as well as hydroxychloroquine and ivermectin, as COVID treatments.

Two of the doctors mentioned by name in this article responded to requests for comment. Dr. Mercola offered documents to rebut criticisms of his hydrogen peroxide COVID treatment and took issue with the center’s “Disinformation Dozen” report methodology. Dr. Buttar defended his positions, saying via email that “the science is clear and anyone who contests it, has a suspect agenda at best and/or lacks a moral compass.” He also pointed to data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Recording System, considered inconclusive by many experts.

Since the onset of the COVID pandemic, misinformation has been widespread on social media platforms. And many experts blame it for undermining efforts to curb the coronavirus’s spread. A recent poll showed that more than 50% of Americans who won’t get vaccinated cited conspiracy theories as their reasons – for example, saying the vaccines cause infertility or alter DNA.

Some physicians have gained notoriety by embracing COVID-related fringe ideas, quack treatments and falsehoods via social media, conservative talk shows, and even in person with patients. Whether promoting the use of ivermectin, an antiparasitic drug for animals, or a mix of vitamins to treat COVID, doctors’ words can be especially powerful. Public opinion polls consistently show that Americans have high trust in doctors.

“There is a sense of credibility that comes with being a doctor,” said Rachel Moran, PhD, a researcher who studies COVID misinformation at the University of Washington. “There is also a sense they have access to insider info that we don’t. This is a very confusing time, and it can seem that if anyone knows what I should be doing in this situation, it’s a doctor.”

While COVID is a novel and complicated infectious disease, physicians spreading misinformation generally have no particular expertise in infectious diseases. Scott Atlas, MD, who endorsed former President Donald Trump’s unproven statements about the course of the pandemic, is a radiation oncologist.

Traditionally, the responsibility of policing physicians has fallen to state medical boards. Beyond overseeing the licensing process, these panels investigate complaints about doctors and discipline those who engage in unethical, unprofessional or, in extreme cases, criminal activity. Any member of the public can submit a complaint about a physician.

“The boards are relatively slow and weak and it’s a long, slow process to pull somebody’s license,” said Arthur Caplan, PhD, founding head of the department of medical ethics at New York University. “In many states, they have their hands full with doctors who have committed felonies, doctors who are molesting their patients. Keeping an eye on misinformation is somewhat down on the priority list.”

To date, only two doctors have reportedly faced such sanctions. In Oregon, Steven LaTulippe, MD, had his license suspended in December 2020 for refusing to wear a face mask at his clinic and telling patients that masks were ineffective in curbing the spread of COVID, and even dangerous. Thomas Cowan, MD, a San Francisco physician who posted a YouTube video that went viral in March 2020 stating that 5G networks cause COVID, voluntarily surrendered his medical license to California’s medical board in February 2021.

Humayun Chaudhry, DO, president of the Federation of State Medical Boards, however, said it’s possible some doctors could already be the subject of inquiries and investigations, since these actions are not made public until sanctions are handed down.

KHN reached out to the medical and osteopathic boards of all 50 states and the District of Columbia to see if they had received COVID misinformation complaints. Of the 43 that responded, only a handful shared specifics.

During a 1-week period in August, Kansas’ medical board received six such complaints. In all, the state has received 35 complaints against 20 licensees about spreading covid misinformation on social media and in person. Indiana has received about 30 in the past year. South Carolina said it had about 10 since January. Rhode Island didn’t share the number of complaints but said it has taken disciplinary action against one doctor for spreading misinformation, though it hasn’t moved to suspend his license. (The disciplinary measures include a fine, a reprimand on the doctor’s record and a mandate to complete an ethics course.) Five states said they had received only a couple, and 11 states reported receiving no complaints regarding COVID misinformation.

Confidentiality laws in 13 states prevented those boards from sharing information about complaints.

Social media companies have also been slow to take action. Some doctors’ accounts – specifically those among the Disinformation Dozen – have been suspended, but others are still active and posting misinformation.

Imran Ahmed, CEO of the Center for Countering Digital Hate, said social media platforms often don’t consistently apply their rules against spreading misinformation.

“Even when it’s the same companies, Facebook will sometimes take posts down, but Instagram will not,” Mr. Ahmed said, referring to Facebook’s ownership of Instagram. “It goes to show their piecemeal, ineffective approach to enforcing their own rules.”

A Facebook spokesperson said the company has removed over 3,000 accounts, pages and groups for repeatedly violating COVID and vaccine misinformation policies since the beginning of the pandemic. Dr. Buttar’s Facebook and Instagram pages and Tenpenny’s Facebook page have been removed, while Dr. Mercola’s Facebook posts have been demoted, which means fewer people will see them. Dr. Tenpenny and Dr. Mercola still have Instagram accounts.

Part of the challenge may be that these doctors sometimes present scientific opinions that aren’t mainstream but are viewed as potentially valid by some of their colleagues.

“It can be difficult to prove that what is being said is outside the range of scientific and medical consensus,” said Dr. Caplan. “The doctors who were advising Trump – like Scott Atlas – recommended herd immunity. That was far from the consensus of epidemiologists, but you couldn’t get a board to take his license away because it was a fringe opinion.”

Even if these physicians don’t face consequences, it is likely, experts said, that the public health will.

“Medical misinformation doesn’t just result in people making bad personal and community health choices, but it also divides communities and families, leaving an emotional toll,” said Dr. Moran. “Misinformation narratives have real sticking power and impact people’s ability to make safe health choices.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

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On Sept. 5, Rashid Buttar, DO, posted on Twitter that COVID-19 “was a planned operation” and shared an article alleging that most people who got the COVID vaccine would be dead by 2025.

His statement is a recent example in what has been a steady stream of spurious claims surrounding the COVID vaccines and treatments that swirl around the public consciousness. Others include testimony in June by Sherri Jane Tenpenny, DO, before Ohio state legislators that the vaccine could cause people to become magnetized. Clips from the hearing went viral on the Internet. On April 9, 2020, Joseph Mercola, DO, posted a video titled “Could hydrogen peroxide treat coronavirus?” which was shared more than 4,600 times. In the video, Dr. Mercola said inhaling hydrogen peroxide through a nebulizer could prevent or cure COVID.

These physicians are identified as members of the “Disinformation Dozen,” a group of top superspreaders of COVID vaccine misinformation on social media, according to a 2021 report by the nonprofit Center for Countering Digital Hate. The report, based on an analysis of antivaccine content on social media platforms, found that 12 people were responsible for 65% of it. The group is composed of physicians, antivaccine activists, and people known for promoting alternative medicine.

The physician voices are of particular concern because their medical credentials lend credence to their unproven, often dangerous pronouncements. All three continue to hold medical licenses and have not faced consequences for their COVID-related statements.

But leaders of professional medical organizations increasingly are calling for that to change and urging medical oversight boards to take more aggressive action.

In July, the Federation of State Medical Boards, the national umbrella organization for the state-based boards, issued a statement making clear that doctors who generate and spread COVID misinformation could be subject to disciplinary action, including the suspension or revocation of their licenses. The American Board of Family Medicine, American Board of Internal Medicine, and American Board of Pediatrics issued a joint statement Sept. 9 in support of the state boards’ position, warning that “such unethical or unprofessional conduct may prompt their respective board to take action that could put their certification at risk.”

And the superspreaders identified by the center’s report are not alone. KHN identified 20 other doctors who have made false or misleading claims about COVID by combing through published fact checks and other news coverage.

For example, at an Indiana school board meeting in August, Dan Stock, MD, claimed the surge in covid cases this summer was due to “antibody mediated viral enhancement” from people receiving covid vaccines. PolitiFact rated his claim “Pants on Fire” false.

Stella Immanuel, MD, a member of a group America’s Frontline Doctors, which has consistently made false statements about COVID, said in a video that went viral in July 2020 that masks weren’t needed because covid could be cured by hydroxychloroquine. Dr. Immanuel’s website currently promotes a set of vitamins, as well as hydroxychloroquine and ivermectin, as COVID treatments.

Two of the doctors mentioned by name in this article responded to requests for comment. Dr. Mercola offered documents to rebut criticisms of his hydrogen peroxide COVID treatment and took issue with the center’s “Disinformation Dozen” report methodology. Dr. Buttar defended his positions, saying via email that “the science is clear and anyone who contests it, has a suspect agenda at best and/or lacks a moral compass.” He also pointed to data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Recording System, considered inconclusive by many experts.

Since the onset of the COVID pandemic, misinformation has been widespread on social media platforms. And many experts blame it for undermining efforts to curb the coronavirus’s spread. A recent poll showed that more than 50% of Americans who won’t get vaccinated cited conspiracy theories as their reasons – for example, saying the vaccines cause infertility or alter DNA.

Some physicians have gained notoriety by embracing COVID-related fringe ideas, quack treatments and falsehoods via social media, conservative talk shows, and even in person with patients. Whether promoting the use of ivermectin, an antiparasitic drug for animals, or a mix of vitamins to treat COVID, doctors’ words can be especially powerful. Public opinion polls consistently show that Americans have high trust in doctors.

“There is a sense of credibility that comes with being a doctor,” said Rachel Moran, PhD, a researcher who studies COVID misinformation at the University of Washington. “There is also a sense they have access to insider info that we don’t. This is a very confusing time, and it can seem that if anyone knows what I should be doing in this situation, it’s a doctor.”

While COVID is a novel and complicated infectious disease, physicians spreading misinformation generally have no particular expertise in infectious diseases. Scott Atlas, MD, who endorsed former President Donald Trump’s unproven statements about the course of the pandemic, is a radiation oncologist.

Traditionally, the responsibility of policing physicians has fallen to state medical boards. Beyond overseeing the licensing process, these panels investigate complaints about doctors and discipline those who engage in unethical, unprofessional or, in extreme cases, criminal activity. Any member of the public can submit a complaint about a physician.

“The boards are relatively slow and weak and it’s a long, slow process to pull somebody’s license,” said Arthur Caplan, PhD, founding head of the department of medical ethics at New York University. “In many states, they have their hands full with doctors who have committed felonies, doctors who are molesting their patients. Keeping an eye on misinformation is somewhat down on the priority list.”

To date, only two doctors have reportedly faced such sanctions. In Oregon, Steven LaTulippe, MD, had his license suspended in December 2020 for refusing to wear a face mask at his clinic and telling patients that masks were ineffective in curbing the spread of COVID, and even dangerous. Thomas Cowan, MD, a San Francisco physician who posted a YouTube video that went viral in March 2020 stating that 5G networks cause COVID, voluntarily surrendered his medical license to California’s medical board in February 2021.

Humayun Chaudhry, DO, president of the Federation of State Medical Boards, however, said it’s possible some doctors could already be the subject of inquiries and investigations, since these actions are not made public until sanctions are handed down.

KHN reached out to the medical and osteopathic boards of all 50 states and the District of Columbia to see if they had received COVID misinformation complaints. Of the 43 that responded, only a handful shared specifics.

During a 1-week period in August, Kansas’ medical board received six such complaints. In all, the state has received 35 complaints against 20 licensees about spreading covid misinformation on social media and in person. Indiana has received about 30 in the past year. South Carolina said it had about 10 since January. Rhode Island didn’t share the number of complaints but said it has taken disciplinary action against one doctor for spreading misinformation, though it hasn’t moved to suspend his license. (The disciplinary measures include a fine, a reprimand on the doctor’s record and a mandate to complete an ethics course.) Five states said they had received only a couple, and 11 states reported receiving no complaints regarding COVID misinformation.

Confidentiality laws in 13 states prevented those boards from sharing information about complaints.

Social media companies have also been slow to take action. Some doctors’ accounts – specifically those among the Disinformation Dozen – have been suspended, but others are still active and posting misinformation.

Imran Ahmed, CEO of the Center for Countering Digital Hate, said social media platforms often don’t consistently apply their rules against spreading misinformation.

“Even when it’s the same companies, Facebook will sometimes take posts down, but Instagram will not,” Mr. Ahmed said, referring to Facebook’s ownership of Instagram. “It goes to show their piecemeal, ineffective approach to enforcing their own rules.”

A Facebook spokesperson said the company has removed over 3,000 accounts, pages and groups for repeatedly violating COVID and vaccine misinformation policies since the beginning of the pandemic. Dr. Buttar’s Facebook and Instagram pages and Tenpenny’s Facebook page have been removed, while Dr. Mercola’s Facebook posts have been demoted, which means fewer people will see them. Dr. Tenpenny and Dr. Mercola still have Instagram accounts.

Part of the challenge may be that these doctors sometimes present scientific opinions that aren’t mainstream but are viewed as potentially valid by some of their colleagues.

“It can be difficult to prove that what is being said is outside the range of scientific and medical consensus,” said Dr. Caplan. “The doctors who were advising Trump – like Scott Atlas – recommended herd immunity. That was far from the consensus of epidemiologists, but you couldn’t get a board to take his license away because it was a fringe opinion.”

Even if these physicians don’t face consequences, it is likely, experts said, that the public health will.

“Medical misinformation doesn’t just result in people making bad personal and community health choices, but it also divides communities and families, leaving an emotional toll,” said Dr. Moran. “Misinformation narratives have real sticking power and impact people’s ability to make safe health choices.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

On Sept. 5, Rashid Buttar, DO, posted on Twitter that COVID-19 “was a planned operation” and shared an article alleging that most people who got the COVID vaccine would be dead by 2025.

His statement is a recent example in what has been a steady stream of spurious claims surrounding the COVID vaccines and treatments that swirl around the public consciousness. Others include testimony in June by Sherri Jane Tenpenny, DO, before Ohio state legislators that the vaccine could cause people to become magnetized. Clips from the hearing went viral on the Internet. On April 9, 2020, Joseph Mercola, DO, posted a video titled “Could hydrogen peroxide treat coronavirus?” which was shared more than 4,600 times. In the video, Dr. Mercola said inhaling hydrogen peroxide through a nebulizer could prevent or cure COVID.

These physicians are identified as members of the “Disinformation Dozen,” a group of top superspreaders of COVID vaccine misinformation on social media, according to a 2021 report by the nonprofit Center for Countering Digital Hate. The report, based on an analysis of antivaccine content on social media platforms, found that 12 people were responsible for 65% of it. The group is composed of physicians, antivaccine activists, and people known for promoting alternative medicine.

The physician voices are of particular concern because their medical credentials lend credence to their unproven, often dangerous pronouncements. All three continue to hold medical licenses and have not faced consequences for their COVID-related statements.

But leaders of professional medical organizations increasingly are calling for that to change and urging medical oversight boards to take more aggressive action.

In July, the Federation of State Medical Boards, the national umbrella organization for the state-based boards, issued a statement making clear that doctors who generate and spread COVID misinformation could be subject to disciplinary action, including the suspension or revocation of their licenses. The American Board of Family Medicine, American Board of Internal Medicine, and American Board of Pediatrics issued a joint statement Sept. 9 in support of the state boards’ position, warning that “such unethical or unprofessional conduct may prompt their respective board to take action that could put their certification at risk.”

And the superspreaders identified by the center’s report are not alone. KHN identified 20 other doctors who have made false or misleading claims about COVID by combing through published fact checks and other news coverage.

For example, at an Indiana school board meeting in August, Dan Stock, MD, claimed the surge in covid cases this summer was due to “antibody mediated viral enhancement” from people receiving covid vaccines. PolitiFact rated his claim “Pants on Fire” false.

Stella Immanuel, MD, a member of a group America’s Frontline Doctors, which has consistently made false statements about COVID, said in a video that went viral in July 2020 that masks weren’t needed because covid could be cured by hydroxychloroquine. Dr. Immanuel’s website currently promotes a set of vitamins, as well as hydroxychloroquine and ivermectin, as COVID treatments.

Two of the doctors mentioned by name in this article responded to requests for comment. Dr. Mercola offered documents to rebut criticisms of his hydrogen peroxide COVID treatment and took issue with the center’s “Disinformation Dozen” report methodology. Dr. Buttar defended his positions, saying via email that “the science is clear and anyone who contests it, has a suspect agenda at best and/or lacks a moral compass.” He also pointed to data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Recording System, considered inconclusive by many experts.

Since the onset of the COVID pandemic, misinformation has been widespread on social media platforms. And many experts blame it for undermining efforts to curb the coronavirus’s spread. A recent poll showed that more than 50% of Americans who won’t get vaccinated cited conspiracy theories as their reasons – for example, saying the vaccines cause infertility or alter DNA.

Some physicians have gained notoriety by embracing COVID-related fringe ideas, quack treatments and falsehoods via social media, conservative talk shows, and even in person with patients. Whether promoting the use of ivermectin, an antiparasitic drug for animals, or a mix of vitamins to treat COVID, doctors’ words can be especially powerful. Public opinion polls consistently show that Americans have high trust in doctors.

“There is a sense of credibility that comes with being a doctor,” said Rachel Moran, PhD, a researcher who studies COVID misinformation at the University of Washington. “There is also a sense they have access to insider info that we don’t. This is a very confusing time, and it can seem that if anyone knows what I should be doing in this situation, it’s a doctor.”

While COVID is a novel and complicated infectious disease, physicians spreading misinformation generally have no particular expertise in infectious diseases. Scott Atlas, MD, who endorsed former President Donald Trump’s unproven statements about the course of the pandemic, is a radiation oncologist.

Traditionally, the responsibility of policing physicians has fallen to state medical boards. Beyond overseeing the licensing process, these panels investigate complaints about doctors and discipline those who engage in unethical, unprofessional or, in extreme cases, criminal activity. Any member of the public can submit a complaint about a physician.

“The boards are relatively slow and weak and it’s a long, slow process to pull somebody’s license,” said Arthur Caplan, PhD, founding head of the department of medical ethics at New York University. “In many states, they have their hands full with doctors who have committed felonies, doctors who are molesting their patients. Keeping an eye on misinformation is somewhat down on the priority list.”

To date, only two doctors have reportedly faced such sanctions. In Oregon, Steven LaTulippe, MD, had his license suspended in December 2020 for refusing to wear a face mask at his clinic and telling patients that masks were ineffective in curbing the spread of COVID, and even dangerous. Thomas Cowan, MD, a San Francisco physician who posted a YouTube video that went viral in March 2020 stating that 5G networks cause COVID, voluntarily surrendered his medical license to California’s medical board in February 2021.

Humayun Chaudhry, DO, president of the Federation of State Medical Boards, however, said it’s possible some doctors could already be the subject of inquiries and investigations, since these actions are not made public until sanctions are handed down.

KHN reached out to the medical and osteopathic boards of all 50 states and the District of Columbia to see if they had received COVID misinformation complaints. Of the 43 that responded, only a handful shared specifics.

During a 1-week period in August, Kansas’ medical board received six such complaints. In all, the state has received 35 complaints against 20 licensees about spreading covid misinformation on social media and in person. Indiana has received about 30 in the past year. South Carolina said it had about 10 since January. Rhode Island didn’t share the number of complaints but said it has taken disciplinary action against one doctor for spreading misinformation, though it hasn’t moved to suspend his license. (The disciplinary measures include a fine, a reprimand on the doctor’s record and a mandate to complete an ethics course.) Five states said they had received only a couple, and 11 states reported receiving no complaints regarding COVID misinformation.

Confidentiality laws in 13 states prevented those boards from sharing information about complaints.

Social media companies have also been slow to take action. Some doctors’ accounts – specifically those among the Disinformation Dozen – have been suspended, but others are still active and posting misinformation.

Imran Ahmed, CEO of the Center for Countering Digital Hate, said social media platforms often don’t consistently apply their rules against spreading misinformation.

“Even when it’s the same companies, Facebook will sometimes take posts down, but Instagram will not,” Mr. Ahmed said, referring to Facebook’s ownership of Instagram. “It goes to show their piecemeal, ineffective approach to enforcing their own rules.”

A Facebook spokesperson said the company has removed over 3,000 accounts, pages and groups for repeatedly violating COVID and vaccine misinformation policies since the beginning of the pandemic. Dr. Buttar’s Facebook and Instagram pages and Tenpenny’s Facebook page have been removed, while Dr. Mercola’s Facebook posts have been demoted, which means fewer people will see them. Dr. Tenpenny and Dr. Mercola still have Instagram accounts.

Part of the challenge may be that these doctors sometimes present scientific opinions that aren’t mainstream but are viewed as potentially valid by some of their colleagues.

“It can be difficult to prove that what is being said is outside the range of scientific and medical consensus,” said Dr. Caplan. “The doctors who were advising Trump – like Scott Atlas – recommended herd immunity. That was far from the consensus of epidemiologists, but you couldn’t get a board to take his license away because it was a fringe opinion.”

Even if these physicians don’t face consequences, it is likely, experts said, that the public health will.

“Medical misinformation doesn’t just result in people making bad personal and community health choices, but it also divides communities and families, leaving an emotional toll,” said Dr. Moran. “Misinformation narratives have real sticking power and impact people’s ability to make safe health choices.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

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Watchful waiting in BCC: Which patients can benefit?

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Tue, 10/05/2021 - 10:38

Basal cell carcinomas (BCCs), the most common form of skin cancer, are generally slow-growing tumors that occur in older patients.

Given the low rates of metastasis and mortality associated with BCC, some patients do not require treatment. However, there have been no evidence-based recommendations on who may benefit from a watch-and-wait approach.

Now, a study published on Sept. 8 in JAMA Dermatology sheds light on which patients with BCC may be appropriate candidates for watchful waiting.

The investigators found that, for older people with low-grade BCCs and limited life expectancy, the risks associated with surgery – bleeding, infection, and wound dehiscence – appeared to outweigh the advantages. According to the authors, these patients “might not live long enough to benefit from treatment.”

This finding mirrors oncologists’ observations regarding low-risk prostate cancer, for which watchful waiting is now the standard of care.

“At present, however, procedure rates [for patients with BCC] increase with age, and many basal cell carcinomas are treated surgically regardless of a patient’s life expectancy,” Eleni Linos, MD, PhD, professor of dermatology at Stanford (Calif.) University, and Mary-Margaret Chren, MD, chair of dermatology at Vanderbilt University, Nashville, Tenn., write in a viewpoint article published in August in JAMA Internal Medicine.

Considering the current treatment patterns for BCC, patients would “benefit from the existence of an evidence-based standard of care that includes active surveillance,” Mackenzie Wehner, MD, assistant professor at MD Anderson Cancer Center, Houston, Tex., writes in an editorial that accompanies the article in JAMA Dermatology.
 

Insights from the Dutch study

The article in JAMA Dermatology presents a cohort study conducted at Radboud University Medical Center in Nijmegen, the Netherlands. The study included 89 patients who were managed with watchful waiting. The patients received no treatment for at least 3 months following their diagnoses.

The median age of the patients was 83 years. The patients had a total of 280 BCCs. The median initial diameter of the BCCs was 9.5 mm. Just over half of the patients were men, and about half of the BCCs were in the head and neck region.

The median follow-up was 9 months; the maximum follow-up was 6.5 years. Remarkably, the investigators say, more than half the tumors (53.2%) did not grow, and some even shrank. The majority of patients were asymptomatic at presentation, and fewer than 10% developed new symptoms, such as bleeding and itching, during follow-up.

Among the tumors that did grow, 70% were low-risk superficial/nodular tumors, which only increased in size by an estimated 1.06 mm over a year. Thirty percent were higher-risk micronodular/infiltrative tumors, which grew an estimated 4.46 mm over a 12-month period.

About two-thirds of patients eventually chose to have at least one of their BCCs removed after a median of about 7 months. Only three BCCs (2.8%) needed more extensive surgery – reconstructive surgery, rather than primary closure, for instance – than would have been necessary with an earlier excision.

No deaths from BCC were reported in the study.

The investigators tracked the reasons patients opted for watchful waiting. Many understood that their tumors likely would not cause problems in their remaining years. Others prioritized dealing with more pressing health or family problems. Logistics came into play for some, such as not having reliable transportation for hospital visits.

“In patients with [limited life expectancy] and asymptomatic low-risk tumors, [watchful waiting] should be discussed as a potentially appropriate approach,” the investigators, led by Marieke E. C. van Winden, MD, a dermatology resident at Radboud University, conclude.

For patients who wish to pursue a watchful waiting approach, the Dutch team recommends conducting follow-up visits every 3-6 months to see whether patients wish to continue with watchful waiting and to determine whether the risk-to-benefit ratio has shifted.

These recommendations are in line with criteria Dr. Linos and Dr. Chren propose in their viewpoint article in JAMA Internal Medicine. They characterize low-risk BCCs as asymptomatic, smaller than 1 cm in diameter, and located on the trunk or extremities in immunocompetent patients. They note that details regarding active surveillance for BCCs need to be worked out.

“Active surveillance should be studied as a management option because it is supported by the available evidence, congruent with the care of other low-risk cancers, and in accord with principles of shared decision-making,” Dr. Linos and Dr. Chren write.

No funding source was reported. Dr. Wehner, Dr. van Winden, Dr. Linos, and Dr. Chren have disclosed no relevant financial relationships. Two of Dr. van Winden’s coauthors report ties to several companies, including Sanofi Genzyme, AbbVie, Novartis, and Janssen.

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

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Basal cell carcinomas (BCCs), the most common form of skin cancer, are generally slow-growing tumors that occur in older patients.

Given the low rates of metastasis and mortality associated with BCC, some patients do not require treatment. However, there have been no evidence-based recommendations on who may benefit from a watch-and-wait approach.

Now, a study published on Sept. 8 in JAMA Dermatology sheds light on which patients with BCC may be appropriate candidates for watchful waiting.

The investigators found that, for older people with low-grade BCCs and limited life expectancy, the risks associated with surgery – bleeding, infection, and wound dehiscence – appeared to outweigh the advantages. According to the authors, these patients “might not live long enough to benefit from treatment.”

This finding mirrors oncologists’ observations regarding low-risk prostate cancer, for which watchful waiting is now the standard of care.

“At present, however, procedure rates [for patients with BCC] increase with age, and many basal cell carcinomas are treated surgically regardless of a patient’s life expectancy,” Eleni Linos, MD, PhD, professor of dermatology at Stanford (Calif.) University, and Mary-Margaret Chren, MD, chair of dermatology at Vanderbilt University, Nashville, Tenn., write in a viewpoint article published in August in JAMA Internal Medicine.

Considering the current treatment patterns for BCC, patients would “benefit from the existence of an evidence-based standard of care that includes active surveillance,” Mackenzie Wehner, MD, assistant professor at MD Anderson Cancer Center, Houston, Tex., writes in an editorial that accompanies the article in JAMA Dermatology.
 

Insights from the Dutch study

The article in JAMA Dermatology presents a cohort study conducted at Radboud University Medical Center in Nijmegen, the Netherlands. The study included 89 patients who were managed with watchful waiting. The patients received no treatment for at least 3 months following their diagnoses.

The median age of the patients was 83 years. The patients had a total of 280 BCCs. The median initial diameter of the BCCs was 9.5 mm. Just over half of the patients were men, and about half of the BCCs were in the head and neck region.

The median follow-up was 9 months; the maximum follow-up was 6.5 years. Remarkably, the investigators say, more than half the tumors (53.2%) did not grow, and some even shrank. The majority of patients were asymptomatic at presentation, and fewer than 10% developed new symptoms, such as bleeding and itching, during follow-up.

Among the tumors that did grow, 70% were low-risk superficial/nodular tumors, which only increased in size by an estimated 1.06 mm over a year. Thirty percent were higher-risk micronodular/infiltrative tumors, which grew an estimated 4.46 mm over a 12-month period.

About two-thirds of patients eventually chose to have at least one of their BCCs removed after a median of about 7 months. Only three BCCs (2.8%) needed more extensive surgery – reconstructive surgery, rather than primary closure, for instance – than would have been necessary with an earlier excision.

No deaths from BCC were reported in the study.

The investigators tracked the reasons patients opted for watchful waiting. Many understood that their tumors likely would not cause problems in their remaining years. Others prioritized dealing with more pressing health or family problems. Logistics came into play for some, such as not having reliable transportation for hospital visits.

“In patients with [limited life expectancy] and asymptomatic low-risk tumors, [watchful waiting] should be discussed as a potentially appropriate approach,” the investigators, led by Marieke E. C. van Winden, MD, a dermatology resident at Radboud University, conclude.

For patients who wish to pursue a watchful waiting approach, the Dutch team recommends conducting follow-up visits every 3-6 months to see whether patients wish to continue with watchful waiting and to determine whether the risk-to-benefit ratio has shifted.

These recommendations are in line with criteria Dr. Linos and Dr. Chren propose in their viewpoint article in JAMA Internal Medicine. They characterize low-risk BCCs as asymptomatic, smaller than 1 cm in diameter, and located on the trunk or extremities in immunocompetent patients. They note that details regarding active surveillance for BCCs need to be worked out.

“Active surveillance should be studied as a management option because it is supported by the available evidence, congruent with the care of other low-risk cancers, and in accord with principles of shared decision-making,” Dr. Linos and Dr. Chren write.

No funding source was reported. Dr. Wehner, Dr. van Winden, Dr. Linos, and Dr. Chren have disclosed no relevant financial relationships. Two of Dr. van Winden’s coauthors report ties to several companies, including Sanofi Genzyme, AbbVie, Novartis, and Janssen.

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

Basal cell carcinomas (BCCs), the most common form of skin cancer, are generally slow-growing tumors that occur in older patients.

Given the low rates of metastasis and mortality associated with BCC, some patients do not require treatment. However, there have been no evidence-based recommendations on who may benefit from a watch-and-wait approach.

Now, a study published on Sept. 8 in JAMA Dermatology sheds light on which patients with BCC may be appropriate candidates for watchful waiting.

The investigators found that, for older people with low-grade BCCs and limited life expectancy, the risks associated with surgery – bleeding, infection, and wound dehiscence – appeared to outweigh the advantages. According to the authors, these patients “might not live long enough to benefit from treatment.”

This finding mirrors oncologists’ observations regarding low-risk prostate cancer, for which watchful waiting is now the standard of care.

“At present, however, procedure rates [for patients with BCC] increase with age, and many basal cell carcinomas are treated surgically regardless of a patient’s life expectancy,” Eleni Linos, MD, PhD, professor of dermatology at Stanford (Calif.) University, and Mary-Margaret Chren, MD, chair of dermatology at Vanderbilt University, Nashville, Tenn., write in a viewpoint article published in August in JAMA Internal Medicine.

Considering the current treatment patterns for BCC, patients would “benefit from the existence of an evidence-based standard of care that includes active surveillance,” Mackenzie Wehner, MD, assistant professor at MD Anderson Cancer Center, Houston, Tex., writes in an editorial that accompanies the article in JAMA Dermatology.
 

Insights from the Dutch study

The article in JAMA Dermatology presents a cohort study conducted at Radboud University Medical Center in Nijmegen, the Netherlands. The study included 89 patients who were managed with watchful waiting. The patients received no treatment for at least 3 months following their diagnoses.

The median age of the patients was 83 years. The patients had a total of 280 BCCs. The median initial diameter of the BCCs was 9.5 mm. Just over half of the patients were men, and about half of the BCCs were in the head and neck region.

The median follow-up was 9 months; the maximum follow-up was 6.5 years. Remarkably, the investigators say, more than half the tumors (53.2%) did not grow, and some even shrank. The majority of patients were asymptomatic at presentation, and fewer than 10% developed new symptoms, such as bleeding and itching, during follow-up.

Among the tumors that did grow, 70% were low-risk superficial/nodular tumors, which only increased in size by an estimated 1.06 mm over a year. Thirty percent were higher-risk micronodular/infiltrative tumors, which grew an estimated 4.46 mm over a 12-month period.

About two-thirds of patients eventually chose to have at least one of their BCCs removed after a median of about 7 months. Only three BCCs (2.8%) needed more extensive surgery – reconstructive surgery, rather than primary closure, for instance – than would have been necessary with an earlier excision.

No deaths from BCC were reported in the study.

The investigators tracked the reasons patients opted for watchful waiting. Many understood that their tumors likely would not cause problems in their remaining years. Others prioritized dealing with more pressing health or family problems. Logistics came into play for some, such as not having reliable transportation for hospital visits.

“In patients with [limited life expectancy] and asymptomatic low-risk tumors, [watchful waiting] should be discussed as a potentially appropriate approach,” the investigators, led by Marieke E. C. van Winden, MD, a dermatology resident at Radboud University, conclude.

For patients who wish to pursue a watchful waiting approach, the Dutch team recommends conducting follow-up visits every 3-6 months to see whether patients wish to continue with watchful waiting and to determine whether the risk-to-benefit ratio has shifted.

These recommendations are in line with criteria Dr. Linos and Dr. Chren propose in their viewpoint article in JAMA Internal Medicine. They characterize low-risk BCCs as asymptomatic, smaller than 1 cm in diameter, and located on the trunk or extremities in immunocompetent patients. They note that details regarding active surveillance for BCCs need to be worked out.

“Active surveillance should be studied as a management option because it is supported by the available evidence, congruent with the care of other low-risk cancers, and in accord with principles of shared decision-making,” Dr. Linos and Dr. Chren write.

No funding source was reported. Dr. Wehner, Dr. van Winden, Dr. Linos, and Dr. Chren have disclosed no relevant financial relationships. Two of Dr. van Winden’s coauthors report ties to several companies, including Sanofi Genzyme, AbbVie, Novartis, and Janssen.

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

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Should I get a COVID-19 booster shot?

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Wed, 09/22/2021 - 14:17

When I was in Florida a few weeks ago, I met a friend outside who approached me wearing an N-95 mask. He said he was wearing it because the Delta variant was running wild in Florida, and several of his younger unvaccinated employees had contracted it, and he encouraged me to get a COVID booster shot. In the late summer, although the federal government recommended booster shots for anyone 8 months after their original vaccination series, national confusion still reigns, with an Food and Drug Administration advisory panel more recently recommending against a Pfizer booster for all adults, but supporting a booster for those ages 65 and older or at a high risk for severe COVID-19.

Dr. Brett M. Coldiron
Dr. Brett M. Coldiron

At the end of December, I was excited when the local hospital whose staff I am on made the Moderna vaccine available. I had to wait several hours but it was worth it, and I did not care about the low-grade fever and malaise I experienced after the second dose. Astoundingly, I still have patients who have not been vaccinated, although many of them are elderly, frail, or immunocompromised. I think people who publicly argue against vaccination need to visit their local intensive care unit.

While less so than some other physicians, dermatologists are also vulnerable to COVID exposure. You can’t look in someone’s throat, or examine facial skin if they are wearing a mask – and you must lean in to see anything. We take all reasonable precautions, wearing masks, wiping down exam rooms and door handles, keeping the waiting room as empty as possible, using HEPA filters, and keeping exhaust fans going in the rooms continuously. My staff have all been vaccinated (I’m lucky there).

Still, if you are seeing 30 or 40 patients a day of all age groups and working in small unventilated rooms, you could be exposed to the Delta variant. While breakthrough infections among fully vaccinated immunocompetent individuals may be rare, if you do develop a breakthrough case, even if mild or asymptomatic, CDC recommendations include quarantining for at least 10 days. Obviously, this can be disastrous to your practice as a COVID infection works through your office.

This brings us to back to booster shots. Personally, I think all health care workers should be eager to get a booster shot. I also think individuals who have wide public exposure, particularly indoors, such as teachers and retail sales workers, should be eager to get one too. Here are some of the pros, as well as some cons for boosters.
 

Arguments for booster shots

  • Booster shots should elevate your antibody levels and make you more resistant to breakthrough infections, but this is still theoretical. Antibody levels decline over time – more rapidly in those over 56 years of age.
  • Vaccine doses go to waste every month in the United States, although specific numbers are lacking.
  • Vaccinated individuals almost never get hospitalized and die from COVID, presumably even fewer do so after receiving a booster.
  • You could unwittingly become a vector. Many of the breakthrough infections are mild and without symptoms. If you do test positive, it could be devastating to your patients, and your medical practice.

Arguments against booster shots

  • These vaccine doses should be going to other countries that have low vaccination levels where many of the nasty variants are developing.
  • You may have side effects from the vaccine, though thrombosis has only been seen with the Astra-Zeneca and Johnson and Johnson vaccines. Myocarditis is usually seen in younger patients and is almost always self limited.
  • Breakthrough infections are rare.

This COVID pandemic is moving and changing so fast, it is bewildering. But with a little luck, COVID could eventually become an annual nuisance like the flu, and the COVID vaccine will become an annual shot based on the newest mutations. For now, my opinion is, get your booster shot.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

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When I was in Florida a few weeks ago, I met a friend outside who approached me wearing an N-95 mask. He said he was wearing it because the Delta variant was running wild in Florida, and several of his younger unvaccinated employees had contracted it, and he encouraged me to get a COVID booster shot. In the late summer, although the federal government recommended booster shots for anyone 8 months after their original vaccination series, national confusion still reigns, with an Food and Drug Administration advisory panel more recently recommending against a Pfizer booster for all adults, but supporting a booster for those ages 65 and older or at a high risk for severe COVID-19.

Dr. Brett M. Coldiron
Dr. Brett M. Coldiron

At the end of December, I was excited when the local hospital whose staff I am on made the Moderna vaccine available. I had to wait several hours but it was worth it, and I did not care about the low-grade fever and malaise I experienced after the second dose. Astoundingly, I still have patients who have not been vaccinated, although many of them are elderly, frail, or immunocompromised. I think people who publicly argue against vaccination need to visit their local intensive care unit.

While less so than some other physicians, dermatologists are also vulnerable to COVID exposure. You can’t look in someone’s throat, or examine facial skin if they are wearing a mask – and you must lean in to see anything. We take all reasonable precautions, wearing masks, wiping down exam rooms and door handles, keeping the waiting room as empty as possible, using HEPA filters, and keeping exhaust fans going in the rooms continuously. My staff have all been vaccinated (I’m lucky there).

Still, if you are seeing 30 or 40 patients a day of all age groups and working in small unventilated rooms, you could be exposed to the Delta variant. While breakthrough infections among fully vaccinated immunocompetent individuals may be rare, if you do develop a breakthrough case, even if mild or asymptomatic, CDC recommendations include quarantining for at least 10 days. Obviously, this can be disastrous to your practice as a COVID infection works through your office.

This brings us to back to booster shots. Personally, I think all health care workers should be eager to get a booster shot. I also think individuals who have wide public exposure, particularly indoors, such as teachers and retail sales workers, should be eager to get one too. Here are some of the pros, as well as some cons for boosters.
 

Arguments for booster shots

  • Booster shots should elevate your antibody levels and make you more resistant to breakthrough infections, but this is still theoretical. Antibody levels decline over time – more rapidly in those over 56 years of age.
  • Vaccine doses go to waste every month in the United States, although specific numbers are lacking.
  • Vaccinated individuals almost never get hospitalized and die from COVID, presumably even fewer do so after receiving a booster.
  • You could unwittingly become a vector. Many of the breakthrough infections are mild and without symptoms. If you do test positive, it could be devastating to your patients, and your medical practice.

Arguments against booster shots

  • These vaccine doses should be going to other countries that have low vaccination levels where many of the nasty variants are developing.
  • You may have side effects from the vaccine, though thrombosis has only been seen with the Astra-Zeneca and Johnson and Johnson vaccines. Myocarditis is usually seen in younger patients and is almost always self limited.
  • Breakthrough infections are rare.

This COVID pandemic is moving and changing so fast, it is bewildering. But with a little luck, COVID could eventually become an annual nuisance like the flu, and the COVID vaccine will become an annual shot based on the newest mutations. For now, my opinion is, get your booster shot.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

When I was in Florida a few weeks ago, I met a friend outside who approached me wearing an N-95 mask. He said he was wearing it because the Delta variant was running wild in Florida, and several of his younger unvaccinated employees had contracted it, and he encouraged me to get a COVID booster shot. In the late summer, although the federal government recommended booster shots for anyone 8 months after their original vaccination series, national confusion still reigns, with an Food and Drug Administration advisory panel more recently recommending against a Pfizer booster for all adults, but supporting a booster for those ages 65 and older or at a high risk for severe COVID-19.

Dr. Brett M. Coldiron
Dr. Brett M. Coldiron

At the end of December, I was excited when the local hospital whose staff I am on made the Moderna vaccine available. I had to wait several hours but it was worth it, and I did not care about the low-grade fever and malaise I experienced after the second dose. Astoundingly, I still have patients who have not been vaccinated, although many of them are elderly, frail, or immunocompromised. I think people who publicly argue against vaccination need to visit their local intensive care unit.

While less so than some other physicians, dermatologists are also vulnerable to COVID exposure. You can’t look in someone’s throat, or examine facial skin if they are wearing a mask – and you must lean in to see anything. We take all reasonable precautions, wearing masks, wiping down exam rooms and door handles, keeping the waiting room as empty as possible, using HEPA filters, and keeping exhaust fans going in the rooms continuously. My staff have all been vaccinated (I’m lucky there).

Still, if you are seeing 30 or 40 patients a day of all age groups and working in small unventilated rooms, you could be exposed to the Delta variant. While breakthrough infections among fully vaccinated immunocompetent individuals may be rare, if you do develop a breakthrough case, even if mild or asymptomatic, CDC recommendations include quarantining for at least 10 days. Obviously, this can be disastrous to your practice as a COVID infection works through your office.

This brings us to back to booster shots. Personally, I think all health care workers should be eager to get a booster shot. I also think individuals who have wide public exposure, particularly indoors, such as teachers and retail sales workers, should be eager to get one too. Here are some of the pros, as well as some cons for boosters.
 

Arguments for booster shots

  • Booster shots should elevate your antibody levels and make you more resistant to breakthrough infections, but this is still theoretical. Antibody levels decline over time – more rapidly in those over 56 years of age.
  • Vaccine doses go to waste every month in the United States, although specific numbers are lacking.
  • Vaccinated individuals almost never get hospitalized and die from COVID, presumably even fewer do so after receiving a booster.
  • You could unwittingly become a vector. Many of the breakthrough infections are mild and without symptoms. If you do test positive, it could be devastating to your patients, and your medical practice.

Arguments against booster shots

  • These vaccine doses should be going to other countries that have low vaccination levels where many of the nasty variants are developing.
  • You may have side effects from the vaccine, though thrombosis has only been seen with the Astra-Zeneca and Johnson and Johnson vaccines. Myocarditis is usually seen in younger patients and is almost always self limited.
  • Breakthrough infections are rare.

This COVID pandemic is moving and changing so fast, it is bewildering. But with a little luck, COVID could eventually become an annual nuisance like the flu, and the COVID vaccine will become an annual shot based on the newest mutations. For now, my opinion is, get your booster shot.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

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Doctor who claimed masks hurt health loses license

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Wed, 09/22/2021 - 15:50

The Oregon Medical Board has revoked the license of a doctor who didn’t follow COVID-19 guidelines in his office and even told some patients that wearing face masks could lead to carbon-dioxide poisoning.

Steven Arthur LaTulippe’s advice to patients about face masking amounted to “gross negligence” in the practice of medicine and was grounds for discipline, the medical board said in a report.

Mr. LaTulippe, who had a family practice in Dallas, was fined $10,000, Insider reported. The board also said he’d overprescribed opioids for some patients.

The medical board report said Mr. LaTulippe and his wife, who ran the clinic with him, didn’t wear face masks while treating patients from March to December 2020.

Mr. LaTulippe told elderly and pediatric patients that mask wearing could hurt their health by exacerbating COPD and asthma and could contribute to heart attacks and other medical problems, the report said.

“Licensee asserts masks are likely to harm patients by increasing the body’s carbon dioxide content through rebreathing of gas trapped behind a mask,” the report said.

The report noted that “the amount of carbon dioxide rebreathed within a mask is trivial and would easily be expelled by an increase in minute ventilation so small it would not be noticed.”

The report said Mr. LaTulippe told patients they didn’t have to wear a mask in the clinic unless they were “acutely ill,” “coughing,” or “congested,” even though the Centers for Disease Control and Prevention and the Oregon governor had recommended masks be worn to prevent the spread of the virus.

Before coming into the office, patients weren’t asked if they’d had recent contact with anybody who was infected or showed COVID symptoms, the report said.

The medical board first suspended his license in September. He said he would not change his conduct concerning face masks.

“Licensee has confirmed that he will refuse to abide by the state’s COVID-19 protocols in the future as well, affirming that in a choice between losing his medical license versus wearing a mask in his clinic and requiring his patients and staff to wear a mask in his clinic, he will, ‘choose to sacrifice my medical license with no hesitation’ ” the medical board’s report said.

Mr. LaTulippe told the medical board that he was “a strong asset to the public in educating them on the real facts about this pandemic” and that “at least 98% of my patients were so extremely thankful that I did not wear a mask or demand wearing a mask in my clinic.”

The medical board found Mr. LaTulippe engaged in 8 instances of unprofessional or dishonorable conduct, 22 instances of negligence in the practice of medicine, and 5 instances of gross negligence in the practice of medicine.

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

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The Oregon Medical Board has revoked the license of a doctor who didn’t follow COVID-19 guidelines in his office and even told some patients that wearing face masks could lead to carbon-dioxide poisoning.

Steven Arthur LaTulippe’s advice to patients about face masking amounted to “gross negligence” in the practice of medicine and was grounds for discipline, the medical board said in a report.

Mr. LaTulippe, who had a family practice in Dallas, was fined $10,000, Insider reported. The board also said he’d overprescribed opioids for some patients.

The medical board report said Mr. LaTulippe and his wife, who ran the clinic with him, didn’t wear face masks while treating patients from March to December 2020.

Mr. LaTulippe told elderly and pediatric patients that mask wearing could hurt their health by exacerbating COPD and asthma and could contribute to heart attacks and other medical problems, the report said.

“Licensee asserts masks are likely to harm patients by increasing the body’s carbon dioxide content through rebreathing of gas trapped behind a mask,” the report said.

The report noted that “the amount of carbon dioxide rebreathed within a mask is trivial and would easily be expelled by an increase in minute ventilation so small it would not be noticed.”

The report said Mr. LaTulippe told patients they didn’t have to wear a mask in the clinic unless they were “acutely ill,” “coughing,” or “congested,” even though the Centers for Disease Control and Prevention and the Oregon governor had recommended masks be worn to prevent the spread of the virus.

Before coming into the office, patients weren’t asked if they’d had recent contact with anybody who was infected or showed COVID symptoms, the report said.

The medical board first suspended his license in September. He said he would not change his conduct concerning face masks.

“Licensee has confirmed that he will refuse to abide by the state’s COVID-19 protocols in the future as well, affirming that in a choice between losing his medical license versus wearing a mask in his clinic and requiring his patients and staff to wear a mask in his clinic, he will, ‘choose to sacrifice my medical license with no hesitation’ ” the medical board’s report said.

Mr. LaTulippe told the medical board that he was “a strong asset to the public in educating them on the real facts about this pandemic” and that “at least 98% of my patients were so extremely thankful that I did not wear a mask or demand wearing a mask in my clinic.”

The medical board found Mr. LaTulippe engaged in 8 instances of unprofessional or dishonorable conduct, 22 instances of negligence in the practice of medicine, and 5 instances of gross negligence in the practice of medicine.

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

The Oregon Medical Board has revoked the license of a doctor who didn’t follow COVID-19 guidelines in his office and even told some patients that wearing face masks could lead to carbon-dioxide poisoning.

Steven Arthur LaTulippe’s advice to patients about face masking amounted to “gross negligence” in the practice of medicine and was grounds for discipline, the medical board said in a report.

Mr. LaTulippe, who had a family practice in Dallas, was fined $10,000, Insider reported. The board also said he’d overprescribed opioids for some patients.

The medical board report said Mr. LaTulippe and his wife, who ran the clinic with him, didn’t wear face masks while treating patients from March to December 2020.

Mr. LaTulippe told elderly and pediatric patients that mask wearing could hurt their health by exacerbating COPD and asthma and could contribute to heart attacks and other medical problems, the report said.

“Licensee asserts masks are likely to harm patients by increasing the body’s carbon dioxide content through rebreathing of gas trapped behind a mask,” the report said.

The report noted that “the amount of carbon dioxide rebreathed within a mask is trivial and would easily be expelled by an increase in minute ventilation so small it would not be noticed.”

The report said Mr. LaTulippe told patients they didn’t have to wear a mask in the clinic unless they were “acutely ill,” “coughing,” or “congested,” even though the Centers for Disease Control and Prevention and the Oregon governor had recommended masks be worn to prevent the spread of the virus.

Before coming into the office, patients weren’t asked if they’d had recent contact with anybody who was infected or showed COVID symptoms, the report said.

The medical board first suspended his license in September. He said he would not change his conduct concerning face masks.

“Licensee has confirmed that he will refuse to abide by the state’s COVID-19 protocols in the future as well, affirming that in a choice between losing his medical license versus wearing a mask in his clinic and requiring his patients and staff to wear a mask in his clinic, he will, ‘choose to sacrifice my medical license with no hesitation’ ” the medical board’s report said.

Mr. LaTulippe told the medical board that he was “a strong asset to the public in educating them on the real facts about this pandemic” and that “at least 98% of my patients were so extremely thankful that I did not wear a mask or demand wearing a mask in my clinic.”

The medical board found Mr. LaTulippe engaged in 8 instances of unprofessional or dishonorable conduct, 22 instances of negligence in the practice of medicine, and 5 instances of gross negligence in the practice of medicine.

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

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